Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective:To investigate the efficacy and safety of immune checkpoint inhibitors (ICI), programmed death receptor 1 (PD-1) inhibitors and programmed death receptor-ligand 1 (PD-L1) inhibitors in the treatment of extensive-stage small cell lung cancer (ES-SCLC).Methods:The databases of CNKI, Wanfang, VIP, China Biology Medicine disc, PubMed, Embase, and Cochrane Clinical Controlled Trial Center Registry (CENTRAL) were retrieved, and the randomized controlled trial literature on the treatment of ES-SCLC with immune checkpoint inhibitors published from the establishment of the database until October 4, 2023 were reviewed. After screening literature and extracting data according to inclusion and exclusion criteria, the risk of bias in the study was evaluated using Review Manager 5.4 software. The disease remission, prognosis and adverse events (AE) of patients treated with ICI combined with chemotherapy (experimental group) and placebo± chemotherapy (control group) in the whole group and liver metastases and brain metastases subgroups were compared.Results:A total of 11 randomized controlled trials were included, with 2 243 cases in the experimental group and 2 059 cases in the control group. The included research data were complete and showed no selective bias. Compared with the control group, the objective response rate (ORR) of patients in the experimental group was higher [control group vs. experimental group, 64% (864/1 358) vs. 70% (1 088/1 532), RR = 1.08 (95% CI: 1.03-1.14), P = 0.003], and the difference was statistically significant; progression free survival (PFS) [experimental group vs. control group, the median PFS time, 5.14 months (95% CI: 4.88-5.40 months) vs. 4.76 months (95% CI: 4.70-4.82 months), HR = 0.72 (95% CI: 0.67-0.78), P < 0.001] and overall survival (OS) [experimental group vs. control group, the median OS time, 12.89 months (95% CI: 12.18-13.60 months) vs. 10.41 months (95% CI: 10.03-10.79 months), HR = 0.72 (95% CI: 0.67-0.78), P < 0.001] were all improved, and the differences were statistically significant. The OS of patients with baseline liver metastasis in the experimental group was better than that in the control group (experimental group vs. control group, HR = 0.82 (95% CI: 0.71-0.95), P = 0.009], and the difference was statistically significant, while the difference in OS of patients with baseline brain metastases was not statistically significant between the experimental group and the control group [experimental group vs. control group, HR = 0.84 (95% CI: 0.66-1.08), P = 0.170]. The incidence of AE [experimental group vs. control group, 31% (597/1 952) (95% CI: 24%-37%) vs. 14% (255/1 762) (95% CI: 9%-22%), RR = 2.25 (95% CI: 1.67-3.02), P < 0.001] and the incidence of drug discontinuation or dose change caused by AE [experimental group vs. control group, 21% (379/1 774) (95% CI: 12%-41%) vs. 19% (307/1 588) (95% CI: 6%-25%), RR = 1.20 (95% CI: 1.07-1.33), P = 0.001] in the experimental group were higher than those in the control group, and the differences were statistically significant. However, the incidence of severe (≥grade 3) AE in both the experimental group and the control group was 34% (620/1 814, 557/1 632) (both 95% CI: 32%-36%), and the difference was not statistically significant [experimental group vs. control group, RR = 1.00 (95% CI: 0.91-1.10), P = 0.960]. The incidence of hypothyroidism [experimental group vs. control group, 11% (118/1 083) (95% CI: 9%-13%) vs. 1% (11/886) (95% CI: 0-2%), RR = 8.56 (95% CI: 4.63-15.80), P < 0.001] and the incidence of hyperthyroidism [experimental group vs. control group, 7% (75/1 083) (95% CI: 5%-8%) vs. 2% (17/886) (95% CI: 1%-4%), RR = 3.27 (95% CI: 1.95-5.46), P < 0.001] in the experimental group were both higher than those in the control group, and the differences were statistically significant. Conclusions:ICI combined with chemotherapy can effectively improve the OS, PFS and disease remission of patients with ES-SCLC, as well as improve the survival of patients with liver metastases. However, there is no benefit in the survival of patients with brain metastases. The incidence of immune-mediated AE to ICI combined with chemotherapy has increased, but the overall safety is good.

