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 monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

This article introduced the research design and main results of the article " Effect of Moderate and Vigorous Aerobic Exercise on Incident Diabetes in Adults with Obesity: A 10-Year Follow-up of a Randomized Clinical Trial" recently published in JAMA Internal Medicine, and addressed the scientific significance of the study. The importance of obesity management has been well discussed recently. This study investigated obesity management strategies for obese individuals and their long-term metabolic benefits.

Objective:To compare the effect of two vs one stitch on outcomes in women with cervical incompetence who undergo emergency transvaginal cervical cerclage.Methods:A retrospective study was conducted on 38 cases of cervical incompetence patients who underwent emergency cervical cerclage at Fujian Maternity and Child Health Hospital from January 2018 to December 2022. These subjects were divided into two groups: one stitch group (loop continuous suture and knot at cervical-vaginal junction level) and two stitches group (the first loop was closed with a single suture set, and the second loop was closed below the first loop near the cervical outlet) with 19 cases in each group. Two independent samples t or t'-test, rank-sum test, Chi-square test and Fisher's exact test were used to compare the differences in perinatal outcomes between the two groups. Kaplan-Meier survival analysis was performed to evaluate the efficacy of the prolongation of gestational age after emergency transvaginal cervical cerclage. Results:There was no statistically significant difference in the gestational age at cervical cerclage between the two stitches and the one stitch group [24.9 weeks (23.9-25.9 weeks) vs 23.6 weeks (22.6-24.9 weeks), Z=－1.61, P=0.108]. The average gestational age at delivery [(33.1±4.8) vs (28.6±4.3) weeks, t=－3.10] and the prolongation of gestational age after cerclage[(8.5±4.6) vs (5.0±2.6) weeks, t=－2.90] were significantly greater in the two stitches group compared to those in the one stitch group, while the rates of preterm birth before 32 weeks (6/19 vs 16/19, χ2=10.80), 34 weeks (8/19 vs 17/19, χ2=9.47), and 37 weeks (14/19 vs 19/19, Fisher's exact test) were lower (all P<0.05). The Kaplan-Meier survival analysis demonstrated that the two stitches group had significantly higher efficacy in prolonging gestational age compared to the one stitch group [log-rank test χ2 (1)=13.10, P<0.05]. Although there was no statistically significant difference in the neonatal mortality between the two groups (2/19 vs 4/19, Fisher's exact test, P=0.660), survival neonates in the two stitches group had significantly higher birth weight [2 370.0 g (1 775.0-2 710.0 g) vs 1 300.0 g (1 210.0-1 660.0 g), Z=－3.14], lower admission rate to the neonatal intensive care unit (9/17 vs 15/15, Fisher's exact test), lower incidence of stage Ⅲ necrotizing enterocolitis (0/17 vs 5/15, Fisher's exact test), moderate-severe respiratory distress syndrome (5/17 vs 10/15, χ2=4.44), and grade Ⅲ-Ⅳ intraventricular hemorrhage (0/17 vs 7/15, Fisher's exact test) compared to those in the one stitch group (all P<0.05). Conclusion:Compared with emergency cervical cerclage with one stitch, the procedure with two stitches can prolong the gestational age and improve the neonatal prognosis more effectively.

