1.Structural and Spatial Analysis of The Recognition Relationship Between Influenza A Virus Neuraminidase Antigenic Epitopes and Antibodies
Zheng ZHU ; Zheng-Shan CHEN ; Guan-Ying ZHANG ; Ting FANG ; Pu FAN ; Lei BI ; Yue CUI ; Ze-Ya LI ; Chun-Yi SU ; Xiang-Yang CHI ; Chang-Ming YU
Progress in Biochemistry and Biophysics 2025;52(4):957-969
ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.
2.Analysis of chloroplast genomes from Salvia miltiorrhiza and its congeneric species
Jindong YANG ; Zhenxi FANG ; Chengyang NIE ; Ruibing CHEN ; Qing LI ; Lei ZHANG
Journal of Pharmaceutical Practice and Service 2025;43(6):275-282
Salvia miltiorrhiza Bunge (Lamiaceae) is a medicinal plant widely used in Traditional Chinese Medicine for treating cardiovascular and cerebrovascular diseases. Chloroplasts are double-membrane-bound, chlorophyll-containing organelles and responsible for photosynthesis in plant cells. The structural information of chloroplast genomes serves as the foundation for precise exogenous gene insertion, site selection, and chloroplast genome modification. In this study, a comprehensive analysis and comparison of 125 chloroplast genomes from S. miltiorrhiza and 76 congeneric species were conducted, focusing on sequence characteristics, codon usage bias, simple sequence repeats (SSRs), contraction/expansion of chloroplast genome boundaries, and phylogenetic relationships, which could provide a theoretical foundation for advancing chloroplast genetic engineering, genetic diversity analysis, molecular breeding, and species identification within the Salvia genus.
3.TLR4 and IFN - γ Activated Mesenchymal Stem Cells Improve Schistosomiasis Liver Fibrosis by Regulating Macrophage Polarization
Yaojia REN ; Fang CHEN ; Wanxian HUANG ; Zhongdao WU ; Junxia LEI
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):410-419
ObjectiveTo investigate whether co-activated mesenchymal stem cells(MSCs) exert therapeutic effects against schistosomiasis by modulating macrophage polarization. MethodsTwenty adult male Balb/c mice were randomly divided into four groups: uninfected, infected, MSC-treated, and MSCTLR4+IFN-γ-treated groups. The Schistosoma japonicum infection model was established via abdominal patch method with cercariae. At week 5 post-infection, praziquantel was administered orally for antiparasitic treatment. At week 6, mice received either MSCs treatments (with or without pre-activation) or no treatment. Body weight changes were monitored weekly. Hepatic pathological alterations were evaluated via HE and Masson staining. RT-qPCR was used to assess α-SMA and collagen (Col-I, Col-Ⅲ) mRNA levels to quantify fibrosis. The mRNA levels of hepatic inflammatory cytokines and matrix metalloproteinases(MMP) were analyzed to explore fibrotic mechanisms. The expressions of i-Nos and Arg-1 in liver tissues were detected by RT-qPCR, and the ratio of M1 or M2 macrophages was detected by immunofluorescence staining, aiming to analyze the correlation between MSCs treatment and macrophage polarization. An in vitro co-culture system validated direct MSC-macrophage interactions. ResultsCompared with the infected group, the MSCTLR4+IFN-γ group exhibited increased body weight gain (P< 0.01), reduced hepatic granulomatous lesion area (P< 0.001), and decreased α-SMA, Col-I, and Col-Ⅲ mRNA levels (P< 0.01). Additionally, the MSCTLR4+IFN-γ group showed reduced TNF-α and IL-1β expression (P< 0.05), as well as elevated MMP2, Mmp9, and MMP13 levels (P< 0.01). The MSCTLR4+IFN-γ group showed higher expression of M2 marker Arg-1 mRNA compared with the infection group (P < 0.001) , while the expression of M1 marker i-Nos decreased (P< 0.05). Immunofluorescence confirmed a lower i-Nos+ cell ratio (P< 0.05) and higher F4/80+CD206+ cell ratio (P< 0.000 1) in the MSCTLR4+IFN-γ group compared with the infection group. In vitro co-culture experiments further demonstrated that MSCTLR4+IFN-γ promoted Arg-1 expression, suppressed pro-inflammatory cytokine i-Nos and TNF-α levels, consistent with ELISA results. ConclusionsThis study reveals that TLR4 and IFN-γ co-activated MSCs alleviate Schistosoma japonicum-induced hepatic fibrosis, potentially through modulating macrophage polarization toward the M2 phenotype. This mechanism may suppress inflammation and enhance extracellular matrix degradation, providing a therapeutic strategy for schistosomiasis-associated liver fibrosis.