OBJECTIVE: To investigate the association between the glucose-to-lymphocyte ratio (GLR) and prognosis of patients with sepsis-associated acute kidney injury (SA-AKI). METHODS: Based on the Medical Information Mart for Intensive Care-IV (MIMIC-IV), SA-AKI patients aged ≥ 18 years were selected. According to the tertiles of GLR, the patients were divided into GLR1 group (GLR ≤ 4.97×10^-9 mmol), GLR2 group (4.97×10^-9 mmol < GLR < 9.75×10^-9 mmol) and GLR3 group (GLR ≥ 9.75×10^-9 mmol). Patients with SA-AKI were divided into survival group and death group according to whether they survived 28 days after admission. The patient's gender, age, vital signs, laboratory test results, comorbidities, sequential organ failure assessment (SOFA), acute physiology score III (APS III) score and treatment measures were extracted from the database. Kaplan-Meier survival analysis was used to make the survival curves of patients with SA-AKI at 28 days, 90 days, 180 days and 1 year. Multivariate Logistic regression analysis model was used to explore the independent risk factors of 28-day mortality in patients with SA-AKI. Receiver operator characteristic curve (ROC curve) was used to analyze the predictive efficacy of GLR for the prognosis of patients with SA-AKI. RESULTS: A total of 1 524 patients with SA-AKI were included, with a median age of 68.28 (58.96, 77.24) years old, including 612 females (40.16%) and 912 males (59.84%). There were 507 patients in the GLR1 group, 509 patients in the GLR2 group and 508 patients in the GLR3 group. There were 1 181 patients in the 28-day survival group and 343 patients in the death group. Grouping according to GLR tertiles showed that with the increase of GLR, the 28-day, 90-day, 180-day and 1-year mortality of SA-AKI patients gradually increased (28-day mortality were 11.64%, 22.00%, 33.86%, respectively; 90-day mortality were 15.98%, 26.72%, 40.55%, respectively; 180-day mortality were 17.16%, 28.29% and 41.73%, and the 1-year mortality were 17.95%, 29.27% and 42.72%, respectively, all P < 0.01). According to 28-day survival status, the GLR of the death group was significantly higher than that of the survival group [×10^-9 mmol: 9.81 (5.75, 20.01) vs. 6.44 (3.64, 10.78), P < 0.01]. Multivariate Logistic regression analysis showed that GLR was an independent risk factor for 28-day mortality in patients with SA-AKI [when GLR was used as a continuous variable: odds ratio (OR) = 1.065, 95% confidence interval (95%CI) was 1.045-1.085, P < 0.001; when GLR was used as a categorical variable, compared with GLR1 group: GLR2 group OR = 1.782, 95%CI was 1.200-2.647, P = 0.004; GLR3 group OR = 2.727, 95%CI was 1.857-4.005, P < 0.001]. ROC curve analysis showed that the area under the ROC curve (AUC) of GLR for predicting 28-day mortality in patients with SA-AKI was 0.674, when the optimal cut-off value was 8.769×10^-9 mmol, the sensitivity was 57.1% and the specificity was 67.1%. The predictive performance was improved when GLR was combined with APS III score and SOFA score, and the AUC was 0.806, the sensitivity was 74.6% and the specificity was 71.4%. CONCLUSIONS GLR is an independent risk factor of 28-day mortality in patients with SA-AKI, and high GLR is associated with poor prognosis in patients with SA-AKI.
Male ; Female ; Humans ; Blood Glucose ; Glucose ; ROC Curve ; Prognosis ; Sepsis/diagnosis* ; Acute Kidney Injury ; Retrospective Studies ; Intensive Care Units

Humans ; Arthroplasty, Replacement, Knee/adverse effects* ; Arthroplasty, Replacement, Hip/adverse effects* ; Reoperation ; Prosthesis-Related Infections ; Retrospective Studies