Objective:To investigate the incidence and risk factors associated with preterm premature rupture of membranes (PPROM) following transvaginal cervical cerclage.Methods:This retrospective cohort study involved 170 singleton pregnancies with cervical incompetence who underwent vaginal cervical cerclage at Fujian Maternity and Child Health Hospital from January 2021 to January 2022. Based on the onset of PPROM after cervical cerclage, the patients were divided into the PPROM group ( n=28) and the non-PPROM group ( n=142). Independent samples t-test, rank-sum test, Chi-square test, or Fisher's exact test were used to compare the general condition, pre- and postoperative data, pregnancy complications or comorbidities between the two groups, with a significance level at α=0.1. Multiple logistic regression analysis was conducted to identify the risk factors for PPROM after cerclage surgery. Results:The overall incidence of PPROM after vaginal cervical cerclage was 16.5% (28/170). Logistic regression analysis showed that a history of cervical conization ( OR=11.966, 95% CI:1.695-84.468), the use of Mersilene RS22 tape as the suture material ( OR=3.318, 95% CI:1.064-9.252), cervical length<2.5 cm after cerclage ( OR=3.486, 95% CI:1.116-10.888), and Mycoplasma genitalium- positive results for cervical secretion culture after surgery ( OR=4.856, 95% CI:1.487-15.861) were the independent risk factors for PPROM after cervical cerclage (all P<0.05). Conclusions:The incidence of PPROM following vaginal cervical cerclage is relatively high and can have unfavorable effects on pregnancy outcomes. Factors such as a history of cervical conization, the use of Mersilene RS22 tape for cerclage, cervical length<2.5 cm after cerclage, and Mycoplasma genitalium-positive results for cervical secretion culture after surgery may increase the risk of PPROM after cerclage.

Objective:To monitor nucleic acid contamination and evaluate the biosecurity risk in a temporary 2019-nCoV nucleic acid testing laboratory situated within designated infectious disease care facilities.Methods:Quantitative real-time PCR technology was used to detect nucleic acid contamination in samples collected from high-risk experimental activity areas and the surface of the laboratory staff′s personal protective equipment. Sampling was conducted every Monday from March 14 to May 16, 2022, both during and after disinfection procedures.Results:A total of 760 samples were collected from 40 sampling sites. A total of 27 out of 100 samples (27%) collected from 8 sampling sites in the sample processing area were positive. Among them, the contaminated area of biological safety cabinet, the outer surface of the sample transport box, and the sample rack were found to have the highest positive detection rates, with rates of 5/10, 4/10, and 6/10, respectively. Ten out of 140 samples (7.1%) obtained from 7 sampling sites in the nucleic acid detection area showed positive results. The inner wall of sample transfer window and the door handle of the nucleic acid detection area had the highest positive detection rates, both at 4/20. The Ct values for the target genes from the positive samples in the sample processing area were significantly higher than those from the nucleic acid detection area. The detection rate for nucleic acid contamination on the surface of the personal protective equipment of the laboratory staff was 20% (16/80), and the positive detection rate of the outer gloves from operator during the experiment reached 9/10. After disinfection, the nucleic acid residues on the surfaces of the various areas of the 2019-nCoV nucleic acid laboratory and the surfaces of the personal protective equipment of the laboratory staff were observed to be effectively removed.Conclusions:During experimental operation, the positive detection rate and nucleic acid contamination intensity of 2019-nCoV are higher in the sample processing area compared to those in the nucleic acid detection area. The laboratory staff are exposed to high biosecurity risk during the experiment. Implementing a scientific disinfection process can significantly reduce the risk of 2019-nCoV residues from the laboratory environment and the surface of the personal protective equipment of the laboratory staff, ensuring the accuracy of inspections and the safety of the laboratory staff.

Objective:To investigate the knowledge, attitudes, and practices (KAP) of pulse oximetry among pediatric healthcare providers in China and analyze the factor influencing the KAP.Methods:A self-developed questionnaire was used for an online research on the KAP of 11 849 pediatric healthcare providers from 31 provinces, autonomous regions, and municipalities of China from March 11 to 14, 2022.The factors influencing the KAP of pulse oximetry among pediatric healthcare providers were examined by Logistic regression. Results:The scores of KAP, of pulse oximetry were 5.57±0.96, 11.24±1.25 and 11.19±4.54, respectively.The corresponding scoring rates were 69.61%, 74.95%, and 55.99%, respectively. Logistic regression results showed that the gender and working years of pediatric healthcare providers, the region they were located, and whether their medical institution was equipped with pulse oximeters were the main factors affecting the knowledge score (all P<0.05). Main factors influencing the attitude score of pediatric healthcare providers included their knowledge score, gender, educational background, working years, region, medical institution level, and whether the medical institution was equipped with pulse oximeters (all P<0.05). For the practice score, the main influencing factors were the knowledge score, gender, age, and whether the medi-cal institution was equipped with pulse oximeters (all P<0.05). Conclusions:Chinese pediatric healthcare providers need to further improve their knowledge about and attitudes towards pulse oximetry.Pulse oximeters are evidently under-used.It is urgent to formulate policies or guidelines, strengthen education and training, improve knowledge and attitudes, equip more institutions with pulse oximeters, and popularize their application in medical institutions.

