Objective: To assess the safety and efficacy of herbal formulation rich in standardized fenugreek seed extract(IND-2) add-on therapy in type 2 diabetes mellitus(T2DM) patients who were on insulin treatment in prospect...Objective: To assess the safety and efficacy of herbal formulation rich in standardized fenugreek seed extract(IND-2) add-on therapy in type 2 diabetes mellitus(T2DM) patients who were on insulin treatment in prospective, single arm, open-label, uncontrolled, multicentre trial.Methods: T2DM patients(n=30) with aged 18-80 years who were stabilized on insulin treatment with fasting blood sugar(FBS) level between 100-140 mg/dL received IND-2 capsules(700 mg, thrice a day) for 16 weeks.The primary endpoints were an assessment of FBS at week 2, 4, 6, 8, 12 and 16.Secondary end-points include post-prandial blood sugar level, glycosylated Hb(HbA1c), reduction in the dose of insulin and number of hypoglycemic attacks, and improvement in lipid profile at various weeks.Safety and adverse events(AEs) were also assessed during the study.Results: Study was completed in twenty T2DM patients, and there was no significant reduction in FBS and post-prandial blood sugar level after addon therapy of IND-2.However, add-on therapy of IND-2 significantly reduced(P<0.01) the HbA1c values, requirements of insulin and hypoglycemic events as compared with baseline.Total cholesterol, high-density lipoproteins-cholesterol, and low-density lipoproteincholesterol levels were significantly increased(P<0.01) after IND-2 add-on therapy.Body weight and safety outcomes did not differ significantly in IND-2 add-on therapy group at week 16.Additionally, add-on therapy of IND-2 did not produce any serious adverse events.Conclusions: The results of present investigation suggest that add-on therapy of IND-2 with insulin in T2DM patients improves glycaemic control through a decrease in levels of HbA1c and number of insulin doses needed per day without an increase in body weight and risk of hypoglycemia.Thus, IND-2 may provide a safe and well-tolerated add-on therapy option for the management of T2DM.展开更多
BACKGROUND Allicin(2-propene-1-sulfinothioic acid S-2-propenyl ester,diallyl thiosulfinate)extracted from garlic,has proven activity against Helicobacter pylori(H.Pylori)infection.In recent years,clinical trials have ...BACKGROUND Allicin(2-propene-1-sulfinothioic acid S-2-propenyl ester,diallyl thiosulfinate)extracted from garlic,has proven activity against Helicobacter pylori(H.Pylori)infection.In recent years,clinical trials have explored its utility as an add-on therapy with variable outcomes reported.AIM To perform a systemic review of allicin as an add-on treatment for H.Pylori infection and assess its efficacy in randomized controlled trials(RCTs).METHODS Electronic databases including MEDLINE,EMBASE,the Web of Science,the Cochrane Database,the China National Knowledge Infrastructure Database,Chinese VIP Information Databases,Chinese Medical Databases,and the Wan-Fang Database were searched for keywords including“allicin”,“Helicobacter pylori”,“randomized clinical trials”,and their synonyms.A meta-analysis was performed using the fixed-effects model for low heterogeneity and the randomeffects model for high heterogeneity with sensitivity analysis.Bias was evaluated using Egger’s tests.Trial sequential analysis(TSA)was used to evaluate information size and treatment benefits.The Grading of Recommendations Assessment,Development and Evaluation(GRADE)was used to assess the level of quality,and studies were classed as“high quality”,“moderate quality”,“low quality”,and“very low quality”.RESULTS A total of eight RCTs consisting of 867 participants(435 from the allicin group and 432 from the control group)were included.Eradication rate in the allicin group(93.33%,406/435)was significantly higher than that of the control group(83.56%,361/432)[I2=0%,odds ratio(OR)=2.75,95%confidence interval(CI):1.74-4.35,P<0.001].The healing rate of ulcers following H.pylori therapy in the allicin group(86.17%,349/405)was significantly higher than that of the control group(75.87%,305/402)[I2=0%,OR=2.05,95%CI:1.39-3.03,P<0.001].The total remission rate of peptic ulcers across all allicin groups was 95.99%,which was significantly higher than that of controls[95.99%(359/374)vs 89.25%(332/372),I2=0,heterogeneity P=0.84,OR=3.13,95%CI:1.51-6.51,P=0.002].No significant differences in side effects were observed.TSA suggested that the trials were of sufficient standard to draw reliable conclusions.The quality of outcomes including eradication rates and side effects was graded as“very low”due to downgrades for“risk of bias”and“indirectness”.Other outcomes such as ulcer healing rates and total ulcer remission rates were graded as"low"due to downgrades for“risk of bias”.CONCLUSION Allicin as an add-on therapy improves H.pylori eradication,healing of ulcers,and remission of symptoms.These results are suggested to be treated with caution due to limited quality.展开更多
Background: Recently, high efficacy of the chemotherapeutic regimen combining clarithromycin (CAM) with lenalidomide (Len) and dexamethasone (Dex) (BiRD) in treating multiple myeloma (MM) patients has been reported. H...Background: Recently, high efficacy of the chemotherapeutic regimen combining clarithromycin (CAM) with lenalidomide (Len) and dexamethasone (Dex) (BiRD) in treating multiple myeloma (MM) patients has been reported. However, the exact mechanism of added CAM has not been fully elucidated. This case report will provide helpful information for understanding the significance and the mechanism of action of CAM as an add-on therapy. Patient: A 78-year-old female patient with IgA-λ type MM was treated with low-dose Len coupled with low-dose Dex (low Rd), and excellent response was achieved for long term, but she later became refractory to this treatment. Then, CAM was added to low Rd (low Rd-CAM, i.e., modified BiRD therapy). This add-on-therapy was found to be effective, but later suspended because of pneumonitis. Then, low-dose Len coupled with CAM (low R-CAM) treatment was applied;but effect of this Dex-free treatment was insufficient. Thus, low Rd-CAM was reapplied and satisfactory reduction of IgA was achieved. This fact suggests that low Rd-CAM is the favorable combination, Dex is requisite and CAM might have enhanced the effect of Dex. In this case, various serum cytokines were examined during the course of illness. Only interleukin-6 showed apparent increase, and tumor necrosis factor-α, transforming growth factor-β, soluble IL-2 receptors and C-reactive protein showed the slight increase during low Rd-CAM treatment. The results seem somewhat conflicting, but it seems that intricate cytokine response due to immune activation might have occurred during low Rd-CAM treatment.展开更多
Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary in...Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary intervention and statins,reduce major adverse cardiovascular events(MACE)by 25%-30%,yet a 20%five-year MACE risk persists in high-risk cohorts.These approaches,histor-ically focused on luminal stenosis,fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation.Specifically,dietary linoleic acid restriction(<5 g/day)reduces oxidized low-density lipoprotein by approximately 15%by limiting peroxidation-prone bisallylic bonds,mitigating arterial inflam-mation,a key atherogenic trigger.Enhanced external counterpulsation,through pulsatile shear stress,enhances nitric oxide-mediated coronary perfusion,alle-viating angina in approximately 70%of refractory cases unresponsive to revascu-larization.Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision,reducing calcium content by up to 30%in preclinical models,offering a novel avenue for lesion reversal.These innovations collectively address residual risk by tackling root causes,oxidative stress,endothelial dysfunction,and plaque instability,potentially halving MACE rates with widespread adoption.Despite promising preliminary data,gaps remain in long-term safety and scalability.Robust clinical trials are needed to validate these approaches,which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration,potentially reducing coronary events to a public health rarity.展开更多
BACKGROUND A dual therapy regimen containing amoxicillin is a common treatment option for the eradication of Helicobacter pylori(H.pylori).While substantial research supports the efficacy and safety of vonoprazan and ...BACKGROUND A dual therapy regimen containing amoxicillin is a common treatment option for the eradication of Helicobacter pylori(H.pylori).While substantial research supports the efficacy and safety of vonoprazan and amoxicillin(VA)dual therapy in the general population,there is still a lack of studies specifically focusing on its safety in elderly patients.AIM To evaluate efficacy and safety of VA dual therapy as first-line or rescue treatment for H.pylori in elderly patients.METHODS As a real-world retrospective study,data were collected from elderly patients aged 60 years and above who accepted VA dual therapy(vonoprazan 20 mg twice daily+amoxicillin 1000 mg thrice daily for 14 days)for H.pylori eradication in the Department of Gastroenterology at Peking University First Hospital between June 2020 and January 2024.H.pylori status was evaluated by^(13)C-urease breath test 6 weeks after treatment.All adverse events(AEs)during treatment were recorded.RESULTS In total,401 cases were screened.Twenty-one cases were excluded due to loss to follow-up,lack of re-examination,or unwillingness to take medication.The total of 380 included cases comprised 250 who received VA dual therapy as first-line treatment and 130 who received VA dual therapy as rescue treatment.H.pylori was successfully eradicated in 239 cases(95.6%)in the first-line treatment group and 116 cases(89.2%)in the rescue treatment group.The overall incidence of AEs was 9.5%for both groups.Specifically,9.2%of patients experienced an AE in the first-line treatment group and 10.0%in the rescue treatment group.Five patients discontinued treatment due to AE,with a discontinuation rate of 1.3%.No serious AE occurred.CONCLUSION The VA dual therapy regimen as a first-line treatment and a rescue therapy was effective and safe for elderly patients aged 60 and older.展开更多
Conventional therapies are primary cancer treatments that directly eliminate or inhibit the growth of tumor cells,reducing the overall tumor burden.Increasing evidence suggests that conventional therapies possess sign...Conventional therapies are primary cancer treatments that directly eliminate or inhibit the growth of tumor cells,reducing the overall tumor burden.Increasing evidence suggests that conventional therapies possess significant immunomodulatory properties in addition to their established direct tumoricidal effects.Emerging immunotherapies have revolutionized the clinical management of various cancer types.Conventional therapy and immunotherapy have demonstrated remarkable clinical efficacy,leading to numerous ongoing clinical investiga-tions exploring their potential synergistic effects.However,trials investigating the combination of conventional therapy and immunotherapy have shown limited synergistic therapeutic efficacy.This unsatisfactory clinical outcome may be attributed to the suboptimal design of the combination approach and the inadequate understanding of the mechanisms and impacts of radiotherapy,chemotherapy,targeted ther-apy regimens(including dosing,timing,and administration route),and surgery on both cancer cells and the host immune system.Here,we comprehensively review preclinical and clinical investigations exploring the therapeutic effects and mechanisms of conventional therapy alone or in combination with immunotherapy.We proposed that optimizing the dosing,timing,and route of administration of conventional therapies can enhance the synergistic efficacy of combination therapies,thus offering significant clinical advantages.展开更多
Colonoscopy represents a safe procedure that is widely used in medical practice either to diagnose or treat various gastrointestinal diseases.During the last few years,the incidence rate of perforations in colonoscopi...Colonoscopy represents a safe procedure that is widely used in medical practice either to diagnose or treat various gastrointestinal diseases.During the last few years,the incidence rate of perforations in colonoscopic procedures has increased,especially in therapeutic colonoscopies.The recent advancements in endoscopic techniques and gastrointestinal tumoral resection procedures such as endoscopic mucosal resection,endoscopic full-thickness resection,and endoscopic submucosal dissection(ESD)could be a risk factor for this increased risk.The incidence rate of mortality of serious colonoscopic perforations is 7.1%.The management plan for these perforations starts with conservative treatment in mild cases,endoscopic closure,and surgical management in severe cases.Recently,endoluminal vacuum therapy was found to be effective in the management of colorectal perforations and this has been reported in multiple case reports.This editorial provides an overview of the current guidelines for the management of iatrogenic colorectal perforations.These insights are from the perspectives of endoscopists and gastroenterologists.We also present a management algorithm based on the guidelines of the European Society of Gastrointestinal Endoscopy,the American Gastroenterological Association,and the World Society of Emergency Surgery.We also discussed in brief the use of endoluminal vacuum therapy in colorectal perforations.展开更多