Objective:To explore the clinical efficacy of ultrasound-indicated cervical cerclage in twin pregnancies.Methods:This retrospective cohort study included 96 asymptomatic twin pregnancies with cervix length (CL)≤2.5 cm at 16-27 +6 weeks indicated by transvaginal ultrasound from January 2013 to May 2022 in Fujian Maternity and Child Health Hospital. They received either cervical cerclage (cerclage group, n=45) or conservative treatment (conservative group, n=51). The subgroup analysis was further performed after stratifying the subjects into the CL≤1.0 cm subgroup, the CL>1.0-≤1.5 cm subgroup, and the CL>1.5 cm subgroup. Two independent samples t-test, Mann-Whitney U test, and Chi-square test were used to compare the differences in the pregnancy and perinatal outcomes between different groups. Multivariate logistic regression was used to analyze the impact of cervical cerclage on pregnancy outcomes of women with different CLs. Results:The average gestational age at delivery and the prolonged gestation were significantly greater in the cerclage group than those in the conservative group [35.9 (34.9-37.0) weeks vs 34.9 (29.1-36.1) weeks; 10.7 (9.6-13.1) weeks vs 8.7 (4.8-11.0) weeks, Z=－2.59 and -3.63, both P<0.05]. The incidences of preterm birth before 34 weeks and 28 weeks, chorioamnionitis, and preterm premature rupture of membrane were lower in the cerclage group than those in the conservative group [17.8% (8/45) vs 45.1% (23/51), χ2=8.16; 2.2% (1/45) vs 15.7% (8/51), Fisher' exact test; 8.9% (4/45) vs 25.5% (13/51), χ2=4.52; 15.6% (7/45) vs 33.3% (17/51), χ2=4.03; all P<0.05]. There were no statistically significant differences in the proportion of postpartum hemorrhage and live births between the two groups (both P>0.05). In the women with CL≤1.0 cm, the cerclage group had a greater gestational age at delivery [36.0 (34.8-37.3) weeks vs 34.9 (28.6-35.4) weeks, Z=－2.61, P=0.009], greater prolonged gestation [12.3 (9.7-13.9) weeks vs 7.3 (3.4-9.1) weeks, Z=－3.34, P=0.001], higher birthweight [2 430.0 (2 173.8-2 646.3) g vs 1 900.0 (1 372.5-2 435.0) g, Z=－3.06, P=0.002], lower incidence of adverse neonatal outcomes [16.7% (6/36) vs 36.7% (11/30), χ2=4.22, P=0.048] compared with the conservative group. Multivariate Logistic regression analysis showed that cerclage reduced the risks of preterm birth before 34 and 32 weeks [ aOR (95% CI)=0.083 (0.009-0.790) and 0.092 (0.009-0.939), both P<0.05]. However, cerclage did not reduce the risk of preterm birth in women with CL>1.5 cm or CL>1.0-≤1.5 cm (both P>0.05). Conclusion:Ultrasound- indicated cervical cerclage can reduce the risk of preterm birth before 34 and 32 weeks, prolong pregnancy, and improve perinatal outcomes in asymptomatic twin pregnancies with CL≤1.0 cm.

Objective:To investigate the implementation status of protective restraints for psychiatric patients.Methods:The self-developed psychiatric protective restraint questionnaire was used to investigate 2 101 patients who had experienced at least one protective restraint during hospitalization in psychiatric institutions in 15 provinces and cities from March to May 2019 to analyze the current status of protective restraint of psychiatric patients.Results:A total of 2 101 questionnaires were distributed and 1 897 valid questionnaires were returned. The duration of constraint of 1 897 patients was 3 (1, 8) h, with the shortest duration of 1 h and the longest duration of 72 h. There were statistically significant differences in duration of restraint for patients with different genders, hospitals, marital status, first diagnosis on admission and history of self-harm or commit suicide ( P<0.05) . Conclusions:There is an urgent need to establish a set of standardized restraint procedures in clinical practice to prevent unreasonable use of restraints.

Objective:The purpose of this study was to conduct a Meta-analysis to assess the influence of physical therapy and respiratory muscle training on rehabilitation of patients with stable chronic obstructive pulmonary disease. To provide a basis for better rehabilitation exercise for patients, families, communities and hospitals.Methods:According to the literature search strategy, the relative literatures of randomized controlled trials (RCTS) of physical therapy and respiratory muscle training on rehabilitation of patients with chronic obstructive pulmonary disease were searched in Cochrane Library、MEDLINE、Embase、CINAHL、CBM、Wan Fang、CNKI and VIP from January 1990 to October 2017. Languages are limited to Chinese and English.The literatures were screened according to the predefined inclusion and exclusion criteria by two people . Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 were used to assess the quality of articles. The data were analyzed by Revman5.3.Results:A total of 7 articles were finally included, among of these 5 of which were written in English , Others were written in Chinese .They included 7 studies of randomized controlled trial and 267 patients with chronic obstructive pulmonary disease .7 studies show that treadmill exercise and respiratory muscle exercise are the most common rehabilitation methods.7 articles result of Meta-analysis showed that there were statistical differences between physical therapy and respiratory muscle training and other therapies in 6MWD、mMRC and FEV 1%;More research is needed on the impact of other outcome measures. Conclusions:Physical therapy and respiratory muscle training is a reliable way of rehabilitation, it to the stabilization of COPD patients FEV 1 % of expected value, activity ability, the influence of the degree of difficulty in breathing has a positive role.It is not stable for the positive effect of FVC and FEV 1 .However, the effects of other outcome measures were not determined.

