With the development of information technology, the massive growth of pharmaceutical electronic data and the significant increase in the reports of drug adverse event reports have brought great challenges to pharmacovigilance research. Data mining techniques can automatically extract the risk signals of adverse drug reaction from real-world data. Therefore, efficient data mining of massive adverse event reporting is a necessary measure to realize the automatic detection of adverse drug reactions. By introducing the current major large-scale adverse drug event reporting databases and related data mining methods, this study reviews the application and limitations of adverse drug reaction data mining technology in pharmacovigilance, which provides reference for pharmacovigilance-related institutions and researchers.

Objective:To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (m SDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods:A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. m SDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of m SDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of m SDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results:A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of m SDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of m SDC2 was negatively correlated with the proportion of advanced colorectal neoplasms ( χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion:The CRC screening strategy of fecal m SDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of m SDC2 may have a certain suggestion on the malignant degree of intestinal tumors.

Objective:To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (m SDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods:A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. m SDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of m SDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of m SDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results:A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of m SDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of m SDC2 was negatively correlated with the proportion of advanced colorectal neoplasms ( χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion:The CRC screening strategy of fecal m SDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of m SDC2 may have a certain suggestion on the malignant degree of intestinal tumors.

Owing to the increasing incidence and prevalence of inflammatory bowel disease (IBD) worldwide, effective and safe treatments for IBD are urgently needed. Hydrogen sulfide (H₂S) is an endogenous gasotransmitter and plays an important role in inflammation. To date, H₂S-releasing agents are viewed as potential anti-inflammatory drugs. The slow-releasing H₂S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), known as a potent therapeutic with chemopreventive and cytoprotective properties, has received attention recently. Here, we reported its anti-inflammatory effects on dextran sodium sulfate (DSS)-induced acute (7 days) and chronic (30 days) colitis. We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length. Moreover, ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway. In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels. In addition, ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter, Mucispirillum, Parasutterella, and Desulfovibrio. Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines. Collectively, ADT-OH is safe without any short-term (5 days) or long-term (30 days) toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.
Humans ; Mice ; Animals ; Gastrointestinal Microbiome ; Intestinal Barrier Function ; Mice, Inbred C57BL ; Colitis/metabolism* ; Inflammatory Bowel Diseases/drug therapy* ; Inflammation ; Anti-Inflammatory Agents/pharmacology* ; Disease Models, Animal

ω-transaminase (ω-TA) is a natural biocatalyst that has good application potential in the synthesis of chiral amines. However, the poor stability and low activity of ω-TA in the process of catalyzing unnatural substrates greatly hampers its application. To overcome these shortcomings, the thermostability of (R)-ω-TA (AtTA) from Aspergillus terreus was engineered by combining molecular dynamics simulation assisted computer-aided design with random and combinatorial mutation. An optimal mutant AtTA-E104D/A246V/R266Q (M3) with synchronously enhanced thermostability and activity was obtained. Compared with the wild- type (WT) enzyme, the half-life t_1/2 (35 ℃) of M3 was prolonged by 4.8-time (from 17.8 min to 102.7 min), and the half deactivation temperature (T¹⁰₅₀) was increased from 38.1 ℃ to 40.3 ℃. The catalytic efficiencies toward pyruvate and 1-(R)-phenylethylamine of M3 were 1.59- and 1.56-fold that of WT. Molecular dynamics simulation and molecular docking showed that the reinforced stability of α-helix caused by the increase of hydrogen bond and hydrophobic interaction in molecules was the main reason for the improvement of enzyme thermostability. The enhanced hydrogen bond of substrate with surrounding amino acid residues and the enlarged substrate binding pocket contributed to the increased catalytic efficiency of M3. Substrate spectrum analysis revealed that the catalytic performance of M3 on 11 aromatic ketones were higher than that of WT, which further showed the application potential of M3 in the synthesis of chiral amines.
Transaminases/chemistry* ; Molecular Docking Simulation ; Amines/chemistry* ; Pyruvic Acid/metabolism* ; Enzyme Stability

[摘 要] 目的：观察扶正方药对晚期三线非小细胞肺癌（NSCLC）患者外周血中12种可溶性免疫检查点分子水平的影响，并分析可溶性免疫检查点基线水平与NSCLC患者无进展生存期（PFS）的关系。方法：纳入2020年10月至2023年4月在龙华医院肿瘤科接受三线治疗（扶正方药联合标准西医方案治疗）的72例晚期NSCLC患者，采用LEGENDplex™多因子试剂盒检测患者治疗前及治疗4疗程后可溶性免疫检查点分子的表达水平，分析基线水平与PFS预后的相关性。结果：治疗4个疗程后，sCD137、sTGF-β1、sPD-L1、sPD-L2等指标均明显下降（P<0.05或P<0.01），Kaplan-Meier生存分析表明sPD-L2高水平患者的PFS短于sPD-L2低水平患者的PFS（P<0.05），COX多因素分析表明sPD-L2水平是晚期三线NSCLC患者PFS的独立影响因子（P<0.05）。结论：扶正方药对外周血可溶性免疫检查点蛋白表达具有一定的调节作用，高水平的sPD-L2预示晚期NSCLC患者较短的PFS，sPD-L2可能是晚期三线治疗NSCLC患者PFS的独立影响因子。

Objective:To understand the epidemiological characteristics and changing trends of HIV-infected patients aged ≥60 years reported in recent years in China and provide reference for the development of HIV prevention and control strategies for the elderly.Methods:The data of newly reported HIV-infected patients aged ≥60 years between 2015 and 2022 were obtained from China Information System for Disease Control and Prevention. The differences in epidemiological characteristics of HIV infections among groups were compared by using t test and Kruskal-Wallis H nonparametric test in software SPSS 24.0. Software Joinpoint 4.9.0 was used to calculate annual percent change (APC) and trend analysis was conducted by using Joinpoint regression model. Software Excel 2019 was used for graph drawing. Results:The number of reported HIV-infected patients aged ≥60 years in China increased from 17 451 in 2015 to 27 004 in 2022, with newly diagnosed rate rising from 9.0/100 000 to 10.2/100 000. The newly diagnosed rate in men was higher than that in women. Trend analysis demonstrated that the newly diagnosed rate in both elderly men and women peaked in 2019 (APC for men=13.5%, P=0.003; APC for women=15.0%, P=0.002), and showed a downward trend after 2019 (APC for men=-12.4%, P=0.006; APC for women=-13.0%, P=0.007). Among the elderly infected men, those infected by heterosexual and homosexual transmission accounted for 93.5% (160 747/171 924) and 5.1% (8 781/171 924), respectively. Among the elderly infected women, those infected by heterosexual transmission accounted for 98.4% (48 899/49 697). The infected elder people diagnosed by medical institutions accounted for 71.5% (158 394/221 621), whose baseline CD4 +T lymphocytes level was lower than that in those diagnosed by other ways ( H=1 079.82, P<0.001). Conclusions:The poor risk awareness and high-risk sexual behavior made the elderly at higher risk for HIV infection. More efforts should be made to improve active surveillance, timely detection and origin-tracing for infected elderly for the accurate and effective prevention and control of HIV infection.

Objective:To analyze the basic characteristics and change trend of mortality in HIV-infected patients aged ≥60 years in China from 2013 to 2021.Methods:The data of HIV-infected patients aged ≥60 years at diagnosis were collected from China Information System for Disease Control and Prevention to calculate the mortality density. The trajectory model was fitted using the Proc traj process in software SAS 9.4 to explore trajectory of AIDS-related mortality density and non-AIDS-related mortality density under different combinations of region, gender and age.Results:Between 2013 and 2021, a total of 244 770 HIV-infected patients were reported with 40 079 AIDS-related deaths and 50 245 non-AIDS-related deaths. The AIDS-related mortality density was 6.32 per 100 person-years, and the non-AIDS-related mortality density was 7.92 per 100 person-years, both of which showed decreasing trends over the years, and the mortality density in men was higher than that in women. Two developmental trajectories could be categorized for different trends of AIDS-related mortality density: the lower mortality density group accounted for 80.95% and showed a slow decreasing trend; the higher mortality density group accounted for 19.05% and showed a three-curve developmental trend. There were three developmental trajectories of non-AIDS-related mortality density trends: the lower mortality density group accounted for 59.52% and the medium mortality density group accounted for 28.57%, with a flat overall trend in these two groups; the higher mortality density group accounted for 11.91% with a three-curve trend.Conclusions:The mortality in HIV-infected patients aged ≥60 years in China is still high. Further attention should be paid to the early detection, diagnosis and treatment of HIV infection to effectively reduce the density of AIDS-related deaths. At the same time, attention should be paid to non-AIDS-related deaths in the elderly, and comprehensive interventions should be taken. It is necessary to conduct targeted HIV/AIDS prevention and control based on actual situation in different areas and populations

