1.Protective effect and mechanism of chikusetsu saponin Ⅳa on the kidney in diabetic nephropathy rats
Yongli WANG ; Hai CHEN ; Xiaofang TIAN ; Xuechun WANG ; Liying YUAN ; Dan LIU ; Zhongfa LI ; Yanfang MENG ; Xiuyong YANG
China Pharmacy 2026;37(7):908-913
OBJECTIVE To study the protective effect and potential mechanism of chikusetsu saponin Ⅳ a (chsⅣ) on renal function in diabetic nephropathy (DN) model rats. METHODS DN rat model was established by high-fat diet combined with streptozotocin injection. Thirty-six model rats were randomly divided into model group (i.g. administration of normal saline, high-fat diet), chsⅣ low-dose and high-dose groups (i.g. administration of 90, 180 mg/kg chsⅣ, high-fat diet), with 12 rats in each group. Additionally, 10 normal rats were set as the control group (i.g. administration of normal saline, regular diet). From the 5th to the 12th week after streptozotocin injection, they were given intragastric administration of relevant drug or normal saline, once a day. After the last medication, the levels of fasting blood glucose, fasting insulin, blood urea nitrogen, serum creatinine and urine protein as well as the levels of reduced glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) in renal tissues were measured. Additionally, the insulin resistance index was calculated. Hematoxylin-eosin, periodic acid-Schiff, and Masson staining techniques were employed to examine the histopathological alterations in the renal tissue. The expressions of Notch signaling pathway-related proteins in renal tissue were detected by immunohistochemical staining and Western blot methods. RESULTS Compared with model group, the histomorphological of renal tissues in the chsⅣ low- and high-dose groups were significantly improved, with significant decreases in renal histological scores, mesangial expansion index, and glomerulosclerosis scores ( P <0.05); the levels of fasting blood glucose, fasting insulin, blood urea nitrogen, serum creatinine, urine protein and homeostasis model assessment for insulin resistance, as well as MDA content, the expression levels of Notch1, Notch intracellular domain, hairy and enhancer of Split 1 and Delta-like protein 1 in renal tissue were all significantly decreased ( P <0.05). The levels of GSH and SOD in renal tissue were significantly elevated ( P <0.05). Moreover, the improvement in these indicators was significantly more pronounced in the chsⅣ high-dose group compared to the chsⅣ low-dose group ( P <0.05). CONCLUSIONS ChsⅣ can ameliorate renal pathological damage and functional impairment in DN rats. Its underlying mechanisms include restoration of glucose homeostasis and insulin sensitivity, attenuation of renal oxidative stress, and suppression of aberrant Notch signaling pathway activation.
2.Effect of Xixintang on Colonic Mucosal Barrier and TLR4 /NF-κB p65 Signaling Pathway in AD Model Rats Induced by D-galactose Combined with Aβ25-35
Yuan TIAN ; Yongchang DIWU ; Siyuan JIA ; Jie GAO ; Meirong WU ; Dengkun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):1-11
ObjectiveThis study aims to investigate whether Xixintang could ameliorate cognitive dysfunction in an Alzheimer's disease (AD) rat model induced by D-galactose and β-amyloid (Aβ25-35), by means of repairing the colonic mucosal barrier, regulating the Toll-like receptor 4 (TLR4)/nuclear factor-κB p65 (NF-κB p65) signaling pathway, and intervening in the pathological process mediated by the gut-brain axis. MethodsSixty specific pathogen-free (SPF) male Sprague-Dawley (SD) rats were randomly divided to five groups (n=12): A control group, a model group, a donepezil group, an Xixintang group, and a probiotic group. Except for those in the control group, rats in all other groups received daily intraperitoneal injections of D-galactose for six consecutive weeks. Subsequently, aggregated Aβ25-35 was injected stereotactically into the bilateral ventricles to establish the AD model. During the intervention periods, the rats in all groups were administered their respective drugs and normal saline by gavage. The Morris water maze test was used to assess the capacity for spatial learning and memory. Hematoxylin-eosin (HE) staining was employed to observe the histopathological changes in the colon tissues. Immunofluorescence was used to detect Aβ1-41 deposition in the hippocampal region and Mucin 2 (MUC2) expression in the colonic mucosa. Western blot was performed to measure the protein expression levels of FFAR2,TLR4, NF-κB p65, occludin (OCLN), zonula occludens-1 (ZO-1), and MUC2 in the colonic tissues. Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), serum amyloid A (SAA), and Aβ1-42 in the hippocampal region from the colonic tissues. The lipopolysaccharide (LPS) concentrations in colon tissues of rats were measured by using a dynamic chromogenic limulus assay. ResultsCompared with those in the control group, the rats in the model group exhibited a significantly prolonged escape latency and a markedly shorter duration in the target quadrant (P<0.01). The integrity of the colonic mucosal structure was compromised, with disordered gland arrangement and a reduced number of goblet cells. The Aβ1-42 deposition in the hippocampal region was significantly increased (P<0.01). The protein expression levels of TLR4 and NF-κB p65 in colonic tissues were significantly upregulated (P<0.01), while those of occludin and ZO-1 were downregulated (P<0.01). The contents of inflammatory factors such as IL-6, TNF-α, and SAA were significantly elevated (P<0.01), and the LPS level in the serum was markedly increased (P<0.01). In comparison to those in the model group, the rats in the Xixintang group showed a significantly shortened escape latency and a prolonged duration in the target quadrant (P<0.01). The colonic mucosal structure was ameliorated, with neat gland arrangement and an increased number of goblet cells. The Aβ1-42 deposition in the hippocampal region was reduced (P<0.01). The protein expressions of TLR4 and NF-κB p65 in the colon tissues were decreased (P<0.05,P<0.01), while the protein levels of occludin and ZO-1 were increased (P<0.01). The contents of IL-6, TNF-α, and serum amyloid A (SAA) were decreased (P<0.01), and the LPS level was reduced (P<0.01). ConclusionXixintang can significantly ameliorate cognitive dysfunction of AD model rats, by means of restoring the colonic mucosal barrier structure, reducing cerebral Aβ deposition, and suppressing peripheral and central inflammatory response. Its mechanism of action may be closely associated with the suppression of the TLR4/NF-κB signaling pathway activation, reduction of endotoxin levels, and regulation of the gut-brain axis.
3.Effect of Xixintang on Colonic Mucosal Barrier and TLR4 /NF-κB p65 Signaling Pathway in AD Model Rats Induced by D-galactose Combined with Aβ25-35
Yuan TIAN ; Yongchang DIWU ; Siyuan JIA ; Jie GAO ; Meirong WU ; Dengkun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):1-11
ObjectiveThis study aims to investigate whether Xixintang could ameliorate cognitive dysfunction in an Alzheimer's disease (AD) rat model induced by D-galactose and β-amyloid (Aβ25-35), by means of repairing the colonic mucosal barrier, regulating the Toll-like receptor 4 (TLR4)/nuclear factor-κB p65 (NF-κB p65) signaling pathway, and intervening in the pathological process mediated by the gut-brain axis. MethodsSixty specific pathogen-free (SPF) male Sprague-Dawley (SD) rats were randomly divided to five groups (n=12): A control group, a model group, a donepezil group, an Xixintang group, and a probiotic group. Except for those in the control group, rats in all other groups received daily intraperitoneal injections of D-galactose for six consecutive weeks. Subsequently, aggregated Aβ25-35 was injected stereotactically into the bilateral ventricles to establish the AD model. During the intervention periods, the rats in all groups were administered their respective drugs and normal saline by gavage. The Morris water maze test was used to assess the capacity for spatial learning and memory. Hematoxylin-eosin (HE) staining was employed to observe the histopathological changes in the colon tissues. Immunofluorescence was used to detect Aβ1-41 deposition in the hippocampal region and Mucin 2 (MUC2) expression in the colonic mucosa. Western blot was performed to measure the protein expression levels of FFAR2,TLR4, NF-κB p65, occludin (OCLN), zonula occludens-1 (ZO-1), and MUC2 in the colonic tissues. Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), serum amyloid A (SAA), and Aβ1-42 in the hippocampal region from the colonic tissues. The lipopolysaccharide (LPS) concentrations in colon tissues of rats were measured by using a dynamic chromogenic limulus assay. ResultsCompared with those in the control group, the rats in the model group exhibited a significantly prolonged escape latency and a markedly shorter duration in the target quadrant (P<0.01). The integrity of the colonic mucosal structure was compromised, with disordered gland arrangement and a reduced number of goblet cells. The Aβ1-42 deposition in the hippocampal region was significantly increased (P<0.01). The protein expression levels of TLR4 and NF-κB p65 in colonic tissues were significantly upregulated (P<0.01), while those of occludin and ZO-1 were downregulated (P<0.01). The contents of inflammatory factors such as IL-6, TNF-α, and SAA were significantly elevated (P<0.01), and the LPS level in the serum was markedly increased (P<0.01). In comparison to those in the model group, the rats in the Xixintang group showed a significantly shortened escape latency and a prolonged duration in the target quadrant (P<0.01). The colonic mucosal structure was ameliorated, with neat gland arrangement and an increased number of goblet cells. The Aβ1-42 deposition in the hippocampal region was reduced (P<0.01). The protein expressions of TLR4 and NF-κB p65 in the colon tissues were decreased (P<0.05,P<0.01), while the protein levels of occludin and ZO-1 were increased (P<0.01). The contents of IL-6, TNF-α, and serum amyloid A (SAA) were decreased (P<0.01), and the LPS level was reduced (P<0.01). ConclusionXixintang can significantly ameliorate cognitive dysfunction of AD model rats, by means of restoring the colonic mucosal barrier structure, reducing cerebral Aβ deposition, and suppressing peripheral and central inflammatory response. Its mechanism of action may be closely associated with the suppression of the TLR4/NF-κB signaling pathway activation, reduction of endotoxin levels, and regulation of the gut-brain axis.
4.Genetic disease diagnosis and treatment in Shanghai: Survey and countermeasures for clinical genetics specialist training.
Xiaoju HUANG ; Lin HAN ; Li CAO ; Taosheng HUANG ; Duan MA ; Jian WANG ; Wenjuan QIU ; Fanyi ZENG ; Luming SUN ; Chenming XU ; Songchang CHEN ; Xinyu KUANG ; Hong TIAN
Chinese Journal of Medical Genetics 2026;43(4):241-247
OBJECTIVE:
To investigate the current status of clinical genetics specialization development and the diagnostic and therapeutic capabilities for hereditary diseases across medical institutions in Shanghai, and to assess the necessity and feasibility of establishing training bases for clinical genetics specialists.
METHODS:
By employing a cross-sectional survey design, the Clinical Genetics Committee of Shanghai Medical Association has conducted questionnaire surveys from March to April 2025 across 54 healthcare institutions in Shanghai (including 33 tertiary hospitals and 21 secondary hospitals). The survey involved administrative departments and medical personnel from 15 clinical specialties. The survey has covered current genetic disease diagnosis and treatment practices, relevant and specialised disease types, genetic department establishment, testing capabilities, personnel teams, and training requirements.
RESULTS:
The results revealed that 78.0% of clinical departments surveyed had treated patients with hereditary disorders. Shanghai possesses diagnostic and therapeutic expertise for over 95% of hereditary diseases listed in its rare disease catalogue, reflecting both the practical clinical demand for such conditions and the city's overall diagnostic and therapeutic strengths in this field. Nevertheless, significant disparities exist in the development of genetics departments across different tiers of healthcare institutions. Resources for genetic testing capabilities (including molecular, cellular, and biochemical testing) are also unevenly distributed across different tiers of hospitals. The survey further revealed that only 26.0% of departments believe that their current physician structure fully meets the diagnostic and treatment demands. Over 90% of departments consider standard training for clinical genetic specialists necessary, with 74.0% expressing willingness to participate in establishing training bases. Based on above findings and thorough deliberation, the Clinical Genetics Committee of the Shanghai Medical Association proposes advancing specialist training and discipline development through establishing a standard training system. The committee has drafted a three-year training protocol featuring a "joint training"-centered model, recommending a pilot-first, dynamically optimized strategy for steadily advancing training base development.
