ObjectiveTo analyze the factors influencing meropenem-related liver injury （MRLI） and to explore their clinical predictive value. MethodsA retrospective case-control study was conducted， and the Chinese Hospital Pharmacovigilance System （CHPS） was used to establish a retrieval scheme. A total of 1 625 hospitalized cases using meropenem from January 2018 to December 2022 were collected. Patients were divided into case group （n=62） and control group （n=1 563） based on the presence or absence of liver injury. Clinical data and laboratory indicators from both groups were collected and analyzed. The t-test was used for comparison of normally distributed continuous data between the two groups， while the Mann-Whitney U test was used for comparison of continuous data not conforming to a normal distribution. The chi-square test was used for comparison of categorical data between the two groups. A multivariate Logistic regression analysis was performed to identify the influencing factors for MRLI. A Logistic regression equation was established， and the predictive value of these factors was assessed using the receiver operating characteristic （ROC） curve. ResultsThe results of univariate analysis indicated that the rates of male patients， hypoproteinemia， shock， intensive care unit （ICU） admissions， sepsis， and liver， gallbladder， and cardiovascular diseases， the levels of alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， gamma-glutamyl transpeptidase （GGT）， aspartate aminotransferase （AST）， creatinine （CREA）， and procalcitonin （PCT）， and the number of hospitalization days were significantly higher in the case group than in the control group （P<0.05）， and that the platelet levels in the case group were significantly lower than those in the control group （P<0.05）. The multivariate Logistic regression analysis showed that male sex （odds ratio ［OR］=2.080， 95% confidence interval ［CI］： 1.050 — 4.123， P=0.036）， admission to the ICU （OR=8.207， 95%CI： 4.094‍ ‍—‍ ‍16.453， P<0.001）， comorbidity with gallbladder disease （OR=8.240， 95%CI： 3.605‍ ‍—‍ ‍18.832， P<0.001）， ALP （OR=1.012， 95%CI： 1.004‍ ‍—‍ ‍1.019， P=0.004）， GGT （OR=1.010， 95%CI： 1.005‍ ‍—‍ ‍1.015， P<0.001）， and PLT （OR=0.997， 95%CI： 0.994‍ ‍—‍ ‍0.999， P=0.020） were the influential factors for MRLI. The areas under the ROC curve of ALP， GGT， and PLT were 0.589， 0.637， and 0.595， respectively， and the AUC of them combined was 0.837. ConclusionMale sex， ICU admission， comorbidity with gallbladder disease， increased ALP， increased GGT， and decreased PLT were influencing factors for MRLI， and a combination of factors has a better predictive value for the occurrence of MRLI.

OBJECTIVE To investigate the implementation effects of the national centralized drug volume-based procurement policy （abbreviated as “national centralized procurement policy”） in Guangxi Zhuang Autonomous Region prefecture， and to provide a reference for the future centralized drug procurement work of the medical institution. METHODS Drug procurement data before and after policy implementation were included in the study. The six secondary indicators （such as availability， affordability， and drug safety） and eighteen third-level indicators （such as completion rate of agreed purchase volume， affordability level， drug revenue proportion） were introduced， guided by the policy objectives and issues of concern to policy beneficiaries. Descriptive statistics was adopted to analyze the data before and after policy implementation （in 2019 and 2020） in terms of differences and change trends. RESULTS In terms of accessibility， the participation rate of medical institutions in Guangxi Zhuang Autonomous Region was 92.55%， the proportion of diseases involved and median completed procurement rate were 40.16%， and 287.82% respectively， and the total centralized delivery rate was 97.20%. In terms of affordability， the total reduction amplitude in drug price was 74.80% from 2019 to 2022； the charge for medicine per capita in hospitalization， the proportion of medicine used for outpatient service and hospitalization， decreased by 17.61%， 10.22%， and 20.10% in order； the burden levels on medical fares for patients were all below 1 in addition to chronic diseases， and anti-tumor drugs. In terms of the impact on medicine， the ratio of adverse drug reaction event cases in 2022 was 66.00%， an increase of 1.29% compared to the previous； since the implementation of the policy， 12 drugs from local pharmaceutical enterprises from Guangxi Zhuang Autonomous Region had passed the consistency evaluation， and the market concentration rate of the top 8 pharmaceutical companies was less than 20.00%. In terms of the impact on healthcare and medical insurance， the public medical institutions achieved generic substitution for originator drugs mostly until 2022； about 9.12% of drugs that were non- centrally purchased in the same category were used； 63.39% of people under investigation did not show a need for a second dressing change； drug expenditure decreased by 2.459 billion yuan. CONCLUSIONS The national centralized procurement policy achieves a significant effect in Guangxi Zhuang Autonomous Region. On the other hand， attention should be paid to these suggestions as follows: expanding the category of drugs used in clinic， conducting clinically comprehensive evaluation of selected drugs， and improving reasonable allocation strategy， etc.