BACKGROUND Helicobacter pylori(H.pylori)is a Gram-negative bacterium that relies on flagellar motility to colonize the stomach,damaging the gastric mucosa through various mechanisms and leading to various digestive di...BACKGROUND Helicobacter pylori(H.pylori)is a Gram-negative bacterium that relies on flagellar motility to colonize the stomach,damaging the gastric mucosa through various mechanisms and leading to various digestive disorders.Accurate assessment and precise treatment are essential in initial intensive therapy.AIM To investigate the efficacy and safety of a vonoprazan(VPZ)-based triple regimen for first-line eradication of H.pylori in China.METHODS This multicenter noninferior randomized controlled trial(June 2022 to November 2023)involved 524 H.pyloripositive patients across 19 centers in Shandong,China.Participants were randomized to 14-day esomeprazole/bismuth/amoxicillin/clarithromycin(EBAC),14-day VPZ/amoxicillin/clarithromycin(VACa),or 10-day VPZ/amoxicillin/clarithromycin(VACb)-all administered twice daily.Primary outcomes(eradication rates)were assessed via intention-to-treat(ITT)and per-protocol(PP)analyses.Secondary endpoints included adverse events and adherence.Noninferiority testing andχ^(2)tests were used for statistical comparisons.RESULTS A total of 524 patients participated in this study.In ITT analysis,the eradication rates of the EBAC,VACa,and VACb groups were 72.6%(127/175),88.0%(154/175),and 83.3%(145/174),respectively(P=0.001).The difference in the eradication rate between the EBAC and VPCa groups was 15.4%[95%confidence interval(CI):7.3-23.6,P<0.001],and that between the EBAC and VACb groups was 10.8%(95%CI:2.1-19.4,P=0.018).In PP analysis,the eradication rates of the EBAC,VACa,and VACb groups were 81.4%(127/156),93.9%(154/164),and 90.6%(145/160),respectively(P=0.001).There was no significant difference in the incidence of adverse reactions among the three groups,which were 36.6%,33.8%and 29.6%,respectively(P=0.50).CONCLUSION VPZ-based triple therapies demonstrate noninferiority to 14-day bismuth-containing regimens,with the 10-day regimen showing comparable efficacy and similar adverse event rates.展开更多
Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied fo...Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.展开更多
Pancreatic cancer remains one of the most challenging malignancies to treat,with a poor prognosis and limited therapeutic options.Despite the success of immunotherapy and targeted therapies for other cancers,these app...Pancreatic cancer remains one of the most challenging malignancies to treat,with a poor prognosis and limited therapeutic options.Despite the success of immunotherapy and targeted therapies for other cancers,these approaches have not yet transformed the treatment landscape for pancreatic cancer.The unique tumor microenvironment(TME)of pancreatic cancer,characterized by dense fibrotic stroma and immunosuppressive myeloid cells,poses significant barriers to effective immunotherapy.Current research highlights the need for an in-depth understanding of the TME and the development of strategies to overcome its immunosuppressive properties.Recent studies have explored various immunotherapeutic approaches,including immune checkpoint inhibitors,cancer vaccines,and adoptive cell therapies,some of which have shown promising results in preclinical and early clinical trials.Furthermore,combining immunotherapy with traditional treatments,such as chemotherapy and radiotherapy,has shown potential for enhancing antitumor efficacy,although targeted therapies for pancreatic cancer are still in their early stages and are being investigated for their ability to disrupt specific molecular pathways involved in tumor growth and survival.This review provides a comprehensive overview of the advances in immunotherapy and targeted therapies for pancreatic cancer,discussing the current state of research,clinical outcomes,and future directions for improving patient prognosis.展开更多
The traditional view of the decompensated stage as a point of no return in the natural history of liver cirrhosis(LC)is currently being questioned.This is due to the appearance of data indicating the possibility of re...The traditional view of the decompensated stage as a point of no return in the natural history of liver cirrhosis(LC)is currently being questioned.This is due to the appearance of data indicating the possibility of restoring the structure and function of the liver,reducing the portal pressure with a positive effect on complications associated with portal hypertension and decreasing the risk of developing hepatocellular carcinoma after elimination of the etiological factor.To create a unified understanding the recompensation of decompensated LC,at the Baveno VII consensus workshop were developed criteria confirming it.At the moment,the efficacy of etiological therapy in achieving established criteria for recompensation has been evaluated only in patients with alcohol-related,as well as hepatitis B virus-related and hepatitis C virus-related decompensated LC.The purpose of the review is to provide up–to-date information on the role of etiological therapy in achieving recompensation of decompensated LC according to Baveno VII criteria.So far,only the first steps have been taken in studying this problem.To further understand it,research is needed to identify pathophysiological mechanisms,modifying factors,predictors,and potential noninvasive biomarkers of recompensation of decompensated LC.展开更多
Radioactive microspheres have demonstrated excellent therapeutic effects and good tolerance in the treatment of unresectable primary and secondary liver malignancies.This is attributed to precise embolization and pote...Radioactive microspheres have demonstrated excellent therapeutic effects and good tolerance in the treatment of unresectable primary and secondary liver malignancies.This is attributed to precise embolization and potent anti-tumor effect.However,certain limitations such as unstable loading,perfusion stasis,heterogeneous distribution,ectopic distribution,and insufficient dosage,restrict their clinical application.Herein,a novel personalized Y-90 carbon microsphere with high uniformity,high specific activity and high availability(^(90)Y-HUACM)is presented.It is synthesized through planar molecular complex adsorption and chemical deposition solidification.^(90)Y-HUACM exhibited controllable size,excellent biocompatibility,outstanding in vitro and in vivo stability.The radiolabeling efficiency of Y-90 exceeded 99%and the leaching rate of Y-90 is far below 0.1%.Furthermore,the excellent anti-tumor effect,nuclide loading stability,anti-reflux characteristics,precise embolization,and biosafety of^(90)Y-HUACM were validated in a rabbit VX2liver tumor model.In summary,this new,high-performance,and customizable radioactive microsphere provides a superior choice for selective internal radiation treatment of advanced liver cancer is expected to be rapidly applied in clinical practice.展开更多