Objective:To investigate the etiology of necrotizing pneumonia (NP) in children and the clinical characteristics of NP caused by different pathogens in China.Methods:A retrospective, case-control study was performed in children with NP who were admitted to 13 hospitals in China from January 2008 to December 2019. The demographic and clinical information, laboratory data, etiological and radiological findings were analyzed. The data were divided into three groups based on the following years: 2008-2011, 2012-2015 and 2016-2019, and the distribution characteristics of the pathogens in different period were compared. Meanwhile, the pathogens of pediatric NP in the southern and northern China were compared. And the clinical characteristics of the Mycoplasma pneumoniae (MP) NP and the bacterial NP were also compared. T-test or Mann-Whitney nonparametric test was used for comparison of numerical variables, and χ 2 test was used for categorical variables. Results:A total of 494 children with NP were enrolled, the median ages were 4.7 (0.1-15.3) years, including 272 boys and 222 girls. Among these patients, pathogens were identified in 347 cases and the pathogen was unclear in the remaining 147 cases. The main pathogens were MP (238 cases), Streptococcus pneumoniae (SP) (61 cases), Staphylococcus aureus (SA) (51 cases), Pseudomonas aeruginosa (13 cases), Haemophilus influenzae (10 cases), adenovirus (10 cases), and influenza virus A (7 cases), respectively. MP was the most common pathogen in all three periods and the proportion increased yearly. The proportion of MP in 2016-2019 was significantly higher than that in 2012-2015 (52.1% (197/378) vs. 36.8% (32/87), χ 2= 6.654, P=0.010), while there was no significant difference in the proportion of MP in 2012-2015 and that in 2008-2011 (36.8% (32/87) vs. 31.0% (9/29), χ2=0.314, P=0.575).Regarding the regional distribution, 342 cases were in the southern China and 152 in the northern China. Also, MP was the most common pathogen in both regions, but the proportion of MP was higher and the proportion of SP was lower in the north than those in the south (60.5% (92/152) vs. 42.7% (146/342), χ 2=13.409, P<0.010; 7.9% (12/152) vs. 14.3% (49/342), χ 2= 4.023, P=0.045). Comparing the clinical characteristics of different pathogens, we found that fever and cough were the common symptoms in both single MP and single bacterial groups, but chest pain was more common (17.0% (34/200) vs. 6.1% (6/98), χ 2=6.697, P=0.010) while shortness of breath and wheezing were less common in MP group (16.0% (32/200) vs. 60.2% (59/98), χ 2=60.688, P<0.01; 4.5% (9/200) vs. 21.4% (21/98), χ 2=20.819, P<0.01, respectively). The white blood cell count, C-reactive protein and procalcitonin in the bacterial group were significantly higher than those in the MP group (14.7 (1.0-67.1)×10 9/L vs. 10.5 (2.5-32.2)×10 9/L, 122.5 (0.5-277.3) mg/L vs. 51.4 (0.5-200.0) g/L, 2.13 (0.05-100.00) μg/L vs. 0.24 (0.01-18.85) μg/L, Z=-3.719, -5.901 and -7.765, all P<0.01). Conclusions:The prevalence of pediatric NP in China shows an increasing trend during the past years. MP, SP and SA are the main pathogens of NP, and the most common clinical symptoms are fever and cough. The WBC count, C-reactive protein and procalcitonin in bacterial NP are significantly higher than those caused by MP.