Objective:To investigate the clinical characteristics and the efficacy of thrombus aspiration in patients with early intrastent thrombosis (EST) following carotid artery stenting (CAS).Methods:This study is a retrospective case series, collecting clinical data of five patients who developed EST after CAS in the Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University from January 2021 to September 2023.All patients were male, with an age of (64.0±11.9) years (range:48 to 77 years), accounting for 2.0% (5/244) of CAS procedures during the same period.Among them, three patients did not receive standard dual antiplatelet therapy before the procedure, and one had an inadequate ADP inhibition rate (45.6%).Four patients received XACT carotid stents, while one received a Wallstent carotid stent.All five patients showed significant residual stenosis ranging from 43% to 55% after CAS.Emergency thrombus aspiration was performed in all cases, and data regarding perioperative conditions, vascular patency, and clinical outcomes were collected.Results:The interval between CAS and the occurrence of EST ranged from 3 hours to 14 days.The main clinical symptoms included sudden onset of consciousness disorders and contralateral limb weakness.None of the patients received preoperative intravenous thrombolysis, and thrombus aspiration was performed during the procedure to restore vascular patency.Four cases underwent balloon angioplasty during the procedure, and two cases utilized overlapping stents.Two patients experienced intraoperative embolization of thrombus to the C 2 segment.In one case, the embolized thrombus was retrieved using an intracranial thrombectomy stent, while in another case, it was aspirated using a guiding catheter.Postoperatively, all patients had a thrombolysis in cerebral infarction grade of 3, and symptoms improved in four cases.One patient showed no improvement in symptoms, and MRI revealed extensive new infarction in the right frontal and insular regions, adjacent to the right lateral ventricle.Regular follow-up examinations after discharge did not reveal restenosis or embolism within the stent.The follow-up period ranged from 7.6 to 21.2 months, with modified Rankin scale scores of 0 to 1 point in four cases and 2 points in one case, indicating good recovery in all patients. Conclusions:Acute intrastent thrombosis is a rare complication after carotid artery stenting.The combined use of percutaneous thrombus aspiration and endovascular techniques, such as balloon angioplasty and stent overlapping, can rapidly restore vessel patency with favorable outcomes.However, further large-scale clinical studies are needed to confirm the effectiveness of these treatments for acute intrastent thrombosis.