BACKGROUND While existing literature on ischiofemoral impingement syndrome(IFI)predominantly emphasizes surgical interventions or generalized physical therapy approaches,there remains a paucity of evidence regarding s...BACKGROUND While existing literature on ischiofemoral impingement syndrome(IFI)predominantly emphasizes surgical interventions or generalized physical therapy approaches,there remains a paucity of evidence regarding structured,multimodal rehabilitation programs targeting biomechanical deficits in IFI.This case report evaluates the efficacy of a multimodal rehabilitation program addressing a critical gap in conservative management strategies.CASE SUMMARY The patient underwent comprehensive physical and clinical examination,including hip X-ray and magnetic resonance imaging investigations.The patient completed the Musculoskeletal Health Questionnaire(MSK-HQ)and numerical pain rating scale(NPRS).The patient underwent a two-month tailored structured physical therapy intervention and repeated the same assessment afterwards.The patient's substantial reduction in pain,reflected by a significant decrease in the patient’s NPRS score from 9 to 3 points,signifies a positive clinical response.This outcome,coupled with the significant improvement in the patient's health-related quality of life according to the MSK-HQ score,which increased from 12 to 48 points,underscores the success of our research.CONCLUSION The study highlights the importance of a comprehensive approach to diagnosing and managing IFI,combining clinical assessment with imaging and implementing a multimodal rehabilitation program for optimal outcomes.展开更多
Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evalua...Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB.Using propensity score matching,the study balanced the comparison groups to investigate overall survival and treatment-related adverse events.The study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB,highlighting the complexities of treatment decisions in these high-risk patients.展开更多
Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxyge...Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.展开更多
Background:Isotonic crystalloids are recommended as the first choice for fluid therapy in acute pan-creatitis(AP),with normal saline(NS)and lactate Ringer’s(LR)used most often.Evidence based recom-mendations on the t...Background:Isotonic crystalloids are recommended as the first choice for fluid therapy in acute pan-creatitis(AP),with normal saline(NS)and lactate Ringer’s(LR)used most often.Evidence based recom-mendations on the type of fluid are conflicting and generally come from small single-center randomized controlled trials(RCTs).We therefore conducted a systematic review and meta-analysis to compare the effect of balanced solutions(BS)versus NS on patient-centered clinical outcomes in AP.Methods:From four databases searched up to October 2024,we included only RCTs of adult patients with AP that compared the use of BS(including LR,acetate Ringer’s,etc.)with NS.The primary out-come was the disease advances from AP to moderately severe and severe AP(MSAP/SAP).Trial sequential analyses(TSA)were conducted to control for type-I and type-II errors and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)was used to assess the quality of evidence.Results:Six RCTs were identified and included,involving 260 patients treated with BS and 298 patients with NS.Patients who received the BS had less MSAP/SAP[odds ratio(OR)=0.50,95%confidence in-terval(CI):0.29 to 0.85,P=0.01,I^(2)=0%;5 studies,299 patients],reduced the need of ICU admission(OR=0.60,95%CI:0.39 to 0.93,P=0.02,I^(2)=0%;5 studies,507 patients)and shorter length of hospital stay[mean difference(MD)=-0.88,95%CI:-1.48 to-0.28,P=0.004,I^(2)=0%;6 studies,558 patients;confirmed by TSA with high certainty]compared with those who received NS.The evidence for most of the clinical outcomes was rated as moderate to low due to the risk of bias,imprecision and inconsistency.Conclusions:BS,compared with NS,was associated with improved clinical outcomes in patients with AP.However,given the moderate to low quality of evidence for most of the outcomes assessed,further trials are warranted.展开更多
In the contemporary medical landscape,the burgeoning interest in natural therapies,particularly for managing gastrointestinal disorders,has brought traditional Chinese medicine(TCM)to the forefront.This article explai...In the contemporary medical landscape,the burgeoning interest in natural therapies,particularly for managing gastrointestinal disorders,has brought traditional Chinese medicine(TCM)to the forefront.This article explains the core principles and clinical applications of TCM in treating these conditions,furthering the discourse through an examination of integrated TCM strategies,as demonstrated in the study by Zhou et al.While TCM has shown promising clinical outcomes,it encounters significant hurdles in standardization,mechanistic research,and clinical validation.Future investigations should aim to solidify the scientific underpinnings of TCM and expand its use in gastrointestinal disease management,striving for a seamless fusion of traditional and contemporary medical practices.展开更多
In this editorial,we comment on the article by Meng et al.Chronic hepatitis B(CHB)is a significant global health problem,particularly in developing countries.Hepatitis B virus(HBV)infection is one of the most importan...In this editorial,we comment on the article by Meng et al.Chronic hepatitis B(CHB)is a significant global health problem,particularly in developing countries.Hepatitis B virus(HBV)infection is one of the most important risk factors for cirrhosis and hepatocellular carcinoma.Prevention and treatment of HBV are key measures to reduce complications.At present,drug therapy can effectively control virus replication and slow disease progression,but completely eliminating the virus remains a challenge.Anti-HBV treatment is a long-term process,and there are many kinds of antiviral drugs with different mechanisms of action,it is essential to evaluate the safety and efficacy of these drugs to reduce side effects and improve patients’compliance.We will summarize the current status of CHB drug treatment,hoping to provide a reference for the selection of clinical antiviral drugs.展开更多
In this work,iron-doped carbon dots(Fe-CDs)with strong peroxidase-mimicking activity were synthesized for tumor-specific therapy.Their intrinsic red fluorescence enabled high-contrast cellular imaging,revealing prefer...In this work,iron-doped carbon dots(Fe-CDs)with strong peroxidase-mimicking activity were synthesized for tumor-specific therapy.Their intrinsic red fluorescence enabled high-contrast cellular imaging,revealing preferen⁃tial mitochondrial accumulation.In the acidic and hydrogen peroxide(H_(2)O_(2))-rich tumor microenvironment,Fe-CDs catalyzed hydroxyl radical(·OH)generation,inducing oxidative stress and lipid peroxidation,ultimately triggering ferroptosis.In vitro and in vivo studies demonstrated potent tumor inhibition.Furthermore,Fe-CDs exhibited excel⁃lent biocompatibility with no significant systemic toxicity.By integrating fluorescence imaging and catalytic therapy,this study presents a promising nanoplatform for tumor treatment and ferroptosis research.展开更多
