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 application value of the global myocardial work parameters in the non-invasive pressure-strain loop (PSL) technology for early assessment of left ventricular systolic function in patients with chronic kidney disease (CKD). Methods A retrospective analysis was performed on 74 patients with normal left ventricular ejection fraction (LVEF) who were hospitalized in the Nephrology Department of Zhongshan Hospital (Xiamen Branch), Fudan University, from August 2021 to December 2021. Based on CKD stages, patients were divided into early group (CKD stages 1-3) and advanced group (CKD stages 4-5). Additionally, 30 healthy volunteers matched for age and gender were selected as the control group. General clinical data, routine left ventricular ultrasound indicators, myocardial strain, and global myocardial work parameters were collected and compared among the three groups. Correlation analysis and multiple linear regression were used to assess the influencing factors of myocardial work. Results There were no statistically significant differences in global work index (GWI) and global constructive work (GCW) among the three groups. Compared to the control group, both CKD groups showed significantly reduced global work efficiency (GWE), along with significantly increased global waste work (GWW, P＜0.05). The absolute value of global longitudinal strain (GLS) in the advanced CKD group (n＝42) was significantly lower than that in the early CKD group (n＝32; [﹣17.09±0.82]% vs [﹣18.33±0.90]%, P＜0.05), and GWE was also significantly lower (93.00%[90.00%, 95.00%] vs 96.00%[92.25%, 96.75%], P＜0.05), while GWW was significantly higher than that in the early CKD group (150.00 mmHg%[105.25 mmHg%, 215.00 mmHg%] vs 88.00 mmHg%[64.25 mmHg%, 144.50 mmHg%], P＜0.05). Correlation analysis showed that GWE was negatively correlated with the absolute value of GLS and peak strain dispersion (PSD; r＝﹣0.396, ﹣0.558, P＜0.05), GWW was positively correlated with absolute value of GLS, and PSD (r＝0.341, 0.610, P＜0.01). Multiple linear regression results indicated that PSD was an independent influencing factor for GWE (β＝﹣0.558, P＜0.001) and GWW (β＝0.538, P＜0.001). Conclusions The myocardial work parameters GWE and GWW in non-invasive left ventricular PSL technology can identify subclinical left ventricular systolic dysfunction in patients with CKD early and quantitatively.

Objective To explore the coronary flow reserve(CFR)in patients with coronary slow flow(CSF)and the diagnostic value of non-invasive myocardial work indices derived from echocardiography for CSF.Methods A retrospective study was conducted on 65 patients who underwent coronary angiography at the Zhongshan Hospital(Xiamen Branch),Fudan University due to angina pectoris,coronary artery risk factors,or electrocardiographic abnormalities from August 2020 to November 2023.Patients were divided into two groups based on the corrected TIMI frame count(cTFC):the CSF group(n=35)and the normal coronary blood flow velocity group(control group,n=30).Both groups underwent an adenosine triphosphate(ATP)drug load test to measure their coronary flow reserve(CFR).Conventional indices and myocardial work indices via echocardiography and two-dimensional speckle-tracking imaging(2D-STI)were acquired:left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF),E/e'ratio,global longitudinal strain(GLS),global constructive work(GCW),global wasted work(GWW),global work index(GWI),and global work efficiency(GWE).Receiver operating characteristic(ROC)curves were used to evaluate the diagnostic value of myocardial work indices for CSF.Results There was no significant difference in CFR values between the two groups,but the proportion of CSF group with CFR less than 2 was higher than that of the control group(P=0.023).Compared with the control group,the CSF group showed significantly lower levels of GLS,GWI,and GCW(P＜0.05).ROC curve analysis revealed that the GLS diagnostic threshold for CSF was-19.5%,with a sensitivity of 64.7%,specificity of 78.6%,and AUC of 0.793.Among the myocardial work indices,the AUC of GWI was the highest(0.825),with a sensitivity of 88.2% and specificity of 75.0% .Conclusions Some CSF patients retain coronary microcirculatory blood flow reserve function,but the proportion of patients with reduced CFR function is increasing.The left ventricular myocardial work indices can identify early myocardial work abnormalities and monitor myocardial ischemic damage in CSF patients.

