Objective To mine and analyze the adverse event data of polatuzumab vedotin(Pola)and fam-trastuzumab deruxtecan-nxki(T-Dxd),so as to provide reference for clinical medication safety.Methods The adverse events reported from January 1,2004 to June 7,2023 were extracted based on openFDA database.The suspicious risk signals were screened by the Open Vigil 2.1 data platform and ranked by signal strength and frequency of occurrence;then ADEs were classified by reference to the MedDRA 26.0.Results A total of 7 164 and 22 870 ADE reports related to Pola and T-Dxd were obtained,and 104 and 95 suspicious ADE signals were detected,respectively.According to the signal intensity,cytomegalovirus enterocolitis(ROR=416.94)for Pola and interstitial lung disease[reporting odds ratio(ROR)=82.55]for T-Dxd ranked first,both of which were recorded in the drug instructions.According to the frequency of occurrence,the two drugs were most frequently associated with death(n=111)and nausea(n=285),respectively.The risk of Pola was associated with 12 systems/organs,of which 26 risk signals were not documented in the drug instruction,and the risk of T-Dxd was associated with 13 systems/organs,of which 18 risk signals were not documented in the drug instruction.Conclusion By tapping the ADE after real-world administration of Pola and T-Dxd,physicians are prompted to pay attention to the risk of adverse reactions in clinical use and actively take preventive and therapeutic measures to ensure the safety of patients'medication.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To systematically evaluate the effect of overtime work on neck musculoskeletal disorders of occupational population in China.Methods:In August 2023, the literatures on the relationship between overtime work and neck musculoskeletal disorders were searched in China National Knowledge Infrasture (CNKI), WanFang Database, Chinese Science & Technology Journal Database (VIP), China Biomedical Literature Service System (SinoMed) and PubMed. The search scope was Chinese and English literatures published before June 30, 2023. The Quality of literature studies was evaluated using the Agency for Healthcare Research and Quality (AHRQ) cross-sectional study quality evaluation criteria. The Stata 15.0 software was used to calculate combined OR values, and subgroup analysis and meta regression were used to explore the sources of heterogeneity. Results:A total of 32 literatures were included, all of which were in Chinese, with a total sample size of 36003 people, and the literature quality scores were 5-7 points. Heterogeneity test showed that there was no heterogeneity between the literatures ( I2=20.3%, P=0.156), so fixed effect model was selected to calculate the combined OR value. The combined OR value of overtime work on neck musculoskeletal disorders was 1.51 (95% CI: 1.42-1.60, P<0.001). Subgroup analysis showed that the combined OR of occupational population <35 years old group was higher than that in the ≥35 years old group ( P<0.05). But there were no significant differences in the combined OR values in the subgroups classified by average years of service, male proportion, type of OR values, sample size and industry classification ( P>0.05) . Conclusion:Overtime work is a risk factor for neck musculoskeletal disorders in Chinese occupational population. Working hours should be rationally arranged to reduce the prevalence of neck musculoskeletal disorders.

Objective:To systematically evaluate the effect of overtime work on neck musculoskeletal disorders of occupational population in China.Methods:In August 2023, the literatures on the relationship between overtime work and neck musculoskeletal disorders were searched in China National Knowledge Infrasture (CNKI), WanFang Database, Chinese Science & Technology Journal Database (VIP), China Biomedical Literature Service System (SinoMed) and PubMed. The search scope was Chinese and English literatures published before June 30, 2023. The Quality of literature studies was evaluated using the Agency for Healthcare Research and Quality (AHRQ) cross-sectional study quality evaluation criteria. The Stata 15.0 software was used to calculate combined OR values, and subgroup analysis and meta regression were used to explore the sources of heterogeneity. Results:A total of 32 literatures were included, all of which were in Chinese, with a total sample size of 36003 people, and the literature quality scores were 5-7 points. Heterogeneity test showed that there was no heterogeneity between the literatures ( I2=20.3%, P=0.156), so fixed effect model was selected to calculate the combined OR value. The combined OR value of overtime work on neck musculoskeletal disorders was 1.51 (95% CI: 1.42-1.60, P<0.001). Subgroup analysis showed that the combined OR of occupational population <35 years old group was higher than that in the ≥35 years old group ( P<0.05). But there were no significant differences in the combined OR values in the subgroups classified by average years of service, male proportion, type of OR values, sample size and industry classification ( P>0.05) . Conclusion:Overtime work is a risk factor for neck musculoskeletal disorders in Chinese occupational population. Working hours should be rationally arranged to reduce the prevalence of neck musculoskeletal disorders.