4.Mechanism of Modified Erxian Decoction Regulating Perimenopausal Syndrome via SIRT1/Kisspeptin/GnRH Signaling Pathway
Ruiyu HUANG ; Fang LEI ; Wuchaonan LIU ; Jingjing YANG ; Qianru ZENG ; Shengping LUO ; Yanling CHEN ; Mengge ZHANG ; Fanshun SHEN ; Yihui DENG ; Dingxiang LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):51-62
ObjectiveTo explore the regulation of hypothalamic-pituitary-gonadal (HPG) axis by modified Erxian decoction in rats with perimenopausal syndrome (PMS) and to further analyze the expression of proteins related to the silent information regulator 1 (SIRT1)/hypothalamic kisspeptin (Kisspeptin)/gonadotropin-releasing hormone (GnRH) signaling pathway in the arcuate nucleus region (ARC) of the hypothalamus, so as to reveal the potential target of action and molecular biological mechanism of modified Erxian decoction for the treatment of perimenopausal syndrome. MethodsAn animal model was established via the incomplete castration method, with successful modeling confirmed by the exfoliated cervical cell smear method. The 48 rats were divided into six groups based on the randomization principle after successful modeling, including a sham operation group, a model group, an estradiol valerate group (0.09 mg∙kg-1∙d-1), high-, medium-, and low-dose modified Erxian decoction groups (7.614, 3.807,1.903 5 g∙kg-1∙d-1), with 8 rats in each group. The estradiol valerate group and the high-, medium- and low-dose modified Erxian decoction groups were continuously administered by gavage for 28 days, and the indicators were detected 24 hours after the last administration. Body weights and uterine indices were measured. The pathological changes of the uterus were observed by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and gonadotropin-releasing hormone (GnRH). Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to determine the expression levels of SIRT1, Kisspeptin, kisspeptin receptor (GPR54), and GnRH in the ARC region of the hypothalamus and gonadotropin-releasing hormone receptor (GnRH-R) in pituitary. ResultsCompared with the sham operation group, rats in the model group had a significantly increased body weight (P0.01), reduced wet weight and index of uterus (P0.01), endometrial thinning or atrophy, glandular atrophy, and a decreasing number of glands. Additionally, serum levels of E2 and the expression of SIRT1 in the ARC region of the hypothalamus significantly decreased (P0.01). Serum levels of FSH, LH, and GnRH, the expression of Kisspeptin, GPR54, and GnRH in the ARC region of the hypothalamus, and GnRH-R in pituitary significantly increased (P0.01). Compared with the model group, the estradiol valerate group and the high-, medium-dose modified Erxian decoction groups had significantly reduced body weight, serum levels of FSH, LH, and GnRH, and expression of Kisspeptin, GPR54, and GnRH in the ARC region of the hypothalamus and GnRH-R in pituitary (P0.05, P0.01) and significantly increased wet weight and index of uterus, serum level of E2, and expression of SIRT1 in the ARC region of the hypothalamus (P0.05, P0.01). In addition, they showed thickened endometrium, increased number of endometrial glands, and improved glandular atrophy. ConclusionModified Erxian decoction regulates the function of the HPG axis through multi-targets, and its mechanism of action may be related to the up-regulation of the expression of SIRT1 in the ARC region of the hypothalamus, the inhibition of the over-activation of the Kisspeptin/GnRH signaling pathway, the regulation of the expression of GnRH-R in the pituitary, the restoration of secretion balance of gonadotropins, and the elevation of the estrogen level. This study provides an experimental basis for the interpretation of the scientific connotation of modified Erxian decoction in the treatment of perimenopausal syndrome and a theoretical reference for the development of a novel therapeutic strategy based on the SIRT1/Kisspeptin/GnRH pathway.
