Objective:To get specific monoclonal antibodies ( mAbs) against PD-L1 which can block PD-1/PD-L1 binding, and explore the feasibility of its application on the treatment of chronic HBV infection preliminarily by in vitro and in vivo model. Methods:E. coli expression and series chromatography purification system were employed to get human and mouse PD-1/PD-L1 that had binding activity in vitro. By immunizing BALB/c mouse with purified recombination proteins of PD-L1,mAb hybridoma cell lines against PD-L1 were obtained. The reactivity with human/mice PD-L1 of individual antibody and the interaction blocking activity of the mAbs to PD-1/PD-L1 in vitro were examined by indirect chemiluminescence immune assay. Results: 8 cell lines against PD-L1 were obtained and 2 Anti-PDL1 mAbs (Ab5 &Ab6) performed strong immune activity to human/mice PD-L1 and blocking activity to PD-1/PD-L1. In the PBMC stimulation experiment of chronic HBV patient,Ab5 and Ab6 could promote theγ-IFN levels. With HBV in-fecting mice model,intravenous injections of these mAbs induced dramatically decrease of HBV DNA copies about 20 times, HBsAg levels in serum reduced to 30% of the baseline level. Conclusion:We obtained 2 PD-L1 mAbs with the reactivity to human/mice PD-L1 and blocking activity to PD-1/PD-L1. The 2 mAbs can promote T cell function in PBMC stimulation culture of chronic HBV patient, have significant antiviral effect in HBV transgenic mice and can be candidates for immunotherapy applications.

Objective To explore the role of long noncoding RNA ( lncRNA) CTD-2012K14. 6 in the development of gestational diabetes mellitus (GDM) related macrosomia. Methods The quantitative real-time PCR ( qRT-PCR) was performed to measure the expression of CTD-2012K14.6 in placentas of women with or without GDM, and the quantity of CTD-2012K14. 6 expression and its association with fetal weights were analyzed; Bioinformatic analysis was performed to predict the downstream molecules. CTD-2012K14. 6 over-expressing lentiviral and siRNA was constructed in human trophoblastic cell line HTR-8/SVneo cells, qRT-PCR and Western blot (WB) were used to invest its effect in modulating the expression of downstream molecules. Results The expression of CTD-2012K14.6 in GDM placentas was significantly higher than that in normal controls (1.70 ± 0.63 vs 1.00 ± 0.56,t=3.68,P＜0.01), and positively correlated with fetal weight (r=0.8501, P＜0.01); on-line analysis showed that CTD-2012K14.6 was located at chr16:67,549,214-67,563,958, which was located in the intron of CCCTC-binding factor( CTCF); Up-regulating CTD-2012K14.6 could significantly reduce the expression of CTCF mRNA and protein, and increase the expression of insulin-like growth factor-Ⅱ( IGF-Ⅱ) mRNA and protein, while down-regulating CTD-2012K14.6 could significantly increase the expression of CTCF mRNA and protein, and reduce the expression of IGF-ⅡmRNA and protein. Conclusion The CTD-2012K14. 6 may play an important role in the pathogenesis of GDM related macrosomia by upregulating the expression of CTCF and IGF-Ⅱ.

