The integration of artificial intelligence(AI)technology,particularly large language models(LLMs),has become essential across various sectors due to their advanced language comprehension and generation capabilities.De...The integration of artificial intelligence(AI)technology,particularly large language models(LLMs),has become essential across various sectors due to their advanced language comprehension and generation capabilities.Despite their transformative impact in fields such as machine translation and intelligent dialogue systems,LLMs face significant challenges.These challenges include safety,security,and privacy concerns that undermine their trustworthiness and effectiveness,such as hallucinations,backdoor attacks,and privacy leakage.Previous works often conflated safety issues with security concerns.In contrast,our study provides clearer and more reasonable definitions for safety,security,and privacy within the context of LLMs.Building on these definitions,we provide a comprehensive overview of the vulnerabilities and defense mechanisms related to safety,security,and privacy in LLMs.Additionally,we explore the unique research challenges posed by LLMs and suggest potential avenues for future research,aiming to enhance the robustness and reliability of LLMs in the face of emerging threats.展开更多
Surface engineering plays a crucial role in improving the performance of high energy materials,and polydopamine(PDA)is widely used in the field of energetic materials for surface modification and functionalization.In ...Surface engineering plays a crucial role in improving the performance of high energy materials,and polydopamine(PDA)is widely used in the field of energetic materials for surface modification and functionalization.In order to obtain high-quality HMX@PDA-based PBX explosives with high sphericity and a narrow particle size distribution,composite microspheres were prepared using co-axial droplet microfluidic technology.The formation mechanism,thermal behavior,mechanical sensitivity,electrostatic spark sensitivity,compressive strength,and combustion performance of the microspheres were investigated.The results show that PDA can effectively enhance the interfacial interaction between the explosive particles and the binder under the synergistic effect of chemical bonds and the physical"mechanical interlocking"structure.Interface reinforcement causes the thermal decomposition temperature of the sample microspheres to move to a higher temperature,with the sensitivity to impact,friction,and electrostatic sparks(for S-1)increasing by 12.5%,31.3%,and 81.5%respectively,and the compressive strength also increased by 30.7%,effectively enhancing the safety performance of the microspheres.Therefore,this study provides an effective and universal strategy for preparing high-quality functional explosives,and also provides some reference for the safe use of energetic materials in practical applications.展开更多
The present study introduces a screw-pressing charging method to tackle deficiencies in automation and charge uniformity during the melt-casting of polymer-based energetic materials.To ensure the safety of the experim...The present study introduces a screw-pressing charging method to tackle deficiencies in automation and charge uniformity during the melt-casting of polymer-based energetic materials.To ensure the safety of the experiments,this study used inert materials with similar physical properties to partially substitute for the actual energetic components in the preparation of simulant materials.By thoroughly analyzing slurry physical properties,a simulation framework and an extensive performance evaluation method were developed.Such tools guide the design of the structure and configuration of process parameters.Results demonstrate that employing the Pin element significantly enhances radial mixing within the screw,minimizes temperature variations in the slurry,and improves both efficiency and safety in the mixing process.Further,adjustments such as widening the cone angle of the barrel,modifying the solid content of the slurry,and varying the speed of the screw can optimize the mechanical and thermal coupling in the flow field.These adjustments promote higher-quality slurry and create a safer production environment for the extrusion process.展开更多
Due to batteries inconsistencies and potential faults in battery management systems,slight overcharging remains a common yet insufficiently understood safety risk,lacking effective warning methods.To illuminate the de...Due to batteries inconsistencies and potential faults in battery management systems,slight overcharging remains a common yet insufficiently understood safety risk,lacking effective warning methods.To illuminate the degradation behavior and failure mechanism of various overcharged states(100%SOC,105%SOC,110%SOC,and 115%SOC),multiple advanced in-situ characterization techniques(accelerating rate calorimeter,electrochemical impedance spectroscopy,ultrasonic scanning,and expansion instrument)were utilized.Additionally,re-overcharge-induced thermal runaway(TR)tests were conducted,with a specific emphasis on the evolution of the expansion force signal.Results indicated significant degradation at 110%SOC including conductivity loss,loss of lithium inventory,and loss of active material accompanied by internal gas generation.These failure behaviors slow down the expansion force rate during reovercharging,reducing the efficacy of active warnings that depend on rate thresholds of expansion force.Specifically,the warning time for 115%SOC battery is only 144 s,which is 740 s shorter than that for fresh battery,and the time to TR is advanced by 9 min.Moreover,the initial self-heating temperature(T1)is reduced by 62.4℃compared to that of fresh battery,reaching only 70.8℃.To address the low safety of overcharged batteries,a passive overcharge warning method utilizing relaxation expansion force was proposed,based on the continued gas generation after stopping charging,leading to a sustained increase in force.Compared to active methods that rely on thresholds of expansion force rate,the passive method can issue warnings 115 s earlier.By combining the passive and active warning methods,guaranteed effective overcharge warning can be issued 863-884 s before TR.This study introduces a novel perspective for enhancing the safety of batteries.展开更多
BACKGROUND Currently,very few studies have examined the analgesic effectiveness and safety of dexmedetomidine-assisted intravenous-inhalation combined general anesthesia in laparoscopic minimally invasive surgery for ...BACKGROUND Currently,very few studies have examined the analgesic effectiveness and safety of dexmedetomidine-assisted intravenous-inhalation combined general anesthesia in laparoscopic minimally invasive surgery for inguinal hernia.AIM To investigate the analgesic effect and safety of dexmedetomidine-assisted intravenous-inhalation combined general anesthesia in laparoscopic minimally invasive surgery for inguinal hernia.METHODS In this retrospective study,94 patients scheduled for laparoscopic minimally invasive surgery for inguinal hernia,admitted to Yiwu Central Hospital between May 2022 and May 2023,were divided into a control group(inhalation combined general anesthesia)and a treatment group(dexmedetomidine-assisted intrave-nous-inhalation combined general anesthesia).Perioperative indicators,analgesic effect,preoperative and postoperative 24-hours blood pressure(BP)and heart rate(HR),stress indicators,immune function levels,and adverse reactions were com-pared between the two groups.RESULTS Baseline data,including age,hernia location,place of residence,weight,monthly income,education level,and underlying diseases,were not significantly different between the two groups,indicating comparability(P>0.05).No significant difference was found in operation time and anesthesia time between the two groups(P>0.05).However,the treatment group exhibited a shorter postoperative urinary catheter removal time and hospital stay than the control group(P<0.05).Preoperatively,no significant differences were found in the visual analog scale(VAS)scores between the two groups(P>0.05).However,at 12,18,and 24 hours postoper-atively,the treatment group had significantly lower VAS scores than the control group(P<0.05).Although no significant differences in preoperative hemodynamic indicators were found between the two groups(P>0.05),both groups experienced some extent of changes in postoperative HR,diastolic BP(DBP),and systolic BP(SBP).Nevertheless,the treatment group showed smaller changes in HR,DBP,and SBP than the control group(P<0.05).Preoperative immune function indicators showed no significant differences between the two groups(P>0.05).However,postoperatively,the treatment group demonstrated higher levels of CD3+,CD4+,and CD4+/CD8+and lower levels of CD8+than the control group(P<0.05).The rates of adverse reactions were 6.38%and 23.40%in the treatment and control groups,respectively,revealing a significant difference(χ2=5.371,P=0.020).CONCLUSION Dexmedetomidine-assisted intravenous-inhalation combined general anesthesia can promote early recovery of patients undergoing laparoscopic minimally invasive surgery for inguinal hernia.It ensures stable blood flow,improves postoperative analgesic effects,reduces postoperative pain intensity,alleviates stress response,improves immune function,facilitates anesthesia recovery,and enhances safety.展开更多