Objectives:To retrieve,evaluate and summarize the contemporary evidence of strategies for weaning from extracorporeal membrane oxygenation(ECMO)of adult patients,and to provide evidence-based reference for clinical practice. Methods:The Web of Science,Embase,Cochrane Library,PubMed,Wanfang Database,CNKI,VIP website,SinoMed,BMJ Best Practice,National Institute for Health and Care Excellence,Joanna Briggs Institute Library,UpToDate and the website of Agency for Healthcare Research and Quality,Society of Critical Care Medicine,American Association of Critical-Care Nurses,European Society of Intensive Care Medicine and Extracorporeal Life Support Organization were researched to collect the literature related to randomized controlled trials,systematic reviews,guidelines,evidence summaries,expert consensuses and clinical decisions in this field.The time limit for the retrieval is from the inception of databases until July 2023. Results:A total of 13 related literature were retrieved,including 4 guidelines,4 expert consensuses,3 clinical decisions and 2 system reviews.Totally 42 evidences were formulated based on retrieved literature,including adequately accessing the ability of gas exchange before weaning from veno-venous ECMO(V-V ECMO)and withdrawing from veno-arterial ECMO(V-A ECMO)as soon as possible when patients's heart function has recovered,involving six aspects such as team composition,anticoagulation measures,assessment before weaning,weaning implementation,cannula and wound management and quality measures. Conclusions:It is suggested to build a professional ECMO team based on the actual hospital situation,to follow the contemporary evidence to standardize the weaning process of patients from ECMO to ensure the patients'safety and improve the outcomes.

ObjectiveTo analyze the epidemic characteristics of foodborne disease outbreaks in Mengla County， Yunnan Province， so as to provide basis for formulating corresponding prevention and control measures. MethodsThe data of foodborne disease outbreaks in Mengla County， Yunnan Province from 2017 to 2021 in the national "foodborne disease outbreak monitoring system" were collected. The time， population， region， place， pathogenic factors and inducing links of the events were statistically analyzed. ResultsFrom 2017 to 2021， a total of 68 incidents were reported， including 526 cases and 5 deaths. The total incidence rate was 23.40% and the case fatality rate was 0.95%. The peak period was from May to July， with the largest number of reported events in July. The reporting areas were mainly Mengla Town （35.29%）， Guanlei Town （11.76%） and Mengpeng Town （10.29%）. The main place of the incident was family （76.47%）. The main pathogenic factors were plant toxins （79.41%）， mainly through the ingestion of wild mushrooms （68.52%）， improper processing of green beans （12.96%） and aconitum （9.26%）. ConclusionAccording to the epidemiological characteristics of Mengla County， we should focus on the public education of health knowledge in key areas and places， especially on the identification of wild mushrooms， to prevent accidental eating. At the same time， we should strengthen the monitoring and risk assessment of foodborne diseases， find potential risks as soon as possible， issue early warning and forecast in time， and constantly improve the clinical treatment ability of poisoned patients.

Objective:To make a self-made fall/fall protection cover and explore its application effect.Methods:Five high-risk fall wards in Songjiang District Central Hospital were selected as the pilot wards. According to the length of stay, 80 elderly patients treated from June to December in 2020 were selected as the control group and 80 patients treated from January to June in 2021 were selected as the experimental group. The control group was treated with routine fall prevention / bed falling intervention measures, and the experimental group was treated with self-made fall prevention / bed falling protective cover on the basis of routine intervention measures. The incidence of falling/falling bed, physical restraint rate, comfort and satisfaction of hospitalized patients were compared between the two groups.Results:During the study period, there was no fall in the experimental group and one patient in the control group. The incidence of fall was 0.125 ‰ (1/8 000) ( t=-0.06, P>0.05). The rate of physical restraint was 8.75%(875/10 000) in the experimental group, and 26.25%(2 100/8 000) in the control group, the difference was statistically significant( t=-5.51, P<0.05). The scores of comfort and satisfaction were (93.43 ± 13.01), (134.50 ± 15.56) points in the experimental group and (81.68 ± 13.41), (111.88 ± 16.22) points in the control group, the differences were statistically significant ( t=8.03, 12.92, both P<0.05). Conclusions:The self-made fall / fall protection cover can reduce the utilization rate of physical constraints, improve the overall comfort of patients, improve patients′ satisfaction.It has clinical promotion value.