Objective: To investigate the epidemiological features of notifiable infectious diseases in Zhejiang Province in 2021, so as to provide the evidence for formulating infectious disease control measures. Methods: The data pertaining to notifiable infectious diseases reported in Zhejiang Province in 2021 were retrieved from the Infectious Disease Surveillance System of China Information System for Disease Control and Prevention. The incidence and mortality of notifiable infectious diseases in Zhejiang Province in 2021 were descriptively analyzed. Results: Totally 29 types of notifiable infectious diseases with 396 623 cases and 391 deaths were reported in Zhejiang Province in 2021, with a reported incidence of 614.28/105 and a reported mortality of 0.605 6/105, respectively. There were 93 204 cases with class B notifiable infectious diseases, with a reported incidence rate of 144.35/105 and 303 419 cases with class C notifiable infectious diseases, with a reported incidence rate of 469.92/105; while no cases with class A notifiable infectious diseases were reported. Syphilis (39.45/105), tuberculosis (37.12/105), viral hepatitis (31.90/105) and gonorrhea (26.34/105) were the four most common class B notifiable infectious diseases, and AIDS (0.477 0/105) and pulmonary tuberculosis (0.116 2/105) were the two most deadly class B notifiable infectious diseases, while hand, foot and mouth disease (192.00/105), other infectious diarrhea (184.24/105) and influenza (86.45/105) were the three most common class C notifiable infectious diseases. According to the transmission route, intestinal and respiratory infectious diseases were the two most common infectious diseases, with reported incidence rates of 384.10/105 and 133.73/105, respectively; and according to the reported region, the highest incidence of class B notifiable infectious diseases was reported in Zhoushan and Ningbo cities, and the highest incidence of class C notifiable infectious diseases was reported in Ningbo City. Totally 1 101 COVID-19 cases were reported in Zhejiang Province in 2021, including 712 confirmed cases and 389 asymptomatic cases, and no deaths occurred. Conclusions The reported incidence of notifiable infectious diseases declined in Zhejiang Province in 2021 as compared to that prior to COVID-19 epidemics, with remarkable reductions in the incidence of respiratory and intestinal infectious diseases. The management of pulmonary tuberculosis, viral hepatitis and AIDS requires to be reinforced during the containment of COVID-19, to prevent the seasonable epidemic of influenza, hand, foot and mouth disease and other infectious diarrhea in Zhejiang Province.

Objective: To establish a prediction model of herpangina epidemic trend based on Baidu index and hand, foot and mouth disease, so as to provide insights into analyses of communicable disease epidemics with limited or missing surveillance data. Methods: The incidence of hand, foot and mouth disease in Zhejiang Province during the period from the first week of 2015 through the 39th week of 2021 was retrieved from the China Information System for Disease Control and Prevention, and the Baidu index of hand, foot and mouth disease and herpangina was collected via the Baidu search engine during the same period. The correlation between the Baidu index and time series of hand, foot and mouth disease was examined using wavelet analysis. In addition, a random forest training model was created based on the Baidu index and incidence of hand, foot and mouth disease, and the fitting effectiveness was evaluated using the mean percentage error, while the Baidu index of herpangina was included in the model to predict the epidemic trend of herpangina during the study period. Results: The Baidu index of herpangina and hand, foot and mouth disease, and the Baidu index and incidence of hand, foot and mouth disease all appeared two peaks at the 26th and 52th week. The phase difference was less than 0.1 week between the Baidu index and time series of hand, foot and mouth disease, and the mean percentage error of the training model was 13.07%, with high concordance between the predicted number and actual report number of cases with hand, foot and mouth disease. The numbers of herpangina cases were predicted to be 28 822, 27 341, 28 422, 51 782, 52 457 and 5 691 from 2015 to 2020, and there were totally 48 702 herpangina cases reported until the 39th week of 2021. Like hand, foot and mouth disease, the incidence of herpangina peaked between May and July. Conclusion The random forest training model based on the Baidu index and incidence of hand, foot and mouth disease is feasible to predict the epidemic trend of herpangina.