Strong surface impact will produce strong vibration,which will pose a threat to the safety of nearby buried pipelines and other important lifeline projects.Based on the verified numerical method,a comprehensive numeri...Strong surface impact will produce strong vibration,which will pose a threat to the safety of nearby buried pipelines and other important lifeline projects.Based on the verified numerical method,a comprehensive numerical parameter analysis is conducted on the key influencing factors of the vibration isolation hole(VIH),which include hole diameter,hole net spacing,hole depth,hole number,hole arrangement,and soil parameters.The results indicate that a smaller ratio of net spacing to hole diameter,the deeper the hole,the multi-row hole,the hole adoption of staggered arrangements,and better site soil conditions can enhance the efficiency of the VIH barrier.The average maximum vibration reduction efficiency within the vibration isolation area can reach 42.2%.The vibration safety of adjacent oil pipelines during a dynamic compaction projection was evaluated according to existing standards,and the measurement of the VIH was recommended to reduce excessive vibration.The single-row vibration isolation scheme and three-row staggered arrangement with the same hole parameters are suggested according to different cases.The research findings can serve as a reference for the vibration safety analysis,assessment,and control of adjacent underground facilities under the influence of strong surface impact loads.展开更多
The construction of the new tunnel under the existing railway will break the original stress balance in the engineering area, resulting in the secondary redistribution of surrounding rock stress. The large amount of e...The construction of the new tunnel under the existing railway will break the original stress balance in the engineering area, resulting in the secondary redistribution of surrounding rock stress. The large amount of excavation unloading of the soil below is also easy to induce the uneven settlement deformation of the existing structure above, affecting the safety of driving. Based on the shield tunnel project between Caoqiao Station and Lize Business District Station of Beijing Metro, this paper restores the construction site by constructing the finite element numerical model of the project area, calculates and analyzes the deformation and stress of the existing railway structure before and after the construction of the tunnel, and determines the safety impact of the new structure on the existing railway. The results show that the shield tunnel undercrossing construction will cause the “concave” settlement of the railway subgrade above. Under the condition of grouting reinforcement, the “concave” settlement curve is slower and the distribution range is wider. With the advancement of the construction step, the settlement deformation of the subgrade gradually increases. When the tunnel approaches and passes directly below the subgrade, the settlement deformation curve of the subgrade changes from slow to steep. After the tunnel passes away, the curve changes from steep to slow, and the deformation of the subgrade reaches the maximum after the tunnel is connected. Under the grouting condition, the maximum settlement deformation of the subgrade is 2.08 mm, which is about 45% of the settlement deformation of the subgrade under the non-grouting condition. The ground grouting reinforcement can effectively control the subgrade settlement, and the field monitoring verifies the rationality of the calculation results. After the tunnel passes underneath, the most unfavorable section of the existing railway frame bridge is located at the top plate of the structure, and the maximum crack width is 0.178 mm. After grouting reinforcement, the stress environment of the structure is improved, the crack width generated by the structure is smaller, the reinforcement area required for calculation is less, and the structural safety meets the requirements.展开更多
Objective:In recent years,the incidence and detection rate of pancreatic cystic lesions(PCLs)have increased significantly.Endoscopic ultrasound(EUS)plays an indispensable role in the diagnosis and differential diagnos...Objective:In recent years,the incidence and detection rate of pancreatic cystic lesions(PCLs)have increased significantly.Endoscopic ultrasound(EUS)plays an indispensable role in the diagnosis and differential diagnosis of PCLs.However,evidence comparing the diagnostic performance of EUS-guided fine-needle aspiration(EUS-FNA)and fine-needle biopsy(FNB)remains limited.This study aims to compare the diagnostic yield,adequacy of tissue acquisition,and safety between EUS-FNA and EUS-FNB in evaluating PCLs to inform clinical practice.Methods:A retrospective review was conducted on patients with PCLs who underwent either EUS-FNA or EUS-FNB between January 2014 and August 2021.The diagnostic yield,tissue acquisition adequacy,and incidence of adverse events were compared between the 2 groups.Results:A total of 90 patients with PCLs were included(52 in the FNA group and 38 in the FNB group).The diagnostic yield was similar between the FNA and FNB groups(94.2%vs 94.7%,P>0.05).The adequacy of tissue acquisition was 71.2%in the FNA group and 81.6%in the FNB group(P>0.05).No statistically significant difference was observed in the incidence of adverse events between the 2 groups(P>0.05).Conclusion:Both EUS-FNA and EUS-FNB demonstrate equally high diagnostic yields and tissue adequacy in PCLs,with excellent safety profiles.Both methods are safe and effective diagnostic tools for evaluating PCLs.展开更多
This paper focuses on the high-voltage safety of drive motor systems in new energy vehicles and conducts standardized research on functional safety design in the concept phase. In view of the lack of high-voltage haza...This paper focuses on the high-voltage safety of drive motor systems in new energy vehicles and conducts standardized research on functional safety design in the concept phase. In view of the lack of high-voltage hazard analysis for drive motor systems in existing standards, based on theories such as GB/T 34590 and ISO 26262, the safety levels are deeply analyzed. The HAZOP method is innovatively used, and 16 types of guidewords are combined to comprehensively analyze the system functions, identifying vehicle hazards such as high-voltage electric shock caused by functional abnormalities, including high-voltage interlock function failure and abnormal active discharge. Subsequently, safety goals such as preventing high-voltage electric shock are set, functional safety requirements such as accurately obtaining collision signals and timely discharging high-voltage electricity are formulated, and requirements for external signal sources and other technologies are clearly defined, constructing a complete high-voltage safety protection system. The research results provide important technical support and standardized references for the high-voltage safety functional design of drive motor systems in new energy vehicles, and are of great significance for improving the high-voltage safety level of the new energy vehicle industry, expecting to play a key role in subsequent product development and standard improvement.展开更多
This webinar is jointly organized by CEN and CENELEC,and Ernst&Young(EY),with the participation of the European Commission Desk Officer,who will deliver the opening remarks.This session will focus specifically on ...This webinar is jointly organized by CEN and CENELEC,and Ernst&Young(EY),with the participation of the European Commission Desk Officer,who will deliver the opening remarks.This session will focus specifically on the Toy Safety Directive and General Product Safety Regulation.Additional sector-specific webinars will follow in the coming months.展开更多
Vegetables are essential and important foods in people s daily production,which are closely related to human health.Focusing on the present situation of vegetable nutrition and safety quality detection from detection ...Vegetables are essential and important foods in people s daily production,which are closely related to human health.Focusing on the present situation of vegetable nutrition and safety quality detection from detection indexes and detection methods,this paper discussed the selection of detection indexes and detection methods for vegetable nutrition and safety quality,and put forward the main research direction of vegetable nutrition and safety quality detection in the future,providing guidance and reference for improving vegetable nutrition and safety quality evaluation.展开更多
This study aims to construct a virtual twin testing framework for the safety of the intended functionality of intelligent connected vehicles to address the safety requirements of intelligent driving and transportation...This study aims to construct a virtual twin testing framework for the safety of the intended functionality of intelligent connected vehicles to address the safety requirements of intelligent driving and transportation systems.The research methods include the construction of a theoretical model of safety for intelligent connected vehicles based on the concept of virtual twins,the correlation study between key concepts and functional safety,and the application research of virtual twin technology in the safety testing of intelligent connected vehicles.The results reveal that the virtual twin testing framework can effectively enhance the functional safety of intelligent connected vehicles,reduce development costs,and shorten the product launch cycle.The conclusion suggests that this framework provides strong support for the healthy development of the intelligent connected vehicle industry and has a positive impact on the safety and efficiency of intelligent transportation systems.展开更多
Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October ...Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October 19,2021,and as combination therapy with metformin when using metformin alone failed in blood glucose control on July 16,2024,by the National Medical Products Administration(NMPA)in China.However,pharmacokinetic(PK)study of this product in patients with renal impairment have not yet been conducted.The purpose of this study is to evaluate the effects of renal impairment on the PK and safety after a single oral dose of Chiglitazar.Methods:This multicenter,open-label,parallel-controlled,single-dose Phase I clinical trial(NCT 05515458)enrolled 24 participants(12/group)with severe renal impairment(SRI)or normal renal function(NRF).All participants received a single oral dose of 48 mg chiglitazar after breakfast and the PK and safety was evaluated.Results:The median Tmax was similar in both SRI and NRF groups(5.01 vs.5.02 hours).The geometric mean ratios(GMR)for Cmax,AUC0-t,and AUC0-∞were 0.807(90%confidence interval[CI]:0.697–0.935),0.853(90%CI:0.713–1.02),and 0.855(90%CI:0.716–1.02),respectively,indicating that SRI did not significantly affect the exposure of chiglitazar.The Cmax was weakly positively correlated with eGFR(r=0.4798,P=0.0177)and creatinine clearance rate(r=0.4667,P=0.0215).Urinary excretion of chiglitazar was negligible in the SRI group,with average values of Ae0-t=2,900 ng,Fe0-t=0.0060%,and CLR=0.323 mL/h within 0–72 hours post-dose.The treatment-emergent adverse event(TEAE)incidence in the SRI group(16.7%,2/12)was comparable to that in the NRF group(25%,3/12).All TEAEs were of mild severity and were adjudicated by the investigators to be unrelated to chiglitazar.No serious AE were reported.Chiglitazar exhibits a favorable safety profile.Conclusion:Severe renal impairment does not significantly affect the PK and safety of chiglitazar,and no dose adjustment for mild,moderate,and severe renal impairments is required.展开更多
BACKGROUND Gastrointestinal angiodysplasias(GIAD)causes recurrent bleeding,and current treatments have limitations.Sirolimus,a mammalian target of rapamycin inhibi-tor,shows promise in inhibiting abnormal angiogenesis...BACKGROUND Gastrointestinal angiodysplasias(GIAD)causes recurrent bleeding,and current treatments have limitations.Sirolimus,a mammalian target of rapamycin inhibi-tor,shows promise in inhibiting abnormal angiogenesis.AIM To evaluate the efficacy and safety of sirolimus in reducing bleeding episodes and improving clinical outcomes in patients with GIAD.METHODS We conducted a self-controlled study with 11 patients taking oral sirolimus.Retrospective data were collected prior to treatment,and prospective data were gathered during the study.Efficacy was assessed primarily by comparing blee-ding episodes before and after sirolimus,with measurements at 3 and 6 months post-administration.The initial dose was 0.8 mg/m^(2)once daily,adjusted to main-tain trough blood concentrations between 5-10 ng/mL.Secondary outcomes included hemoglobin(Hb)levels,blood transfusion volume,and vascular lesions.Safety was monitored by tracking adverse reactions.RESULTS The average number of bleeding episodes decreased significantly from 2.09±1.04 to 1.00±0.75 in the 3 months preceding treatment,and from 3.80±1.93 to 2.00±1.63 in the 6 months preceding treatment.Sirolimus also increased Hb levels,reduced the need for transfusions,and decreased vascular lesions,improving clinical outcomes.All adverse effects were mild and resolved or improved within 1 week to 1 month without stopping sirolimus or needing lipid-lowering treatment.CONCLUSION Sirolimus reduced bleeding and transfusion needs while improving Hb levels in GIAD patients.Although these findings are encouraging,the limited sample size and lack of a control group warrant caution.Future controlled trials with larger populations are needed to validate sirolimus’s potential in GIAD.展开更多
BACKGROUND Blonanserin,a novel antipsychotic,has demonstrated efficacy in treating both positive and negative symptoms.However,limited research exists on its dose-dependent effectiveness and safety in patients with an...BACKGROUND Blonanserin,a novel antipsychotic,has demonstrated efficacy in treating both positive and negative symptoms.However,limited research exists on its dose-dependent effectiveness and safety in patients with and without prominent nega-tive symptoms(PNS).AIM To evaluate the effectiveness and safety of blonanserin monotherapy for first-episode schizophrenia in real-world clinical settings and to explore the efficacy and safety of different doses of blonanserin for patients with PNS and without PNS.METHODS A 12-week,multicenter,prospective post-marketing surveillance was conducted.In this study,we included patients with first-episode schizophrenia who received blonanserin monotherapy.Patients were divided into those with PNS and without PNS,based on the Brief Psychiatric Rating Scale(BPRS)negative symptoms subscale scores.Additionally,patients were labeled as high-dose and low-dose was evaluated through the incidence of adverse drug reactions(ADRs).RESULTS A total of 653 patients were included in the analysis,with 613 completing the study.The BPRS total score decreased significantly from 47.94±16.31 at baseline to 26.88±9.47 at 12 weeks(P<0.001).A significant interaction of PNS×dose×time was observed for BPRS total scores(F=3.47,P=0.040)and negative symptom subscale scores(F=6.76,P=0.002).In the PNS group,the high-dose group showed greater reductions in BPRS total scores(P=0.001)and negative symptom subscale scores(P=0.003)than the low-dose group in week 12.In the without PNS group,no significant difference was observed between the high-dose and low-dose groups at any visit.Most adverse reactions were mild or moderate,with extrapyramidal symptoms(9.3%)being most common;1.5%of patients gained≥7%body weight at 12 weeks.CONCLUSION Blonanserin effectively alleviated the clinical symptoms of first-episode schizophrenia with an acceptable safety profile.High-dose blonanserin is particularly beneficial for patients with PNS in the acute phase of first-episode schizophrenia.However,due to the limitation of ADR reporting the real world,the ADR incidence observed in this study may be underestimated.展开更多
Objective:To analyze the clinical efficacy and safety of toripalimab combined with the GC chemotherapy regimen in the treatment of advanced urothelial carcinoma.Methods:A retrospective study was conducted on 102 patie...Objective:To analyze the clinical efficacy and safety of toripalimab combined with the GC chemotherapy regimen in the treatment of advanced urothelial carcinoma.Methods:A retrospective study was conducted on 102 patients with advanced urothelial carcinoma treated at our hospital between March 2021 and August 2024.Based on treatment regimens,patients were divided into a chemotherapy group(n=52)and a combination group(n=50).The chemotherapy group received the GC chemotherapy regimen,while the combination group received GC chemotherapy combined with toripalimab.Both groups underwent 4-6 cycles of treatment based on patient tolerance.Clinical efficacy,immune-related factor levels,survival outcomes,and safety were observed and compared.Results:The disease control rate(DCR)and overall response rate(ORR)in the combination group were slightly higher than those in the chemotherapy group,but the differences were not statistically significant(P>0.05).After treatment,levels of IFN-γand IL-2 increased significantly,while VEGF levels decreased significantly in both groups(P<0.05),with superior outcomes observed in the combination group(P<0.05).Follow-up analysis showed progression-free survival(PFS)and median overall survival(OS)in the chemotherapy group were 5.19 and 10.15 months,respectively,compared to 8.24 and 18.23 months in the combination group,with statistically significant differences(P<0.05).During treatment,the incidence of adverse reactions such as rash,immune-related pneumonia,and immune-related diarrhea was higher in the combination group than in the chemotherapy group(P<0.05).However,the incidence of gastrointestinal reactions,fever,and leukopenia did not differ significantly between the two groups(P>0.05).Conclusion:The use of toripalimab combined with the GC chemotherapy regimen for advanced urothelial carcinoma can effectively improve clinical outcomes and extend patient survival,with good overall safety.However,attention should be given to preventing adverse reactions such as rash and pneumonia during treatment.展开更多