Objective:To consolidate the current evidences regarding the efficacy of vitamin D supplementation in age-related sarcopenia.Methods:In this systemic review, a comprehensive literature search of scientific research including journal articles and academic dissertations was performed in prominent databases such as PubMed, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang Database platforms, spanning from January 31, 2014 to January 31, 2024. Two search protocols integrating keywords and citation tracking were adopted to ensure comprehensiveness of the literature. Using “vitamin D” “ergocalciferols” “cholecalciferol” “sarcopenia” “muscle mass” “muscle strength” “myopenia” “muscle loss” “muscle reduction” “gait speed” “grip strength” “handgrip” as the main key words, focusing on the systematic reviews, meta-analyses of randomized controlled trials (RCT), and individual RCT, the scientific evidence of individual vitamin D intervention on age-related sarcopenia was evaluated and summarized. Research concerning particular disease conditions, children and adolescents, menopausal women, athletes and other specific populations were excluded.Results:A initial search yielded 2 448 articles in Chinese or English. A total of 8 systemic reviews/meta-analysis and 22 individual RCT literatures were included in the final analysis. Although some earlier lower-quality studies reported subtle improvements in skeletal muscle strength with vitamin D supplementation, high-quality systematic reviews/meta-analysis over the past three years had not shown significant positive effects of vitamin D intervention on sarcopenia and its breakdown parameters, such as skeletal muscle mass, muscle strength, and muscle function. Furthermore, the efficiency was influenced to some extent by the participants′ baseline status, such as muscle health and vitamin D nutritional status.Conclusions:Present evidence does not robustly support the efficacy of sole vitamin D supplement on age-related sarcopenia. High-quality clinical trials are imperative to accumulate more robust evidence in the future.

Objective To systematically evaluate the efficacy and safety of hydroxychloroquine(HCQ)in obstetric antiphospholipid syndrome(OAPS).Methods PubMed,Embase,Cochrane Library,Web of Science,SinoMed,Wanfang Data,CNKI,and VIP databases were searched electronically to collect clinical research on HCQ treatment for OAPS from inception to January 31,2023.Two researchers independently screened the literature,extracted data,and assessed the risk of bias of the included studies,Meta-analysis and GRADE evaluation were performed using RevMan 5.4 software and GRADE Profile 3.6 softwares.Results Five cohort studies and three randomized controlled trias(RCTs)were included,with a total of 644 OAPS patients(732 pregnancies).The results of Meta-analysis showed that compared with conventional treatment,HCQ supplementation significantly increased the live birth rate of OAPS(RR=1.29,95％CI 1.10 to 1.51,P=0.001),the negative conversion rate of lupus anticoagulant(RR=1.29,95％CI 1.13 to 1.47,P＜0.001),the anticardiolipin antibody negative conversion rate(RR=1.27,95％CI 1.12 to 1.45,P＜0.001)and the anti-β2 glycoprotein I antibody negative conversion rate(RR=1.31,95％CI 1.12 to 1.52,P＜0.001),the rate of early abortion(＜10 weeks)was significantly reduced(RR=0.31,95％CI 0.10 to 0.93,P=0.04).However,there was no significant difference between the two groups in reducing the rate of premature birth,late abortion(＞10 weeks)and the incidence of preeclampsia(P＞0.05).In terms of safety analysis,two studies described HCQ adverse effects including skin reactions and dry eyes,symptoms are mild.Three RCTs were used to compare the incidence of adverse reactions between the two groups,the incidence of adverse reaction of HCQ group was lower than that of control group(RR=0.40,95％CI 0.25 to 0.66,P＜0.001),and no serious adverse reactions occurred in both groups.The sensitivity analysis results were robust and reliable.The results of GRADE evaluation showed that the quality of index evidence included in this study were low or very low,with weak recommendations.Conclusion HCQ can significantly improve the live birth rate of OAPS and the negative conversion rate of antiphospholipid antibody,and reduce the fetal abortion rate before 10 weeks with fewer adverse reactions,but there is insufficient evidence to reduce the incidence of premature birth,fetal abortion after 10 weeks and preeclampsia.Due to the limited number and quality of included studies,the above conclusions need to be confirmed by more high-quality studies.