Objective:To evaluate the effect of combined use of Guben-Tiaoping Decoction on the success rate of stepwise treatment and life quality of asthma patients. Methods:A total of 76 patients with asthma in remission stage who were using ICS were divided into treatment group (38 cases) and control group(38 cases) according to random number table. Both groups were treated with ICS reduction based on the 2017 Gina Protocol. The treatment group was treated with Guben-Tiaoping Decoction for 12 weeks. The number of patients who were able to successfully complete the stepwise treatment after the end of the trial was calculated, the relevant indexes of Asthma Control Test (ACT), TCM Syndrome score, St. George’s respiratory questionnaire (SGRQ) and lung function were collected before and after treatment. Result:After 12 weeks’ treatment, the success rate of stepwise was 89.5% (34/38) in the treatment group and 78.9% (30/38) in the control group ( χ2=14.862, P=0.001). Meanwhile, the ACT score of the treatment group were better than those in the control group (Daytime symptoms t=-3.860, P=0.001, Dyspnea t=-2.007, P=0.40, Night waking t=-2.732, P=0.009, Reliever needed for symptoms t=-2.262, P=0.031, Control situation t=-6.994, P=0.001, Total Score t=-9.562, P=0.001). The score of TCM Syndrome in the treatment group was significantly lower than that of the control group ( P=0.001); PEF in treatment group [(6.92 ± 1.71) L vs. (5.84 ± 1.22) L; t=-2.880, P=0.005] was significantly better than that of the control group. Conclusion:Guben-Tiaoping Decoction is helpful to improve the success rate of ICS stepwise treatment and the life quality of patients.

Objective:To determine the expression of matrix metalloproteinase 13 (MMP13) in patients with psoriasis, and to evaluate the effect of tazarotene and narrow-band ultraviolet B (NB-UVB) on the expression of MMP13 in mice with psoriasis-like dermatitis.Methods:Lesional skin tissues and normal skin tissues were collected from 18 patients with psoriasis vulgaris and 10 healthy controls respectively, who were enrolled from General Hospital of Tianjin Medical University between May 2019 and August 2019, and serum samples were collected from all the subjects. A total of 25 specific pathogen-free (SPF) male BALB/c mice were randomly divided into control group, imiquimod group, imiquimod+NB-UVB group, imiquimod+tazarotene group and imiquimod+tazarotene+NB-UVB group. The control group received topical vaseline cream on the back once every morning; imiquimod group and imiquimod+NB-UVB group received imiquimod cream on the back once every morning; imiquimod+tazarotene group and imiquimod+tazarotene+NB-UVB group received imiquimod cream on the back once every morning, and tazarotene cream on the back once at night; imiquimod+NB-UVB group and imiquimod+tazarotene+NB-UVB group received NB-UVB irradiation on the back every other day at noon, with the dose being 300 mJ/cm 2 in the first session and increasing by 50 mJ/cm 2 in every session. The modeling lasted 7 days. After successful modeling, blood samples were obtained from the eyeballs of the mice, and skin tissues were resected from the back of the mice after being sacrificed by cervical dislocation on day 8. Changes in the epidermal thickness and pathological manifestations were observed by hematoxylin and eosin (HE) staining, protein expression of MMP13 in skin tissues was determined by immunohistochemical study, and the serum level of MMP13 was detected by enzyme-linked immunosorbent assay. Comparisons between 2 groups were performed by using two-independent-sample t test, comparisons among several groups by using one-way analysis of variance, multiple comparisons by using least significant difference- t test, and comparisons of enumeration data by using chi-square test. Results:The skin lesions of the patients with psoriasis were strongly positive for MMP13, and the MMP13 expression levels in the epidermis and serum (84.11±17.16, 13.29±3.95 μg/L, respectively) were significantly higher in the patients with psoriasis than in the healthy controls (11.98±4.08, 7.46±1.58 μg/L, respectively, both P< 0.01) . Compared with the control group (1.26±0.04 μm, 25.40±2.34, 185.76±7.22 μg/L, respectively) , a significant increase was observed in the epidermis thickness (7.93±0.59 μm, P< 0.01) , as well as MMP13 levels in the epidermis and serum in the imiquimod group (147.14±5.53, 215.98±15.17 μg/L, respectively, both P< 0.01) . Compared with the imiquimod group, the imiquimod+tazarotene group, imiquimod+NB-UVB group, and imiquimod+tazarotene+NB-UVB group all showed significantly decreased epidermal thickness (3.56±0.37 μm, 3.83±0.39 μm, 2.14±0.34 μm, respectively, all P< 0.05) , MMP13 levels in the epidermis (120.42±3.23, 91.08±0.46, 71.12±7.11, respectively, all P< 0.05) and serum (197.39±3.92 μg/L, 196.13±11.76 μg/L, 183.21±14.99 μg/L, respectively, all P< 0.05) . Conclusions:MMP13 protein expression markedly increased in the skin lesions and sera of patients with psoriasis, and decreased in skin lesions and sera of mice with psoriasis-like dermatitis after the treatment with tazarotene and NB-UVB. MMP13 may be involved in the development of psoriasis, and tazarotene and NB-UVB may inhibit the development of psoriasis by reducing the expression of MMP13.