Process safety for synthesis of tert-butyl hydroperoxide(TBHP) by tert-butyl alcohol(TBA) to react with H_(2)O_(2) was studied in this paper.On-line Raman spectroscopy and gas chromatography jointed analysis method wa...Process safety for synthesis of tert-butyl hydroperoxide(TBHP) by tert-butyl alcohol(TBA) to react with H_(2)O_(2) was studied in this paper.On-line Raman spectroscopy and gas chromatography jointed analysis method was researched to monitor and analyze the changes of each components during the process to study reaction mechanism.The reaction kinetics was reproduced by apparent thermodynamics study and simulation for whole process,and the kinetics model of TBHP synthesis was obtained and with the first reported.The process safety parameter of the maximum temperature of the synthesis reaction(MTSR) and yield were predicted by response surface methodology(RSM) method and go through experimental verification further.It was found that the sulfuric acid and the concentration of TBA had great influences to reaction selectivity and yield.According to our research results,we supposed that the mechanism of TBHP synthesis would be followed by SN_(1)+SN_(2).Focus on process safety,process risk assessment was done and pipe reaction to optimize TBHP synthesis was developed to change the batch process to pipe continuously.The yield of TBHP was 91.1%,conversion of TBA was 93.1%,and the selectivity of TBHP was 97.8%.The process safety parameters of heat accumulation and MTSR decreased40.5% and 37.7% respectively comparison of the pipe continuous reaction and batch process.This study will provide guidance for intrinsic safety improvement of peroxidation reactions.展开更多
AIM:To evaluate the short-term efficacy and safety of ultrasound cycloplasty(UCP)procedure in Chinese patients with angle-closure glaucoma(ACG),and the mechanisms of its intraocular pressure(IOP)lowering effects.METHO...AIM:To evaluate the short-term efficacy and safety of ultrasound cycloplasty(UCP)procedure in Chinese patients with angle-closure glaucoma(ACG),and the mechanisms of its intraocular pressure(IOP)lowering effects.METHODS:Fifty-six patients(56 eyes)diagnosed with primary and/or secondary ACG were enrolled in this prospective study.Visual acuity,IOP,slit-lamp examinations,structural parameters of anterior segments including anterior chamber depth(ACD),pupillary diameter(PD),anterior chamber area(ACAr),anterior chamber angle(ACAn),and side effects were evaluated.Seven rhesus macaques(Macaca Mulatta)were used for the analyses of IOP lowering effects,including inflammatory reactions,pathohistological evaluation,scanning electron microscopy(SEM),and aqueous outflow pathway via 1%basic fuchsin perfusion.RESULTS:Fifty six eyes of 24 male and 32 female patients with an average age of 58.93±15.97 years old were recruited in primary and secondary ACG affected 31 and 25 eyes,respectively.Clinically,the mean IOP was 17.89±7.93 mm Hg(n=53,53.63%reduction,P<0.001)at 1wk and 22.47±12.00 mm Hg at 12mo(n=16,18.67%reduction,P<0.01)after UCP,compared to the baseline of 39.08±14.75 mm Hg(n=56).Postoperative tolerance was favorable in 94.64%of cases,with visual acuity unchanged or improved in 96.43%of patients.Mild and transient inflammatory reactions were observed post UCP.UBM analysis revealed statistically significant changes in anterior chamber parameters:increased ACD(n=22,P<0.05),enlarged PD(n=22,P<0.05),expanded ACAr(n=16,P<0.01),and widened ACAn(n=19,P<0.05)compared to preoperative measurements.As in normal monkey eyes,IOP was also reduced upon UCP.Mild inflammatory reactions were seen 1-7d post treatment.Hematoxylin and Eosin(H&E)staining showed enlarged spaces among ciliary muscle bundles.Ciliary process stromal edema was evident,but significant loss of two layers of ciliary epitheliums was not seen.SEM confirmed ciliary muscle fibers concentrated.Fuchsin anterior chamber perfusion showed the whole ciliary body staining in UCP group,but only surface staining in controls.CONCLUSION:UCP is efficient and safe to lower the IOP of patients with ACG.Changed anterior chamber structure and increased aqueous humour outflow via uveoscleral pathway may significantly attribute to IOP lowering effects of UCP.展开更多
BACKGROUND Gastric cancer(GC)remains a major global health burden,particularly in East Asia,due to its high incidence,aggressive progression,and poor prognosis in advanced stages.Although surgery is the mainstay of cu...BACKGROUND Gastric cancer(GC)remains a major global health burden,particularly in East Asia,due to its high incidence,aggressive progression,and poor prognosis in advanced stages.Although surgery is the mainstay of curative treatment,outcomes for locally advanced cases remain unsatisfactory despite perioperative chemotherapy.In recent years,immune checkpoint inhibitors,especially anti-PD-1 antibodies like sintilimab,have shown promise in improving survival when combined with chemotherapy.However,the comparative efficacy and safety of SOX plus sintilimab vs established regimens such as P-SOX and SOX alone in the neoadjuvant setting have not been fully explored.AIM To compare the efficacy and safety of three neoadjuvant chemotherapy regimens—SOX combined with sintilimab(SOX+PD-1),albumin-bound paclitaxel plus oxaliplatin and S-1(P-SOX),and SOX—in patients with advanced GC.METHODS A retrospective analysis was conducted on 299 patients with advanced GC who received both neoadjuvant and adjuvant chemotherapy along with standard D2 radical gastrectomy.Among them,81 patients received SOX plus sintilimab,118 received the P-SOX regimen,and 100 received the SOX regimen.All patients were randomly assigned to training(70%)or validation(30%)cohorts using the R software sample function.Short-term efficacy,long-term survival outcomes,and adverse events were assessed across the three groups.Additionally,clinical factors associated with progression-free survival(PFS)were further investigated.RESULTS In terms of short-term efficacy,the SOX+sintilimab group had higher objective response rates[91.4%and 70.4%according to the tumor regression grade(TRG)and Response Evaluation Criteria in Solid Tumors(RECIST)1.1 criteria,respectively]than did the P-SOX(88.1%and 59.3%)and SOX groups(84.0%and 55.0%),although the intergroup differences were not statistically significant(P=0.167).For long-term outcomes,the SOX+sintilimab group demonstrated significantly better OS rates at 1 year(98.8%),18 months(92.6%),2 years(84.0%),and 3 years(48.1%)than did the P-SOX(93.2%,86.4%,71.2%,30.5%)and SOX(91.0%,84.0%,72.0%,29.0%)groups,with the 3-year overall survival(OS)difference being statistically significant(P=0.007).Similarly,PFS rates in the SOX+sintilimab group(1 year:92.6%;18 months:77.8%;2 years:65.4%;3 years:35.8%)were significantly greater than those in the P-SOX(82.2%,68.6%,53.4%,26.3%)and SOX(77.0%,66.0%,43.0%,27.0%)groups,with significant differences at 1 year(P=0.021)and 2 years(P=0.011).In terms of safety,grade 1-2 gastrointestinal reactions,peripheral neuropathy,and alopecia were the main TRAEs across groups.The P-SOX group had a significantly greater incidence of alopecia(54.2%vs 53.0%vs 23.5%,P=0.009)and more cases of grade 2 alopecia(6.8%vs 1.2%),potentially due to the accumulation of triple-agent toxicity.No significant intergroup differences were observed in hematologic toxicity or liver dysfunction(all P>0.05).CONCLUSION Compared with the SOX and P-SOX regimens,the SOX plus sintilimab combination demonstrated significantly improved short-and long-term efficacy with favorable safety,with superior advantages in terms of 2-and 3-year OS and early PFS,suggesting that this combination is a more promising therapeutic option for patients with advanced GC.Patients who achieved good perioperative chemotherapy responses(meeting the TRG and RECIST 1.1 criteria)and had tumor diameters≤2 cm,well-differentiated histology,earlier cTNM stages,and no lymph node metastasis had a better prognosis.展开更多
BACKGROUND There is a scarcity of evidence and systematic reviews on endoscopic gastroplasty(EG)compared to other management options for the treatment of obesity.AIM To assess the published meta-analyses through a sys...BACKGROUND There is a scarcity of evidence and systematic reviews on endoscopic gastroplasty(EG)compared to other management options for the treatment of obesity.AIM To assess the published meta-analyses through a systematic review approach and provide further insight into the current status of available evidence through a critical appraisal.METHODS PubMed/MEDLINE,Scopus,Embase and Cochrane Library were searched from inception to November 2022.The meta-analyses that compared the efficacy and safety of EG to other interventions were considered for this overview.The outcomes of interest were total body weight loss(TBWL),excessive weight loss,and average weight loss along with occurrence of adverse effects.Methodological quality,heterogeneity,and limitations were also reviewed.RESULTS A total of six meta-analyses out of 364 records were considered for this review with a major contribution from the United States.Overall methodological quality of included studies were moderate to good.EG treatments were significantly better in terms of TBWL,excessive weight loss,and average weight loss.However,there was no significant difference between endoscopic transoral outlet reduction and full-thickness suturing plus argon plasma mucosal coagulation.Lack of comparative studies and randomized trials,lack of long-term follow-up,reporting bias,selection bias,lack of control groups,and considerable level of heterogeneity were the major limitations in the available evidence.CONCLUSION Though EG was significantly effective for treatment of obesity,there is limited comparative evidence on this topic.High-quality well-controlled evidence is required to strengthen the current evidence base on EG treatment for obesity.展开更多
基金supported by the National Key R&D Program of China under Grant No.2022YFB3103500the National Natural Science Foundation of China under Grants No.62402087 and No.62020106013+3 种基金the Sichuan Science and Technology Program under Grant No.2023ZYD0142the Chengdu Science and Technology Program under Grant No.2023-XT00-00002-GXthe Fundamental Research Funds for Chinese Central Universities under Grants No.ZYGX2020ZB027 and No.Y030232063003002the Postdoctoral Innovation Talents Support Program under Grant No.BX20230060.