In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B ...In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B virus(HBV)infection,the pathogenesis of hepatocellular carcinoma(HCC),and the role of antiviral therapy in treating HCC related to HBV infection.HBV infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways,as well as by inhibiting the immune functions of macrophages,natural killer cells and dendritic cells.In addition,HBV leads to an immunosuppressive cascade by expressing inhibitory molecules to induce exhaustion of HBV-specific cluster of differentiation 8+T cells,ultimately leading to long-term viral infection.The loss of immune cell function caused by HBV infection ultimately leads to HCC.Long-term antiviral therapy can improve the prognosis of patients with HCC and prevent tumor recurrence and metastasis.展开更多
文摘Objective: To assess the safety and efficacy of herbal formulation rich in standardized fenugreek seed extract(IND-2) add-on therapy in type 2 diabetes mellitus(T2DM) patients who were on insulin treatment in prospective, single arm, open-label, uncontrolled, multicentre trial.Methods: T2DM patients(n=30) with aged 18-80 years who were stabilized on insulin treatment with fasting blood sugar(FBS) level between 100-140 mg/dL received IND-2 capsules(700 mg, thrice a day) for 16 weeks.The primary endpoints were an assessment of FBS at week 2, 4, 6, 8, 12 and 16.Secondary end-points include post-prandial blood sugar level, glycosylated Hb(HbA1c), reduction in the dose of insulin and number of hypoglycemic attacks, and improvement in lipid profile at various weeks.Safety and adverse events(AEs) were also assessed during the study.Results: Study was completed in twenty T2DM patients, and there was no significant reduction in FBS and post-prandial blood sugar level after addon therapy of IND-2.However, add-on therapy of IND-2 significantly reduced(P<0.01) the HbA1c values, requirements of insulin and hypoglycemic events as compared with baseline.Total cholesterol, high-density lipoproteins-cholesterol, and low-density lipoproteincholesterol levels were significantly increased(P<0.01) after IND-2 add-on therapy.Body weight and safety outcomes did not differ significantly in IND-2 add-on therapy group at week 16.Additionally, add-on therapy of IND-2 did not produce any serious adverse events.Conclusions: The results of present investigation suggest that add-on therapy of IND-2 with insulin in T2DM patients improves glycaemic control through a decrease in levels of HbA1c and number of insulin doses needed per day without an increase in body weight and risk of hypoglycemia.Thus, IND-2 may provide a safe and well-tolerated add-on therapy option for the management of T2DM.
基金Supported by BeiJingJiShuiTan Hospital Foundation for Young Scholars,No.QN-201906
文摘BACKGROUND Allicin(2-propene-1-sulfinothioic acid S-2-propenyl ester,diallyl thiosulfinate)extracted from garlic,has proven activity against Helicobacter pylori(H.Pylori)infection.In recent years,clinical trials have explored its utility as an add-on therapy with variable outcomes reported.AIM To perform a systemic review of allicin as an add-on treatment for H.Pylori infection and assess its efficacy in randomized controlled trials(RCTs).METHODS Electronic databases including MEDLINE,EMBASE,the Web of Science,the Cochrane Database,the China National Knowledge Infrastructure Database,Chinese VIP Information Databases,Chinese Medical Databases,and the Wan-Fang Database were searched for keywords including“allicin”,“Helicobacter pylori”,“randomized clinical trials”,and their synonyms.A meta-analysis was performed using the fixed-effects model for low heterogeneity and the randomeffects model for high heterogeneity with sensitivity analysis.Bias was evaluated using Egger’s tests.Trial sequential analysis(TSA)was used to evaluate information size and treatment benefits.The Grading of Recommendations Assessment,Development and Evaluation(GRADE)was used to assess the level of quality,and studies were classed as“high quality”,“moderate quality”,“low quality”,and“very low quality”.RESULTS A total of eight RCTs consisting of 867 participants(435 from the allicin group and 432 from the control group)were included.Eradication rate in the allicin group(93.33%,406/435)was significantly higher than that of the control group(83.56%,361/432)[I2=0%,odds ratio(OR)=2.75,95%confidence interval(CI):1.74-4.35,P<0.001].The healing rate of ulcers following H.pylori therapy in the allicin group(86.17%,349/405)was significantly higher than that of the control group(75.87%,305/402)[I2=0%,OR=2.05,95%CI:1.39-3.03,P<0.001].The total remission rate of peptic ulcers across all allicin groups was 95.99%,which was significantly higher than that of controls[95.99%(359/374)vs 89.25%(332/372),I2=0,heterogeneity P=0.84,OR=3.13,95%CI:1.51-6.51,P=0.002].No significant differences in side effects were observed.TSA suggested that the trials were of sufficient standard to draw reliable conclusions.The quality of outcomes including eradication rates and side effects was graded as“very low”due to downgrades for“risk of bias”and“indirectness”.Other outcomes such as ulcer healing rates and total ulcer remission rates were graded as"low"due to downgrades for“risk of bias”.CONCLUSION Allicin as an add-on therapy improves H.pylori eradication,healing of ulcers,and remission of symptoms.These results are suggested to be treated with caution due to limited quality.
文摘Background: Recently, high efficacy of the chemotherapeutic regimen combining clarithromycin (CAM) with lenalidomide (Len) and dexamethasone (Dex) (BiRD) in treating multiple myeloma (MM) patients has been reported. However, the exact mechanism of added CAM has not been fully elucidated. This case report will provide helpful information for understanding the significance and the mechanism of action of CAM as an add-on therapy. Patient: A 78-year-old female patient with IgA-λ type MM was treated with low-dose Len coupled with low-dose Dex (low Rd), and excellent response was achieved for long term, but she later became refractory to this treatment. Then, CAM was added to low Rd (low Rd-CAM, i.e., modified BiRD therapy). This add-on-therapy was found to be effective, but later suspended because of pneumonitis. Then, low-dose Len coupled with CAM (low R-CAM) treatment was applied;but effect of this Dex-free treatment was insufficient. Thus, low Rd-CAM was reapplied and satisfactory reduction of IgA was achieved. This fact suggests that low Rd-CAM is the favorable combination, Dex is requisite and CAM might have enhanced the effect of Dex. In this case, various serum cytokines were examined during the course of illness. Only interleukin-6 showed apparent increase, and tumor necrosis factor-α, transforming growth factor-β, soluble IL-2 receptors and C-reactive protein showed the slight increase during low Rd-CAM treatment. The results seem somewhat conflicting, but it seems that intricate cytokine response due to immune activation might have occurred during low Rd-CAM treatment.
