1.Mechanism of Yiqi Huoxue Therapy Regulating IL-33/ST2/IL-1RAP to Improve Nasal Mucosal Tissue Remodeling and Intervene in Allergic Rhinitis
Huan WANG ; Hongping LUO ; Meiya WANG ; Yuyin LIU ; Chenlin WANG ; Chao LIAO ; Fangqi LIANG ; Peizheng XIONG ; Li TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):298-307
ObjectiveTo explore the mechanism by which Qidan Yifei Tongqiao granules (QDYF) alleviate nasal mucosal remodeling in allergic rhinitis (AR) via the interleukin-33 (IL-33)/growth stimulation expressed gene 2 (ST2)/interleukin-1 receptor accessory protein (IL-1RAP) signaling pathway from the perspective of Qi-replenishing and blood-activating therapy. MethodsFirst, according to the previous network pharmacology results, this study predicted the potential mechanisms of QDYF in treating AR by screening key pathways, components, and targets. Molecular docking was performed via AutoDock and PyMOL 2.5.5. Subsequently, a rat model of ovalbumin (OVA)-induced AR was used for validation through in vivo experiments. Forty-eight rats were assigned into 6 groups: Control, model, low-dose QDYF (QDYF-L, 4.04 g·kg-1), medium-dose QDYF (QDYF-M, 8.08 g·kg-1), high-dose QDYF (QDYF-H, 16.16 g·kg-1), and loratadine (0.9 mg·kg-1). After 14 days of intervention, behavioral scores of the rats were observed. The morphological changes of nasal mucosa tissue were observed by hematoxylin-eosin (HE) staining. Masson staining was used to observe collagen fiber deposition in the nasal mucosal tissue and to calculate the collagen volume fraction (CVF). The expression of E-cadherin (E-cad) in the nasal mucosa tissue was detected by immunofluorescence. The serum levels of helper T cell 2 (Th2) cytokines interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13) as well as helper T cell 1 (Th1) cytokines interleukin-2 (IL-2) and interferon-γ (INF-γ) were quantified by enzyme-linked immunosorbent assay (ELISA). The protein levels of transforming growth factor-beta 1 (TGF-β1), IL-33, ST2, and IL-1RAP in the nasal mucosa tissue were determined by Western blot. ResultsIL-33, ST2, and IL-1RAP had strong binding ability with the main active ingredients—wogonin, 7-methoxy-2-methylisoflavone, formononetin, naringenin, stigmasterol, and beta-sitosterol of QDYF, with the binding energy < -4.25 kcal⋅mol-1(1 cal≈4.184 J). The results of in vivo experiments showed that compared with the control group, the model group exhibited increased behavioral scores (P<0.05), aggravated pathological damage of nasal mucosa, increased collagen fiber deposition and CVF (P<0.05), elevated serum levels of IL-4, IL-5, and IL-13, up-regulated protein levels of TGF-β1, IL-33, ST2, and IL-1RAP in the nasal mucosa (P<0.05), down-regulated expression of E-cad, and declined serum levels of IL-2, IFN-γ, and IFN-γ/IL-4 ratio (P<0.05). Compared with the model group, the QDYF groups and loratadine group showed reduced behavioral scores (P<0.05), alleviated pathological damage of nasal mucosa, reduced collagen fiber deposition and CVF (P<0.05), and up-regulated E-cad expression (P<0.05). Compared with the model group, the QDYF-H group and the loratadine group showed raised levels of INF-γ and IFN-γ/IL-4 ratio (P<0.05), declined serum levels of IL-4, IL-5, and IL-13, and down-regulated protein levels of TGF-β1, IL-33, ST2, and IL-1RAP in the nasal mucosa (P<0.05). In addition, the QDYF-H group exhibited an elevated serum IL-2 level (P<0.05). The QDYF-M group showed down-regulated protein levels of TGF-β1, IL-33 and IL-1RAP in the nasal mucosa (P<0.05). The QDYF-L group demonstrated a down-regulated protein level of ST2 in the nasal mucosa (P<0.05). ConclusionQDYF may regulate the Th1/Th2 balance through the IL-33/ST2/IL-1RAP signaling pathway, thereby ameliorating nasal mucosal tissue remodeling and alleviating AR.
