Domain randomization is a widely adopted technique in deep reinforcement learning(DRL)to improve agent generalization by exposing policies to diverse environmental conditions.This paper investigates the impact of diff...Domain randomization is a widely adopted technique in deep reinforcement learning(DRL)to improve agent generalization by exposing policies to diverse environmental conditions.This paper investigates the impact of different reset strategies,normal,non-randomized,and randomized,on agent performance using the Deep Deterministic Policy Gradient(DDPG)and Twin Delayed DDPG(TD3)algorithms within the CarRacing-v2 environment.Two experimental setups were conducted:an extended training regime with DDPG for 1000 steps per episode across 1000 episodes,and a fast execution setup comparing DDPG and TD3 for 30 episodes with 50 steps per episode under constrained computational resources.A step-based reward scaling mechanism was applied under the randomized reset condition to promote broader state exploration.Experimental results showthat randomized resets significantly enhance learning efficiency and generalization,with DDPG demonstrating superior performance across all reset strategies.In particular,DDPG combined with randomized resets achieves the highest smoothed rewards(reaching approximately 15),best stability,and fastest convergence.These differences are statistically significant,as confirmed by t-tests:DDPG outperforms TD3 under randomized(t=−101.91,p<0.0001),normal(t=−21.59,p<0.0001),and non-randomized(t=−62.46,p<0.0001)reset conditions.The findings underscore the critical role of reset strategy and reward shaping in enhancing the robustness and adaptability of DRL agents in continuous control tasks,particularly in environments where computational efficiency and training stability are crucial.展开更多
Objectives:To explore the efficacy and safety of virtual reality(VR)in relieving negative emotions in patients with breast cancer with different personalities.Methods:A randomized controlled trial was conducted.Betwee...Objectives:To explore the efficacy and safety of virtual reality(VR)in relieving negative emotions in patients with breast cancer with different personalities.Methods:A randomized controlled trial was conducted.Between April 2023 and October 2023,we enrolled patients with breast cancer treated in the Department of Breast Cancer and Oncology at Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangdong Province.The patients were randomly divided into an intervention group(n=118)and a control group(n=119)using block randomization.The intervention group received the VR intervention 3-5 times over 5±2 weeks using natural landscapes with music or relaxation guidance,and the duration of each VR intervention was 15±3 min.The control group received routine nursing care,including disease education and psychological counseling.Patients were assessed using the Type D Scale,Positive and Negative Affect Scale,and Distress Thermometer,and adverse events during the intervention were recorded.Results:Overall,85 patients completed the study(44 in the intervention group and 41 in the control group).Patients with Type D personalities showed more negative emotions[25.0(21.5,27.5)vs.19.0(16.0,24.0),P=0.001]and distressed attitudes[4.0(2.0,5.0)vs.3.0(1.0,4.0),P=0.020]with fewer positive emotions(27.2±5.6 vs.31.0±5.9,P=0.014)than those with non-Type D personalities.Total population analysis revealed no significant differences between the groups.However,in the subgroup analysis,patients with Type D personalities in the intervention group showed greater relief from negative emotions than those in the control group[median difference,-5.0(-9.0,-2.5)vs.-2.0(-4.0,2.0),P=0.046].No significant differences were found between groups of patients with non-Type D personality traits.The proportion of adverse events was not significantly different between groups(P=0.110).Conclusions:Breast cancer patients with Type D personalities suffer more severe negative emotions and distress,and more attention should be paid to them.VR intervention significantly and safely reduced negative emotions in patients with Type D personalities.展开更多
Adaptor signature,a new primitive that alleviates the scalability issue of blockchain to some extent,has been widely adopted in the off-chain payment channel and atomic swap.As an extension of standard digital signatu...Adaptor signature,a new primitive that alleviates the scalability issue of blockchain to some extent,has been widely adopted in the off-chain payment channel and atomic swap.As an extension of standard digital signature,adaptor signature can bind the release of a complete digital signature with the exchange of a secret value.Existing constructions of adaptor signatures are mainly based on Schnorr or ECDSA signature algorithms,which suffer low signing efficiency and long signature length.In this paper,to address these issues,we propose a new construction of adaptor signature using randomized EdDSA,which has Schnorr-like structure with higher signing efficiency and shorter signature length.We prove the required security properties,including unforgeability,witness extractability and pre-signature adaptability,of the new adaptor signature scheme in the random oracle model.We conduct a comparative analysis with an ECDSA-based adaptor signature scheme to demonstrate the effectiveness and feasibility of our new proposal.展开更多
The current study aimed to evaluate the efficacy and safety of Compound Danshen Dripping Pills(CDDP)in improving cardiac function in patients with acute anterior ST-segment elevation myocardial infarction(AAMI).Betwee...The current study aimed to evaluate the efficacy and safety of Compound Danshen Dripping Pills(CDDP)in improving cardiac function in patients with acute anterior ST-segment elevation myocardial infarction(AAMI).Between February 2021 and February 2023,247 eligible patients with AAMI after primary percutaneous coronary intervention were enrolled and randomly assigned(1∶1)to receive CDDP(n=126)or placebo(n=121),with a follow-up of 48 weeks.Compared with the placebo group,the CDDP group demonstrated a significant increase in left ventricular ejection fraction values after 24 weeks of treatment(least squares mean:3.31;95%confidence interval[CI]:1.72–4.90;P<0.001)and at the 48-week follow-up(least squares mean:4.35;95%CI:2.76–5.94;P<0.001).Significant reductions in N-terminal pro-B-type natriuretic peptide levels were observed in both groups at the 24-and 48-week visits with no significant difference between the two groups(P>0.1 for all).The incidence of major adverse cardiovascular and cerebrovascular events was 6.35%in the CDDP group and 5.79%in the placebo group(P=0.822).Notably,no serious adverse events were attributed to CDDP.These findings suggest that CDDP may be well tolerated and could improve left ventricular ejection fraction in patients with AAMI at 24 and 48 weeks.展开更多
OBJECTIVE:In recent years,the number of clinical research reports on acupuncture and manipulation for the treatment of greater occipital neuralgia has gradually increased,but the quality is uneven.There is currently n...OBJECTIVE:In recent years,the number of clinical research reports on acupuncture and manipulation for the treatment of greater occipital neuralgia has gradually increased,but the quality is uneven.There is currently no literature evaluating the quality of published reports,which is not conducive to the promotion of clinical use of these therapies.Therefore,this article assessed the reporting quality of randomized controlled trials on acupuncture and manipulation for greater occipital neuralgia.METHODS:Cochrane Library,PubMed,Web of Science,Embase,China National Knowledge Infrastructure(CNKI),VIP,WanFang Data,and Chinese BioMedical Literature Database(CBM)from inception to May 20,2024 were searched.The reporting quality of included randomized controlled trials was independently evaluated by two investigators using the CONSORT statement,STRICTA checklist,and Cochrane bias of risk assessment tool.A third investigator resolved any disagreement.RESULTS:A total of 62 articles were included.Based on the CONSORT statement,59.46%(22/37)of all entries had a reporting rate of less than 50%,mainly including“Identification as a randomized trial in the title(1/62,1.61%),”“How sample size was determined(7/62,11.29%),”“Implementation(1/62,1.61%),”“Blinding(1/62,1.61%),”and“Reports of Funding(4/62,6.45%).”According to the STRICTA checklist,29.41%(5/17)of all entries had a reporting rate of less than 50%,mainly including“Details of other interventions(7/58,12.07%),”“Setting and context of treatment(0/58,0%),”and“Description of participating acupuncturists(0/58,0%).”CONCLUSION:The reporting quality of randomized controlled trials on acupuncture and manipulation therapy for greater occipital neuralgia remains low.Future researchers need to make greater efforts to strictly adhere to the CONSORT statement and STRICTA checklist during trial design,implementation,and reporting.This will facilitate the standardization of research in this field and enhance the reliability and reproducibility of the research results.展开更多
BACKGROUND Nutritional psychiatry is a rapidly expanding field of research,with mounting evidence suggesting that nutritional factors may play a role in the development of psychiatric disorders.AIM To examine the leve...BACKGROUND Nutritional psychiatry is a rapidly expanding field of research,with mounting evidence suggesting that nutritional factors may play a role in the development of psychiatric disorders.AIM To examine the level of evidence for nutritional psychiatry.METHODS A scoping review was conducted to assess the current state of nutritional psychiatry,including a search for randomized controlled trials(RCTs).RESULTS The review identified a total of seven papers,with many concentrating on the relationship between depression and the gut microbiome.A salient issue that emerged from this review was the paucity of sample size in many studies.The inherent complexity of nutritional studies,characterized by a multitude of potential factors and exposures that often act as confounders,poses significant challenges to the development of effective RCT designs.The analysis revealed that probiotics,though demonstrating efficacy,exhibited a modest effect size.CONCLUSION Conducting RCTs with effective markers is imperative from these studies.The implementation of Mendelian randomization and the investigation of mechanisms in basic research are essential complementary approaches.展开更多