OBJECTIVE: To explore the genetic basis for a juvenile with maturity-onset diabetes of the young type 12(MODY12). METHODS: High-throughput sequencing was carried out to screen for the variants. Candidate variant was verified by Sanger sequencing. Pathogenity of the variant was predicted by searching the genetic databases and analysis by using bioinformatic software. RESULTS: Genetic testing indicated that the patient and his mother have both carried a heterozygous c.3976G>A variant (p.Glu1326Lys) in exon 32 of the ABCC8 gene. Prediction of the protein structure suggested the variant to be deleterious. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be uncertain significance. CONCLUSION Whether the c.3976G>A variant of the ABCC8 gene is the cause of the disease in this patient or not depends on the functional studies and more case data. Above finding has enriched the spectrum of ABCC8 gene variants.
Diabetes Mellitus, Type 2/genetics* ; Genetic Testing ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation

Objective:To explore the effects of different temperature settings on patients with acute hypoxic respiratory failure (AHRF) during application of high-flow nasal cannula (HFNC) .Methods:A total of 90 patients with AHRF who were admitted to the Department of Critical Care Medicine of Zhejiang Hospital and underwent HFNC from January 2019 to May 2020 were selected as research objects by the convenient sampling method. The patients were randomly divided into 3 groups by the random number table method, namely, group A (T=31 ℃) , group B (T=34 ℃) and group C (T=37 ℃) , with 30 cases in each group. The VAS and Borg Scale were used to compare the comfort and dyspnea of patients of 3 groups, and to compare the satisfaction of patients of 3 groups.Results:After applying HFNC for 2 h and 12 h, the scores of VAS and Borg Scale in group B were lower than those in groups A and C, and the differences were statistically significant ( P<0.01) . The VAS scores of the three groups after applying HFNC for 12 h were higher than that after applying HFNC for 2 h, and the scores of Borg Scale were lower than that after applying HFNC for 2 h, and the differences were statistically significant ( P<0.05) . The satisfaction of patients in group B was higher than that in group A and C, and the differences were statistically significant ( P< 0.01) . Conclusions:Different temperature settings of HFNC will affect the comfort, dyspnea and satisfaction of AHRF patients. Among them, 34 ℃ is a more suitable temperature. As time progresses, nursing staff should intervene in time to maintain the comfort of patients, reduce the degree of dyspnea and provide guidance for the clinical application of HFNC.