文摘Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary intervention and statins,reduce major adverse cardiovascular events(MACE)by 25%-30%,yet a 20%five-year MACE risk persists in high-risk cohorts.These approaches,histor-ically focused on luminal stenosis,fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation.Specifically,dietary linoleic acid restriction(<5 g/day)reduces oxidized low-density lipoprotein by approximately 15%by limiting peroxidation-prone bisallylic bonds,mitigating arterial inflam-mation,a key atherogenic trigger.Enhanced external counterpulsation,through pulsatile shear stress,enhances nitric oxide-mediated coronary perfusion,alle-viating angina in approximately 70%of refractory cases unresponsive to revascu-larization.Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision,reducing calcium content by up to 30%in preclinical models,offering a novel avenue for lesion reversal.These innovations collectively address residual risk by tackling root causes,oxidative stress,endothelial dysfunction,and plaque instability,potentially halving MACE rates with widespread adoption.Despite promising preliminary data,gaps remain in long-term safety and scalability.Robust clinical trials are needed to validate these approaches,which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration,potentially reducing coronary events to a public health rarity.
基金Supported by National High Level Hospital Clinical Research Funding(Youth Clinical Research Project of Peking University First Hospital),No.2023YC27Capital’s Funds for Health Improvement and Research,No.2022-2-40711National High Level Hospital Clinical Research Funding(Interdepartmental Research Project of Peking University First Hospital),No.2024IR20.
文摘BACKGROUND A dual therapy regimen containing amoxicillin is a common treatment option for the eradication of Helicobacter pylori(H.pylori).While substantial research supports the efficacy and safety of vonoprazan and amoxicillin(VA)dual therapy in the general population,there is still a lack of studies specifically focusing on its safety in elderly patients.AIM To evaluate efficacy and safety of VA dual therapy as first-line or rescue treatment for H.pylori in elderly patients.METHODS As a real-world retrospective study,data were collected from elderly patients aged 60 years and above who accepted VA dual therapy(vonoprazan 20 mg twice daily+amoxicillin 1000 mg thrice daily for 14 days)for H.pylori eradication in the Department of Gastroenterology at Peking University First Hospital between June 2020 and January 2024.H.pylori status was evaluated by^(13)C-urease breath test 6 weeks after treatment.All adverse events(AEs)during treatment were recorded.RESULTS In total,401 cases were screened.Twenty-one cases were excluded due to loss to follow-up,lack of re-examination,or unwillingness to take medication.The total of 380 included cases comprised 250 who received VA dual therapy as first-line treatment and 130 who received VA dual therapy as rescue treatment.H.pylori was successfully eradicated in 239 cases(95.6%)in the first-line treatment group and 116 cases(89.2%)in the rescue treatment group.The overall incidence of AEs was 9.5%for both groups.Specifically,9.2%of patients experienced an AE in the first-line treatment group and 10.0%in the rescue treatment group.Five patients discontinued treatment due to AE,with a discontinuation rate of 1.3%.No serious AE occurred.CONCLUSION The VA dual therapy regimen as a first-line treatment and a rescue therapy was effective and safe for elderly patients aged 60 and older.
基金supported by the National Science Foundation of China(No.82172726)the Youth Project of Science and Technology Department of Shanxi Province(No.202203021212105)the Research Project Supported by the Shanxi Scholarship Council of China(2021-156).
文摘Conventional therapies are primary cancer treatments that directly eliminate or inhibit the growth of tumor cells,reducing the overall tumor burden.Increasing evidence suggests that conventional therapies possess significant immunomodulatory properties in addition to their established direct tumoricidal effects.Emerging immunotherapies have revolutionized the clinical management of various cancer types.Conventional therapy and immunotherapy have demonstrated remarkable clinical efficacy,leading to numerous ongoing clinical investiga-tions exploring their potential synergistic effects.However,trials investigating the combination of conventional therapy and immunotherapy have shown limited synergistic therapeutic efficacy.This unsatisfactory clinical outcome may be attributed to the suboptimal design of the combination approach and the inadequate understanding of the mechanisms and impacts of radiotherapy,chemotherapy,targeted ther-apy regimens(including dosing,timing,and administration route),and surgery on both cancer cells and the host immune system.Here,we comprehensively review preclinical and clinical investigations exploring the therapeutic effects and mechanisms of conventional therapy alone or in combination with immunotherapy.We proposed that optimizing the dosing,timing,and route of administration of conventional therapies can enhance the synergistic efficacy of combination therapies,thus offering significant clinical advantages.
文摘Colonoscopy represents a safe procedure that is widely used in medical practice either to diagnose or treat various gastrointestinal diseases.During the last few years,the incidence rate of perforations in colonoscopic procedures has increased,especially in therapeutic colonoscopies.The recent advancements in endoscopic techniques and gastrointestinal tumoral resection procedures such as endoscopic mucosal resection,endoscopic full-thickness resection,and endoscopic submucosal dissection(ESD)could be a risk factor for this increased risk.The incidence rate of mortality of serious colonoscopic perforations is 7.1%.The management plan for these perforations starts with conservative treatment in mild cases,endoscopic closure,and surgical management in severe cases.Recently,endoluminal vacuum therapy was found to be effective in the management of colorectal perforations and this has been reported in multiple case reports.This editorial provides an overview of the current guidelines for the management of iatrogenic colorectal perforations.These insights are from the perspectives of endoscopists and gastroenterologists.We also present a management algorithm based on the guidelines of the European Society of Gastrointestinal Endoscopy,the American Gastroenterological Association,and the World Society of Emergency Surgery.We also discussed in brief the use of endoluminal vacuum therapy in colorectal perforations.