Objective:To study the expression levels of peripheral blood helper T cell 17 (Th17) cells and interleukin (IL)-17A in newly diagnosed acute myeloid leukemia (AML) patients and its significance.Methods:A total of 32 newly diagnosed AML patients in Binzhou People's Hospital of Shandong Province from September 2017 to January 2019 were treated as the study group, and 28 iron deficiency anemia patients were used as the control group. Flow cytometry (FCM) was used to detect the proportion of Th17 (CD3 + CD4 + IL-17 +) in CD4 + T cells (Th17 ratio) and the concentration of IL-17A in peripheral bloods for both groups. And then the correlation and significance of Th17 ratio and the concentration of IL-17A with proportion of bone marrow blast cells, chromosome karyotype in AML patients was also analyzed. Results:The proportion of Th17 cells in peripheral bloods of newly diagnosed AML patients was higher than that in the control group [(2.74±0.85)% vs. (1.02±0.12)%, t = 10.397, P < 0.01]; the concentration of IL-17A in the serums of AML patients was higher than that of the control group [(3.16±1.54) pg/ml vs. (2.22±0.21) pg/ml, t = 3.206, P = 0.002]. Th17 ratio and the concentration of IL-17A in patients with bone marrow blast cells percentage≥0.50 were higher than those in patients with bone marrow blast cells percentage <0.50. Th17 ratio and the concentration of IL-17A in the peripheral bloods for AML patients in the high-risk group was higher than that in the low-risk group, and the difference was statistically significant (both P < 0.05). There was no statistical difference between low-risk group and intermediate-group (both P > 0.05). Conclusions:The levels of Th17 cells and IL-17A in the peripheral bloods are associated with the proportion of bone marrow blast cells and cytogenetics/molecular genetics risk degree in AML patients. The regular detection of Th17 and IL-17A may help to monitor immune status, evaluate prognosis and provide the basis for immunotherapy of AML patients.

OBJECTIVE: To investigate the effect of working time on the prognosis of patients with ischemic stroke undergoing intravenous thrombolysis. METHODS: Clinical data of 3050 patients with ischemic stroke received intravenous thrombolysis from 71 hospitals in Zhejiang Province during June 2017 and September 2018 were retrospective analyzed. Whole day of Saturday and Sunday were defined as weekend; whole day of Monday to Friday were defined as weekdays; Monday to Friday 8:00-17:00 were defined as daytime of weekdays; Monday to Friday 17:01-07:59 on next day were defined as nights of weekdays; unconventional working time were defined as weekend and nights of weekdays. Good outcome was defined as mRS 0-2 at 3 months. Univariate analyses of baseline and prognostic variables in group of weekend and weekdays, nights of weekdays and daytime of weekdays, unconventional working time and daytime of weekdays were performed. Binary logistic regression was used to investigate whether weekend, nights of weekdays and unconventional working time were independent predicting factors of outcome after intravenous thrombolysis, respectively. RESULTS: There was no difference in 7-day mortality, 3-month mortality and good outcome at 3-month between weekend group and weekdays group, nights of weekdays group and daytime of weekdays group, unconventional working time group and daytime of weekdays group (all >0.05). Binary logistic regression results showed that weekends, nights of weekdays and unconventional working time were not independent predicting factors for outcome after intravenous thrombolysis (all >0.05). CONCLUSIONS The working time has not affected the outcomes of patients with ischemic stroke undergoing intravenous thrombolysis in studied hospitals of Zhejiang province.
Brain Ischemia ; drug therapy ; Humans ; Prognosis ; Retrospective Studies ; Stroke ; drug therapy ; Thrombolytic Therapy ; Time Factors