Objective: To analyze the epidemiological characteristics of overseas imported cases with coronavirus disease 2019 (COVID-19) in Zhejiang Province, so as to provide insights into containment of overseas imported COVID-19. Methods: The pertaining to overseas imported COVID-19 cases in Zhejiang Province during the period between January 1, 2020 and May 31, 2022 were captured from the Chinese Disease Prevention and Control Information System. The temporal, spatial and population distributions, the duration from entry to the first time of positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test, and COVID-19 vaccination of overseas imported COVID-19 cases were analyzed using a descriptive epidemiological method. Results: A total of 1 535 overseas imported COVID-19 cases were reported in Zhejiang Province during the period between January 1, 2020 and May 31, 2022, including 596 confirmed cases and 939 asymptomatic infections, and all reported cases were imported from 102 countries and territories. Overseas imported COVID-19 cases were reported in each month during the period between March 2020 and May 2022 except May 2020, and the mean monthly number of reported overseas imported COVID-19 cases was 125 during the period between December 2021 and May 2022. Overseas imported COVID-19 cases were reported across 11 cities of Zhejiang Province, with the largest numbers reported in Hangzhou (978 cases) and Jiaxing cities (177 cases), and imported cases were reported in 76.09% of counties (districts) in Zhejiang Province. The overseas imported COVID-19 cases were predominantly identified among individuals with Chinese nationality (88.79%), at ages of 20 to 39 years (59.09%), and students (21.82%), workers (17.20%) and business servants (17.00%) were predominant occupations among the overseas imported COVID-19 cases. The median duration from entry to the first time of positive SARS-CoV-2 nucleic acid test was 3.98 (7.06) d during the period between January 1, 2020 and May 31, 2022, and was 3.23 (4.97) d during the period between December 1, 2021 and May 31, 2022, which was significantly shorter than that during the period between January 1, 2020 and November 30, 2021 (P<0.001). The proportion of normal and more severe types of COVID-19 was 15.69% among cases without COVID-19 vaccination, which was significantly higher than that (7.77%) among those receiving booster vaccination (χ2=5.345, P=0.021), but was not significantly different from that (12.65%) among those receiving full-dose vaccination (χ2=0.971, P=0.324). Conclusions Students with Chinese nationality, workers and business servants were predominant among overseas imported COVID-19 cases in Zhejiang Province until May 31, 2022. The duration from entry after December 1, 2021 to identification of overseas imported COVID-19 cases shortened, and booster COVID-19 vaccination facilitated the alleviation of severity of clinical symptoms. There is a long-term risk of overseas importation of COVID-19 in Zhejiang Province, and the containment of imported COVID-19 requires to be sustainably implemented among entry personnel.

Objective: To investigate the characteristics of public health emergencies and related information in schools of Zhejiang Province from 2012 to 2021, so as to provide insights into the management of public health risks in schools. Methods: The public health emergencies and related information in schools of Zhejiang Province during the period from 2012 to 2021 were retrieved from the Public Health Emergency Management Information System of Chinese Disease Prevention and Control Information System. The type, temporal distribution and regional distribution of the events and the type of schools were analyzed, and the trends in disease attack rates were evaluated. Results: A total of 1 284 public health emergencies and related information were reported in schools of Zhejiang Province from 2012 to 2021, accounting for 72.34% of all public health emergencies and related information, and a total of 40 562 cases were reported, accounting for 87.72% of all cases; no death was recorded. There were 1 276 infectious disease events reported, accounting for 99.38%, and norovirus enteritis (649 cases), varicella (281 cases), influenza (181 cases), hand, foot and mouth disease (94 cases) and mumps (22 cases) were predominant infectious diseases, accounting for 95.56% of all public health emergencies and related information in schools. The number of public health emergencies and related information in schools peaked during the period between March and June (361 events, 28.12% of all events) and the period between November and December each year from 2012 to 2021 (629 events, 48.99% of all events), and the events occurred across 11 cities of Zhejiang Province, with the largest number of events reported in Hangzhou City (507 events). In addition, there were 627, 328 and 242 events reported in primary schools, kindergartens, and middle schools, accounting for 93.22%, and the events predominantly occurred in city schools. Nevertheless, there were no significant changes in the trends for attack rates of norovirus enteritis, varicella, influenza and hand, foot and mouth disease and mumps in schools of Zhejiang Province from 2012 to 2021. Conclusions Norovirus enteritis, varicella, influenza, hand, foot and mouth disease and mumps were the predominant types of public health emergencies and related information in schools of Zhejiang Province from 2012 to 2021, and the largest number of events were reported in primary schools.