Background Unsedated colonoscopy is an important method used for diagnosing colorectal cancer,but it can cause discomfort such as pain and bloating,as well as anxiety.At present,the relief is mainly achieved through m...Background Unsedated colonoscopy is an important method used for diagnosing colorectal cancer,but it can cause discomfort such as pain and bloating,as well as anxiety.At present,the relief is mainly achieved through methods such as changing positions and manual pressing,but the efficacy is limited.Hence alternative therapies for sedation and analgesia in unsedated colonoscopy warrant further study.Electroacupuncture(EA)can simplify the procedure of anesthesia and analgesia,while the efficacy of EA on unsedated colonoscopy remains unclear.Therefore,a well-designed randomized controlled trial is needed to demonstrate the potential efficacy of acupuncture in unsedated colonoscopy,particularly for pain relief.Methods In this prospective randomized sham-controlled trial,105 eligible participants will be recruited and randomly assigned to either EA group(n=35),sham EA group(n=35),or control group(n=35)in a 1:1:1 ratio.The EA group will receive acupuncture intervention on bilateral Hegu(LI4),Neiguan(PC6),Zusanli(ST36),and Shenmen(HT7),with LI4 and PC6 on both sides connected to the EA device.The sham EA group will received non transdermal needling on points of no meridian,and deliberately connect the needle to the incorrect output socket of EA device to block the stimulation.The needling will conducted from 30 min before the unsedated colonoscopy to the end of the colonoscopy,the whole retention time would be approximately 40 min.The participants in the control group will not receive any acupuncture intervention.All participants of the three groups will not receive any other treatment.Primary outcomes:Numerical Rating Scale(NRS)reported by participants and Face Pain Scale Revised(FPS-R)evaluated by observers of four areas of the participants during the unsedated colonoscopy.Secondary outcomes:tolerance reported by endoscopists,tolerance reported by participants,satisfaction reported by endoscopists,satisfaction reported by participants,adverse events during the unsedated colonoscopy,postoperative discomfort,unsedated colonoscopy smoothness(cecal insertion time,unwinding time,success rate of one-time intubation).Both intention-to-treat(ITT)and per-protocol(PP)analyses will be performed to assess the efficacy of EA.Discussion The trial will explore the efficacy of relieving pain,improving tolerability,and reducing undesirable adverse events of EA for unsedated colonoscopy.The results of this trial will provide sound evidence for promoting the clinical application of EA for unsedated colonoscopy.Trial registration ClinicalTrials.gov Identifier:ChiCTR2300069903,retrospectively registered on March 16,2023.展开更多
Background:Electroacupuncture(EA)may affect the severity of hot flashes(HFs)associated with natural menopause and provide additional benefits for postmenopausal women.However,the evidence for its effectiveness in the ...Background:Electroacupuncture(EA)may affect the severity of hot flashes(HFs)associated with natural menopause and provide additional benefits for postmenopausal women.However,the evidence for its effectiveness in the management of early postmenopausal HFs remains inadequately understood.Objective:We designed this trial to assess the efficacy and safety of EA for relieving early postmenopausal HFs.Design,setting,participants and interventions:This randomized sham-controlled trial involved 72 women with HFs.The participants were divided equally into the intervention and control groups.The intervention group was treated with EA,while the control group was treated with sham acupuncture.The main acupoints used were Hegu(LI4),Guanyuan(RN4),Sanyinjiao(SP6),Taixi(KI3),Fuliu(KI7)and Shenshu(BL23).All participants received 18 treatment sessions,distributed across a 6-week period.The treatment was administered on three occasions per week,adhering to a fixed weekday schedule(Monday,Wednesday,Friday or Tuesday,Thursday,Saturday)with a minimum interval of one day between sessions.Each patient received a 12-week follow-up.Main outcome measures:The HF score was the primary outcome.Participants documented the frequency and severity of HFs in a 7-day symptom diary,which provided data for calculating the HF score.Secondary outcomes were the Menopause Rating Scale(MRS),Menopause-Specific Quality of Life Questionnaire(MENQOL),Pittsburgh Sleep Quality Index(PSQI)and Traditional Chinese Medicine Syndrome Score Scale(TCMSSS),as well as estradiol(E2),luteinizing hormone(LH)and folliclestimulating hormone(FSH)levels.Results:Both groups demonstrated significant reductions in HF scores after the treatment and during the follow-up(P<0.001).Immediately after completion of the 6-week treatment cycle and at 12 weeks postintervention,the HF scores were similar in both groups.At week 6,the intervention group showed significantly greater improvements in MRS,MENQOL(vasomotor,psychosocial,and physical),PSQI and TCMSSS scores(P<0.05).The improvements in the MENQOL(vasomotor,and psychosocial)and PSQI total scores persisted through the follow-up(P<0.05).However,the results showed no significant inter-or intragroup differences in sexual scores on the MENQOL(P>0.05).EA did not significantly decrease E2,LH or FSH levels compared to placebo.The incidence of adverse events was similar in both groups.Conclusion:EA does not significantly improve HFs in early postmenopausal patients.However,it enhances the quality of sleep and decreases menopausal symptoms across vasomotor,psychosocial and physical domains.Trial registration:Chinese Clinical Trial Registry(http://www.chictr.org.cn);Trial ID:Chi CTR2300072002.Please cite this article as:Wang HX,Yu XT,Hu J,Chen JJ,Mei YT,Chen YF.Electroacupuncture for hot flashes in early menopause:A randomized sham-controlled trial.J Integr Med.2025;23(5):519-527.?2025 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine.Published by Elsevier B.V.All rights are reserved,including those for text and data mining,AI training,and similar technologies.展开更多
OBJECTIVE:To evaluate the efficacy of electroacupuncture(EA)at scalp motor area for treating post-stroke wrist dyskinesia and its influence on the function of wrist movement-related agonistic muscles.METHODS:A randomi...OBJECTIVE:To evaluate the efficacy of electroacupuncture(EA)at scalp motor area for treating post-stroke wrist dyskinesia and its influence on the function of wrist movement-related agonistic muscles.METHODS:A randomized,single-blind,controlled clinical trial was conducted.Sixty-six patients undergoing post-stroke wrist dyskinesia were enrolled and randomized 1:1 to EA or control group.Patients in the control group received manual acupuncture in the scalp motor area(MS 6)on the lesion side.The same acupoint was selected to accept EA stimulation in the EA group.All patients were treated six times a week for three weeks.The primary outcome was the Chinese Stroke Scale(CSS)score.The secondary outcomes included upper limb-related Barthel Index(BI)score,active range of motion(AROM)of the wrist joint,and root mean square(RMS)of the four agonistic muscles associated with wrist motion on the hemiplegic side of patients,i.e.,the extensor carpi radialis longus(ECRL),extensor digitorum(ED),flexor carpi radialis(FCR)and flexor carpi ulnaris(FCU).The above indicators were measured before and after three weeks of treatment.RESULTS:After 3-week treatment,the CSS score and AROM of wrist dorsiflexion of the EA group were better than those in the control group(P=0.038,P=0.047).The differences between the two groups of BI scores and AROM of wrist flexion were not significant(P>0.05).All RMS of the EA group were higher than those in the control group(ECRL:P=0.047,ED:P=0.048,FCR:P=0.049,FCU:P=0.047).The total effective rate in the EA group was 87.50%(28/32),which was higher than that in the control group(77.42%,24/31,P=0.048).CONCLUSION:EA stimulation of the scalp motor area can promote the recovery of the strength and function of the agonistic muscles related to wrist movement and effectively improve post-stroke wrist dyskinesia.展开更多
BACKGROUND In randomized controlled trials(RCTs),the placebo arm has often been ignored as the attention tends to be focused on the treatment arm.We undertook a meta-analysis based on the data from the placebo arm in ...BACKGROUND In randomized controlled trials(RCTs),the placebo arm has often been ignored as the attention tends to be focused on the treatment arm.We undertook a meta-analysis based on the data from the placebo arm in RCTs of hepatocellular carci-noma(HCC),the response rates and survival status,and adverse events(AEs)were summarized and evaluated.AIM To systematically evaluate the response rates,survival status and AEs in the placebo arms of RCTs for HCC.METHODS A systematic search was performed on PubMed,Ovid MEDLINE,Embase and Cochrane Library to identify relevant trials evaluating the efficacy of drugs for the treatment of HCC,published until December 31,2023.Statistical analysis was performed using R statistical software(version 4.3.2).RESULTS A total of 18 RCTs,involving 2390 patients,met the criteria for inclusion in the meta-analysis.The pooled overall disease control rate and objective response rate in the placebo group were 38%[95%confidence interval(CI):33%-42%]and 1%(95%CI:1%-2%),respectively.Overall survival and progression-free survival in the placebo group were 7.9 months(95%CI:7.6-8.31 months)and 1.9 months(95%CI:1.6-2.1 months),respectively.The incidence of grade 3 or 4 AEs was 37%(95%CI:30%-43%).Additionally,the incidence of interruptions or dose reductions due to AEs was 20%(95%CI:13%-27%),while the incidence of treatment discontinuation due to AEs was 9%(95%CI:6%-12%).CONCLUSION Over one-third of advanced HCC patients exhibit therapy-free disease control,with placebo-arm AEs observed.These findings guide single-arm trials design and enhance patient acceptance of anticancer therapies.展开更多