文摘The integration of artificial intelligence(AI)technology,particularly large language models(LLMs),has become essential across various sectors due to their advanced language comprehension and generation capabilities.Despite their transformative impact in fields such as machine translation and intelligent dialogue systems,LLMs face significant challenges.These challenges include safety,security,and privacy concerns that undermine their trustworthiness and effectiveness,such as hallucinations,backdoor attacks,and privacy leakage.Previous works often conflated safety issues with security concerns.In contrast,our study provides clearer and more reasonable definitions for safety,security,and privacy within the context of LLMs.Building on these definitions,we provide a comprehensive overview of the vulnerabilities and defense mechanisms related to safety,security,and privacy in LLMs.Additionally,we explore the unique research challenges posed by LLMs and suggest potential avenues for future research,aiming to enhance the robustness and reliability of LLMs in the face of emerging threats.
基金supported by the National Natural Science Foundation of China(Grant No.22005275).
文摘Surface engineering plays a crucial role in improving the performance of high energy materials,and polydopamine(PDA)is widely used in the field of energetic materials for surface modification and functionalization.In order to obtain high-quality HMX@PDA-based PBX explosives with high sphericity and a narrow particle size distribution,composite microspheres were prepared using co-axial droplet microfluidic technology.The formation mechanism,thermal behavior,mechanical sensitivity,electrostatic spark sensitivity,compressive strength,and combustion performance of the microspheres were investigated.The results show that PDA can effectively enhance the interfacial interaction between the explosive particles and the binder under the synergistic effect of chemical bonds and the physical"mechanical interlocking"structure.Interface reinforcement causes the thermal decomposition temperature of the sample microspheres to move to a higher temperature,with the sensitivity to impact,friction,and electrostatic sparks(for S-1)increasing by 12.5%,31.3%,and 81.5%respectively,and the compressive strength also increased by 30.7%,effectively enhancing the safety performance of the microspheres.Therefore,this study provides an effective and universal strategy for preparing high-quality functional explosives,and also provides some reference for the safe use of energetic materials in practical applications.
基金financially supported by the Fundamental Research Funds for the Central Universities(Grant No.30923011018)。
文摘The present study introduces a screw-pressing charging method to tackle deficiencies in automation and charge uniformity during the melt-casting of polymer-based energetic materials.To ensure the safety of the experiments,this study used inert materials with similar physical properties to partially substitute for the actual energetic components in the preparation of simulant materials.By thoroughly analyzing slurry physical properties,a simulation framework and an extensive performance evaluation method were developed.Such tools guide the design of the structure and configuration of process parameters.Results demonstrate that employing the Pin element significantly enhances radial mixing within the screw,minimizes temperature variations in the slurry,and improves both efficiency and safety in the mixing process.Further,adjustments such as widening the cone angle of the barrel,modifying the solid content of the slurry,and varying the speed of the screw can optimize the mechanical and thermal coupling in the flow field.These adjustments promote higher-quality slurry and create a safer production environment for the extrusion process.
基金supported by the National Natural Science Foundation of China(52476200,52106244)the Guangdong Basic and Applied Basic Research Foundation(2024A1515030124)+1 种基金the Science and Technology Project of China Southern Power Grid under Grant GDKJXM20230246(030100KC23020017)the Fundamental Research Funds for the Central Universities。
文摘Due to batteries inconsistencies and potential faults in battery management systems,slight overcharging remains a common yet insufficiently understood safety risk,lacking effective warning methods.To illuminate the degradation behavior and failure mechanism of various overcharged states(100%SOC,105%SOC,110%SOC,and 115%SOC),multiple advanced in-situ characterization techniques(accelerating rate calorimeter,electrochemical impedance spectroscopy,ultrasonic scanning,and expansion instrument)were utilized.Additionally,re-overcharge-induced thermal runaway(TR)tests were conducted,with a specific emphasis on the evolution of the expansion force signal.Results indicated significant degradation at 110%SOC including conductivity loss,loss of lithium inventory,and loss of active material accompanied by internal gas generation.These failure behaviors slow down the expansion force rate during reovercharging,reducing the efficacy of active warnings that depend on rate thresholds of expansion force.Specifically,the warning time for 115%SOC battery is only 144 s,which is 740 s shorter than that for fresh battery,and the time to TR is advanced by 9 min.Moreover,the initial self-heating temperature(T1)is reduced by 62.4℃compared to that of fresh battery,reaching only 70.8℃.To address the low safety of overcharged batteries,a passive overcharge warning method utilizing relaxation expansion force was proposed,based on the continued gas generation after stopping charging,leading to a sustained increase in force.Compared to active methods that rely on thresholds of expansion force rate,the passive method can issue warnings 115 s earlier.By combining the passive and active warning methods,guaranteed effective overcharge warning can be issued 863-884 s before TR.This study introduces a novel perspective for enhancing the safety of batteries.
文摘BACKGROUND Currently,very few studies have examined the analgesic effectiveness and safety of dexmedetomidine-assisted intravenous-inhalation combined general anesthesia in laparoscopic minimally invasive surgery for inguinal hernia.AIM To investigate the analgesic effect and safety of dexmedetomidine-assisted intravenous-inhalation combined general anesthesia in laparoscopic minimally invasive surgery for inguinal hernia.METHODS In this retrospective study,94 patients scheduled for laparoscopic minimally invasive surgery for inguinal hernia,admitted to Yiwu Central Hospital between May 2022 and May 2023,were divided into a control group(inhalation combined general anesthesia)and a treatment group(dexmedetomidine-assisted intrave-nous-inhalation combined general anesthesia).Perioperative indicators,analgesic effect,preoperative and postoperative 24-hours blood pressure(BP)and heart rate(HR),stress indicators,immune function levels,and adverse reactions were com-pared between the two groups.RESULTS Baseline data,including age,hernia location,place of residence,weight,monthly income,education level,and underlying diseases,were not significantly different between the two groups,indicating comparability(P>0.05).No significant difference was found in operation time and anesthesia time between the two groups(P>0.05).However,the treatment group exhibited a shorter postoperative urinary catheter removal time and hospital stay than the control group(P<0.05).Preoperatively,no significant differences were found in the visual analog scale(VAS)scores between the two groups(P>0.05).However,at 12,18,and 24 hours postoper-atively,the treatment group had significantly lower VAS scores than the control group(P<0.05).Although no significant differences in preoperative hemodynamic indicators were found between the two groups(P>0.05),both groups experienced some extent of changes in postoperative HR,diastolic BP(DBP),and systolic BP(SBP).Nevertheless,the treatment group showed smaller changes in HR,DBP,and SBP than the control group(P<0.05).Preoperative immune function indicators showed no significant differences between the two groups(P>0.05).However,postoperatively,the treatment group demonstrated higher levels of CD3+,CD4+,and CD4+/CD8+and lower levels of CD8+than the control group(P<0.05).The rates of adverse reactions were 6.38%and 23.40%in the treatment and control groups,respectively,revealing a significant difference(χ2=5.371,P=0.020).CONCLUSION Dexmedetomidine-assisted intravenous-inhalation combined general anesthesia can promote early recovery of patients undergoing laparoscopic minimally invasive surgery for inguinal hernia.It ensures stable blood flow,improves postoperative analgesic effects,reduces postoperative pain intensity,alleviates stress response,improves immune function,facilitates anesthesia recovery,and enhances safety.