2.Perioperative immune dynamics and clinical outcomes in patients undergoing on-pump cardiac surgery
Zhiyuan CHENG ; Xinyi LIAO ; Juan WU ; Ping YANG ; Tingting WANG ; Qinjuan WU ; Wentong MENG ; Zongcheng TANG ; Jiayi SUN ; Jia TAN ; Jing LIN ; Dan LUO ; Hao WANG ; Chaonan LIU ; Jiyue XIONG ; Liqin LING ; Jing ZHOU ; Lei DU
Chinese Journal of Blood Transfusion 2026;39(1):31-43
Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10
/L vs preoperative 3.07×10
/L, P<0.001), with significant upregulation of CD11b (7.30×10
/L vs preoperative 3.05×10
/L, P<0.001) and CD54 (7.15×10
/L vs preoperative 2.99×10
/L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10
/L vs preoperative 1.12×10
/L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10
/L vs preoperative 1.12×10
/L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.
3.Proteomics and molecular simulation analyses of COX17 involvement in demethylzeylasteral-mediated inhibition of proliferation and invasion of MGC-803 gastric cancer cells
Yang Dan1 ; Xiong Xinya2 ; Liao Conghui2 ; Chen Jie2 ; Sun Hanghang2 ; Han Ran3
Chinese Journal of Cancer Biotherapy 2026;33(8):867-875
[摘 要] 目的:探讨细胞色素c氧化酶铜伴侣蛋白17(COX17)是否参与去甲泽拉木醛(DML)抑制胃癌细胞增殖和侵袭的作用。方法: 采用5、10和20 μmol/L DML处理MGC-803细胞,通过显微镜计数和Transwell实验评价DML对细胞增殖和侵袭的影响;采用非标记定量蛋白质组学比较DML处理组与DMSO组的蛋白表达谱,结合差异表达分析和GO功能富集筛选候选蛋白,并采用Western blotting验证DML处理后COX17蛋白表达变化。分别构建COX17敲低和过表达稳定细胞株,通过细胞计数和Transwell实验评价COX17对MGC-803细胞增殖和侵袭的影响。采用分子对接和50 ns分子动力学模拟分析DML与COX17的潜在结合模式及复合物构象稳定性;进一步通过COX17过表达回复实验评价COX17在DML抑制细胞增殖和侵袭过程中的作用。结果:DML显著抑制MGC-803细胞增殖和侵袭,且随DML浓度升高,抑制作用逐渐增强(均P < 0.000 1)。蛋白质组学共筛选出72个差异表达蛋白,其中21个上调、51个下调;结合差异表达特征、GO功能富集结果及前期研究基础,选取COX17进行后续验证。DML可显著下调MGC-803细胞中COX17蛋白表达(P < 0.000 1)。敲低COX17可抑制细胞增殖和侵袭,过表达COX17则促进上述表型。分子对接提示DML与COX17之间可能存在疏水接触、氢键和盐桥等相互作用,对接评分为−6.8 kcal/mol;分子动力学模拟显示DML-COX17复合物在50 ns模拟过程中整体趋于相对稳定。COX17过表达可部分减弱DML对MGC-803细胞增殖和侵袭的抑制作用(P < 0.01)。结论:DML可抑制MGC-803细胞增殖和侵袭并下调COX17蛋白表达,COX17可能参与DML对胃癌细胞恶性表型的调控。
4.COX17 regulates the proliferation, migration and invasion of SGC-7901 gastric cancer cells: a preliminary study
Yang Dan1 ; Xiong Xinya2 ; Liao Conghui2 ; Chen Jie2 ; Sun Hanghang2 ; Han Ran3
Chinese Journal of Cancer Biotherapy 2026;33(9):951-959
[摘 要] 目的:探讨细胞色素c氧化酶铜伴侣蛋白17(COX17)在胃癌中的表达及其对胃癌细胞恶性生物学行为的调控作用。方法:运用TIMER、UALCAN、TCGA、HPA、Kaplan‑Meier Plotter数据库,分析COX17基因在泛癌、胃癌及正常胃组织中的表达差异及其与胃癌临床病理特征和预后的关系;通过STRING数据库构建COX17蛋白质相互作用网络并进行GO功能注释与KEGG通路分析;通过TIMER数据库分析COX17表达水平与免疫细胞浸润程度的相关性。采用慢病毒系统构建稳定敲低或过表达COX17的SGC-7901细胞,Western blotting法验证COX17敲低与过表达效率。通过细胞计数法检测稳转细胞模型增殖能力,Transwell细胞侵袭实验评估细胞侵袭能力;划痕愈合实验检测细胞迁移能力。结果:数据库分析显示胃癌组织及细胞中COX17 mRNA呈高表达;COX17 mRNA高表达的胃癌患者总生存期(OS)、无进展生存期(PFS)及进展后生存期(PPS)更长;COX17及其相关基因主要参与线粒体细胞色素c氧化酶、电子传递链等功能,富集于非酒精性脂肪性肝病、氧化磷酸化、产热等KEGG通路;COX17表达水平与CD4⁺ T细胞、巨噬细胞浸润呈负相关。成功构建稳定敲低或过表达COX17的胃癌细胞。功能实验表明,敲低COX17可显著抑制胃癌细胞增殖、侵袭和迁移(均P < 0.000 1);而过表达COX17则产生相反效应(均P < 0.000 1)。结论:COX17 mRNA在胃癌组织和细胞中高表达,其高表达与胃癌患者较好的生存预后相关;但体外功能实验显示COX17可促进胃癌SGC-7901细胞增殖、侵袭和迁移。COX17在胃癌中的作用可能具有复杂性,其临床预后意义与体外恶性表型调控之间的差异尚需进一步研究。