OBJECTIVE:To explore the efficacy and safety of acupuncture combined with atlantoaxial joint bone-setting therapy for the treatment of Tourette syndrome.METHODS:We randomly divided 600 patients at a ratio of 1∶1∶1 i...OBJECTIVE:To explore the efficacy and safety of acupuncture combined with atlantoaxial joint bone-setting therapy for the treatment of Tourette syndrome.METHODS:We randomly divided 600 patients at a ratio of 1∶1∶1 into three groups:group A(acupuncture combined with atlantoaxial joint bone setting therapy group),group B(acupuncture group),and group C(tiapride group).After two months of treatment,the Yale global tic severity scale(YGTSS)score reduction,improvement in social function impairment,clinical efficacy,and long-term efficacy in the three groups were compared.RESULTS:After treatment,in the analysis of YGTSS score reduction,social function impairment improvement,the clinical control rate,and long-term efficacy,the results were all Group A>Group B>Group C,with a statistically significant difference(P<0.05).However,the total clinical efficacy of treatment in group A(94.9%)was not significantly different from that in group B(91.8%).Adverse reactions did not occur in groups A and B,and several adverse reactions occurred in 29%(n=58)of the group C patients.CONCLUSION:Compared with traditional drug therapy,acupuncture combined with atlantoaxial joint bone setting therapy has better clinical and long-term efficacy.This treatment strategy can improve the social function of children and prevent adverse reactions to drugs.展开更多
BACKGROUND Systematic reviews(SRs)synthesize and evaluate data,mainly from randomized trials,which then guides the development of clinical recommendations in evidence-based medicine.However,the data and methodological...BACKGROUND Systematic reviews(SRs)synthesize and evaluate data,mainly from randomized trials,which then guides the development of clinical recommendations in evidence-based medicine.However,the data and methodological information in the included papers can often be lacking or unclear,and reviewers usually need to contact the authors of included studies for clarifications.Contacting authors is recommended,but it is unclear how often SR teams do it,or what the level of response is.AIM To investigate how often reviewers undertake contact with the authors of included randomized controlled trials(RCTs)for clarification on data and risk of bias concerns,to explore the factors that influence whether SR authors contact or do not contact the authors,and the content and level of responses.METHODS We conducted a systematic electronic database search in MEDLINE using the search string“(systematic review)”AND“(RCT OR randomized OR trial)”for articles published between 1 January 2024 and 19 February 2024,without language restrictions.Screening and data extraction was done independently by two reviewers,and conflicts resolved by a senior author.Contact authors of included SRs were contacted for clarifications.RESULTS Of the 329 included SRs,38%(n=125)explicitly mentioned contact with the authors of included studies.The remaining 62%(n=204)did not.We attempted contact with all SR teams for clarifications and received 90 responses(19.4%).Of the 50 respondents who did not explicitly mention contact in their SRs,25(50%)replied that they did make contact.We received a total of 64 responses on the level and content of information sought.The mean±SD contacts SR teams made were 10(10),replies received 5(6.7),and response waiting time 10.1(28.3)weeks.Resources,time,poor previous experience,perceived likelihood of poor response and bias concerns were reported as barriers to attempting contact.CONCLUSION The majority of SRs published in 2024 did not confirm seeking clarifying or missing information from primary study authors.However,SR teams reported that 50%of contacted primary authors respond.Additional research can clarify this rate of response and establish methods to increase the integration of this core methodological element in SRs.展开更多
OBJECTIVE:To evaluate the efficacy and safety of 14-day Qingwei Zhitong pellets(清胃止痛微丸,QZ)-containing quadruple therapy(QZQT)compared to bismuth-containing quadruple therapy(BQT)in treatment-naive patients with ...OBJECTIVE:To evaluate the efficacy and safety of 14-day Qingwei Zhitong pellets(清胃止痛微丸,QZ)-containing quadruple therapy(QZQT)compared to bismuth-containing quadruple therapy(BQT)in treatment-naive patients with Helicobacter pylori(H.pylori)infection.METHODS:This single-center,randomized controlled clinical trial enrolled 333 patients,who were divided into either the QZQT group(QZ pellets,3.2 g,three times daily;rabeprazole,10 mg,twice daily;amoxicillin 1000 mg,twice daily;clarithromycin,500 mg,twice daily)or the BQT group(bismuth potassium citrate,1000 mg,three times daily;rabeprazole,10 mg,twice daily;amoxicillin,1000 mg,twice daily;clarithromycin,500 mg,twice daily)for 14 d.The 13C-urea breath test assessed eradication success at least four weeks after treatment.The primary outcome focused on the eradication rate,with secondary outcomes including safety and patient compliance.RESULTS:From August 2022 to June 2023,342 subjects were screened,and 333 were randomized.The QZQT and BQT groups showed eradication rates of 68.9%and 67.8%(P=0.838)by intention-to-treat(ITT)analysis,respectively,and 71.1%and 68.3%(P=0.612)by perprotocol(PP)analysis,respectively.QZQT was non-inferior to BQT in both ITT and PP analyses.QZQT was associated with fewer side effects(57.8%of patients)than BQT(90.4%)(P<0.001).CONCLUSION:The 14 d QZQT treatment demonstrates equal efficacy in eradicating H.pylori infection and improved patient compliance and safety compared to BQT.These results provide evidence supporting 14-day QZQT as an acceptable treatment for H.pylori infection.展开更多
OBJECTIVE:To examine the effect of electroacupuncture(EA)application on postoperative pain levels and the amount of analgesic use in patients who underwent periodontal flap surgery.METHODS:In this prospective,randomiz...OBJECTIVE:To examine the effect of electroacupuncture(EA)application on postoperative pain levels and the amount of analgesic use in patients who underwent periodontal flap surgery.METHODS:In this prospective,randomized and controlled study,patients planned for periodontal surgery were divided into two groups[EA group(n=22):patients who received electroacupuncture and control group(n=22):patients who did not receive electroacupuncture].Electroacupuncture was applied bilaterally to the Hegu(LI4),Daying(ST5),and Jiache(ST5)points of the patients in the EA group immediately before and after the flap surgery for 30 min at a frequency of 50 Hz to each point at a current that the patient could tolerate.The patients in the control group underwent flap surgery without applying electroacupuncture.Patients were asked to record their pain levels on the visual analog scale and the number of analgesic tablets they took during the 7 postoperative days on the given form.RESULTS:The total mean score of pain felt in the EA group(16.60±2.78)was found to be significantly lower than that in the control group(31.37±2.78)(P=0.001).No significant difference was found between the groups regarding the amount of analgesics taken(4.77±4.72,5.82±3.11)(P=0.111).CONCLUSIONS:Our study shows that electroacupuncture application is beneficial in reducing pain after periodontal flap surgery.Overall,more research is needed to fully understand the effects of electroacupuncture on postoperative pain.展开更多
BACKGROUND Osteoarthritis(OA)of the knee is a prevalent degenerative joint disease that significantly impairs quality of life and functional mobility.Emerging regenerative therapies,such as stromal vascular fraction(S...BACKGROUND Osteoarthritis(OA)of the knee is a prevalent degenerative joint disease that significantly impairs quality of life and functional mobility.Emerging regenerative therapies,such as stromal vascular fraction(SVF)and nanofat,have demonstrated potential in cartilage repair and symptom alleviation.However,comparative clinical evidence evaluating their efficacy and safety remains limited.AIM To compare the clinical outcomes of SVF vs nanofat therapy in patients with primary knee OA.METHODS Conducted at Mother Cell Regenerative Centre,Trichy,over 18 months(June 2025 to December 2026),the study will enroll 30 patients,randomly assigned to two groups of 15 each.Both interventions will be administered as a single intra-articular injection under sterile conditions,with cell viability(>85%)confirmed by a standardized assay.Group A will receive autologous SVF injections,while Group B will receive autologous nanofat injections.The primary outcome measure is the change in pain scores at 12 months using the visual analog scale(VAS).Secondary outcomes include functional improvement assessed by Osteoarthritis Outcome Score(KOOS),Western Ontario and McMaster Universities(WOMAC),and International Knee Documentation Committee(IKDC)scores,cartilage regeneration evaluated via magnetic resonance imaging with colour coded mapping of the cartilage volume(MR cartigram),and monitoring of adverse events.RESULTS This study aims to evaluate pain reduction at 12 months post-injection,using the VAS as the primary outcome.Secondary outcomes include functional improvement(KOOS,WOMAC,IKDC),cartilage regeneration(T2 cartigram),adverse event incidence,patient satisfaction(standardized questionnaires,Likert scale),and quality of life(EQ-5D).Ethical considerations follow the Declaration of Helsinki and Good Clinical Practice,with IRB approval and participant informed consent ensured.Confidentiality and data security comply with regulations,and a Data Safety Monitoring Board oversees trial safety.Results will be shared via peer-reviewed journals,presentations at international orthopedic conferences,and detailed summaries for stakeholders and participants.The trial is registered under CTRI/2024/03/064076.Findings emphasize patient-centered advancements in knee osteoarthritis management.CONCLUSION This trial evaluates the efficacy and safety of SVF and nanofat therapies in knee OA,addressing a significant evidence gap.It employs robust methods to enhance cartilage repair and patient quality of life.Future research should standardize dosages,protocols,and injection techniques,explore autologous/allogenic preparations,and advance radiological tools,broadening accessibility and clinical applications.展开更多