基金National Natural Science Foundation of China under Grant Nos.52078386 and 52308496SINOMACH Youth Science and Technology Fund under Grant No.QNJJ-PY-2022-02+2 种基金Young Elite Scientists Sponsorship Program under Grant No.BYESS2023432Fund of State Key Laboratory of Precision Blasting and Hubei Key Laboratory of Blasting Engineering,Jianghan University under Grant No.PBSKL2023A9Fund of China Railway Construction Group Co.,Ltd.under Grant No.LX19-04b。
文摘Strong surface impact will produce strong vibration,which will pose a threat to the safety of nearby buried pipelines and other important lifeline projects.Based on the verified numerical method,a comprehensive numerical parameter analysis is conducted on the key influencing factors of the vibration isolation hole(VIH),which include hole diameter,hole net spacing,hole depth,hole number,hole arrangement,and soil parameters.The results indicate that a smaller ratio of net spacing to hole diameter,the deeper the hole,the multi-row hole,the hole adoption of staggered arrangements,and better site soil conditions can enhance the efficiency of the VIH barrier.The average maximum vibration reduction efficiency within the vibration isolation area can reach 42.2%.The vibration safety of adjacent oil pipelines during a dynamic compaction projection was evaluated according to existing standards,and the measurement of the VIH was recommended to reduce excessive vibration.The single-row vibration isolation scheme and three-row staggered arrangement with the same hole parameters are suggested according to different cases.The research findings can serve as a reference for the vibration safety analysis,assessment,and control of adjacent underground facilities under the influence of strong surface impact loads.
文摘The construction of the new tunnel under the existing railway will break the original stress balance in the engineering area, resulting in the secondary redistribution of surrounding rock stress. The large amount of excavation unloading of the soil below is also easy to induce the uneven settlement deformation of the existing structure above, affecting the safety of driving. Based on the shield tunnel project between Caoqiao Station and Lize Business District Station of Beijing Metro, this paper restores the construction site by constructing the finite element numerical model of the project area, calculates and analyzes the deformation and stress of the existing railway structure before and after the construction of the tunnel, and determines the safety impact of the new structure on the existing railway. The results show that the shield tunnel undercrossing construction will cause the “concave” settlement of the railway subgrade above. Under the condition of grouting reinforcement, the “concave” settlement curve is slower and the distribution range is wider. With the advancement of the construction step, the settlement deformation of the subgrade gradually increases. When the tunnel approaches and passes directly below the subgrade, the settlement deformation curve of the subgrade changes from slow to steep. After the tunnel passes away, the curve changes from steep to slow, and the deformation of the subgrade reaches the maximum after the tunnel is connected. Under the grouting condition, the maximum settlement deformation of the subgrade is 2.08 mm, which is about 45% of the settlement deformation of the subgrade under the non-grouting condition. The ground grouting reinforcement can effectively control the subgrade settlement, and the field monitoring verifies the rationality of the calculation results. After the tunnel passes underneath, the most unfavorable section of the existing railway frame bridge is located at the top plate of the structure, and the maximum crack width is 0.178 mm. After grouting reinforcement, the stress environment of the structure is improved, the crack width generated by the structure is smaller, the reinforcement area required for calculation is less, and the structural safety meets the requirements.
基金supported by the Special Project for the Construction of Innovative Provinces in Hunan Province,China(2020SK2013)。
文摘Objective:In recent years,the incidence and detection rate of pancreatic cystic lesions(PCLs)have increased significantly.Endoscopic ultrasound(EUS)plays an indispensable role in the diagnosis and differential diagnosis of PCLs.However,evidence comparing the diagnostic performance of EUS-guided fine-needle aspiration(EUS-FNA)and fine-needle biopsy(FNB)remains limited.This study aims to compare the diagnostic yield,adequacy of tissue acquisition,and safety between EUS-FNA and EUS-FNB in evaluating PCLs to inform clinical practice.Methods:A retrospective review was conducted on patients with PCLs who underwent either EUS-FNA or EUS-FNB between January 2014 and August 2021.The diagnostic yield,tissue acquisition adequacy,and incidence of adverse events were compared between the 2 groups.Results:A total of 90 patients with PCLs were included(52 in the FNA group and 38 in the FNB group).The diagnostic yield was similar between the FNA and FNB groups(94.2%vs 94.7%,P>0.05).The adequacy of tissue acquisition was 71.2%in the FNA group and 81.6%in the FNB group(P>0.05).No statistically significant difference was observed in the incidence of adverse events between the 2 groups(P>0.05).Conclusion:Both EUS-FNA and EUS-FNB demonstrate equally high diagnostic yields and tissue adequacy in PCLs,with excellent safety profiles.Both methods are safe and effective diagnostic tools for evaluating PCLs.
文摘This paper focuses on the high-voltage safety of drive motor systems in new energy vehicles and conducts standardized research on functional safety design in the concept phase. In view of the lack of high-voltage hazard analysis for drive motor systems in existing standards, based on theories such as GB/T 34590 and ISO 26262, the safety levels are deeply analyzed. The HAZOP method is innovatively used, and 16 types of guidewords are combined to comprehensively analyze the system functions, identifying vehicle hazards such as high-voltage electric shock caused by functional abnormalities, including high-voltage interlock function failure and abnormal active discharge. Subsequently, safety goals such as preventing high-voltage electric shock are set, functional safety requirements such as accurately obtaining collision signals and timely discharging high-voltage electricity are formulated, and requirements for external signal sources and other technologies are clearly defined, constructing a complete high-voltage safety protection system. The research results provide important technical support and standardized references for the high-voltage safety functional design of drive motor systems in new energy vehicles, and are of great significance for improving the high-voltage safety level of the new energy vehicle industry, expecting to play a key role in subsequent product development and standard improvement.
文摘This webinar is jointly organized by CEN and CENELEC,and Ernst&Young(EY),with the participation of the European Commission Desk Officer,who will deliver the opening remarks.This session will focus specifically on the Toy Safety Directive and General Product Safety Regulation.Additional sector-specific webinars will follow in the coming months.
基金Supported by Construction Project of High-quality Vegetable Quality Characteristic Index System in Hebei Province.
文摘Vegetables are essential and important foods in people s daily production,which are closely related to human health.Focusing on the present situation of vegetable nutrition and safety quality detection from detection indexes and detection methods,this paper discussed the selection of detection indexes and detection methods for vegetable nutrition and safety quality,and put forward the main research direction of vegetable nutrition and safety quality detection in the future,providing guidance and reference for improving vegetable nutrition and safety quality evaluation.
文摘This study aims to construct a virtual twin testing framework for the safety of the intended functionality of intelligent connected vehicles to address the safety requirements of intelligent driving and transportation systems.The research methods include the construction of a theoretical model of safety for intelligent connected vehicles based on the concept of virtual twins,the correlation study between key concepts and functional safety,and the application research of virtual twin technology in the safety testing of intelligent connected vehicles.The results reveal that the virtual twin testing framework can effectively enhance the functional safety of intelligent connected vehicles,reduce development costs,and shorten the product launch cycle.The conclusion suggests that this framework provides strong support for the healthy development of the intelligent connected vehicle industry and has a positive impact on the safety and efficiency of intelligent transportation systems.