5.Preliminary validation of applicability of flight potential evaluation system
Yan ZHANG ; Yang LIAO ; Jian DU ; Hanxiao GE ; Yishuang ZHANG ; Haiou XIONG ; Hongchang SUN ; Liu YANG
Chinese Journal of Aerospace Medicine 2025;36(1):33-37
Objective:To verify the applicability of the flight potential evaluation system in the psychological selection of pilots by testing the reliability and validity of the system.Methods:Between September and October 2021, 82 subjects, including 32 pilots and 50 volunteers, were recruited from the Aviation Force and the Air Force Medical Center to complete the flight potential evaluation system test. The pilots and volunteers were divided into the high score group (the top 27% in terms of scores) and low score group (the 27% from the bottom) according to the total score of the evaluation. In order to ensure the consistency of evaluation conditions, some subjects were selected to complete a second evaluation test one week later for reliability analysis. Six flight experts completed the Content Evaluation Form of the Flight Potential Evaluation System while the officer completed the Flight Performance Evaluation Questionnaire as the performance data of the pilots. The pass rates of the pilots and volunteers and discriminability of the flight potential evaluation system were analyzed to test the stability and effectiveness of the system.Results:①The flight potential evaluation system demonstrated a pass rate of 0.75 and a discriminability of 0.30 in pilots, compared with 0.30 and 0.51 in volunteers. The total scores of pilots and volunteers were (7.00±1.16) points and (3.38±2.15) points, respectively, with a statistically significant difference ( t=9.87, P<0.001). Significant differences were found in test scores between high-score group and low-score group for both pilots ( t=10.01, P<0.001) and volunteers ( Z=-4.65, P<0.001). ②Thirty-seven subjects (including 32 pilots and 5 volunteers, all from the Aviation Force) were tested twice, and the Pearson product-moment correlation coefficient for the paired results of 2 identical tests was r=0.750 ( P<0.001). ③As for the content of the evaluation system test, the experts′ degree of agreement and unanimity rate were 1. The evaluation score by the officer was positively correlated with the test score ( r=0.389, P=0.041). Conclusions:The flight potential evaluation system has a strong ability to distinguish flight-related abilities, suggesting that the system can be applied to the psychological selection of pilots and provide data for subsequent tests during the recruitment of candidates.
6.Analysis of CRRT withdrawal failure in patients with infectious shock complicating AKI based on decision tree algorithm
Wei XIONG ; Hao LIAO ; Wenjuan XU ; Yan TU
China Modern Doctor 2025;63(3):22-26
Objective To establish a risk prediction model of continuous renal replacement therapy(CRRT)withdrawal failure in patients with infectious shock complicating acute kidney injury(AKI)based on the decision tree algorithm,and to explore the influencing factors of CRRT withdrawal failure in patients with infectious shock complicating AKI.Methods 220 patients with infectious shock complicating AKI admitted to our hospital from May 2020 to May 2023 were retrospectively analyzed,and divided into success group and failure group according to the success or failure of the withdrawal,univariate and multivariate Logistic regression analysis were used to screen risk factors of CRRT withdrawal failure in patients with septic shock complicated with AKI,C-reactive protein/albumin(CRP/ALB)at admission and sepsis-related organ failure assessment(SOFA)score at withdrawal,acute physiology and chronic health evaluation(APACHE Ⅱ)score,N-terminal B-type natriuretic peptide(NT-proBNP)level at the beginning of CRRT,mean arterial pressure(MAP)grading,urine volume after withdrawal,and serum creatinine(Scr)level after withdrawal were taken into constructing a decision tree model and validating the model efficacy.Results In this study,there were 41.82%of patients failed to withdrawal.Combination of univariate and multivariate Logistic regression analysis showed that SOFA score at withdrawal,APACHE Ⅱ scores,urine volume after withdrawal,Scr level after withdrawal,NT-proBNP at the beginning of CRRT,and MAP grading,CRP/ALB at the time of admission were an independent risk factor for CRRT withdrawal failure in patients with septic shock complicated with AKI(P<0.05).The results showed that the higher CRP/ALB was the most important influencing factor on the failure of CRRT evacuation in patients with infectious shock complicating AKI,and the area under the receiver operating characteristic curve was 0.965.Conclusion The decision tree model constructed by CRP/ALB at admission,SOFA score at withdrawal,urine volume after withdrawal,Scr level after withdrawal,APACHE Ⅱ score,and MAP grading has a better predictive efficacy of CRRT withdrawal failure in patients with infectious shock complicating AKI,which is a guideline for patients'prognostic assessment.
7.Preliminary validation of applicability of flight potential evaluation system
Yan ZHANG ; Yang LIAO ; Jian DU ; Hanxiao GE ; Yishuang ZHANG ; Haiou XIONG ; Hongchang SUN ; Liu YANG
Chinese Journal of Aerospace Medicine 2025;36(1):33-37
Objective:To verify the applicability of the flight potential evaluation system in the psychological selection of pilots by testing the reliability and validity of the system.Methods:Between September and October 2021, 82 subjects, including 32 pilots and 50 volunteers, were recruited from the Aviation Force and the Air Force Medical Center to complete the flight potential evaluation system test. The pilots and volunteers were divided into the high score group (the top 27% in terms of scores) and low score group (the 27% from the bottom) according to the total score of the evaluation. In order to ensure the consistency of evaluation conditions, some subjects were selected to complete a second evaluation test one week later for reliability analysis. Six flight experts completed the Content Evaluation Form of the Flight Potential Evaluation System while the officer completed the Flight Performance Evaluation Questionnaire as the performance data of the pilots. The pass rates of the pilots and volunteers and discriminability of the flight potential evaluation system were analyzed to test the stability and effectiveness of the system.Results:①The flight potential evaluation system demonstrated a pass rate of 0.75 and a discriminability of 0.30 in pilots, compared with 0.30 and 0.51 in volunteers. The total scores of pilots and volunteers were (7.00±1.16) points and (3.38±2.15) points, respectively, with a statistically significant difference ( t=9.87, P<0.001). Significant differences were found in test scores between high-score group and low-score group for both pilots ( t=10.01, P<0.001) and volunteers ( Z=-4.65, P<0.001). ②Thirty-seven subjects (including 32 pilots and 5 volunteers, all from the Aviation Force) were tested twice, and the Pearson product-moment correlation coefficient for the paired results of 2 identical tests was r=0.750 ( P<0.001). ③As for the content of the evaluation system test, the experts′ degree of agreement and unanimity rate were 1. The evaluation score by the officer was positively correlated with the test score ( r=0.389, P=0.041). Conclusions:The flight potential evaluation system has a strong ability to distinguish flight-related abilities, suggesting that the system can be applied to the psychological selection of pilots and provide data for subsequent tests during the recruitment of candidates.