Aim To explore the improvement effect of Bazi Bushen capsule on thymic degeneration in SAMP6 mice and the possible mechanism.Methods Twenty 12 week old male SAMP6 mice were randomly divided into the model group(SAMP6)and the Bazi Busheng capsule treatment group(SAMP6+BZBS).Ten SAMR1 mice were assigned to a homologous control group(SAMR1).The SAMP6+BZBS group was oral-ly administered Bazi Bushen capsule suspension(2.8 g·kg-1)daily,while the other two groups were orally administered an equal amount of distilled water.After nine weeks of administration,the morphology of the thymus in each group was observed and the thymus in-dex was calculated;HE staining was used to observe the structural changes of thymus tissue;SA-β-gal stai-ning was used to detect thymic aging;flow cytometry was used to detect the proportion of thymic CD3+T cells in each group;Western blot was used to detect the levels of p16,Bax,Bcl-2,and cleaved caspase-3 proteins in thymus;immunofluorescence was applied to detect the proportion of cortical thymic epithelial cells in each group;ELISA was employed to detect IL-7 lev-els in thymus.Results Compared with the SAMP6 group,the thymic index of the SAMP6+BZBS group significantly increased(P＜0.05);the disordered thy-mic structure was significantly improved;the positive proportion of SA-β-gal staining significantly decreased(P＜0.01);the proportion of CD3+T cells apparently increased(P＜0.05);the level of p16 protein signifi-cantly decreased(P＜0.05);the level of Bcl-2 pro-tein significantly increased(P＜0.05),while the lev-el of cleaved caspase-3 protein markedly decreased(P＜0.05);the proportion of cortical thymic epithelial cells evidently increased;the level of IL-7 significantly increased(P＜0.01).Conclusions Bazi Bushen capsule can delay thymic degeneration,inhibit cell ap-optosis in thymus and promote thymic cell development in SAMP6 mice,which may be related to increasing the proportion of cortical thymic epithelial cells and promoting IL-7 secretion.

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
Humans ; Nitric Oxide ; Uric Acid ; Hyperuricemia ; Biological Availability ; Cytokines

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.
Humans ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Asteraceae/chemistry* ; Lung Neoplasms/drug therapy*