Objective To compare the effectiveness and safety of semaglutide with dulaglutide in patients diagnosed with type 2 diabetes.Methods A multicenter retrospective cohort study was conducted to include patients with type 2 diabetes who received semaglutide or dulaglutide treatment at three hospitals between April 2021 and July 2023 in the study.The patients were divided into the semaglutide group(SEMA group)and the dulaglutide group(DULA group)based on their treatment.Propensity score matching was used to pair the two groups in a 1:1 ratio,aligning them based on baseline characteristics such as gender,age,body mass index,blood glucose levels,duration of diabetes,and complications.Various parameters including fasting blood glucose,2-hour postprandial blood glucose,glycosylated hemoglobin(HbA1c),serum creatinine,urea nitrogen levels,estimated glomerular filtration rate(eGFR),urinary albumin/creatinine ratio(UACR),and occurrences of adverse reactions were assessed at 3,6,9,and 12 months after the treatment.Results After propensity score matching,98 patients were included in both the SEMA and DULA groups,showing no statistically significant differences in baseline characteristics between the groups(P＞0.05).At each follow-up point,the fasting blood glucose,2-hour postprandial blood glucose,and HbA1c levels of both groups showed a significant decrease compared to the baseline(P≤0.05).The inter-group comparison revealed no statistically significant differences in the changes in fasting blood glucose,2-hour postprandial blood glucose,and HbA1c levels between the two groups(P＞0.05).At the 6th month,the SEMA group exhibited a statistically significant higher rate of HbA1c＜7％compared to the DULA group(P＜0.05).In the SEMA group,serum creatinine and urea nitrogen decreased significantly at the 6th month compared to baseline,while eGFR showed an increase at the 3rd and 6th month,and UACR decreased,all with statistical significance(P＜0.05).In the DULA group,there was a statistically significant increase in serum creatinine and decrease at the 3rd and 6th months in eGFR,respectively.Additionally,urea nitrogen levels decreased significantly at the 9th month,all differences were statistically significant(P＜0.05).The inter-group comparison revealed that at the 3rd and 6th month,the SEMA group exhibited a greater reduction in serum creatinine levels compared to the DULA group.Additionally,the SEMA group demonstrated a more pronounced increase in eGFR levels than the DULA group,with statistical significance(P＜0.05).At the 6th month,the SEMA group exhibited a significantly greater decrease in UACR and a significantly lower incidence of renal insufficiency compared to the DULA group(P＜0.05).There were no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Semaglutide and dulaglutide can significantly improve blood glucose control,exhibit comparable effectiveness and safety in lowering blood glucose levels,and semaglutide has a potentially protective effect on renal function.

Objective:To investigate the clinical characteristics and the efficacy of thrombus aspiration in patients with early intrastent thrombosis (EST) following carotid artery stenting (CAS).Methods:This study is a retrospective case series, collecting clinical data of five patients who developed EST after CAS in the Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University from January 2021 to September 2023.All patients were male, with an age of (64.0±11.9) years (range:48 to 77 years), accounting for 2.0% (5/244) of CAS procedures during the same period.Among them, three patients did not receive standard dual antiplatelet therapy before the procedure, and one had an inadequate ADP inhibition rate (45.6%).Four patients received XACT carotid stents, while one received a Wallstent carotid stent.All five patients showed significant residual stenosis ranging from 43% to 55% after CAS.Emergency thrombus aspiration was performed in all cases, and data regarding perioperative conditions, vascular patency, and clinical outcomes were collected.Results:The interval between CAS and the occurrence of EST ranged from 3 hours to 14 days.The main clinical symptoms included sudden onset of consciousness disorders and contralateral limb weakness.None of the patients received preoperative intravenous thrombolysis, and thrombus aspiration was performed during the procedure to restore vascular patency.Four cases underwent balloon angioplasty during the procedure, and two cases utilized overlapping stents.Two patients experienced intraoperative embolization of thrombus to the C 2 segment.In one case, the embolized thrombus was retrieved using an intracranial thrombectomy stent, while in another case, it was aspirated using a guiding catheter.Postoperatively, all patients had a thrombolysis in cerebral infarction grade of 3, and symptoms improved in four cases.One patient showed no improvement in symptoms, and MRI revealed extensive new infarction in the right frontal and insular regions, adjacent to the right lateral ventricle.Regular follow-up examinations after discharge did not reveal restenosis or embolism within the stent.The follow-up period ranged from 7.6 to 21.2 months, with modified Rankin scale scores of 0 to 1 point in four cases and 2 points in one case, indicating good recovery in all patients. Conclusions:Acute intrastent thrombosis is a rare complication after carotid artery stenting.The combined use of percutaneous thrombus aspiration and endovascular techniques, such as balloon angioplasty and stent overlapping, can rapidly restore vessel patency with favorable outcomes.However, further large-scale clinical studies are needed to confirm the effectiveness of these treatments for acute intrastent thrombosis.