CONCLUSION
Shanghai faces substantial demand for genetic disease diagnosis and treatment, yet exhibits shortcomings in clinical genetics specialization development, resource allocation, and talent pipeline cultivation. To establish a standard training system holds significant practical importance and is underpinned by a broad demand.
Humans
;
China
;
Surveys and Questionnaires
;
Genetic Diseases, Inborn/genetics*
;
Cross-Sectional Studies
;
Genetics, Medical/education*
;
Genetic Testing
5.Epidemiological characteristics of category C intestinal infectious diseases among children and adolescents in Shenzhen from 2012 to 2024 and the association with meteorological factors
Chinese Journal of School Health 2026;47(4):553-557
Objective:
To analyze the epidemiological characteristics of category C intestinal infectious diseases among children and adolescents in Shenzhen from 2012 to 2024 and the association with meteorological factors, so as to provide a scientific basis for the targeted prevention and control of infectious diseases for children and adolescents.
Methods:
Using data from the "Infectious Disease Reporting Information Management System" of the "China Disease Prevention and Control Information System" covering the period from January 1, 2012 to December 31, 2024, the study analyzed clinical and confirmed cases of hand, foot, and mouth disease, other infectious diarrhea, and acute hemorrhagic conjunctivitis among individuals aged 6-19 years old to describe demographic and temporal characteristics. It used Joinpoint regression to calculate the average annual percent change (AAPC) and annual percent change (APC) to analyze incidence trends, and Spearman s correlation was combined to generalize linear models so as to assess the association between category C intestinal infectious diseases and meteorological factors.
Results:
From 2012 to 2024, a cumulative total of 61 019 cases of hand, foot, and mouth disease among children and adolescents, 58 498 cases of other infectious diarrhea, and 6 377 cases of acute hemorrhagic conjunctivitis were reported. The AAPC in the incidence rates of these three diseases was 19.19%, 31.03% and 31.48 %, respectively(all P <0.05). Notably, the incidence of hand, foot, and mouth disease increased significantly after 2022 (APC= 133.66 %, P <0.01). The temporal distribution showed that hand,foot,and mouth disease was most prevalent in May,June and July (seasonal index of 2.39,3.64,1.97), other infectious diarrhea was most prevalent in February,March and December (seasonal index of 1.22,1.25,1.47), and acute hemorrhagic conjunctivitis peaked in September and October (seasonal index of 4.22,2.16). Monthly average temperature could increase the risk of hand,foot,and mouth disease( β = 0.18 ,95% CI =0.11-0.25); as monthly average wind speed increased, the incidence of other infectious diarrhea ( β =-0.86, 95% CI = -1.50 to -0.22) and acute hemorrhagic conjunctivitis ( β =-1.32, 95% CI =-2.60 to -0.05) both decreased (all P < 0.05 ).
Conclusions
Among children and adolescents in Shenzhen, category C intestinal infectious diseases remain prevalent throughout the year;the number of reported hand, foot, and mouth disease cases has shown an upward trend in recent years.Temperature and wind speed significantly affect the number of reported cases of three types with category C intestinal infectious diseases.