5.Overview of the establishment of Shanghai twin birth cohort
Shan JIN ; Naisi QIAN ; Weixiao LIN ; Liping FANG ; Lei CHEN ; Bo FANG ; Tian XIA ; Chunfang WANG ; Huiting YU
Shanghai Journal of Preventive Medicine 2024;36(1):16-20
ObjectiveTo establish the Shanghai twin birth cohort (STBC) and analyze the effects of genetic factors, shared environment, and non-shared environment interactions on birth health and growth and development of newborns. MethodsBased on the population-wide birth cohort in Shanghai, a comprehensive survey was conducted on the families with double and multiple babies born after January 1, 2015 to collect information on birth health, growth and development, and the family environment of the babies. ResultsBy December 31, 2021, a total of 7 195 pairs (14 405 cases) of twins were successfully included in the STBC survey. The average birth length of twins was 47.2 cm and average birth weight was 2 465.3 g. Heterozygous twins accounted for 69.05% and preterm babies accounted for 57.07%. The average age of the mothers of twins was 31.82 years, and the average age of the fathers was 33.87 years, with more than 80% of the parents having a college degree or above. 44.50% of the mothers used assisted reproductive technologies, 7.40% had illnesses during pregnancy, and 15.90% were exposed to passive smoking during pregnancy. During the survey period, the average monthly increase in the length of the twin infants was 2.09 cm, and the average monthly weight gain was 0.53 kg. ConclusionThe incidence of adverse outcomes such as maternal cesarean section rate, preterm birth, and low birth weight is higher in the twin birth population. Information on birth health as well as growth and development in childhood and adolescence in the twin birth population is collected based on STBC, which can provide a solid data foundation for studying children’s chronic non-communicable diseases, psychological and behavioral disorders and other complex health problems caused by the combined effects of genetics and the environment.
6.Real-world research on Panlongqi tablets in the treatment of fractures
Shiyuan FANG ; Jian QIN ; Liyong ZHANG ; Zerong WU ; Tuanmao GUO ; Ting DONG ; Wei XU ; Jiazhao YANG ; Lei CHEN ; Bin LIU
China Pharmacy 2024;35(24):3046-3051
OBJECTIVE To evaluate the effectiveness and safety of Panlongqi tablets in the treatment of fractures based on real-world research. METHODS From September 2021 to September 2023, fracture patients admitted to 33 medical institutions were collected retrospectively. Patients who received conventional treatment were divided into control group (n=3 750), and patients who received combination of Panlongqi tablets on the basis of conventional treatment were divided into observation group (n= 3 706). Self-reported indicators of patients were collected through telephone follow-up at 0, 4, 7 and 14 days after treatment. The improvement values of pain score, swelling score and health utility value, as well as effective rate and adverse drug reactions were compared between 2 groups. The propensity matching score (PSM) method was adopted to perform baseline matching on patient’s age, gender, fracture site, fracture severity, surgical type, type of hospital, and other indicators. Statistical analysis was performed on each therapeutic effect indicator. RESULTS After PSM, a total of 6 425 patients were included, of which 3 055 were in the observation group and 3 370 were in the control group. After 14 days of treatment, the observation group showed significant improvement in pain score (4.768 vs. 4.353), swelling fangshiyuan2008@126.com grading score (2.979 vs. 2.391), and life quality utility value (0.430 vs. 0.363), as well as effective rate (87.20% vs.75.99%) compared to the control group (P<0.05). The results of subgroup analyses conducted by gender, age, hospital type, and fracture site were consistent with the aforementioned results. In terms of safety, the observation group had no serious adverse reactions, with a total of 29 cases of mild adverse reactions such as dizziness, stomach pain, and allergies, with an incidence rate of 0.78%. CONCLUSIONS Panlongqi tablets combined with conventional treatment are significantly better than conventional treatment in improving pain, swelling, quality of life, and effective rate in patients with fractures, and have good safety.
7.Nested case-control study on children with severe birth defects in Shanghai
Naisi QIAN ; Shan JIN ; Wenwei ZHENG ; Lei CHEN ; Bo FANG ; Chunfang WANG ; Tian XIA ; Huiting YU
Shanghai Journal of Preventive Medicine 2024;36(5):463-468
ObjectiveTo design a prospective nested case-control study based on a city-wide birth cohort of Shanghai, so as to understand their health status and explore the influencing factors of birth defects. MethodsBased on the birth registration covering the entire city of Shanghai, the nested case-control study of children with severe birth defects was designed. Children born with severe birth defects were selected as the case group, and healthy children were matched as the control group. Basic information, health status, maternal pregnancy history, and survival outcome of children both in the case group and the control group were collected through medical history review and home visits. The logistic regression model was used for multivariate analysis. ResultsA total of 18 875 infants born between January 1, 2011, and December 31, 2021, were included, among which 11 500 (60.93%) were children with severe birth defects and 7 375 (39.07%) were healthy children. The logistic regression model analysis showed that being male (OR=1.20, 95%CI:1.13‒1.29), non-Shanghai residency (OR=1.16, 95%CI: 1.06‒1.25), multiple births (OR=8.41, 95%CI:6.25‒11.30), artificial insemination (OR=2.31, 95%CI:1.34‒3.99), in vitro fertilization (IVF) (OR=1.85, 95%CI:1.44‒2.38), maternal exposure to radiation (OR=1.83, 95%CI:1.07‒3.14), maternal illness during pregnancy (OR=1.61, 95%CI:1.49‒1.74), experiencing a traumatic event during pregnancy (OR=2.34, 95%CI:1.88‒2.92), paternal chemical exposure (OR=1.88, 95%CI:1.32‒2.69), paternal radiation exposure (OR=1.65, 95%CI: 1.18‒2.33), family history of birth defects (OR=8.18, 95%CI: 3.96‒16.89), being overweight before pregnancy (OR=1.16, 95%CI: 1.07‒1.27), being obese before pregnancy (OR=1.15, 95%CI:1.03‒1.30), and being excessively obese before pregnancy (OR=1.52, 95%CI:1.26‒1.83) were risk factors for the occurrence of birth defects. Analysis by type of birth defect found that prematurity was a risk factor for cardiac malformations and cheilopalatoschisis (OR=27.87, 95%CI: 20.84‒37.27), especially ranking first in cardiac malformations. ConclusionAfter controlling for influencing factors, maternal overweight, obesity, and excessive obesity before pregnancy, artificial insemination, and IVF are independent risk factors for the occurrence of birth defects. Choosing a healthy lifestyle, improving physical and mental health during pregnancy, and controlling BMI during pregnancy are beneficial in reducing the risk of birth defects.
8.Research progress on the influence of ligands on the stability of albumin
Lieqing YANG ; Rongchao YIN ; Lei YANG ; Jinrong JING ; Haitao FANG ; Jiaquan CHEN ; Weixin LIU
Chinese Journal of Blood Transfusion 2024;37(1):120-124
It is necessary to improve the stability of human serum albumin in response to the complex temperature, light and other conditions during the manufacture and storage. In this paper, the stabilization effect and simple stabilization mechanism of ligands on albumin were described from the perspective of ligand binding to albumin.Through review and comparison, it can be concluded that the common ligand sodium octanoate mainly plays a role in improving thermal stability, and the common ligand N-acetyl-L-tryptophan mainly plays a role in improving antioxidant activity, N-acetyl-L-methionine has better antioxidant and anti-photooxidation than N-acetyl-L-tryptophan.