BACKGROUND Hyponatremia is a prevalent and serious electrolyte imbalance in pediatric pneumonia and is linked to increased disease severity and adverse outcomes.Oral rehydration solution(ORS)is an available,inexpensiv...BACKGROUND Hyponatremia is a prevalent and serious electrolyte imbalance in pediatric pneumonia and is linked to increased disease severity and adverse outcomes.Oral rehydration solution(ORS)is an available,inexpensive,safe,and ready-touse oral solution that can supplement sodium in such cases.AIM To assess the impact of prophylactic sodium supplementation via ORS on clinical and hospital outcomes in infants and children admitted with pneumonia.METHODS A randomized,interventional controlled trial was conducted on 140 infants and children admitted with pneumonia(70 per group).The primary outcome was hospital length of stay,with secondary outcomes including serum sodium and potassium levels,clinical respiratory scores,modified shock index,and nutritional/inflammatory markers.The hospital length of stay and both the laboratory and clinical parameters of the interventional and control groups were compared.RESULTS The hospital stay was longer in the control group than in the intervention group(P value=0.001;effect size=0.59).Clinical respiratory scores on day 4 were significantly lower in the intervention group than in the control group(P value=0.001).Sodium levels were significantly lower in the control group than in the intervention group at discharge(P value=0.002).CONCLUSION Prophylactic oral sodium supplementation through ORS may have a health-promoting effect on infants and children admitted with pneumonia.展开更多
Background:Evidence regarding the effectiveness of prenatal nutritional supplements has mainly considered anthropometric pregnancy outcomes.The effect on markers of health and disease,such as offspring telomere length...Background:Evidence regarding the effectiveness of prenatal nutritional supplements has mainly considered anthropometric pregnancy outcomes.The effect on markers of health and disease,such as offspring telomere length(TL)and mitochondrial DNA content(mtDNAc)is unknown.Objectives:We assessed the efficacy of maternal multiple micronutrient(MMN)-fortified balanced-energy protein(BEP)and iron-folic acid(IFA)supplementation on newborn TL as a secondary outcome and mtDNAc as a non-declared outcome.Design:We conducted a randomized controlled trial in rural Burkina Faso,among pregnant females(15-40 years old)enrolled at<21 weeks of gestation.Mothers received either MMN-fortified BEP and IFA(intervention)or IFA only(control)throughout pregnancy.Whole arterial blood samples were collected from the umbilical cord of 104 control and 90 intervention group infants,respectively.Average relative TL and mtDNAc were measured using quantitative polymerase chain reaction.Linear regression models were fitted to assess TL and mtDNAc differences across trial arms.Results:We found that a combined daily MMN-fortified BEP supplement and IFA tablet did not affect newborn TL[β=-0.010(95%CI:-0.057,0.036);P=0.662]or mtDNAc[β=0.065(95%CI:-0.203,0.073);P=0.354],as compared to an IFA tablet alone.These findings were confirmed(P>0.05)by adjusting the regression models for potential prognostic factors of study outcomes at enrollment.Exploratory analyses indicated higher,but non-significantly different mtDNAc among children born either small-for-gestational age,low birthweight,or preterm.Conclusion:Newborns from mothers who received daily nutritional supplements across gestation did not have different relative TL or mtDNAc.展开更多
BACKGROUND Pharmacological treatments are commonly used in individuals experiencing perinatal depression(PPD);however,a debate regarding the reproductive safety of antidepressants is ongoing.Many pregnant women opt to...BACKGROUND Pharmacological treatments are commonly used in individuals experiencing perinatal depression(PPD);however,a debate regarding the reproductive safety of antidepressants is ongoing.Many pregnant women opt to discontinue antidepressant out of concern about potential negative effects on the developing fetus,while slow and ineffective antidepressant medications hinder improved outcomes in women with PPD.In recent years,bright light therapy(BLT)has gained traction as a treatment option for PPD;however,clinical trials findings examining the efficacy of BLT in this population have been inconclusive.AIM To validate the feasibility and safety of BLT for the treatment of PPD.METHODS We performed a meta-analysis of randomized controlled trials of patients with PPD treated with BLT vs placebo following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis.We searched PubMed,Embase,the Cochrane Library,and Web of Science for randomized controlled studies published up to December 2023.The results were evaluated using the standardized mean difference of improvement for depression scores and odds ratios(ORs)for remission rate,response rate,incidence of adverse events,and dropout rate.RESULTS The BLT group had higher PPD response rate[50.68%vs 33.08%;OR=2.05;95% confidence interval(CI):1.25-3.35;P=0.004;I^(2)=35%]and remission rate(54.10%vs 18.52%;OR=5.00;95%CI:2.09-11.99;P=0.0003;I^(2)=0%)than the placebo group.Improvements in depression scores were higher in the BLT group than the placebo group for the overall efficacy(standardized mean difference=-0.47;95%CI:-0.80 to-0.13;P=0.007).No significant differences between the two groups in drop-outs(21.84%vs 29.63%;OR=0.63;95%CI:0.31-1.29;P=0.21;I^(2)=0%)or adverse events(17.89%vs 9.68%;OR=2.01;95%CI:0.95-4.25;P=0.07;I^(2)=0%)were observed.CONCLUSION BLT can potentially treat PPD,showing better results than the control group in this study.BLT is effective and safe and could increase the available therapeutic options for PPD.展开更多
OBJECTIVE:To investigate the efficacy and safety of Angong Jiangya pill(AGJY,安宫降压丸)in the treatment of grade 2 hypertension with liver-fire hyperactivity syndrome.METHODS:This multicenter,randomized,double-blind,...OBJECTIVE:To investigate the efficacy and safety of Angong Jiangya pill(AGJY,安宫降压丸)in the treatment of grade 2 hypertension with liver-fire hyperactivity syndrome.METHODS:This multicenter,randomized,double-blind,placebo-controlled trial was conducted in eight medical institutions.Eligible patients with grade 2 hypertension were randomly allocated to receive AGJY or a placebo for 12 weeks.The primary outcome was the change in blood pressure(BP).The secondary outcomes were BP compliance rate,Traditional Chinese Medicine(TCM)symptoms,and Duchenne Hypertension Quality of Life Scale score.RESULTS:Data were analyzed for 117 participants in the AGJY group and 118 participants in the placebo group.After 12 weeks of treatment,AGJY compared with placebo resulted in a higher and significant reduction in systolic/diastolic BP(-15.58±10.16/-9.72±7.41 vs-8.13±8.28/-4.86±5.68 mm Hg,P<0.0001,<0.0001,respectively).BP compliance rate(31.86%vs 19.13%,P=0.027)was significantly higher in the AGJY group than in the placebo group.The AGJY group showed a significant reduction in TCM symptom score compared with the placebo group(10.82±2.03 vs 7.83±1.24,P<0.0001).Single TCM syndrome clinical control rates of the primary symptoms(dizziness,headache,and irritability)were superior in the AGJY group(71.95%,94.62%,72.53%,respectively)compared with the placebo group(48.39%,68.00%,30.52%,respectively).Scores on the Duchenne Hypertension Quality of Life Scale showed a significant increase in the AGJY group compared with the placebo group(30.65±21.06 vs 9.96±10.72,P=0.000).No serious adverse events occurred.CONCLUSION:AGJY demonstrated efficacy in lowering BP,increasing the rate of BP compliance,and improving TCM symptoms and quality of life in patients with grade 2 hypertension liver-fire hyperactivity syndrome.However,further in-depth studies are required to determine the mechanism of TCM in treating hypertension.展开更多
BACKGROUND Knee osteoarthritis(OA)imposes a substantial burden through pain,functional limitation,and progressive cartilage loss.Bone marrow aspirate concentrate(BMAC)has emerged as a promising regenerative therapy fo...BACKGROUND Knee osteoarthritis(OA)imposes a substantial burden through pain,functional limitation,and progressive cartilage loss.Bone marrow aspirate concentrate(BMAC)has emerged as a promising regenerative therapy for OA due to its rich composition of mesenchymal stromal cells(MSCs)and bioactive factors.While intra-articular BMAC injections provide short-term symptomatic relief,recent literature suggests that targeting the subchondral bone—an area crucial to OA progression—may offer superior and longer-lasting clinical benefits.AIM To compares the outcomes of subchondral vs intra-articular BMAC injections in patients with primary knee OA.METHODS In this unicentric,double-blinded,randomized controlled trial,30 patients with radiologically confirmed primary knee OA(Kellgren-Lawrence grades II and III)will be equally randomized to receive either subchondral(Group A)or intra-articular(Group B)BMAC injections.BMAC will be harvested from the posterior iliac crest,processed using a standardized centrifugation protocol to yield a product with>85%cell viability,and administered under image guidance.The primary outcome is the change in pain intensity at 12 months as measured by the Visual Analog Scale(VAS).Secondary outcomes include functional improvement assessed by Knee Injury and Osteoarthritis Outcome Score(KOOS),International Knee Documentation Committee(IKDC),and Western Ontario and McMaster Universities Arthritis Index(WOMAC)scores,structural changes evaluated through advanced magnetic resonance imaging using(MRI)the whole-organ MRI Score,and safety as determined by the incidence of adverse events.RESULTS This study aims to evaluate pain reduction at 12 months post-injection,using the VAS as the primary outcome.Secondary outcomes include functional improvement(KOOS,WOMAC,IKDC),cartilage regeneration(T2 cartigram),adverse event incidence,patient satisfaction(standardized questionnaires,Likert scale),and quality of life(EQ-5D).Ethical considerations follow the Declaration of Helsinki and Good Clinical Practice,with institutional review board approval and participant informed consent ensured.Confidentiality and data security comply with regulations,and a data safety monitoring board oversees trial safety.Results will be shared via peer-reviewed journals,presentations at international orthopedic conferences,and detailed summaries for stakeholders and participants.The trial is registered under clinical trial registry of India/2024/04/065284.Findings emphasize patient-centered advancements in knee osteoarthritis management.CONCLUSION This trial aims to refine regenerative strategies for knee OA by comparing subchondral vs intra-articular BMAC injections,addressing long-term efficacy,safety,and treatment standardization to guide targeted interventions.This trial will provide critical insights into the comparative efficacy and safety of subchondral vs intra-articular BMAC injections in treating primary knee OA.展开更多
基金supported by the Deputyship for Research&Innovation,Ministry of Education in Saudi Arabia(Project No.MoE-IF-UJ-R2-22-04220773-1).