6.Potential drug targets for the treatment of rheumatoid arthritis:large sample analysis from European databases
Ying GUO ; Feng TIAN ; Chunfang WANG
Chinese Journal of Tissue Engineering Research 2026;30(6):1549-1557
BACKGROUND:Rheumatoid arthritis is influenced by complex genetic and environmental factors.Although observational studies have found some correlation between plasma proteins and rheumatoid arthritis,the susceptibility to confounding and reverse causation makes it difficult to clarify whether these proteins are pathogenic factors of rheumatoid arthritis.OBJECTIVE:To explore the potential of plasma proteins as biomarkers and therapeutic targets in rheumatoid arthritis through Mendelian randomization analysis of plasma proteins in the onset and progression of rheumatoid arthritis.METHODS:A large-scale two-sample Mendelian randomization analysis was conducted to comprehensively assess the causal relationships between 1 553 circulating proteins and rheumatoid arthritis based on the Decode database(developed by Decode Genetics in Iceland,which contains genomic data from the Icelandic population),the MR-Base platform(developed by a team of researchers at the University of Oxford in the United Kingdom,specifically designed to provide genetic and phenotypic data for Mendelian randomization analyses),and the GWAS Catalog platform(developed by the European Institute of Bioinformatics,which provides data for genome wide association studies worldwide).The causal effects were estimated using the Wald ratio and inverse variance weighting methods,with Bonferroni correction applied to control for false positives caused by multiple testing.To ensure the robustness of the results,sensitivity analyses were performed to validate the positive causal relationship between circulating proteins and rheumatoid arthritis,and Bayesian colocalization and phenome scanning were used to exclude confounding effects and horizontal pleiotropy.Additionally,external validation was carried out using new plasma protein datasets to reduce the likelihood of false discoveries.Finally,small-molecule compounds associated with candidate proteins were identified using the Drug Signatures Database(DsigDB),and molecular docking was performed to predict the binding patterns and energies between proteins and compounds,identifying the most stable and likely binding molecules and mechanisms.RESULTS AND CONCLUSION:(1)Sensitivity analyses,including Bayesian colocalization and phenome scanning,identified four plasma proteins with reliable causal relationships with rheumatoid arthritis:FCRL3,IL6R,ICOSLG,and TNFAIP3.Their genetic effects were estimated as follows:FCRL3[odds ratio(OR)=1.12,95%confidence interval(CI):1.07-1.17],IL6R(OR=0.94,95%CI:0.91-0.96),ICOSLG(OR=2.42,95%CI:1.67-3.52),and TNFAIP3(OR=2.19,95%CI:1.88-2.56).Furthermore,molecular docking analysis revealed that the small-molecule compound benzo[a]pyrene exhibited favorable binding with these candidate proteins,suggesting its potential as a therapeutic agent for rheumatoid arthritis.(2)This study provides a comprehensive analysis of the genetic causal relationships of FCRL3,IL6R,ICOSLG,and TNFAIP3 in rheumatoid arthritis.These proteins not only serve as potential molecular biomarkers for rheumatoid arthritis risk screening and disease prevention,but also offer key candidate targets for further understanding the pathogenic mechanisms of rheumatoid arthritis and developing targeted therapies.Although the study is based on European populations,its findings offer important insights for biomedical research in China.By incorporating Mendelian randomization methods to analyze genetic causality,future research on rheumatoid arthritis in the Chinese population could provide more accurate causal inferences,offering theoretical support for localized risk assessment and treatment strategies.