Objective:To understand the epidemiological characteristics of HIV-infected farmers aged ≥60 years in China and provide evidence for the development of AIDS prevention and control policies for elderly farmers.Methods:Data of newly HIV-infected farmers aged ≥60 years reported between 2018 and 2022 were obtained from China Information System for Disease Control and Prevention. The differences in epidemiological characteristics of HIV infection between farmers and other populations were compared using χ2 test. Based on 6 representative indicators, 31 provinces were divided into three sub-epidemic areas of A, B, and C by using sample system clustering method in SPSS 24.0 software. Results:From 2018 to 2022, a total of 113 311 HIV infection cases in farmers aged ≥60 years were reported, accounting for 71.8% of the reported cases in this age group nationwide (113 311/157 792). In the 113 311 HIV infection cases, 86 517 (76.4%) were men, 80 176 (70.8%) were diagnosed by medical institutions, 80 667 (71.2%) were distributed in the western region and 92 191 (81.4%) had education level of primary school or below [higher than the proportion in other populations (49.8%, 22 165/44 481)]. In 113 311 HIV infection cases, 96.7%(109 562/113 311) were infected through heterosexual transmission, in whom 50.4% (55 184/109 562) had commercial heterosexual behavior, 9.1%(9 958/109 562) had fixed sexual partners, 40.5%(44 420/109 562) had other heterosexual behaviors. The clustering analysis indicated that in region A (Guangxi, Chongqing, Guizhou, Sichuan, Yunnan and Xinjiang), the proportions of people living with HIV (30.2/10 000), HIV-infected farmers aged ≥60 years in rural population (22.8/10 000), counties reported HIV-infected elderly farmers (93.4%), the population had HIV test (44.2%), were all higher than those in region B and C. Compared with region B and C, The net income of farmers (10 000 yuan) was lower in region A, and the proportion of commercial heterosexual behavior in male farmers in region A (41.0%) was slightly lower than that in region B (46.1%), but higher than that in region C (15.2%).Conclusions:HIV infections in farmers aged ≥60 years were mainly caused by heterosexual behaviors, such as commercial heterosexual sex, in China from 2018 to 2022. The low awareness of self-protection against AIDS and high-risk sexual behaviors are closely associated with HIV infection in elderly farmers. Attention should be paid to the behavior intervention and health education about AIDS prevention in elderly farmers and the prevention and intervention in rural female sex workers and HIV positive spouses should be strengthened.

Objective:To explore the current status and research hotspots of structural equation modeling in nursing from 2012 to 2021.Methods:We searched for literature on the structural equation modeling in nursing based on Web of Science core collection database. CiteSpace and Excel were used to analyze the time, space, and keywords included in 742 articles.Results:From 2012 to 2021, the number of domestic and international publications showed a rapid growth trend with the growth of the year. China was the country with the highest number of publications. The Western University in Canada was the institution with the highest number of publications. The frequency of keywords such as structural equation modeling, quality of life, job satisfaction, health, social support and stress was high. The clustering effect of keywords was significant ( Q=0.72, S=0.87) , and research hotspots mainly included physical and mental health care and nursing work management. Conclusions:The structural equation modeling in nursing is showing a rapid development trend. In the future, numerous studies should be conducted on the construction and validation of nursing structural relationship models to promote the development of nursing.