文摘Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October 19,2021,and as combination therapy with metformin when using metformin alone failed in blood glucose control on July 16,2024,by the National Medical Products Administration(NMPA)in China.However,pharmacokinetic(PK)study of this product in patients with renal impairment have not yet been conducted.The purpose of this study is to evaluate the effects of renal impairment on the PK and safety after a single oral dose of Chiglitazar.Methods:This multicenter,open-label,parallel-controlled,single-dose Phase I clinical trial(NCT 05515458)enrolled 24 participants(12/group)with severe renal impairment(SRI)or normal renal function(NRF).All participants received a single oral dose of 48 mg chiglitazar after breakfast and the PK and safety was evaluated.Results:The median Tmax was similar in both SRI and NRF groups(5.01 vs.5.02 hours).The geometric mean ratios(GMR)for Cmax,AUC0-t,and AUC0-∞were 0.807(90%confidence interval[CI]:0.697–0.935),0.853(90%CI:0.713–1.02),and 0.855(90%CI:0.716–1.02),respectively,indicating that SRI did not significantly affect the exposure of chiglitazar.The Cmax was weakly positively correlated with eGFR(r=0.4798,P=0.0177)and creatinine clearance rate(r=0.4667,P=0.0215).Urinary excretion of chiglitazar was negligible in the SRI group,with average values of Ae0-t=2,900 ng,Fe0-t=0.0060%,and CLR=0.323 mL/h within 0–72 hours post-dose.The treatment-emergent adverse event(TEAE)incidence in the SRI group(16.7%,2/12)was comparable to that in the NRF group(25%,3/12).All TEAEs were of mild severity and were adjudicated by the investigators to be unrelated to chiglitazar.No serious AE were reported.Chiglitazar exhibits a favorable safety profile.Conclusion:Severe renal impairment does not significantly affect the PK and safety of chiglitazar,and no dose adjustment for mild,moderate,and severe renal impairments is required.
基金Supported by the Air Force Medical Center Youth Talent Program Project,No.22YXQN034Capital Health Development Research Special Project,No.2020-4-5123Beijing Haidian District Health and Wellness Development Scientific Research Cultivation Program,No.HP2021-03-80803.
文摘BACKGROUND Gastrointestinal angiodysplasias(GIAD)causes recurrent bleeding,and current treatments have limitations.Sirolimus,a mammalian target of rapamycin inhibi-tor,shows promise in inhibiting abnormal angiogenesis.AIM To evaluate the efficacy and safety of sirolimus in reducing bleeding episodes and improving clinical outcomes in patients with GIAD.METHODS We conducted a self-controlled study with 11 patients taking oral sirolimus.Retrospective data were collected prior to treatment,and prospective data were gathered during the study.Efficacy was assessed primarily by comparing blee-ding episodes before and after sirolimus,with measurements at 3 and 6 months post-administration.The initial dose was 0.8 mg/m^(2)once daily,adjusted to main-tain trough blood concentrations between 5-10 ng/mL.Secondary outcomes included hemoglobin(Hb)levels,blood transfusion volume,and vascular lesions.Safety was monitored by tracking adverse reactions.RESULTS The average number of bleeding episodes decreased significantly from 2.09±1.04 to 1.00±0.75 in the 3 months preceding treatment,and from 3.80±1.93 to 2.00±1.63 in the 6 months preceding treatment.Sirolimus also increased Hb levels,reduced the need for transfusions,and decreased vascular lesions,improving clinical outcomes.All adverse effects were mild and resolved or improved within 1 week to 1 month without stopping sirolimus or needing lipid-lowering treatment.CONCLUSION Sirolimus reduced bleeding and transfusion needs while improving Hb levels in GIAD patients.Although these findings are encouraging,the limited sample size and lack of a control group warrant caution.Future controlled trials with larger populations are needed to validate sirolimus’s potential in GIAD.
文摘BACKGROUND Blonanserin,a novel antipsychotic,has demonstrated efficacy in treating both positive and negative symptoms.However,limited research exists on its dose-dependent effectiveness and safety in patients with and without prominent nega-tive symptoms(PNS).AIM To evaluate the effectiveness and safety of blonanserin monotherapy for first-episode schizophrenia in real-world clinical settings and to explore the efficacy and safety of different doses of blonanserin for patients with PNS and without PNS.METHODS A 12-week,multicenter,prospective post-marketing surveillance was conducted.In this study,we included patients with first-episode schizophrenia who received blonanserin monotherapy.Patients were divided into those with PNS and without PNS,based on the Brief Psychiatric Rating Scale(BPRS)negative symptoms subscale scores.Additionally,patients were labeled as high-dose and low-dose was evaluated through the incidence of adverse drug reactions(ADRs).RESULTS A total of 653 patients were included in the analysis,with 613 completing the study.The BPRS total score decreased significantly from 47.94±16.31 at baseline to 26.88±9.47 at 12 weeks(P<0.001).A significant interaction of PNS×dose×time was observed for BPRS total scores(F=3.47,P=0.040)and negative symptom subscale scores(F=6.76,P=0.002).In the PNS group,the high-dose group showed greater reductions in BPRS total scores(P=0.001)and negative symptom subscale scores(P=0.003)than the low-dose group in week 12.In the without PNS group,no significant difference was observed between the high-dose and low-dose groups at any visit.Most adverse reactions were mild or moderate,with extrapyramidal symptoms(9.3%)being most common;1.5%of patients gained≥7%body weight at 12 weeks.CONCLUSION Blonanserin effectively alleviated the clinical symptoms of first-episode schizophrenia with an acceptable safety profile.High-dose blonanserin is particularly beneficial for patients with PNS in the acute phase of first-episode schizophrenia.However,due to the limitation of ADR reporting the real world,the ADR incidence observed in this study may be underestimated.
文摘Objective:To analyze the clinical efficacy and safety of toripalimab combined with the GC chemotherapy regimen in the treatment of advanced urothelial carcinoma.Methods:A retrospective study was conducted on 102 patients with advanced urothelial carcinoma treated at our hospital between March 2021 and August 2024.Based on treatment regimens,patients were divided into a chemotherapy group(n=52)and a combination group(n=50).The chemotherapy group received the GC chemotherapy regimen,while the combination group received GC chemotherapy combined with toripalimab.Both groups underwent 4-6 cycles of treatment based on patient tolerance.Clinical efficacy,immune-related factor levels,survival outcomes,and safety were observed and compared.Results:The disease control rate(DCR)and overall response rate(ORR)in the combination group were slightly higher than those in the chemotherapy group,but the differences were not statistically significant(P>0.05).After treatment,levels of IFN-γand IL-2 increased significantly,while VEGF levels decreased significantly in both groups(P<0.05),with superior outcomes observed in the combination group(P<0.05).Follow-up analysis showed progression-free survival(PFS)and median overall survival(OS)in the chemotherapy group were 5.19 and 10.15 months,respectively,compared to 8.24 and 18.23 months in the combination group,with statistically significant differences(P<0.05).During treatment,the incidence of adverse reactions such as rash,immune-related pneumonia,and immune-related diarrhea was higher in the combination group than in the chemotherapy group(P<0.05).However,the incidence of gastrointestinal reactions,fever,and leukopenia did not differ significantly between the two groups(P>0.05).Conclusion:The use of toripalimab combined with the GC chemotherapy regimen for advanced urothelial carcinoma can effectively improve clinical outcomes and extend patient survival,with good overall safety.However,attention should be given to preventing adverse reactions such as rash and pneumonia during treatment.
基金the financial support provided by the National Key Research and Development Program of 14th Five-Year Plan,China(2021YFC3001101)。
文摘Process safety for synthesis of tert-butyl hydroperoxide(TBHP) by tert-butyl alcohol(TBA) to react with H_(2)O_(2) was studied in this paper.On-line Raman spectroscopy and gas chromatography jointed analysis method was researched to monitor and analyze the changes of each components during the process to study reaction mechanism.The reaction kinetics was reproduced by apparent thermodynamics study and simulation for whole process,and the kinetics model of TBHP synthesis was obtained and with the first reported.The process safety parameter of the maximum temperature of the synthesis reaction(MTSR) and yield were predicted by response surface methodology(RSM) method and go through experimental verification further.It was found that the sulfuric acid and the concentration of TBA had great influences to reaction selectivity and yield.According to our research results,we supposed that the mechanism of TBHP synthesis would be followed by SN_(1)+SN_(2).Focus on process safety,process risk assessment was done and pipe reaction to optimize TBHP synthesis was developed to change the batch process to pipe continuously.The yield of TBHP was 91.1%,conversion of TBA was 93.1%,and the selectivity of TBHP was 97.8%.The process safety parameters of heat accumulation and MTSR decreased40.5% and 37.7% respectively comparison of the pipe continuous reaction and batch process.This study will provide guidance for intrinsic safety improvement of peroxidation reactions.