8.Clinical and genetic analysis of four patients with Phelan-McDermid syndrome due to variants of SHANK3 gene
Liangqiong DENG ; Xuan ZENG ; Linyan LIAO ; Xiaobo XIONG ; Aiwen LI ; Yan MEI ; Liujuan ZHANG ; Dejian YUAN
Chinese Journal of Medical Genetics 2025;42(5):563-567
Objective:To explore the clinical phenotype and genetic characteristics of four patients with Phelan-McDermid syndrome (PMS) due to variants of SHANK3 gene. Methods:Four patients diagnosed with PMS at Guangzhou Women and Children′s Medical Center Liuzhou Hospital from January 2020 to January 2025 were selected as the study subjects. Clinical data of the patients were collected. Peripheral venous blood samples were collected from each patient for the extraction of genomic DNA, followed by whole-exome sequencing (WES) and validation by Sanger sequencing. Pathogenicity of candidate variants was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), and multiple bioinformatic tools were used to assess the pathogenic effects of the variants. The study was approved by the Ethics Committee of the Guangzhou Women′s and Children′s Medical Center Liuzhou Hospital (Ethics No. 2025-007).Results:All four patients had exhibited language delay and intellectual disability (IQ 35 ~ 65). Some also presented with autism spectrum disorder and schizophrenia, albeit with significant phenotypic heterogeneity. All patients were found to harbor deletions of 22q13.33 region, ranging from 55.46 kb to 112.64 kb, primarily involving the SHANK3 gene. Conclusion:PMS is typically caused by deletions or mutations of the SHANK3 gene. The clinical manifestations are diverse, with developmental delay and intellectual disability being the most common. Accurate diagnosis requires integration of genetic testing and standardized clinical assessment. Genetic screening for suspected patients and at-risk pregnant women is recommended to facilitate their genetic counseling.
9.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
10.Research on the association between tetracyclines use during pregnancy and congenital malformations in offspring
Jin GUO ; Peng ZHAO ; Chunrong LIU ; Mingyu LIAO ; Jingwen CHEN ; Jianru WU ; Yan REN ; Biao RONG ; Huanyang QI ; Moliang CHEN ; Xin SUN ; Jing TAN ; Yiquan XIONG
Adverse Drug Reactions Journal 2025;27(9):530-536
Objective:To explore the association between the use of tetracyclines during pregnancy and congenital malformations, with the aim of providing evidence-based guidance for the rational use of antibiotics during pregnancy.Methods:Data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Canada Vigilance Adverse Reaction (CVAR) database from January 2015 to September 2024 were collected. Five methods including Tree-based scan statistic (TreeScan), proportional reporting ratio (PRR), reporting odds ratio (ROR), the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard, and the Bayesian confidence propagation neural network (BCPNN) were used to detect signals of risk for congenital malformations in offspring following maternal use of tetracyclines during pregnancy. A signal that met the threshold criteria of all above 5 methods was considered as a risk signal. Based on population-based cohort of the drug exposures and adverse pregnancy outcomes (DEEP) data from January 2013 to December 2021 in Xiamen City, propensity score matching (PSM)-based Poisson regression was applied to evaluate the association between the first-trimester tetracyclines exposure and congenital malformations in offspring. Adjusted relative risk (a RR) and its 95% confidence interval ( CI) were calculated. Sensitivity analysis was conducted to validate the reliability of the results. Results:A total of 304 098 reports of adverse events during pregnancy were obtained from the FAERS and CVAR databases. Among them, 5 028 reports were related to tetracyclines, including 1 026 reports of congenital malformations in offspring, involving congenital malformations of musculoskeletal system, other digestive system, and other congenital malformations. Signal detection results suggested that tetracyclines may be a risk signal for above congenital malformations in offspring. The DEEP data included 411 936 pregnant women. After PSM, 240 pregnant women exposed to tetracyclines were included. The results showed no significant association between the first-trimester tetracyclines exposure and congenital malformations in offspring (a RR=0.75, 95% CI: 0.26-2.17), sensitivity analysis also showed no correlation. Conclusions:Data mining from the FAERS and CVAR databases suggests a potential association between tetracyclines use during pregnancy and congenital malformations in offspring. However, the DEEP data study shows no significant correlation.

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