Objective:To investigate whether the squirrels in Yunnan Province carried Yersinia pestis phages and their epidemiological significance. Methods:From 2015 to 2018, plague host animals were investigated in five of Yunnan plague foci and non-plague foci. The spleen, liver and intestinal specimens of the squirrels captured in the investigation were taken and stored at low temperature for later use. Intestinal specimens with PBS solution, were filtered by 0.22 μm and added to LB liquid medium containing 100 μl suspension of plague vaccine strain (EV76) and then oscillated in a constant temperature gas bath at 28 ℃ and 220 r/min for 18 to 24 h. The double-layer plate method was used to isolate and observe the growth of plaque. The morphology and structure of Yersinia pestis phages were observed under electron microscope. Meanwhile, spleen, liver and intestinal specimens were taken for detection of Yersinia pestis specific marker gene caf1. Results:A total of 10 squirrels were captured (8 Callosciurus erythraeus and 2 Dremomys pernyi), and four Yersinia pestis phages were isolated (2 in Callosciurus erythraeus and 2 in Dremomys pernyi). Two were isolated from non-plague foci (Yongshan County), two from house rats plague foci (Mile County and Xinping County), and none was isolated from wild radents plague foci (Jianchuan County and Eryuan County). By naked eye observation, two bacteriophages from the plague foci produced transparent plaques and grew well, while two bacteriophages from non-plague foci produced translucent plaques and with poor growth. By electron microscopy, these Yersinia pestis phages were of typical Myoviridae family, their head diameter was about 40 nm, muscle tail was about 120 nm, and tail filament cluster was slightly visible at the end of muscle tail. And all the 10 samples of squirrels were negative of plague-specific caf1 gene. Conclusions:The proportion of plague phages carried by Yunnan squirrels is relatively high. Although the detection of caf1 is negative. Squirrels may be a carrier of plague transmission due to the existence of Yersinia pestis phages.

Objective To investigate the incidence rate and risk factors for spontaneous hemorrhagic transformation(HT) in acute cerebral infarction(ACI) patients.Methods We retrospectively reviewed the clinical records of 216 ACI patients undergoing drug conservative treatment in the First People's Hospital of Changde City from January 2018 to January 2019.According to the occurrence of the spontaneous HT in each person within 14 days after onset,all patients were divided into two groups:the HT group and none-HT group,the clinical data between each group were be compared,univariate and multivariate logistic regression were used to analyze the relevant risk factors,the association between the risk factor and the spontaneous HT were further assessed by linear regression models and smooth curve fitting in addition to threshold effect analysis.Results Among 216 patients with ACI,27 cases(12.5%) had spontaneous HT during hospitalization.Multivariate logistic regression analysis showed that the etiological types in the trial of Org10172 in acute stroke treatment(TOAST)of cardiac embolism(CE)(OR=11.05,95%CI 1.97~61.98;P=0.0063),high National Institutes of Health Stroke Scale (NIHSS) score on the first day of admission (OR=1.6,95%CI 1.3~2.0;P<0.001),and excessive peripheral leukocyte counts excluding inflammatory response at admission (OR=1.41,95%CI 1.01~1.95;P=0.0408) were independent risk factors for the spontaneous HT after ACI.Smooth curve fitting analysis showed that the peripheral white blood cell count and the occurrence of the spontaneous HT were positively correlated.Conclusion TOAST classification of CE,high NIHSS score on the first day of admission and excessive peripheral leukocyte counts excluding inflammatory response at admission were independent risk factors of spontaneous HT after ACI.The excessive peripheral leukocyte counts after acute cerebral infarction,independently of the occurrence of infections,could be a potential predictor of the spontaneous HT after ACI.