文摘Domain randomization is a widely adopted technique in deep reinforcement learning(DRL)to improve agent generalization by exposing policies to diverse environmental conditions.This paper investigates the impact of different reset strategies,normal,non-randomized,and randomized,on agent performance using the Deep Deterministic Policy Gradient(DDPG)and Twin Delayed DDPG(TD3)algorithms within the CarRacing-v2 environment.Two experimental setups were conducted:an extended training regime with DDPG for 1000 steps per episode across 1000 episodes,and a fast execution setup comparing DDPG and TD3 for 30 episodes with 50 steps per episode under constrained computational resources.A step-based reward scaling mechanism was applied under the randomized reset condition to promote broader state exploration.Experimental results showthat randomized resets significantly enhance learning efficiency and generalization,with DDPG demonstrating superior performance across all reset strategies.In particular,DDPG combined with randomized resets achieves the highest smoothed rewards(reaching approximately 15),best stability,and fastest convergence.These differences are statistically significant,as confirmed by t-tests:DDPG outperforms TD3 under randomized(t=−101.91,p<0.0001),normal(t=−21.59,p<0.0001),and non-randomized(t=−62.46,p<0.0001)reset conditions.The findings underscore the critical role of reset strategy and reward shaping in enhancing the robustness and adaptability of DRL agents in continuous control tasks,particularly in environments where computational efficiency and training stability are crucial.
基金supported by a project of the National Natural Science Foundation of China:Research on the integration of artificial intelligence and virtual reality technology to promote psychological rehabilitation of breast cancer patients with different personalities(project approval no.82073408).
文摘Objectives:To explore the efficacy and safety of virtual reality(VR)in relieving negative emotions in patients with breast cancer with different personalities.Methods:A randomized controlled trial was conducted.Between April 2023 and October 2023,we enrolled patients with breast cancer treated in the Department of Breast Cancer and Oncology at Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangdong Province.The patients were randomly divided into an intervention group(n=118)and a control group(n=119)using block randomization.The intervention group received the VR intervention 3-5 times over 5±2 weeks using natural landscapes with music or relaxation guidance,and the duration of each VR intervention was 15±3 min.The control group received routine nursing care,including disease education and psychological counseling.Patients were assessed using the Type D Scale,Positive and Negative Affect Scale,and Distress Thermometer,and adverse events during the intervention were recorded.Results:Overall,85 patients completed the study(44 in the intervention group and 41 in the control group).Patients with Type D personalities showed more negative emotions[25.0(21.5,27.5)vs.19.0(16.0,24.0),P=0.001]and distressed attitudes[4.0(2.0,5.0)vs.3.0(1.0,4.0),P=0.020]with fewer positive emotions(27.2±5.6 vs.31.0±5.9,P=0.014)than those with non-Type D personalities.Total population analysis revealed no significant differences between the groups.However,in the subgroup analysis,patients with Type D personalities in the intervention group showed greater relief from negative emotions than those in the control group[median difference,-5.0(-9.0,-2.5)vs.-2.0(-4.0,2.0),P=0.046].No significant differences were found between groups of patients with non-Type D personality traits.The proportion of adverse events was not significantly different between groups(P=0.110).Conclusions:Breast cancer patients with Type D personalities suffer more severe negative emotions and distress,and more attention should be paid to them.VR intervention significantly and safely reduced negative emotions in patients with Type D personalities.
基金supported by the National Key R&D Program of China(2022YFB2701500)the National Natural Science Foundation of China(62272385,62311540156)+2 种基金Shaanxi Distinguished Youth Project(2022JC-47)the Key Research and Development Program of Shaanxi(2021ZDLGY06-04)Major Program of Shandong Provincial Natural Science Foundation for the Fundamental Research(ZR2022ZD03).
文摘Adaptor signature,a new primitive that alleviates the scalability issue of blockchain to some extent,has been widely adopted in the off-chain payment channel and atomic swap.As an extension of standard digital signature,adaptor signature can bind the release of a complete digital signature with the exchange of a secret value.Existing constructions of adaptor signatures are mainly based on Schnorr or ECDSA signature algorithms,which suffer low signing efficiency and long signature length.In this paper,to address these issues,we propose a new construction of adaptor signature using randomized EdDSA,which has Schnorr-like structure with higher signing efficiency and shorter signature length.We prove the required security properties,including unforgeability,witness extractability and pre-signature adaptability,of the new adaptor signature scheme in the random oracle model.We conduct a comparative analysis with an ECDSA-based adaptor signature scheme to demonstrate the effectiveness and feasibility of our new proposal.
基金supported by Tasly Pharmaceutical Group Co.,Ltd.(Grant No.303100031BA20)。
文摘The current study aimed to evaluate the efficacy and safety of Compound Danshen Dripping Pills(CDDP)in improving cardiac function in patients with acute anterior ST-segment elevation myocardial infarction(AAMI).Between February 2021 and February 2023,247 eligible patients with AAMI after primary percutaneous coronary intervention were enrolled and randomly assigned(1∶1)to receive CDDP(n=126)or placebo(n=121),with a follow-up of 48 weeks.Compared with the placebo group,the CDDP group demonstrated a significant increase in left ventricular ejection fraction values after 24 weeks of treatment(least squares mean:3.31;95%confidence interval[CI]:1.72–4.90;P<0.001)and at the 48-week follow-up(least squares mean:4.35;95%CI:2.76–5.94;P<0.001).Significant reductions in N-terminal pro-B-type natriuretic peptide levels were observed in both groups at the 24-and 48-week visits with no significant difference between the two groups(P>0.1 for all).The incidence of major adverse cardiovascular and cerebrovascular events was 6.35%in the CDDP group and 5.79%in the placebo group(P=0.822).Notably,no serious adverse events were attributed to CDDP.These findings suggest that CDDP may be well tolerated and could improve left ventricular ejection fraction in patients with AAMI at 24 and 48 weeks.
文摘OBJECTIVE:In recent years,the number of clinical research reports on acupuncture and manipulation for the treatment of greater occipital neuralgia has gradually increased,but the quality is uneven.There is currently no literature evaluating the quality of published reports,which is not conducive to the promotion of clinical use of these therapies.Therefore,this article assessed the reporting quality of randomized controlled trials on acupuncture and manipulation for greater occipital neuralgia.METHODS:Cochrane Library,PubMed,Web of Science,Embase,China National Knowledge Infrastructure(CNKI),VIP,WanFang Data,and Chinese BioMedical Literature Database(CBM)from inception to May 20,2024 were searched.The reporting quality of included randomized controlled trials was independently evaluated by two investigators using the CONSORT statement,STRICTA checklist,and Cochrane bias of risk assessment tool.A third investigator resolved any disagreement.RESULTS:A total of 62 articles were included.Based on the CONSORT statement,59.46%(22/37)of all entries had a reporting rate of less than 50%,mainly including“Identification as a randomized trial in the title(1/62,1.61%),”“How sample size was determined(7/62,11.29%),”“Implementation(1/62,1.61%),”“Blinding(1/62,1.61%),”and“Reports of Funding(4/62,6.45%).”According to the STRICTA checklist,29.41%(5/17)of all entries had a reporting rate of less than 50%,mainly including“Details of other interventions(7/58,12.07%),”“Setting and context of treatment(0/58,0%),”and“Description of participating acupuncturists(0/58,0%).”CONCLUSION:The reporting quality of randomized controlled trials on acupuncture and manipulation therapy for greater occipital neuralgia remains low.Future researchers need to make greater efforts to strictly adhere to the CONSORT statement and STRICTA checklist during trial design,implementation,and reporting.This will facilitate the standardization of research in this field and enhance the reliability and reproducibility of the research results.
文摘BACKGROUND Nutritional psychiatry is a rapidly expanding field of research,with mounting evidence suggesting that nutritional factors may play a role in the development of psychiatric disorders.AIM To examine the level of evidence for nutritional psychiatry.METHODS A scoping review was conducted to assess the current state of nutritional psychiatry,including a search for randomized controlled trials(RCTs).RESULTS The review identified a total of seven papers,with many concentrating on the relationship between depression and the gut microbiome.A salient issue that emerged from this review was the paucity of sample size in many studies.The inherent complexity of nutritional studies,characterized by a multitude of potential factors and exposures that often act as confounders,poses significant challenges to the development of effective RCT designs.The analysis revealed that probiotics,though demonstrating efficacy,exhibited a modest effect size.CONCLUSION Conducting RCTs with effective markers is imperative from these studies.The implementation of Mendelian randomization and the investigation of mechanisms in basic research are essential complementary approaches.
基金Supported by National Basic Evidence-based Capacity Building Project of Traditional Chinese Medicine([2019]130)Natural Science Foundation of Liaoning Province:2024-MS-042+1 种基金Xingliao Talent Program Medical Master Project:YXMJ-QNMZY-10Liaoning University of Traditional Chinese Medicine Key Laboratory of Traditional Chinese Medicine Theory and Application of Ministry of Education open fund project:zyzx2302.