基金Supported by Qilu Health Outstanding Young Talent Cultivation Project,No.QDFY-3839。
文摘BACKGROUND Helicobacter pylori(H.pylori)is a Gram-negative bacterium that relies on flagellar motility to colonize the stomach,damaging the gastric mucosa through various mechanisms and leading to various digestive disorders.Accurate assessment and precise treatment are essential in initial intensive therapy.AIM To investigate the efficacy and safety of a vonoprazan(VPZ)-based triple regimen for first-line eradication of H.pylori in China.METHODS This multicenter noninferior randomized controlled trial(June 2022 to November 2023)involved 524 H.pyloripositive patients across 19 centers in Shandong,China.Participants were randomized to 14-day esomeprazole/bismuth/amoxicillin/clarithromycin(EBAC),14-day VPZ/amoxicillin/clarithromycin(VACa),or 10-day VPZ/amoxicillin/clarithromycin(VACb)-all administered twice daily.Primary outcomes(eradication rates)were assessed via intention-to-treat(ITT)and per-protocol(PP)analyses.Secondary endpoints included adverse events and adherence.Noninferiority testing andχ^(2)tests were used for statistical comparisons.RESULTS A total of 524 patients participated in this study.In ITT analysis,the eradication rates of the EBAC,VACa,and VACb groups were 72.6%(127/175),88.0%(154/175),and 83.3%(145/174),respectively(P=0.001).The difference in the eradication rate between the EBAC and VPCa groups was 15.4%[95%confidence interval(CI):7.3-23.6,P<0.001],and that between the EBAC and VACb groups was 10.8%(95%CI:2.1-19.4,P=0.018).In PP analysis,the eradication rates of the EBAC,VACa,and VACb groups were 81.4%(127/156),93.9%(154/164),and 90.6%(145/160),respectively(P=0.001).There was no significant difference in the incidence of adverse reactions among the three groups,which were 36.6%,33.8%and 29.6%,respectively(P=0.50).CONCLUSION VPZ-based triple therapies demonstrate noninferiority to 14-day bismuth-containing regimens,with the 10-day regimen showing comparable efficacy and similar adverse event rates.
文摘Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.
文摘Pancreatic cancer remains one of the most challenging malignancies to treat,with a poor prognosis and limited therapeutic options.Despite the success of immunotherapy and targeted therapies for other cancers,these approaches have not yet transformed the treatment landscape for pancreatic cancer.The unique tumor microenvironment(TME)of pancreatic cancer,characterized by dense fibrotic stroma and immunosuppressive myeloid cells,poses significant barriers to effective immunotherapy.Current research highlights the need for an in-depth understanding of the TME and the development of strategies to overcome its immunosuppressive properties.Recent studies have explored various immunotherapeutic approaches,including immune checkpoint inhibitors,cancer vaccines,and adoptive cell therapies,some of which have shown promising results in preclinical and early clinical trials.Furthermore,combining immunotherapy with traditional treatments,such as chemotherapy and radiotherapy,has shown potential for enhancing antitumor efficacy,although targeted therapies for pancreatic cancer are still in their early stages and are being investigated for their ability to disrupt specific molecular pathways involved in tumor growth and survival.This review provides a comprehensive overview of the advances in immunotherapy and targeted therapies for pancreatic cancer,discussing the current state of research,clinical outcomes,and future directions for improving patient prognosis.
文摘The traditional view of the decompensated stage as a point of no return in the natural history of liver cirrhosis(LC)is currently being questioned.This is due to the appearance of data indicating the possibility of restoring the structure and function of the liver,reducing the portal pressure with a positive effect on complications associated with portal hypertension and decreasing the risk of developing hepatocellular carcinoma after elimination of the etiological factor.To create a unified understanding the recompensation of decompensated LC,at the Baveno VII consensus workshop were developed criteria confirming it.At the moment,the efficacy of etiological therapy in achieving established criteria for recompensation has been evaluated only in patients with alcohol-related,as well as hepatitis B virus-related and hepatitis C virus-related decompensated LC.The purpose of the review is to provide up–to-date information on the role of etiological therapy in achieving recompensation of decompensated LC according to Baveno VII criteria.So far,only the first steps have been taken in studying this problem.To further understand it,research is needed to identify pathophysiological mechanisms,modifying factors,predictors,and potential noninvasive biomarkers of recompensation of decompensated LC.
基金supported by the National Major Scientific and Technological Special Project for“Significant New Drugs Development”(No.2018ZX09201018–028)the nuclear energy development projects of China during the 13thFive Year Plan periodthe key research and development project of the Sichuan Provincial Department of Science and Technology(No.18ZDYF1466)。
文摘Radioactive microspheres have demonstrated excellent therapeutic effects and good tolerance in the treatment of unresectable primary and secondary liver malignancies.This is attributed to precise embolization and potent anti-tumor effect.However,certain limitations such as unstable loading,perfusion stasis,heterogeneous distribution,ectopic distribution,and insufficient dosage,restrict their clinical application.Herein,a novel personalized Y-90 carbon microsphere with high uniformity,high specific activity and high availability(^(90)Y-HUACM)is presented.It is synthesized through planar molecular complex adsorption and chemical deposition solidification.^(90)Y-HUACM exhibited controllable size,excellent biocompatibility,outstanding in vitro and in vivo stability.The radiolabeling efficiency of Y-90 exceeded 99%and the leaching rate of Y-90 is far below 0.1%.Furthermore,the excellent anti-tumor effect,nuclide loading stability,anti-reflux characteristics,precise embolization,and biosafety of^(90)Y-HUACM were validated in a rabbit VX2liver tumor model.In summary,this new,high-performance,and customizable radioactive microsphere provides a superior choice for selective internal radiation treatment of advanced liver cancer is expected to be rapidly applied in clinical practice.
文摘BACKGROUND While existing literature on ischiofemoral impingement syndrome(IFI)predominantly emphasizes surgical interventions or generalized physical therapy approaches,there remains a paucity of evidence regarding structured,multimodal rehabilitation programs targeting biomechanical deficits in IFI.This case report evaluates the efficacy of a multimodal rehabilitation program addressing a critical gap in conservative management strategies.CASE SUMMARY The patient underwent comprehensive physical and clinical examination,including hip X-ray and magnetic resonance imaging investigations.The patient completed the Musculoskeletal Health Questionnaire(MSK-HQ)and numerical pain rating scale(NPRS).The patient underwent a two-month tailored structured physical therapy intervention and repeated the same assessment afterwards.The patient's substantial reduction in pain,reflected by a significant decrease in the patient’s NPRS score from 9 to 3 points,signifies a positive clinical response.This outcome,coupled with the significant improvement in the patient's health-related quality of life according to the MSK-HQ score,which increased from 12 to 48 points,underscores the success of our research.CONCLUSION The study highlights the importance of a comprehensive approach to diagnosing and managing IFI,combining clinical assessment with imaging and implementing a multimodal rehabilitation program for optimal outcomes.