Objective: To investigate epidemiological characteristics of notifiable infectious diseases in Zhejiang Province in 2023, so as to provide the evidence for strengthening prevention and control of infectious diseases. Methods: Data pertaining to notifiable infectious diseases reported in Zhejiang Province in 2023 were retrieved from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. The incidence and mortality were analyzed according to the classification of notifiable infectious diseases and transmission routes, and epidemiological characteristics of infectious diseases were descriptively analyzed. Results: Thirty types of notifiable infectious diseases with 2 955 699 cases and 427 deaths were reported in Zhejiang Province in 2023, with a reported incidence rate of 4 493.93/105 and a reported mortality rate of 0.649 2/105. A total of 679 notifiable infectious disease emergencies were reported, with 26 514 cases and 1 case death (rabies). The emergencies mainly occurred in schools and preschool institutions, with 621 cases accounting for 91.46%. There were 1 case of cholera reported in class A notifiable infectious diseases and no death, 22 types of class B notifiable infectious diseases, with a reported incidence rate of 552.46/105 and a reported mortality rate of 0.644 7/105, and 8 types of class C notifiable infectious diseases, with a reported incidence rate of 3 941.48/105 and a reported mortality rate of 0.004 6/105. The incidence rates of respiratory, intestinal, blood-borne and sexually transmitted, natural and insect-borne infectious diseases were 4 028.67/105, 381.59/105, 81.15/105 and 1.35/105, respectively, according to transmission routes. Influenza (3 561.78/105) and COVID-19 (423.77/105) reported the highest incidence, and AIDS (0.477 4/105) and tuberculosis (0.130 8/105) reported the highest mortality. Conclusion The incidence rates of respiratory and intestinal infectious diseases were high in Zhejiang Province in 2023, and schools and preschool institutions were the main places of diseases occurred.

Objective: To investigate the characteristics of public health emergencies in Zhejiang Province in 2023, so as to provide the reference for public health risk management. Methods: Data of public health emergencies and related information in Zhejiang Province from January 1 to December 31, 2023 was collected through Emergency Public Reporting System of Chinese Disease Prevention and Control Information System. Attack rates, disease types, distribution of time and places, and responses were descriptively analyzed. Results: A total of 718 public health emergencies were reported in 2023 in Zhejiang Province, and all were infectious disease events. There were 27 128 reported cases and 3 deaths, with an attack rate of 3.22%. The top five infectious diseases with the highest number of reported events were influenza, norovirus infection, monkeypox, varicella and hand, foot and mouth disease, accounting for 95.54% of total reported events. There were 355 public health emergencies with less than 30 cases each, accounting for 49.44%. The reported emergencies peaked from February to March (186 events, 25.91%) and from November to December (327 events, 45.54%), and mainly occurred in schools and preschool institutions (651 events, 90.67%). The median responding time, reporting time and duration of emergencies were 6.50 (interquartile range, 10.84) h, 0.53 (interquartile range, 0.63) h and 7.24 (interquartile range, 11.71) d, respectively. Conclusion Public health emergencies in Zhejiang Province in 2023 were mainly caused by influenza and norovirus infection, with February, March, November and December being the peak reporting periods, and schools and preschool institutions being the main places where these events occurred.

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Objective To study and investigate the efficacy of alteplase combined with low molecular weight heparin sodium in the treatment of patients with submaximal pulmonary embolism and its influence on related indicators, and to guide clinical medication. Methods Eighty patients with large pulmonary embolism treated in our department from August 2013 to August 2017 were randomly divided into observation group and control group, with 40 cases in each group. The control group was treated with subcutaneous injection of low molecular weight heparin sodium. In combination with oral anticoagulation with warfarin, the observation group was treated with alteplase on the basis of the control group. After 1 week of continuous treatment, the clinical efficacy was compared between the 2 groups, and pulmonary function and arterial partial pressure of oxygen (PaO2) were compared before and after the treatment. The partial pressure of carbon dioxide (PaCO2) was used to compare the levels of serum B-type natriuretic peptide (BNP) , troponin Ⅰ (cTnⅠ) , homocysteine (Hey) , Ddimer (D-D) , and bleeding before and after the treatment in both groups. Results The total effective rate was97.50％ in the observation group, which was significantly higher than that in the control group of 75.00％ (P <0.05). There was no significant difference in terms of FEV1％, FEV1/FVC, PaO2 and PaCO2 between the two groups before the treatment (P> 0.05) , but FEV1％, FEV1/FVC, PaO2 in the observation group were significantly higher than those in the control group after the treatment, and PaCO2 was significantly lower (P <0.05); There was no significant difference regarding to serum BNP, cTnl, Hey and D-D levels between the two groups before the treatment (P> 0.05) , but after the treatment, the indexes of the observation group were significantly lower than those of the control group (P < 0.05). There was no statistical difference in the incidence of bleeding between the two groups (P> 0.05). Conclusion Alteplase combined with low-molecular-weight heparin sodium in the treatment of the next large-area pulmonary embolism can improve the efficiency of treatment, lung function and the prognosis, but will not inc-rease the risk of bleeding. It could be widely used in clinical practice.