文摘Background Unsedated colonoscopy is an important method used for diagnosing colorectal cancer,but it can cause discomfort such as pain and bloating,as well as anxiety.At present,the relief is mainly achieved through methods such as changing positions and manual pressing,but the efficacy is limited.Hence alternative therapies for sedation and analgesia in unsedated colonoscopy warrant further study.Electroacupuncture(EA)can simplify the procedure of anesthesia and analgesia,while the efficacy of EA on unsedated colonoscopy remains unclear.Therefore,a well-designed randomized controlled trial is needed to demonstrate the potential efficacy of acupuncture in unsedated colonoscopy,particularly for pain relief.Methods In this prospective randomized sham-controlled trial,105 eligible participants will be recruited and randomly assigned to either EA group(n=35),sham EA group(n=35),or control group(n=35)in a 1:1:1 ratio.The EA group will receive acupuncture intervention on bilateral Hegu(LI4),Neiguan(PC6),Zusanli(ST36),and Shenmen(HT7),with LI4 and PC6 on both sides connected to the EA device.The sham EA group will received non transdermal needling on points of no meridian,and deliberately connect the needle to the incorrect output socket of EA device to block the stimulation.The needling will conducted from 30 min before the unsedated colonoscopy to the end of the colonoscopy,the whole retention time would be approximately 40 min.The participants in the control group will not receive any acupuncture intervention.All participants of the three groups will not receive any other treatment.Primary outcomes:Numerical Rating Scale(NRS)reported by participants and Face Pain Scale Revised(FPS-R)evaluated by observers of four areas of the participants during the unsedated colonoscopy.Secondary outcomes:tolerance reported by endoscopists,tolerance reported by participants,satisfaction reported by endoscopists,satisfaction reported by participants,adverse events during the unsedated colonoscopy,postoperative discomfort,unsedated colonoscopy smoothness(cecal insertion time,unwinding time,success rate of one-time intubation).Both intention-to-treat(ITT)and per-protocol(PP)analyses will be performed to assess the efficacy of EA.Discussion The trial will explore the efficacy of relieving pain,improving tolerability,and reducing undesirable adverse events of EA for unsedated colonoscopy.The results of this trial will provide sound evidence for promoting the clinical application of EA for unsedated colonoscopy.Trial registration ClinicalTrials.gov Identifier:ChiCTR2300069903,retrospectively registered on March 16,2023.
基金supported by Shanghai Clinical Research Center for Acupuncture and Moxibustion(No.20MC1920500)National Administration of Traditional Chinese Medicine High-Level Disciplines Construction Project(No.ZYYZDXK-2023068)Three Year Action Plan for Shanghai to Further Accelerate the Inheritance,Innovation and Development of Traditional Chinese Medicine(2025-2027)(No.1-1-2)。
文摘Background:Electroacupuncture(EA)may affect the severity of hot flashes(HFs)associated with natural menopause and provide additional benefits for postmenopausal women.However,the evidence for its effectiveness in the management of early postmenopausal HFs remains inadequately understood.Objective:We designed this trial to assess the efficacy and safety of EA for relieving early postmenopausal HFs.Design,setting,participants and interventions:This randomized sham-controlled trial involved 72 women with HFs.The participants were divided equally into the intervention and control groups.The intervention group was treated with EA,while the control group was treated with sham acupuncture.The main acupoints used were Hegu(LI4),Guanyuan(RN4),Sanyinjiao(SP6),Taixi(KI3),Fuliu(KI7)and Shenshu(BL23).All participants received 18 treatment sessions,distributed across a 6-week period.The treatment was administered on three occasions per week,adhering to a fixed weekday schedule(Monday,Wednesday,Friday or Tuesday,Thursday,Saturday)with a minimum interval of one day between sessions.Each patient received a 12-week follow-up.Main outcome measures:The HF score was the primary outcome.Participants documented the frequency and severity of HFs in a 7-day symptom diary,which provided data for calculating the HF score.Secondary outcomes were the Menopause Rating Scale(MRS),Menopause-Specific Quality of Life Questionnaire(MENQOL),Pittsburgh Sleep Quality Index(PSQI)and Traditional Chinese Medicine Syndrome Score Scale(TCMSSS),as well as estradiol(E2),luteinizing hormone(LH)and folliclestimulating hormone(FSH)levels.Results:Both groups demonstrated significant reductions in HF scores after the treatment and during the follow-up(P<0.001).Immediately after completion of the 6-week treatment cycle and at 12 weeks postintervention,the HF scores were similar in both groups.At week 6,the intervention group showed significantly greater improvements in MRS,MENQOL(vasomotor,psychosocial,and physical),PSQI and TCMSSS scores(P<0.05).The improvements in the MENQOL(vasomotor,and psychosocial)and PSQI total scores persisted through the follow-up(P<0.05).However,the results showed no significant inter-or intragroup differences in sexual scores on the MENQOL(P>0.05).EA did not significantly decrease E2,LH or FSH levels compared to placebo.The incidence of adverse events was similar in both groups.Conclusion:EA does not significantly improve HFs in early postmenopausal patients.However,it enhances the quality of sleep and decreases menopausal symptoms across vasomotor,psychosocial and physical domains.Trial registration:Chinese Clinical Trial Registry(http://www.chictr.org.cn);Trial ID:Chi CTR2300072002.Please cite this article as:Wang HX,Yu XT,Hu J,Chen JJ,Mei YT,Chen YF.Electroacupuncture for hot flashes in early menopause:A randomized sham-controlled trial.J Integr Med.2025;23(5):519-527.?2025 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine.Published by Elsevier B.V.All rights are reserved,including those for text and data mining,AI training,and similar technologies.
基金Supported by the National Natural Science Foundation of China:Exploration of Key Factors and Mechanisms of Modulating Motor Function Reconstruction After Cerebral Infarction Through Multimodal Brain Functional Connectivity Perspective in Procedural Acupoint Electrical Stimulation Research(No.82374601)the Jointly Guided Program of Natural Science Foundation of Heilongjiang Province:Quantitative Study on the Role of Scalp Acupuncture in the Motor Area in Promoting Motor Function Reconstruction after Stroke(No.LH2019H113)+1 种基金the Innovation Team Construction Project of Heilongjiang University of Chinese Medicine:Construction of a Doctoral Research and Innovation Team in Acupuncture Science(No.2017sit01)the Traditional Chinese Medicine Research Project of Heilongjiang Province:Clinical Study on the Promotion of Upper Limb Motor Function Reconstruction in Post-Stroke Patients Using Optimal Limb Positioning with Electroacupuncture(No.ZHY2022-171)。
文摘OBJECTIVE:To evaluate the efficacy of electroacupuncture(EA)at scalp motor area for treating post-stroke wrist dyskinesia and its influence on the function of wrist movement-related agonistic muscles.METHODS:A randomized,single-blind,controlled clinical trial was conducted.Sixty-six patients undergoing post-stroke wrist dyskinesia were enrolled and randomized 1:1 to EA or control group.Patients in the control group received manual acupuncture in the scalp motor area(MS 6)on the lesion side.The same acupoint was selected to accept EA stimulation in the EA group.All patients were treated six times a week for three weeks.The primary outcome was the Chinese Stroke Scale(CSS)score.The secondary outcomes included upper limb-related Barthel Index(BI)score,active range of motion(AROM)of the wrist joint,and root mean square(RMS)of the four agonistic muscles associated with wrist motion on the hemiplegic side of patients,i.e.,the extensor carpi radialis longus(ECRL),extensor digitorum(ED),flexor carpi radialis(FCR)and flexor carpi ulnaris(FCU).The above indicators were measured before and after three weeks of treatment.RESULTS:After 3-week treatment,the CSS score and AROM of wrist dorsiflexion of the EA group were better than those in the control group(P=0.038,P=0.047).The differences between the two groups of BI scores and AROM of wrist flexion were not significant(P>0.05).All RMS of the EA group were higher than those in the control group(ECRL:P=0.047,ED:P=0.048,FCR:P=0.049,FCU:P=0.047).The total effective rate in the EA group was 87.50%(28/32),which was higher than that in the control group(77.42%,24/31,P=0.048).CONCLUSION:EA stimulation of the scalp motor area can promote the recovery of the strength and function of the agonistic muscles related to wrist movement and effectively improve post-stroke wrist dyskinesia.
文摘BACKGROUND In randomized controlled trials(RCTs),the placebo arm has often been ignored as the attention tends to be focused on the treatment arm.We undertook a meta-analysis based on the data from the placebo arm in RCTs of hepatocellular carci-noma(HCC),the response rates and survival status,and adverse events(AEs)were summarized and evaluated.AIM To systematically evaluate the response rates,survival status and AEs in the placebo arms of RCTs for HCC.METHODS A systematic search was performed on PubMed,Ovid MEDLINE,Embase and Cochrane Library to identify relevant trials evaluating the efficacy of drugs for the treatment of HCC,published until December 31,2023.Statistical analysis was performed using R statistical software(version 4.3.2).RESULTS A total of 18 RCTs,involving 2390 patients,met the criteria for inclusion in the meta-analysis.The pooled overall disease control rate and objective response rate in the placebo group were 38%[95%confidence interval(CI):33%-42%]and 1%(95%CI:1%-2%),respectively.Overall survival and progression-free survival in the placebo group were 7.9 months(95%CI:7.6-8.31 months)and 1.9 months(95%CI:1.6-2.1 months),respectively.The incidence of grade 3 or 4 AEs was 37%(95%CI:30%-43%).Additionally,the incidence of interruptions or dose reductions due to AEs was 20%(95%CI:13%-27%),while the incidence of treatment discontinuation due to AEs was 9%(95%CI:6%-12%).CONCLUSION Over one-third of advanced HCC patients exhibit therapy-free disease control,with placebo-arm AEs observed.These findings guide single-arm trials design and enhance patient acceptance of anticancer therapies.