文摘Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB.Using propensity score matching,the study balanced the comparison groups to investigate overall survival and treatment-related adverse events.The study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB,highlighting the complexities of treatment decisions in these high-risk patients.
基金support from the National Natural Science Foundation of China(Nos.22277056,21977052)the Distinguished Young Scholars of Jiangsu Province(No.BK20230006)+2 种基金the Natural Science Foundation of Jiangsu Province(Nos.BK20230977,BK20231090)the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(No.23KJB150020)the Jiangsu Excellent Postdoctoral Program(No.2022ZB758)。
文摘Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.
文摘Background:Isotonic crystalloids are recommended as the first choice for fluid therapy in acute pan-creatitis(AP),with normal saline(NS)and lactate Ringer’s(LR)used most often.Evidence based recom-mendations on the type of fluid are conflicting and generally come from small single-center randomized controlled trials(RCTs).We therefore conducted a systematic review and meta-analysis to compare the effect of balanced solutions(BS)versus NS on patient-centered clinical outcomes in AP.Methods:From four databases searched up to October 2024,we included only RCTs of adult patients with AP that compared the use of BS(including LR,acetate Ringer’s,etc.)with NS.The primary out-come was the disease advances from AP to moderately severe and severe AP(MSAP/SAP).Trial sequential analyses(TSA)were conducted to control for type-I and type-II errors and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)was used to assess the quality of evidence.Results:Six RCTs were identified and included,involving 260 patients treated with BS and 298 patients with NS.Patients who received the BS had less MSAP/SAP[odds ratio(OR)=0.50,95%confidence in-terval(CI):0.29 to 0.85,P=0.01,I^(2)=0%;5 studies,299 patients],reduced the need of ICU admission(OR=0.60,95%CI:0.39 to 0.93,P=0.02,I^(2)=0%;5 studies,507 patients)and shorter length of hospital stay[mean difference(MD)=-0.88,95%CI:-1.48 to-0.28,P=0.004,I^(2)=0%;6 studies,558 patients;confirmed by TSA with high certainty]compared with those who received NS.The evidence for most of the clinical outcomes was rated as moderate to low due to the risk of bias,imprecision and inconsistency.Conclusions:BS,compared with NS,was associated with improved clinical outcomes in patients with AP.However,given the moderate to low quality of evidence for most of the outcomes assessed,further trials are warranted.
基金Supported by the 2023 Government Funded Project of the Outstanding Talents Training Program in Clinical Medicine,No.ZF2023165Key Research and Development Projects of Hebei Province,No.18277731DNatural Science Foundation of Hebei Province,No.H202423105.
文摘In the contemporary medical landscape,the burgeoning interest in natural therapies,particularly for managing gastrointestinal disorders,has brought traditional Chinese medicine(TCM)to the forefront.This article explains the core principles and clinical applications of TCM in treating these conditions,furthering the discourse through an examination of integrated TCM strategies,as demonstrated in the study by Zhou et al.While TCM has shown promising clinical outcomes,it encounters significant hurdles in standardization,mechanistic research,and clinical validation.Future investigations should aim to solidify the scientific underpinnings of TCM and expand its use in gastrointestinal disease management,striving for a seamless fusion of traditional and contemporary medical practices.
基金Supported by the Project of Guizhou Provincial Department of Science and Technology,No.Qiankehechengguo-LC[2024]109.
文摘In this editorial,we comment on the article by Meng et al.Chronic hepatitis B(CHB)is a significant global health problem,particularly in developing countries.Hepatitis B virus(HBV)infection is one of the most important risk factors for cirrhosis and hepatocellular carcinoma.Prevention and treatment of HBV are key measures to reduce complications.At present,drug therapy can effectively control virus replication and slow disease progression,but completely eliminating the virus remains a challenge.Anti-HBV treatment is a long-term process,and there are many kinds of antiviral drugs with different mechanisms of action,it is essential to evaluate the safety and efficacy of these drugs to reduce side effects and improve patients’compliance.We will summarize the current status of CHB drug treatment,hoping to provide a reference for the selection of clinical antiviral drugs.
文摘In this work,iron-doped carbon dots(Fe-CDs)with strong peroxidase-mimicking activity were synthesized for tumor-specific therapy.Their intrinsic red fluorescence enabled high-contrast cellular imaging,revealing preferen⁃tial mitochondrial accumulation.In the acidic and hydrogen peroxide(H_(2)O_(2))-rich tumor microenvironment,Fe-CDs catalyzed hydroxyl radical(·OH)generation,inducing oxidative stress and lipid peroxidation,ultimately triggering ferroptosis.In vitro and in vivo studies demonstrated potent tumor inhibition.Furthermore,Fe-CDs exhibited excel⁃lent biocompatibility with no significant systemic toxicity.By integrating fluorescence imaging and catalytic therapy,this study presents a promising nanoplatform for tumor treatment and ferroptosis research.
基金Supported by the Natural Science Foundation of China,No.81970529the Natural Science Foundation of Jilin Province,No.20230508074RC and No.YDZJ202401218ZYTS.
文摘In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B virus(HBV)infection,the pathogenesis of hepatocellular carcinoma(HCC),and the role of antiviral therapy in treating HCC related to HBV infection.HBV infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways,as well as by inhibiting the immune functions of macrophages,natural killer cells and dendritic cells.In addition,HBV leads to an immunosuppressive cascade by expressing inhibitory molecules to induce exhaustion of HBV-specific cluster of differentiation 8+T cells,ultimately leading to long-term viral infection.The loss of immune cell function caused by HBV infection ultimately leads to HCC.Long-term antiviral therapy can improve the prognosis of patients with HCC and prevent tumor recurrence and metastasis.