7.High tibial osteotomy on a single plane:femorofibular angle as a reference marker for mechanical axis correction
Xiaomin LI ; Xiangdong TIAN ; Chaolu WANG
Chinese Journal of Tissue Engineering Research 2026;30(3):570-576
BACKGROUND:The femorofibular angle is a commonly used reference angle for mechanical axis correction in high tibial osteotomy on a single plane,but there has been no in-depth study on the application of this angle in high tibial osteotomy on a single plane.OBJECTIVE:To explore the application effect of the femorofibular angle as a reference for mechanical axis correction in high tibial osteotomy on a single plane.METHODS:A retrospective analysis was conducted on 64 cases of knee osteoarthritis patients who underwent high tibial osteotomy on a single plane at Third Affiliated Hospital of Beijing University of Chinese Medicine from January 2023 to January 2024.The patients were grouped according to the intraoperative mechanical axis correction reference method.The observation group consisted of 32 cases,which used the femorofibular angle as a reference for mechanical axis correction during surgery.The control group consisted of 32 cases,which used electrocautery line measurement as a reference for mechanical axis correction during surgery.Both groups received the same perioperative treatment and management.The lower limb mechanical axis ratio,hip-knee-ankle angle,proximal medial tibial angle,and femorofibular angle were recorded before and after surgery to assess changes in the lower limb mechanical state.The operation time and number of fluoroscopies were recorded.The visual analog scale score and Lysholm score for pain and knee function were recorded before surgery and at 1 and 3 months after surgery to evaluate changes in knee pain and function.RESULTS AND CONCLUSION:(1)All patients completed the treatment and follow-up,and no serious adverse events occurred.(2)Before surgery,there was no statistically significant difference in the lower limb mechanical axis ratio,proximal medial tibial angle,hip-knee-ankle angle,and femorofibular angle between the two groups(P>0.05).At 3 months after surgery,the lower limb mechanical axis ratio,proximal medial tibial angle,hip-knee-ankle angle,and femorofibular angle were significantly improved in both groups compared to before surgery,with statistically significant differences(P<0.05).There was no significant difference between the two groups(P>0.05).(3)During surgery,the operation time and number of fluoroscopies in the observation group were less than those in the control group,with statistically significant differences(P<0.05).(4)At each follow-up point before and after surgery,there was no statistically significant difference in the visual analog scale score and Lysholm score between the two groups(P>0.05).With the passage of time after surgery,the visual analog scale score and Lysholm score in both groups were significantly improved compared to before surgery(P<0.05).(5)It is suggested that the application of the femorofibular angle as a reference for mechanical axis correction in high tibial osteotomy on a single plane can accurately locate the range of lower limb mechanical axis correction,is simple and reliable,and reduces the number of fluoroscopies and operation time compared to traditional electrocautery line measurement.
8.Differences in scapular kinematics between healthy individuals and rotator cuff tear patients based on biplane X-ray
Zicheng GUO ; Jingyuan MENG ; Jiechao ZHANG ; Li DING ; Xiaoye TANG ; Lichao TIAN ; Yilin WANG ; Yong HE
Chinese Journal of Tissue Engineering Research 2026;30(3):652-660
BACKGROUND:Due to the complex movement of the scapula,which is a six-degree-of-freedom activity in three-dimensional space,it is difficult to measure it accurately using traditional methods.The image and model matching technology based on dual-plane X-ray is a three-dimensional measurement method that has gradually developed and matured in recent years.Two high-speed cameras are used to project and shoot from orthogonal directions.Compared with a single perspective,this method has advantages in observation range and reduction of out-of-plane errors,and is suitable for the study of scapula kinematics.OBJECTIVE:X-ray biplane and image-model registration technology were used to explore the differences in scapular kinematics between normal individuals and patients with rotator cuff tears,providing a basis for the treatment and rehabilitation of rotator cuff tear patients.METHODS:From April 2023 to January 2024,10 patients with normal shoulders and 10 patients with rotator cuff tears who met the inclusion criteria were enrolled from Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine.The subjects underwent a shoulder CT scan to create a 3D model and a local scapular coordinate system.X-ray biplane images were taken during shoulder abduction with two C-arm machines.The 2D and 3D images were registered to compare scapular kinematic differences between the two groups at 0°,15°,30°,45°,60°,75°,and 90° of abduction,including scapular rotation angle and displacement distance.RESULTS AND CONCLUSION:(1)During shoulder abduction,the scapula of both groups showed upward rotation,but the upward rotation of the rotator cuff tear group was greater than that of the control group,and the difference was significant when the abduction was 30°-90°(P<0.01).At the same time,the scapula internal rotation of both groups gradually increased,but the rotator cuff tear group was significantly greater than the control group when the abduction was 45°-90°(P<0.01).In addition,the anteroposterior tilt of the scapula of the two groups was significantly different when the abduction was 15°-90°(P<0.01).The scapula posterior tilt of the control group gradually increased during abduction,while the scapula of the rotator cuff tear group tilted forward except for a slight posterior tilt at 15°-30° abduction.(2)In terms of displacement,the upward displacement of the rotator cuff tear group was less than that of the control group during abduction,and the difference was significant at 15°-90°(P<0.05),but there was no significant difference in lateral and anterior-posterior displacement between the two groups(P>0.05).(3)Rotator cuff tear can cause scapular dyskinesis,characterized by increased upward rotation,internal rotation,and abnormal forward tilt during shoulder abduction.Identifying and addressing scapular dyskinesis is crucial for treating rotator cuff tear.
9.Gene-predicted associations between 731 immune cell phenotypes and rheumatoid arthritis
Fengzhi LIU ; Yuna DONG ; Wenyi TIAN ; Chunlei WANG ; Xiaodong LIANG ; Lin BAO
Chinese Journal of Tissue Engineering Research 2026;30(5):1311-1319
BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.
10.Effect of Yangjing Tongluo Prescription on Oxidative Damage of Endometrium in Rats with Intrauterine Adhesion Based on Keap1/Nrf2/HO-1 Signaling Pathway
Jiaying CHEN ; Jing ZENG ; Zhaoling YOU ; Yonglian WANG ; Muya LIU ; Fang ZHOU ; Li TANG ; Sainan TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):100-108
ObjectiveTo explore the mechanisms of Yangjing Tongluo prescription (YJTL) in the treatment of intrauterine adhesion (IUA) from the perspective of oxidative stress mediated by the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Keap1/Nrf2/HO-1) signaling pathway. MethodsA total of 48 rats with normal estrous cycles were selected and randomly divided into a normal group (n=8) and a modeling group (n=40). An IUA rat model was established using a dual-injury method combining surgical curettage and infection. Eight rats were randomly selected from the modeling group for a pilot experiment to confirm successful model establishment. After successful modeling, the remaining 32 rats were randomly divided into a model group, a low-dose YJTL group (YJTL-L), a high-dose YJTL group (YJTL-H), and a Progynova group. Rats in the normal and model groups were administered purified water (15 mL·kg-1) by gavage daily, while rats in the YJTL-L, YJTL-H, and Progynova groups received YJTL at doses of 6.43 and 12.86 g·kg-1 and Progynova at 2.06 × 10-4 g·kg-1, respectively, for 14 consecutive days. The general condition, uterine morphology, and uterine index of the rats were monitored. Histopathological changes in uterine tissue were observed using hematoxylin-eosin (HE) staining. Serum levels of reactive oxygen species (ROS) and glutathione peroxidase (GSH-Px) were measured by enzyme-linked immunosorbent assay (ELISA). Protein expression levels of Keap1, Nrf2, and HO-1 in endometrial tissue were detected by Western blot. Immunofluorescence (IF) was used to assess the distribution of Nrf2 and HO-1, as well as the expression of Nrf2 in the cytoplasm and nucleus. ResultsCompared with the normal group, rats in the model group exhibited poor mental status and reduced mobility, markedly edematous and tortuous uterine morphology, decreased gland number, and inflammatory reactions in the endometrium, along with an increased uterine organ index (P<0.05). Serum ROS levels were significantly increased (P<0.05), while serum GSH-Px levels were significantly decreased (P<0.05). In endometrial tissue, Keap1 protein expression was increased (P<0.05), whereas Nrf2 and HO-1 protein expression was decreased. Mild nuclear translocation of Nrf2 was observed, accompanied by increased relative fluorescence intensity of nuclear Nrf2 and decreased relative fluorescence intensity of cytoplasmic HO-1. Compared with the model group, all treatment groups showed varying degrees of improvement in the above symptoms and pathological changes. Serum ROS levels were reduced (P<0.05), serum GSH-Px levels were increased (P<0.05), Keap1 protein expression in endometrial tissue was decreased, and Nrf2 and HO-1 protein expression was increased in a dose-dependent manner (P<0.05). Notably, significant nuclear translocation of Nrf2 was observed, with correspondingly increased relative fluorescence intensity of nuclear Nrf2 and enhanced relative fluorescence intensity of cytoplasmic HO-1. ConclusionYJTL may enhance antioxidant capacity and repair oxidative damage to the endometrial basal layer by regulating the Keap1/Nrf2/HO-1 signaling pathway.


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