9.Experts consensus on standard items of the cohort construction and quality control of temporomandibular joint diseases (2024)
Min HU ; Chi YANG ; Huawei LIU ; Haixia LU ; Chen YAO ; Qiufei XIE ; Yongjin CHEN ; Kaiyuan FU ; Bing FANG ; Songsong ZHU ; Qing ZHOU ; Zhiye CHEN ; Yaomin ZHU ; Qingbin ZHANG ; Ying YAN ; Xing LONG ; Zhiyong LI ; Yehua GAN ; Shibin YU ; Yuxing BAI ; Yi ZHANG ; Yanyi WANG ; Jie LEI ; Yong CHENG ; Changkui LIU ; Ye CAO ; Dongmei HE ; Ning WEN ; Shanyong ZHANG ; Minjie CHEN ; Guoliang JIAO ; Xinhua LIU ; Hua JIANG ; Yang HE ; Pei SHEN ; Haitao HUANG ; Yongfeng LI ; Jisi ZHENG ; Jing GUO ; Lisheng ZHAO ; Laiqing XU
Chinese Journal of Stomatology 2024;59(10):977-987
Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.
10.Study of the effects of dietary patterns on glycemic control in community type 2 diabetic mellitus patients
Liyun LEI ; Li QIN ; Zhanguo WANG ; Jun WANG ; Qun ZHAO ; Chaoqin JI ; Bo CHEN ; Qingjun ZHANG ; Fang ZHOU ; Ming WU ; Jinyi ZHOU ; Wenjuan WANG
Chinese Journal of Epidemiology 2024;45(2):242-249
Objective:To understand the impact of diet on glycemic control in community-managed patients with type 2 diabetes mellitus (T2DM) and provide evidence for implementing prevention strategies and measures for diabetes patients.Methods:Eight communities were randomly selected from Changshu and Wuhan in 2015, and T2DM patients managed in the community were selected to conduct questionnaire surveys, physical measurements, and blood glucose testing. Factor analysis was used to obtain dietary patterns. A binary logistic regression model was used to analyze the factors affecting glycemic control.Results:Finally, 1 818 T2DM patients were included, and the control rate of FPG was 57.59% (95% CI: 55.30%-59.86%), and the control rate of 2 h postprandial blood glucose (2 h PBG) was 24.90% (95% CI: 22.93%- 26.91%). Five dietary patterns were obtained by factor analysis: animal food pattern, fruit-aquatic products-potato patterns, vegetable-grain pattern, egg-milk-bean pattern, and oil-salt patterns. No-conditional multivariate logistic regression analysis showed that after adjusting for confounding factors, the reduced probability of FPG control was related to animal food pattern ( OR=0.71, 95% CI: 0.52-0.98) and fruit-aquatic products-potato patterns ( OR=0.71, 95% CI: 0.51-0.97). The decrease in the 2 h PBG control probability was related to fruit-aquatic products-potato patterns ( OR=0.60, 95% CI: 0.40-0.90). The increased probability of FPG and 2 h postprandial glucose control were both related to vegetable-grain pattern ( OR=1.41, 95% CI: 1.03-1.94; OR=1.68, 95% CI: 1.13-2.51) and egg-milk-bean pattern ( OR=1.75, 95% CI: 1.25-2.46; OR=1.56, 95% CI: 1.00-2.42). Compared with the Q4 group of egg-milk-bean pattern, the FPG control rate of the combination of "fruit-aquatic products-potato pattern ( Q4 group), vegetable-grain pattern ( Q2 group), egg-milk-bean pattern ( Q3 group)" was higher ( OR=6.79, 95% CI: 1.15-40.23, P=0.035). Compared with the Q4 group of vegetable-grain pattern, the combination of "fruit-aquatic products-potato pattern ( Q4 group), vegetable-grain pattern ( Q3 group), egg-milk-bean pattern ( Q2 group), oil-salt pattern ( Q2 group)" had higher control rate of 2 h PBG ( OR=12.78, 95% CI: 1.26-130.05, P=0.031). Conclusions:A proper combination of dietary patterns and dietary patterns are more conducive to the control of FPG and 2 h PBG in T2DM patients managed in the communities of Wuhan and Changshu. Patient nutrition education should be strengthened, and the food-matching ability of patients should be improved.

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