We investigated the impact and predictive value of bladder function in patients with benign prostatic hyperplasia (BPH) on the efficacy of transurethral prostatectomy. Symptomatic, imaging, and urodynamic data of patients who underwent transurethral prostatectomy at West China Hospital of Sichuan University (Chengdu, China) from July 2019 to December 2021 were collected. Follow-up data included the quality of life (QoL), International Prostate Symptom Score (IPSS), and IPSS storage and voiding (IPSS-s and IPSS-v). Moreover, urinary creatinine (Cr), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and prostaglandin estradiol (PGE2) were measured in 30 patients with BPH and 30 healthy participants. Perioperative indicators were determined by subgroup analyses and receiver operating characteristic (ROC) curve analysis. Among the 313 patients with BPH included, patients with severe micturition problems had more improvements but higher micturition grades postoperatively than those with moderate symptoms. Similarly, good bladder sensation, compliance, and detrusor contractility (DC) were predictors of low postoperative IPSS and QoL. The urinary concentrations of BDNF/Cr, NGF/Cr, and PGE2/Cr in patients were significantly higher than those in healthy participants (all P < 0.001). After evaluation, only DC was significantly related to both urinary indicators and postoperative recovery of patients. Patients with good DC, as predicted by urinary indicators, had lower IPSS and IPSS-v than those with reduced DC at the 1st month postoperatively (both P < 0.05). In summary, patients with impaired bladder function had poor recovery. The combined levels of urinary BDNF/Cr, NGF/Cr, and PGE2/Cr in patients with BPH may be valid predictors of preoperative bladder function and postoperative recovery.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical bacterial isolates from bloodstream infections in China in 2021.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2021 to December 2021. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 11 013 bacterial strains were collected from 51 hospitals, of which 2 782 (25.3%) were Gram-positive bacteria and 8 231 (74.7%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.6%), Klebsiella pneumoniae (18.9%), Staphylococcus aureus (9.8%), coagulase-negative Staphylococci (6.3%), Pseudomonas aeruginosa (3.6%), Enterococcus faecium (3.6%), Acinetobacter baumannii (2.8%), Enterococcus faecalis (2.7%), Enterobacter cloacae (2.5%) and Klebsiella spp (2.1%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 25.3% and 76.8%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci was detected; more than 95.0% of Staphylococcus aureus were sensitive to ceftobiprole. No vancomycin-resistant Enterococci strains were detected. The rates of extended spectrum B-lactamase (ESBL)-producing isolated in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 49.6%, 25.5% and 39.0%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.2% and 15.8%, respectively; 7.9% of carbapenem-resistant Klebsiella pneumoniae was resistant to ceftazidime/avibactam combination. Ceftobiprole demonstrated excellent activity against non-ESBL-producing Escherichia coli and Klebsiella pneumoniae. Aztreonam/avibactam was highly active against carbapenem-resistant Escherichia coli and Klebsiella pneumoniae. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii (5.5% and 4.5%). The prevalence of carbapenem-resistance in Pseudomonas aeruginosa was 18.9%. Conclusions:The BRICS surveillance results in 2021 shows that the main pathogens of blood stream infection in China are gram-negative bacteria, in which Escherichia coli is the most common. The MRSA incidence shows a further decreasing trend in China and the overall prevalence of vancomycin-resistant Enterococci is low. The prevalence of Carbapenem-resistant Klebsiella pneumoniae is still on a high level, but the trend is downwards.

OBJECTIVE: To investigate the expression and clinical significance of soluble Fas (sFas) and sFasL in patients with secondary hemophagocytic lymphohistiocytosis (sHLH). METHODS: From September 2015 to December 2020, 86 sHLH patients who met the HLH2004 diagnostic criteria were collected. They were divided into 55 cases in the MAHLH group and 31 cases in the NonMAHLH group according to the etiology. Thirty healthy persons were chosen as the normal control group, and 20 patients with systemic lupus erythematosus (SLE) were chosen as the disease control group. The expression levels of sFas and sFasL in the serum of patients with each group were detected by ELISA, and the clinical data were collected for statistical analysis. The significance of sFas and sFasL in sHLH was analyzed by ROC curve. RESULTS: Serum levels of sFas and sFasL in patients with newly diagnosed sHLH were significantly higher than those in disease control group and normal control group (P<0.01). The levels of sFas and sFasL in MAHLH group were significantly higher than those in nonMAHLH (infection related HLH and autoimmune disease related HLH) group (P<0.01). The serum levels of sFas and sFasL in 17 newly treated patients with sHLH (17/86) after treatment were significantly lower than those before treatment (P<0.01). The serum sFas level in newly diagnosed sHLH patients was positively correlated with SF(r=0.35), sCD25(r=0.79) and sFasL(r=0.73). The serum sFasL level was positively correlated with SF(r=0.39), sCD25(r=0.64) and sFas(r=0.73). Compared with the NonMAHLH group, the area under the ROC curve was 0.707 (95% CI: 0.593-0.821) (P=0.0015). The optimal critical value for diagnosing MAHLH by sFas level was 12 743 pg/ml, and the sensitivity and specificity were 70.9% and 71% respectively. Compared with the NonMAHLH group, the area under the ROC curve was 0.765(95% CI: 0.659-0.87)(P<0.01). The median OS time of sFas high expression group (≥16798.5 pg/ml) and sFasL high expression group (≥4 785 pg/ml) was significantly shorter than that of the low expression group (P<0.001). CONCLUSION Serum levels of sFas and sFasL can be used for the early diagnosis and differential diagnosis of sHLH disease, and are the factor related to the poor prognosis of sHLH.
Humans ; Lymphohistiocytosis, Hemophagocytic ; Clinical Relevance ; ROC Curve ; Sensitivity and Specificity ; Lupus Erythematosus, Systemic