基金Supported by the National Natural Science Foundation of China(No.82471071)Fujian Provincial Natural Science Foundation of China(No.2023J011580)+1 种基金Natural Science Foundation of Xiamen,China(No.3502Z20227401)Huanhua Scholar Program and the Sichuan Provincial People’s Hospital Postdoctoral Fund(No.2022BH02).
文摘AIM:To evaluate the short-term efficacy and safety of ultrasound cycloplasty(UCP)procedure in Chinese patients with angle-closure glaucoma(ACG),and the mechanisms of its intraocular pressure(IOP)lowering effects.METHODS:Fifty-six patients(56 eyes)diagnosed with primary and/or secondary ACG were enrolled in this prospective study.Visual acuity,IOP,slit-lamp examinations,structural parameters of anterior segments including anterior chamber depth(ACD),pupillary diameter(PD),anterior chamber area(ACAr),anterior chamber angle(ACAn),and side effects were evaluated.Seven rhesus macaques(Macaca Mulatta)were used for the analyses of IOP lowering effects,including inflammatory reactions,pathohistological evaluation,scanning electron microscopy(SEM),and aqueous outflow pathway via 1%basic fuchsin perfusion.RESULTS:Fifty six eyes of 24 male and 32 female patients with an average age of 58.93±15.97 years old were recruited in primary and secondary ACG affected 31 and 25 eyes,respectively.Clinically,the mean IOP was 17.89±7.93 mm Hg(n=53,53.63%reduction,P<0.001)at 1wk and 22.47±12.00 mm Hg at 12mo(n=16,18.67%reduction,P<0.01)after UCP,compared to the baseline of 39.08±14.75 mm Hg(n=56).Postoperative tolerance was favorable in 94.64%of cases,with visual acuity unchanged or improved in 96.43%of patients.Mild and transient inflammatory reactions were observed post UCP.UBM analysis revealed statistically significant changes in anterior chamber parameters:increased ACD(n=22,P<0.05),enlarged PD(n=22,P<0.05),expanded ACAr(n=16,P<0.01),and widened ACAn(n=19,P<0.05)compared to preoperative measurements.As in normal monkey eyes,IOP was also reduced upon UCP.Mild inflammatory reactions were seen 1-7d post treatment.Hematoxylin and Eosin(H&E)staining showed enlarged spaces among ciliary muscle bundles.Ciliary process stromal edema was evident,but significant loss of two layers of ciliary epitheliums was not seen.SEM confirmed ciliary muscle fibers concentrated.Fuchsin anterior chamber perfusion showed the whole ciliary body staining in UCP group,but only surface staining in controls.CONCLUSION:UCP is efficient and safe to lower the IOP of patients with ACG.Changed anterior chamber structure and increased aqueous humour outflow via uveoscleral pathway may significantly attribute to IOP lowering effects of UCP.
基金Supported by Qinghai Provincial Science and Technology Plan,No.2023-ZJ-787.
文摘BACKGROUND Gastric cancer(GC)remains a major global health burden,particularly in East Asia,due to its high incidence,aggressive progression,and poor prognosis in advanced stages.Although surgery is the mainstay of curative treatment,outcomes for locally advanced cases remain unsatisfactory despite perioperative chemotherapy.In recent years,immune checkpoint inhibitors,especially anti-PD-1 antibodies like sintilimab,have shown promise in improving survival when combined with chemotherapy.However,the comparative efficacy and safety of SOX plus sintilimab vs established regimens such as P-SOX and SOX alone in the neoadjuvant setting have not been fully explored.AIM To compare the efficacy and safety of three neoadjuvant chemotherapy regimens—SOX combined with sintilimab(SOX+PD-1),albumin-bound paclitaxel plus oxaliplatin and S-1(P-SOX),and SOX—in patients with advanced GC.METHODS A retrospective analysis was conducted on 299 patients with advanced GC who received both neoadjuvant and adjuvant chemotherapy along with standard D2 radical gastrectomy.Among them,81 patients received SOX plus sintilimab,118 received the P-SOX regimen,and 100 received the SOX regimen.All patients were randomly assigned to training(70%)or validation(30%)cohorts using the R software sample function.Short-term efficacy,long-term survival outcomes,and adverse events were assessed across the three groups.Additionally,clinical factors associated with progression-free survival(PFS)were further investigated.RESULTS In terms of short-term efficacy,the SOX+sintilimab group had higher objective response rates[91.4%and 70.4%according to the tumor regression grade(TRG)and Response Evaluation Criteria in Solid Tumors(RECIST)1.1 criteria,respectively]than did the P-SOX(88.1%and 59.3%)and SOX groups(84.0%and 55.0%),although the intergroup differences were not statistically significant(P=0.167).For long-term outcomes,the SOX+sintilimab group demonstrated significantly better OS rates at 1 year(98.8%),18 months(92.6%),2 years(84.0%),and 3 years(48.1%)than did the P-SOX(93.2%,86.4%,71.2%,30.5%)and SOX(91.0%,84.0%,72.0%,29.0%)groups,with the 3-year overall survival(OS)difference being statistically significant(P=0.007).Similarly,PFS rates in the SOX+sintilimab group(1 year:92.6%;18 months:77.8%;2 years:65.4%;3 years:35.8%)were significantly greater than those in the P-SOX(82.2%,68.6%,53.4%,26.3%)and SOX(77.0%,66.0%,43.0%,27.0%)groups,with significant differences at 1 year(P=0.021)and 2 years(P=0.011).In terms of safety,grade 1-2 gastrointestinal reactions,peripheral neuropathy,and alopecia were the main TRAEs across groups.The P-SOX group had a significantly greater incidence of alopecia(54.2%vs 53.0%vs 23.5%,P=0.009)and more cases of grade 2 alopecia(6.8%vs 1.2%),potentially due to the accumulation of triple-agent toxicity.No significant intergroup differences were observed in hematologic toxicity or liver dysfunction(all P>0.05).CONCLUSION Compared with the SOX and P-SOX regimens,the SOX plus sintilimab combination demonstrated significantly improved short-and long-term efficacy with favorable safety,with superior advantages in terms of 2-and 3-year OS and early PFS,suggesting that this combination is a more promising therapeutic option for patients with advanced GC.Patients who achieved good perioperative chemotherapy responses(meeting the TRG and RECIST 1.1 criteria)and had tumor diameters≤2 cm,well-differentiated histology,earlier cTNM stages,and no lymph node metastasis had a better prognosis.
文摘BACKGROUND There is a scarcity of evidence and systematic reviews on endoscopic gastroplasty(EG)compared to other management options for the treatment of obesity.AIM To assess the published meta-analyses through a systematic review approach and provide further insight into the current status of available evidence through a critical appraisal.METHODS PubMed/MEDLINE,Scopus,Embase and Cochrane Library were searched from inception to November 2022.The meta-analyses that compared the efficacy and safety of EG to other interventions were considered for this overview.The outcomes of interest were total body weight loss(TBWL),excessive weight loss,and average weight loss along with occurrence of adverse effects.Methodological quality,heterogeneity,and limitations were also reviewed.RESULTS A total of six meta-analyses out of 364 records were considered for this review with a major contribution from the United States.Overall methodological quality of included studies were moderate to good.EG treatments were significantly better in terms of TBWL,excessive weight loss,and average weight loss.However,there was no significant difference between endoscopic transoral outlet reduction and full-thickness suturing plus argon plasma mucosal coagulation.Lack of comparative studies and randomized trials,lack of long-term follow-up,reporting bias,selection bias,lack of control groups,and considerable level of heterogeneity were the major limitations in the available evidence.CONCLUSION Though EG was significantly effective for treatment of obesity,there is limited comparative evidence on this topic.High-quality well-controlled evidence is required to strengthen the current evidence base on EG treatment for obesity.