Objective This study aimed to investigate the glycosyltransferase gene DsUGT11 involved in the biosynthesis of flavonoids in Desmodium styracifolia,and to analyze the function of its encoding protein by bioinformatic tools,gene cloning,prokaryotic expression,and other technologies.Methods The sequence characteristics and potential biological functions of DsUGT11 were analyzed and predicted by bioinformatics analysis,respectively.Total RNA was extracted from fresh leaves and reverse transcribed into cDNA,from which DsUGT11 gene was successfully amplified and cloned.Heterologous expressed protein was induced and purified,followed by functional characterization using enzymatic reaction in vitro.Results A candidate glycosyltransferase gene,designated as DsUGT11,was identified from the transcriptome data of D.styracifolia.The length of the open reading frame of DsUGT11 is 1426 bp,and the molecular weight of its encoding protein is expected to be 52.14 KDa.By bioinformatic analysis,DsUGT11 was found to harvest a conserved motif of"PSPG"that is unique to the UGT family.Moreover,DsUGT11 was successfully amplified and cloned using the prokaryotic expression vector pMALc5X.Recombinant protein was induced and purified subsequently.Next,the purified protein was used to perform the enzymatic reaction in vitro,the result of which suggested that DsUGT11 was able to catalyze the conversion of 2-OH-naringenin and UDP-glucose into three different compounds,one of which was authenticated as apigenin-7-O-β-D-glucoside(also known as Apigetrin),with two others unknown.Conclusion In this study,the DsUGT11 gene was identified and cloned,whose encoding protein is a flavone-oxyglycosyltransferase catalyzing the conversion of 2-OH-naringenin and UDP-glucose into three different compounds including Apigetrin.

Objective : To investigate the effects of the exposure of sludge from sewage treatment plants and microplastic extracted from sludge on the oxidative stress levels in zebrafish, so as to put insights into the research into the impact of sludge and microplastics on human health. Methods : Adult wild AB zebrafish were exposed to five groups of sludge (0, 12.5, 25, 50 and 75 g/L) and four groups of microplastics extract from sludge (0, 240, 480, 960/L), with 24 zebrafish in each group. The color, activity and death of zebrafish were observed every day. The contents of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) were detected 0 h, 24 h, 48 h, 72 h, 96 h and 7 d post-exposure. A two-factor ANOVA was used to analyze the effects of different concentrations and time of exposure on the indicators above. Results : Under 75 g/L sludge exposure, zebrafish began to show mortality at 72 h and all died after 7 d. The zebrafish in the other sludge groups and all microplastic groups had normal color and activity, and no mortality was observed. Sludge concentration interacted with exposure time to affect SOD, CAT, GSH and MDA (P<0.05). With increasing sludge concentration and exposure time, SOD decreased, MDA increased, CAT increased first and then decreased, GSH decreased first and then increased, and GSH continued to decrease since 24 h in the 75 g/L group. The microplastic concentration interacted with exposure time to affect SOD and GSH (P<0.05), but not CAT or MDA (P>0.05). With increasing microplastic concentration and exposure time, SOD and MDA increased, CAT increased first and then decreased, the GSH was slightly increased at 24 h and decreased after 72 h. Conclusion Both sludge and microplastics extracted from sludge can induce oxidative stress damage in zebrafish, and exposure time and concentration can interact to affect oxidative stress levels. The microplastics extracted from sludge have less effect on oxidative stress levels in zebrafish than sludge.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone