[Progress and prospect of clinical application of anti-rabies virus monoclonal antibody preparation].

Rabies is a severe infectious disease caused by the rabies virus, which seriously damages the central nervous system. Once it occurs, the fatality rate is close to 100%. The World Health Organization's position paper on rabies vaccines recognizes that rabies immunoglobulin (RIG) should be used for post-exposure prophylaxis (PEP) in all category Ⅲ exposure for the first time, as well as in category Ⅱ exposure that suffer from severe immune deficiency, long-term massive use of immunosuppressants, and head and face exposure. The anti-rabies virus monoclonal antibody has high purity and specific activity, can be produced on a sustainable scale, and has no risk of blood source virus contamination. Preclinical pharmacodynamic studies and clinical trial results of the anti-rabies virus monoclonal antibody preparation have confirmed that the preparation has a broad-spectrum neutralization effect on the rabies virus. Additionally, its combined application with the vaccine has little impact on the active immunity of the vaccine. Therefore, the anti-rabies virus monoclonal antibody preparation shows great potential for clinical application in PEP.

[Meta analysis on acceptance rate of HIV pre-exposure prophylaxis among men who have sex with men in China].

Objective: To systematically evaluate the acceptance of pre-exposure prophylaxis (PrEP)among men who have sex with men (MSM) in China, so as to provide reference for the promotion of preventive drug use before human immunodeficiency virus exposure in China. Methods: By searching the databases of China national knowledge infrastructure, VIP database, Wanfan knowledge service platform, PubMed, Web of Science, Embase and The Cochrane Library with key words of "men who have sex with men" "pre-exposure prophylaxis" "PrEP" and "MSM". The literature on the willingness of Chinese MSM population to accept PrEP was systematically collected, and the data of the literature meeting the inclusion criteria were extracted for Meta analysis. Results: A total of 12 articles were selected in this study, including 6 articles in English and 6 in Chinese. The score of bias risk assessment of eligible articles was 14-18, which was more than 70% of the total score. The total number of samples was 11 269. The overall acceptance rate of PrEP was 0.77(95%CI:0.71-0.82). In subgroup analysis, the acceptance rates of different nationalities, marriage, household registration, age, education background, income, sexual orientation, sexual behavior and awareness of PrEP were statistically significant. Conclusion: In general, the acceptance rate of PrEP in MSM population is higher, but the awareness rate is low. There are differences in the acceptance rate among different groups.

[Cortical morphological study in cerebral small vessel disease patients with subcortical ischemic depression].

Objective: To explore the characteristics of cortical morphology in cerebral small vessel disease (CSVD) patients with subcortical ischemic depression (SID) and its relationship with clinical symptoms. Methods: A total of 88 patients with CSVD in the First Affiliated Hospital of Anhui Medical University were enrolled from July 2017 to July 2020. The subjects were divided into CSVD-non depression group (CSVD-ND, n=58) and SID group (n=30) according to the geriatric depression scale (GDS). The 3D-T1 MRI images were obtained from all subjects. The computed anatomy toolbox 12 (CAT 12) was used for image processing and cortical segmentation to obtain the cortical thickness (CTh) and surface metrics, including gyrification index (GI), sulcus depth (SD) and fractal dimension (FD). A comparison at the vertex- and region-of-interest (ROI)-wise levels were performed by the general linear model, and correlation analysis were conducted between cortical morphometric measurements and GDS scores. Finally, mean CTh (mCTh) was extracted for binary logistic regression analysis. Results: At the vertex-wise level, compared with the CSVD-ND group, the SID patients showed increased CTh in clusters mainly located in the posterior default mode network (pDMN), such as the precuneus(Pcu), the superior parietal gyrus (SPG) and the right postcentral gyrus (PoCG). As for the surface measurements, the GI value and the FD value were increased in clusters of Pcu and inferior temporal gyrus (ITG), respectively, in the SID group. ROIs analyses showed that apart from the Pcu, the SPG and the right PoCG, CTh alterations in the SID group were involved in a wider range of regions, extending to the right precentral gyrus ((2.27±0.20) cm3 vs (2.12±0.26) cm3, P=0.007), the left paracentral gyrus ((2.18±0.20) cm3 vs (2.05±0.23) cm3, P=0.008) and so on, than that in the CSVD-ND group.Compared with the CSVD-ND patients, the SID patients showed increased GI in the right PoCG ((25.31±1.11) vs (24.23±1.27), P<0.05). Correlation analysis showed that CTh in the right Pcu was positively correlated with the GDS scores (r=0.4, P<0.05). Further binary logistic regression analysis showed that in comparison with the subjects in the reference group (<2.367 cm3), the odds ratio(95%CI) for SID patients in the highest tertile of mCTh (>2.473 cm3) were 6.373 (1.254-32.389) after multivariable adjustment (sex, age, years of education, total intracranial volume, traditional imaging findings of CSVD, cognitive function (CAMCOG-C) and mCTh). Conclusion: Both CTh and cortical complexity were increased in CSVD patients with SID, especially in the clusters of pDMN, and CTh may be an important risk factor for SID.

[Early containment strategies and core measures for prevention and control of novel coronavirus pneumonia in China].

In December 2019, novel coronavirus pneumonia epidemic occurred in Wuhan, Hubei Province, and spread rapidly across the country. In the early stages of the epidemic, China adopted the containment strategy and implemented a series of core measures around this strategic point, including social mobilization, strengthening case isolation and close contacts tracking management, blocking epidemic areas and traffic control to reduce personnel movements and increase social distance, environmental measures and personal protection, with a view to controlling the epidemic as soon as possible in limited areas such as Wuhan. This article summarizes the background, key points and core measures in the country and provinces. It sent prospects for future prevention and control strategies.

[Expert consensus on rabies exposure prophylaxis].

Rabies is a zoonotic infectious disease caused by lyssavirus and characterized by central nervous system symptoms. The fatality rate of rabies is almost 100%. About 59 000 cases die of rabies worldwide every year, mainly in Asia and Africa. China is an epidemic country of rabies. Grade II and III exposures are the main types of rabies exposures in China. Standardized post-exposure prophylaxis (PEP) can prevent rabies almost 100%. Human Rabies Vaccine Technical Working Group, National Immunization Advisory Committee and invited experts reached an expert consensus on PEP by referring to the World Health Organization's position paper on rabies vaccine in 2018 and related research progress in recent.

[Reduced frequency of natural killer cell on siglec-7(+) is associated with progression of hepatitis B virus-related cirrhosis].

Objective: To explore the relationship between sialic-acid-binding immunoglobulin-like lectin 7 (Siglec-7) expressed on NK cells and hepatitis B virus-related cirrhosis. Methods: Peripheral venous blood samples were collected from 23 healthy controls and 31 patients with hepatitis B virus-related cirrhosis (Child-Pugh A, n = 7; Child-Pugh B, n = 12; Child-Pugh C, n = 12). Peripheral blood mononuclear cells (PBMCs) were obtained by using Ficoll-Hypaque density gradient centrifugation and the expression of Siglec-7 and NK cells phenotype and their subpopulations were detected by flow cytometry. Comparisons between various groups were performed using t -test, one-way analysis of variance (ANOVA), and correlations between variables were analyzed using Pearson's-correlation coefficient. Results: (1) There was no significant difference in the percentage of NK cells and in their subpopulations with HBV-related cirrhosis and healthy controls. (2) Siglec-7 expression on NK cells in patients with HBV-related cirrhosis(62.44±13.45%)was significantly down-regulated than that to healthy controls(75.39±12.19%)while the frequency of Siglec-7(+) NK cells were negatively correlated with Child-Pugh score. (3) Subpopulation analysis showed that Siglec-7 expression on CD56(bright)CD16(-)NK cells(66.99±15.93%)was significantly lower than CD56(dim)CD16(+)NK cells(76.54±13.9%) in HBV-related cirrhosis. However, the expression of Siglec-7 in healthy controls showed no difference in these two NK cell subsets. (4) Phenotypic analysis showed that Siglec-7(+) NK cells express higher levels of activating receptor CD16, CD38, NKp46 and lower levels of inhibitory receptor CD158b. Indeed, the frequency of CD16 and CD38 on Siglec-7(+) NK cells in HBV-related cirrhosis was lower than that in healthy controls. Conclusion: The disease progression in patients with hepatitis B virus-related cirrhosis is associated to decreased frequencies of Siglec-7(+)NK cells.

[Functional effects of killer cell lectin-like receptor subfamily G member 1 on natural killer cells in chronic hepatitis B infection].

Objective: To study the functional effects of killer cell lectin-like receptor subfamily G member 1 (KLRG1) expression on natural killer cells (NK cell) in chronic hepatitis B virus infection (HBV). Methods: Peripheral blood mononuclear cells (PBMC) were extracted from 120 patients with chronic hepatitis B virus infection and 19 healthy persons. The frequency of NK cells and KLRG1+ NK cells in peripheral blood was detected by flow cytometry. Interferon-γ levels secreted by NK cells were detected in peripheral blood. Statistical analysis of experimental data was performed using GraphPad Prism 6.03 software. Results: The frequency of NK cells in HBV-infected group (16.92% ± 7.9%) was not significantly different from that in healthy controls (10.57% ± 6.5%). The frequency of KLRG1+NK cells in HBV-infected group was significantly higher (49.43% ± 21.2%) than that to healthy control group (31.60% ± 17.9%), (t = 7.347 6, P < 0.001). IFN-γ secretion of KLRG1 + NK cells in HBV-infected patients (2.59% ± 1.0%) were significantly lower than healthy controls (5.96% ± 2.4%), (P = 0.009). Conclusion: HBV infection can increase the expression of KLRG1 in NK cells and further reduce the secretion of IFN-γ in NK cells, which may be an important cause for chronic HBV infection.

Siglec-7 Defines a Highly Functional Natural Killer Cell Subset and Inhibits Cell-Mediated Activities.

Sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7) is an inhibitory receptor expressed on natural killer (NK) cells. In this study, we investigated the relationship between Siglec-7 expression and NK cell functions. Siglec-7 was highly expressed on NK cells and was preferentially expressed by mature NK cells from peripheral blood of healthy adults. Siglec-7(+) NK cells displayed higher levels of activating receptors CD38, CD16, DNAM1, NKp30 and NKp46, but lower levels of inhibitory receptors such as NKG2A and CD158b, compared with Siglec-7(-) NK cells. Functional tests showed that Siglec-7(+) NK cells displayed more CD107a degranulation and IFN-γ production than Siglec-7(-) NK cells. Siglec-7 inhibited NK cell functions when interacting with specific antibodies. These data suggest that Siglec-7 defines a highly functional NK cell subset and suppresses NK cell-mediated functions when cross-linked with specific antibodies.

[Interpretation of the key points of Regulation for Diagnosis and Treatment of Non-neonatal Tetanus (2024 Edition)].

Non-neonatal tetanus is an acute, specific, toxic disease in patients over 28 days of age, characterized by continuous rigidity and paroxysmal spasms of the skeletal muscles throughout the body caused by the intrusion of Clostridium tetani through skin or mucosal membrane into the body and reproducing in anaerobic environments to produce exotoxins. The mortality rate of severe patients is close to 100% without medical intervention. Even with aggressive comprehensive treatment, the global mortality rate remains at 30%-50%, making it a potentially fatal disease. In order to standardize the diagnosis, treatment and prevention of non-neonatal tetanus, based on "Regulation for Diagnosis and Treatment of Non-Neonatal Tetanus (2019)", experts have revised this regulation according to clinical practice and recent research progress in this field to guide medical institutions in the prevention and control of non-neonatal tetanus. This article interprets the key points and basis for updating the 2024 edition regulation to guide clinical implementation and application.

[Interpretation of the National Regulation for the Rabies Exposure Prophylaxis (2023 Edition)].

Rabies is one of the important zoonotic infectious diseases, with a mortality rate of almost 100%. Rabies is a vaccine preventable disease, and proper rabies exposure prophylaxis can effectively prevent the occurrence of human rabies. In recent years, there has been significant progress in clinical research on the rabies exposure prophylaxis both domestically and internationally. World Health Organization (WHO) released the Rabies Vaccine: WHO Position Paper-April 2018. In order to guide medical institutions of all levels in rabies exposure prophylaxis, the National Administration of Disease Prevention and Control, in conjunction with the National Health Commission of the People's Republic of China, organized the Rabies Vaccine Working Group of the National Immunization Program Technical Working Group and invited experts to revise and issue the National Regulation for the Rabies Exposure Prophylaxis (2023 Edition). This article compares the National Regulation for the Rabies Exposure Prophylaxis (2009 Edition) and interprets the updated key points and supporting basis of the new version of the guidelines to guide clinical application and implementation.

[Epidemiological characteristics of severe fever with thtrombocytopenia syndrome in China, 2011-2021].

Objective: To analyze the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in China from 2011 to 2021, and provide evidence for the prevention and control of SFTS. Methods: The incidence data of SFTS were collected from the National Disease Reporting Information System of Chinese Center for Disease Control and Prevention for a descriptive epidemiological analysis and Cochran-Armitage trend test was used to evaluate the association between age and the morbidity rate and case fatality rate (CFR) of SFTS. Results: From 2011 to 2021, a total of 18 902 laboratory confirmed cases of SFTS, including 966 deaths, were reported in 533 counties (districts) of 154 prefecture-level cities in 27 provinces. The annual average morbidity rate was 0.125/100 000, and the annual average CFR was 5.11%. From 2011 to 2021 the overall morbidity rate of SFTS was in increase with an average annual percentage change (AAPC) of 14.80% (P=0.001). Most cases (99.23%) occurred in 7 provinces, including Shandong, Henan, Anhui, Hubei, Liaoning, Zhejiang and Jiangsu, with 70.28% of the cases in 11 prefecture-level cities. The average annual CFRs in the 7 provinces varied greatly from 1.30% to 11.27%. In 2011, SFTS cases were reported in 108 counties (districts) of 51 prefecture-level cities in 13 provinces, but SFTS cases were reported in 277 counties (districts) of 88 prefecture-level cities in 19 provinces in 2021, the disease spread from central area to the northeast and from the west and the south. SFTS mainly occurred in summer and autumn in both southern and northern China, and 96.63% of the cases were reported from April to October, and the incidence peak was during May-June. The cases mainly occurred in age group 50-74 years (69.46%), and the deaths mainly occurred in age group ≥60 years (79.71%). Both the morbidity rate and the CFR increased with age. The morbidity rate increased from 0.040/100 000 in age group 0-4 years to 4.480/100 000 in age group ≥80 years in males (χ²=13 185.21, P<0.001) and from 0.038/100 000 in age group 0-4 years to 3.318/100 000 in age group ≥80 years in females (χ²=12 939.83, P<0.001); the CFR increased from 0.70% in age group 30-34 years to 11.58% in age group ≥80 years in males (χ²=115.70, P<0.001) and from 1.56% in age group 35-39 years to 8.98% in age group ≥80 years in females (χ²=103.42, P<0.001). Conclusion: From 2011 to 2021, the incidence of SFTS increased in China, and the spread and obvious spatiotemporal distribution of SFTS were observed. The reported CFR varied greatly with area, and both the morbidity and mortality risk were high in the elderly.

[Epidemiological characteristics of dengue fever outbreaks in China, 2015-2018].

Objective: To analyze the epidemiological characteristics of outbreaks of dengue fever in China from 2015 to 2018, and provide evidence for the prevention and control of dengue fever. Methods: We extracted the incidence data of dengue fever from China Disease Prevention and Control Information System, Public Health Emergency Reporting Management Information System and Vector Biological Monitoring System, and explored the epidemiological characteristics of the outbreaks in the past four years. Excel 2010 software and SPSS 20.0 software were used for data processing and analysis, ArcGIS 10.5 software was used for mapping. Results: A total of 111 outbreaks of dengue fever were reported nationwide from 2015 to 2018, involving 12 490 cases, accounting for 73.7% of the total cases in China. These outbreaks occurred in 85 counties and districts of 4 provinces, namely Guangdong (77 outbreaks), Yunnan (14 outbreaks), Zhejiang (8 outbreaks) and Fujian (8 outbreaks). The outbreaks occurred during May-November. Small-scale outbreaks with no more than 10 cases ended within 30 days (28/34, 82.4%) and larger-scale outbreaks lasted for several months. Dengue virus type 1 and type 2 were the main epidemic pathogens of dengue fever outbreaks in China. The outbreaks mainly occurred in areas with high population density and poor sanitary environment. There were significant differences in the age and occupational composition of the cases in the main outbreak provinces. Conclusions: Outbreaks of dengue fever can been seen in more areas in China, even in high latitudes areas. The epidemiologic characteristics of the outbreaks were different among provinces, showing as port type, rural type and urban type. Each province should adjust the control strategies accordingly.

[Spatial-temporal analysis on imported dengue fever in six provinces of China, 2016-2018].

Objective: To explore the spatio-temporal patterns and epidemic characteristics of imported dengue fever cases in six provinces (Yunnan, Guangxi, Guangdong, Hainan, Fujian and Zhejiang) of China from 2016 to 2018. Methods: In this study, we collected the surveillance data of imported dengue fever cases from 2016 to 2018 in six southern provinces of China. The risk intensity, spatio-temporal distribution and epidemiological characteristics of imported dengue fever cases in the six provinces were analyzed from the perspective of space, time and population. Results: Among the imported cases of dengue fever in China from other countries in the world, most of them were from Southeast Asia. In Zhejiang, Fujian and Guangdong provinces, there were greater number of imported cases with wide range of sources. While in Yunnan, Guangxi and Hainan provinces, the imported cases were almost from Southeast Asia. The incidence of imported dengue fever increased during the past three years, and the annual incidence peak was during August-November, but slight differences were observed among provinces. The age of the imported cases in Hainan[(37.0±19.6) years] was higher than that in southeastern coastal provinces[(36.0±11.7) years] and in southwestern provinces[(32.0±16.3) years]. The male-female ratio of the cases in southeastern coastal provinces (2.18∶1) were higher than those in southwestern provinces (1.04∶1) and Hainan (1.38∶1). The occupations of the cases were mainly workers and unemployed people in southeastern coastal provinces and farmers in southwestern provinces, but commercial personnel was the population with high incidence in both southeastern and southwestern provinces. Less imported dengue fever cases were reported in Hainan, the population distribution varied. Conclusions: There were differences in incidence pattern of imported dengue fever between southeastern coastal provinces and southwestern provinces as well as Hainan in China. Different prevention and control measures should be carried out in different areas to implement more precise prevention strategies.

[Strategy for prevention and control of imported infectious disease].

The process of globalization increases the risk of global transmission of infectious diseases, resulting in pressure for country's prevention and control of imported infectious disease. Based on the risk assessment of disease importation and local transmission, a strategy that conducting importation prevention and routine prevention and control before the importation of disease and taking emergency control measures after the importation of disease was developed. In addition, it is important to take part in global infectious disease response action, aid the countries with outbreak or epidemic to actively decrease the risk of disease importation.

[Analysis on the epidemiological features of human brucellosis in northern and southern areas of China, 2015-2016].

Objective: To analyze the epidemiological characteristics of human brucellosis in northern and southern areas of China, and to develop national strategies for brucellosis prevention and control. Methods: Individual data on human brucellosis was collected from the National Notifiable Infectious Disease Reporting Information System to describe the situation of brucellosis in China during 2015-2016. Epidemiological features of the disease in northern and southern areas of China were analyzed. Results: A total of 104 125 cases were reported in mainland China during 2015-2016, with an average incidence rate as 3.81/100 000. The overall incidence rate from the northern provinces was 7.77/100 000 in 2016, a 18.6% decrease from 2015 (9.55/100 000), whereas the incidence rate in the southern provinces was 0.27/100 000 in 2016, with an increase of 28.6% than 0.21/100 000 in 2015. 90.0% of the newly infected counties mainly distributed in southern China. As for the locations of reporting cases, most of them were in the same counties in the northern areas (52.3%) while most cases in the southern areas (59.6%) were imported from other counties. The median age of the cases was 48 (IQR: 38-58) years, with male-to-female ratios as 2.7∶1 in the north and 2.2∶1 in the south. Majority of the cases were occupation-related, from both the northern (86.8%) and southern (62.7%) areas. Human brucellosis occurred every month throughout the year but with an obvious seasonal increase between March and July. Conclusions: Different epidemiological features of human brucellosis appeared in both northern and southern areas of China. The disease was seen endemic in the northern and dispersal in the southern provinces. Appropriate strategies for brucellosis prevention and control should be developed, according to the different epidemiological characteristics in the northern or southern areas.

[Technical guideline for human rabies prevention and control (2016)].

In order to promote the prevention and control programs on rabies in our country, to regulate the prevention and disposition of rabies and to reduce the deaths caused by rabies, the Chinese Center for Disease Control and Prevention has organized a panel of experts, in the reference with Guidelines issued by WHO, American Advisory Committee on Immunization Practices, and the latest research progress from home and abroad, and compiled this document-"Technical Guidelines for Human Rabies Prevention and Control (2016)". The Guidelines conducted a systematic review on the etiology, clinical characteristics, laboratory diagnosis, epidemiology of rabies and provided evidence on varieties, mechanisms, effects, side-effects and security of rabies vaccine, as well as on other preparations on passive immunity of its kind, on methods related to prevention and disposition of exposure etc, finally to have come up with the recommendation on the above mentioned various techniques. The guidelines will be used by staff working on prevention and control of rabies from the Center for Disease Control and Prevention at all levels, from the departments of outpatient and divisions of infection and emergency control in all the medical institutions. The guideline will be updated and revised, following the research progress from home and abroad.

Experimental evaluation of a hyperbolic ion trap for fourier transform ion cyclotron resonance mass spectrometry.

The Penning ion trap, consisting of hyperbolically curved electrodes arranged as an unbroken ring electrode capped by two end electrodes whose interelectrode axis lies along the direction of an applied static magnetic field, has long been used for single-ion trapping. More recently, it has been used in "parametric" mode for ion cyclotron resonance (lCR) detection of off-axis ions. In this article, we describe and test a Penning trap whose ring electrode has been cut into four equal quadrants for conventional dipolar ICR excitation (on one pair of opposed ring quadrants) and dipolar ICR detection (on the other pair). In direct comparisons to a cubic trap, the present hyperbolic trap offers somewhat improved ICR mass spectral peak shape, higher mass resolving power, and comparable frequency shift as a function of trapping voltage. Mass measurement accuracy over a wide mass range is improved twofold and mass discrimination is somewhat worse than for a cubic trap. The relative advantages of parametric, dipolar, and quadrupole modes are briefly discussed in comparison to screened and unscreened cubic traps.