基金Supported by Traditional Chinese medicine foundation of Zhejiang province:Clinical Study on the Correlation Between Tourette Syndrome and Anatomical Changes in the Atlantoaxial Joint(2010ZB162)Medical Health Science and Technology Project of Zhejiang Provincial Health Commission:Study on Protein Fingerprinting of Tourette Syndrome(2011KYB142)+1 种基金Renowned Traditional Chinese Medicine Expert Inheritance Studio Construction Project of Zhejiang province(No.GZS2020049)Key Disciplines of Traditional Chinese Medicine Foundation of Zhejiang Province(2012-XK-D20)。
文摘OBJECTIVE:To explore the efficacy and safety of acupuncture combined with atlantoaxial joint bone-setting therapy for the treatment of Tourette syndrome.METHODS:We randomly divided 600 patients at a ratio of 1∶1∶1 into three groups:group A(acupuncture combined with atlantoaxial joint bone setting therapy group),group B(acupuncture group),and group C(tiapride group).After two months of treatment,the Yale global tic severity scale(YGTSS)score reduction,improvement in social function impairment,clinical efficacy,and long-term efficacy in the three groups were compared.RESULTS:After treatment,in the analysis of YGTSS score reduction,social function impairment improvement,the clinical control rate,and long-term efficacy,the results were all Group A>Group B>Group C,with a statistically significant difference(P<0.05).However,the total clinical efficacy of treatment in group A(94.9%)was not significantly different from that in group B(91.8%).Adverse reactions did not occur in groups A and B,and several adverse reactions occurred in 29%(n=58)of the group C patients.CONCLUSION:Compared with traditional drug therapy,acupuncture combined with atlantoaxial joint bone setting therapy has better clinical and long-term efficacy.This treatment strategy can improve the social function of children and prevent adverse reactions to drugs.
文摘BACKGROUND Systematic reviews(SRs)synthesize and evaluate data,mainly from randomized trials,which then guides the development of clinical recommendations in evidence-based medicine.However,the data and methodological information in the included papers can often be lacking or unclear,and reviewers usually need to contact the authors of included studies for clarifications.Contacting authors is recommended,but it is unclear how often SR teams do it,or what the level of response is.AIM To investigate how often reviewers undertake contact with the authors of included randomized controlled trials(RCTs)for clarification on data and risk of bias concerns,to explore the factors that influence whether SR authors contact or do not contact the authors,and the content and level of responses.METHODS We conducted a systematic electronic database search in MEDLINE using the search string“(systematic review)”AND“(RCT OR randomized OR trial)”for articles published between 1 January 2024 and 19 February 2024,without language restrictions.Screening and data extraction was done independently by two reviewers,and conflicts resolved by a senior author.Contact authors of included SRs were contacted for clarifications.RESULTS Of the 329 included SRs,38%(n=125)explicitly mentioned contact with the authors of included studies.The remaining 62%(n=204)did not.We attempted contact with all SR teams for clarifications and received 90 responses(19.4%).Of the 50 respondents who did not explicitly mention contact in their SRs,25(50%)replied that they did make contact.We received a total of 64 responses on the level and content of information sought.The mean±SD contacts SR teams made were 10(10),replies received 5(6.7),and response waiting time 10.1(28.3)weeks.Resources,time,poor previous experience,perceived likelihood of poor response and bias concerns were reported as barriers to attempting contact.CONCLUSION The majority of SRs published in 2024 did not confirm seeking clarifying or missing information from primary study authors.However,SR teams reported that 50%of contacted primary authors respond.Additional research can clarify this rate of response and establish methods to increase the integration of this core methodological element in SRs.
基金the China Zhongguancun Precision Medicine Science and Technology Foundation:Study on the Evaluation of Eradication Rate and Safety of Helicobacter Pylori in a Quadruple Therapy using Qingwei Zhitong Pellets as a Substitute for Bismuth Agent(320.6799.2022.09.24)。
文摘OBJECTIVE:To evaluate the efficacy and safety of 14-day Qingwei Zhitong pellets(清胃止痛微丸,QZ)-containing quadruple therapy(QZQT)compared to bismuth-containing quadruple therapy(BQT)in treatment-naive patients with Helicobacter pylori(H.pylori)infection.METHODS:This single-center,randomized controlled clinical trial enrolled 333 patients,who were divided into either the QZQT group(QZ pellets,3.2 g,three times daily;rabeprazole,10 mg,twice daily;amoxicillin 1000 mg,twice daily;clarithromycin,500 mg,twice daily)or the BQT group(bismuth potassium citrate,1000 mg,three times daily;rabeprazole,10 mg,twice daily;amoxicillin,1000 mg,twice daily;clarithromycin,500 mg,twice daily)for 14 d.The 13C-urea breath test assessed eradication success at least four weeks after treatment.The primary outcome focused on the eradication rate,with secondary outcomes including safety and patient compliance.RESULTS:From August 2022 to June 2023,342 subjects were screened,and 333 were randomized.The QZQT and BQT groups showed eradication rates of 68.9%and 67.8%(P=0.838)by intention-to-treat(ITT)analysis,respectively,and 71.1%and 68.3%(P=0.612)by perprotocol(PP)analysis,respectively.QZQT was non-inferior to BQT in both ITT and PP analyses.QZQT was associated with fewer side effects(57.8%of patients)than BQT(90.4%)(P<0.001).CONCLUSION:The 14 d QZQT treatment demonstrates equal efficacy in eradicating H.pylori infection and improved patient compliance and safety compared to BQT.These results provide evidence supporting 14-day QZQT as an acceptable treatment for H.pylori infection.
文摘OBJECTIVE:To examine the effect of electroacupuncture(EA)application on postoperative pain levels and the amount of analgesic use in patients who underwent periodontal flap surgery.METHODS:In this prospective,randomized and controlled study,patients planned for periodontal surgery were divided into two groups[EA group(n=22):patients who received electroacupuncture and control group(n=22):patients who did not receive electroacupuncture].Electroacupuncture was applied bilaterally to the Hegu(LI4),Daying(ST5),and Jiache(ST5)points of the patients in the EA group immediately before and after the flap surgery for 30 min at a frequency of 50 Hz to each point at a current that the patient could tolerate.The patients in the control group underwent flap surgery without applying electroacupuncture.Patients were asked to record their pain levels on the visual analog scale and the number of analgesic tablets they took during the 7 postoperative days on the given form.RESULTS:The total mean score of pain felt in the EA group(16.60±2.78)was found to be significantly lower than that in the control group(31.37±2.78)(P=0.001).No significant difference was found between the groups regarding the amount of analgesics taken(4.77±4.72,5.82±3.11)(P=0.111).CONCLUSIONS:Our study shows that electroacupuncture application is beneficial in reducing pain after periodontal flap surgery.Overall,more research is needed to fully understand the effects of electroacupuncture on postoperative pain.
文摘BACKGROUND Osteoarthritis(OA)of the knee is a prevalent degenerative joint disease that significantly impairs quality of life and functional mobility.Emerging regenerative therapies,such as stromal vascular fraction(SVF)and nanofat,have demonstrated potential in cartilage repair and symptom alleviation.However,comparative clinical evidence evaluating their efficacy and safety remains limited.AIM To compare the clinical outcomes of SVF vs nanofat therapy in patients with primary knee OA.METHODS Conducted at Mother Cell Regenerative Centre,Trichy,over 18 months(June 2025 to December 2026),the study will enroll 30 patients,randomly assigned to two groups of 15 each.Both interventions will be administered as a single intra-articular injection under sterile conditions,with cell viability(>85%)confirmed by a standardized assay.Group A will receive autologous SVF injections,while Group B will receive autologous nanofat injections.The primary outcome measure is the change in pain scores at 12 months using the visual analog scale(VAS).Secondary outcomes include functional improvement assessed by Osteoarthritis Outcome Score(KOOS),Western Ontario and McMaster Universities(WOMAC),and International Knee Documentation Committee(IKDC)scores,cartilage regeneration evaluated via magnetic resonance imaging with colour coded mapping of the cartilage volume(MR cartigram),and monitoring of adverse events.RESULTS This study aims to evaluate pain reduction at 12 months post-injection,using the VAS as the primary outcome.Secondary outcomes include functional improvement(KOOS,WOMAC,IKDC),cartilage regeneration(T2 cartigram),adverse event incidence,patient satisfaction(standardized questionnaires,Likert scale),and quality of life(EQ-5D).Ethical considerations follow the Declaration of Helsinki and Good Clinical Practice,with IRB approval and participant informed consent ensured.Confidentiality and data security comply with regulations,and a Data Safety Monitoring Board oversees trial safety.Results will be shared via peer-reviewed journals,presentations at international orthopedic conferences,and detailed summaries for stakeholders and participants.The trial is registered under CTRI/2024/03/064076.Findings emphasize patient-centered advancements in knee osteoarthritis management.CONCLUSION This trial evaluates the efficacy and safety of SVF and nanofat therapies in knee OA,addressing a significant evidence gap.It employs robust methods to enhance cartilage repair and patient quality of life.Future research should standardize dosages,protocols,and injection techniques,explore autologous/allogenic preparations,and advance radiological tools,broadening accessibility and clinical applications.
文摘BACKGROUND Hyponatremia is a prevalent and serious electrolyte imbalance in pediatric pneumonia and is linked to increased disease severity and adverse outcomes.Oral rehydration solution(ORS)is an available,inexpensive,safe,and ready-touse oral solution that can supplement sodium in such cases.AIM To assess the impact of prophylactic sodium supplementation via ORS on clinical and hospital outcomes in infants and children admitted with pneumonia.METHODS A randomized,interventional controlled trial was conducted on 140 infants and children admitted with pneumonia(70 per group).The primary outcome was hospital length of stay,with secondary outcomes including serum sodium and potassium levels,clinical respiratory scores,modified shock index,and nutritional/inflammatory markers.The hospital length of stay and both the laboratory and clinical parameters of the interventional and control groups were compared.RESULTS The hospital stay was longer in the control group than in the intervention group(P value=0.001;effect size=0.59).Clinical respiratory scores on day 4 were significantly lower in the intervention group than in the control group(P value=0.001).Sodium levels were significantly lower in the control group than in the intervention group at discharge(P value=0.002).CONCLUSION Prophylactic oral sodium supplementation through ORS may have a health-promoting effect on infants and children admitted with pneumonia.
基金supported by the Bill&Melinda Gates Foundation(OPP1175213)supported by the Research Foundation Flanders(12X9620N and 12X9623N)the European Research Council(ERC)under the European Union’s Horizon 2020 research and innovation program(946192,HUMYCO)。
文摘Background:Evidence regarding the effectiveness of prenatal nutritional supplements has mainly considered anthropometric pregnancy outcomes.The effect on markers of health and disease,such as offspring telomere length(TL)and mitochondrial DNA content(mtDNAc)is unknown.Objectives:We assessed the efficacy of maternal multiple micronutrient(MMN)-fortified balanced-energy protein(BEP)and iron-folic acid(IFA)supplementation on newborn TL as a secondary outcome and mtDNAc as a non-declared outcome.Design:We conducted a randomized controlled trial in rural Burkina Faso,among pregnant females(15-40 years old)enrolled at<21 weeks of gestation.Mothers received either MMN-fortified BEP and IFA(intervention)or IFA only(control)throughout pregnancy.Whole arterial blood samples were collected from the umbilical cord of 104 control and 90 intervention group infants,respectively.Average relative TL and mtDNAc were measured using quantitative polymerase chain reaction.Linear regression models were fitted to assess TL and mtDNAc differences across trial arms.Results:We found that a combined daily MMN-fortified BEP supplement and IFA tablet did not affect newborn TL[β=-0.010(95%CI:-0.057,0.036);P=0.662]or mtDNAc[β=0.065(95%CI:-0.203,0.073);P=0.354],as compared to an IFA tablet alone.These findings were confirmed(P>0.05)by adjusting the regression models for potential prognostic factors of study outcomes at enrollment.Exploratory analyses indicated higher,but non-significantly different mtDNAc among children born either small-for-gestational age,low birthweight,or preterm.Conclusion:Newborns from mothers who received daily nutritional supplements across gestation did not have different relative TL or mtDNAc.
基金Supported by the Hebei Province Natural Science Foundation,No.H2018206034 and No.H2022206544Hebei Province clinical medicine outstanding personnel training project,No.ZF2024135.
文摘BACKGROUND Pharmacological treatments are commonly used in individuals experiencing perinatal depression(PPD);however,a debate regarding the reproductive safety of antidepressants is ongoing.Many pregnant women opt to discontinue antidepressant out of concern about potential negative effects on the developing fetus,while slow and ineffective antidepressant medications hinder improved outcomes in women with PPD.In recent years,bright light therapy(BLT)has gained traction as a treatment option for PPD;however,clinical trials findings examining the efficacy of BLT in this population have been inconclusive.AIM To validate the feasibility and safety of BLT for the treatment of PPD.METHODS We performed a meta-analysis of randomized controlled trials of patients with PPD treated with BLT vs placebo following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis.We searched PubMed,Embase,the Cochrane Library,and Web of Science for randomized controlled studies published up to December 2023.The results were evaluated using the standardized mean difference of improvement for depression scores and odds ratios(ORs)for remission rate,response rate,incidence of adverse events,and dropout rate.RESULTS The BLT group had higher PPD response rate[50.68%vs 33.08%;OR=2.05;95% confidence interval(CI):1.25-3.35;P=0.004;I^(2)=35%]and remission rate(54.10%vs 18.52%;OR=5.00;95%CI:2.09-11.99;P=0.0003;I^(2)=0%)than the placebo group.Improvements in depression scores were higher in the BLT group than the placebo group for the overall efficacy(standardized mean difference=-0.47;95%CI:-0.80 to-0.13;P=0.007).No significant differences between the two groups in drop-outs(21.84%vs 29.63%;OR=0.63;95%CI:0.31-1.29;P=0.21;I^(2)=0%)or adverse events(17.89%vs 9.68%;OR=2.01;95%CI:0.95-4.25;P=0.07;I^(2)=0%)were observed.CONCLUSION BLT can potentially treat PPD,showing better results than the control group in this study.BLT is effective and safe and could increase the available therapeutic options for PPD.
基金the Program of Discipline Backbone of high-level Public Health Talents of Beijing Municipal Health Commission:Epidemiological Survey of Acute Myocardial Infarction Inpatients in Hospital of Traditional Chinese Medicine in Beijing Area(Discipline backbone-02-25)Beijing Municipal Hospital Administration Green Seedling Talent Project:Study on Characteristics of Clinical Syndromes,Status of Traditional Chinese Medicine Treatment and Prognosis of Patients with Chronic Heart Failure in Traditional Chinese Medicine Regional Health Service Center(QML20231006)。
文摘OBJECTIVE:To investigate the efficacy and safety of Angong Jiangya pill(AGJY,安宫降压丸)in the treatment of grade 2 hypertension with liver-fire hyperactivity syndrome.METHODS:This multicenter,randomized,double-blind,placebo-controlled trial was conducted in eight medical institutions.Eligible patients with grade 2 hypertension were randomly allocated to receive AGJY or a placebo for 12 weeks.The primary outcome was the change in blood pressure(BP).The secondary outcomes were BP compliance rate,Traditional Chinese Medicine(TCM)symptoms,and Duchenne Hypertension Quality of Life Scale score.RESULTS:Data were analyzed for 117 participants in the AGJY group and 118 participants in the placebo group.After 12 weeks of treatment,AGJY compared with placebo resulted in a higher and significant reduction in systolic/diastolic BP(-15.58±10.16/-9.72±7.41 vs-8.13±8.28/-4.86±5.68 mm Hg,P<0.0001,<0.0001,respectively).BP compliance rate(31.86%vs 19.13%,P=0.027)was significantly higher in the AGJY group than in the placebo group.The AGJY group showed a significant reduction in TCM symptom score compared with the placebo group(10.82±2.03 vs 7.83±1.24,P<0.0001).Single TCM syndrome clinical control rates of the primary symptoms(dizziness,headache,and irritability)were superior in the AGJY group(71.95%,94.62%,72.53%,respectively)compared with the placebo group(48.39%,68.00%,30.52%,respectively).Scores on the Duchenne Hypertension Quality of Life Scale showed a significant increase in the AGJY group compared with the placebo group(30.65±21.06 vs 9.96±10.72,P=0.000).No serious adverse events occurred.CONCLUSION:AGJY demonstrated efficacy in lowering BP,increasing the rate of BP compliance,and improving TCM symptoms and quality of life in patients with grade 2 hypertension liver-fire hyperactivity syndrome.However,further in-depth studies are required to determine the mechanism of TCM in treating hypertension.
文摘BACKGROUND Knee osteoarthritis(OA)imposes a substantial burden through pain,functional limitation,and progressive cartilage loss.Bone marrow aspirate concentrate(BMAC)has emerged as a promising regenerative therapy for OA due to its rich composition of mesenchymal stromal cells(MSCs)and bioactive factors.While intra-articular BMAC injections provide short-term symptomatic relief,recent literature suggests that targeting the subchondral bone—an area crucial to OA progression—may offer superior and longer-lasting clinical benefits.AIM To compares the outcomes of subchondral vs intra-articular BMAC injections in patients with primary knee OA.METHODS In this unicentric,double-blinded,randomized controlled trial,30 patients with radiologically confirmed primary knee OA(Kellgren-Lawrence grades II and III)will be equally randomized to receive either subchondral(Group A)or intra-articular(Group B)BMAC injections.BMAC will be harvested from the posterior iliac crest,processed using a standardized centrifugation protocol to yield a product with>85%cell viability,and administered under image guidance.The primary outcome is the change in pain intensity at 12 months as measured by the Visual Analog Scale(VAS).Secondary outcomes include functional improvement assessed by Knee Injury and Osteoarthritis Outcome Score(KOOS),International Knee Documentation Committee(IKDC),and Western Ontario and McMaster Universities Arthritis Index(WOMAC)scores,structural changes evaluated through advanced magnetic resonance imaging using(MRI)the whole-organ MRI Score,and safety as determined by the incidence of adverse events.RESULTS This study aims to evaluate pain reduction at 12 months post-injection,using the VAS as the primary outcome.Secondary outcomes include functional improvement(KOOS,WOMAC,IKDC),cartilage regeneration(T2 cartigram),adverse event incidence,patient satisfaction(standardized questionnaires,Likert scale),and quality of life(EQ-5D).Ethical considerations follow the Declaration of Helsinki and Good Clinical Practice,with institutional review board approval and participant informed consent ensured.Confidentiality and data security comply with regulations,and a data safety monitoring board oversees trial safety.Results will be shared via peer-reviewed journals,presentations at international orthopedic conferences,and detailed summaries for stakeholders and participants.The trial is registered under clinical trial registry of India/2024/04/065284.Findings emphasize patient-centered advancements in knee osteoarthritis management.CONCLUSION This trial aims to refine regenerative strategies for knee OA by comparing subchondral vs intra-articular BMAC injections,addressing long-term efficacy,safety,and treatment standardization to guide targeted interventions.This trial will provide critical insights into the comparative efficacy and safety of subchondral vs intra-articular BMAC injections in treating primary knee OA.
