Objective To investigate the regulatory mechanism of transforming growth factor-β1 (TGF-β1) in different types of mitral valvular disease (MVD) with atrial fibrillation (AF). Methods From August 2011 to August 2012, patients with moderate to severe MVD accompanied by AF who required mitral valve replacement at the Department of Cardiovascular Surgery, West China Hospital, Sichuan University, were included. Based on echocardiographic results, patients were divided into two groups: a mitral regurgitation (MR) with AF (MR-AF) group and a mitral stenosis (MS) with AF (MS-AF) group. Left atrial tissue samples were collected during surgery. Techniques such as enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, immunohistochemistry, and Western blotting were used to detect key molecules in the TGF-β1/JNK pathway. Results Sixteen patients were enrolled. There were 8 patients in the MR-AF group, including 5 males and 3 females, with an average age of (41.38±11.19) years; and 8 patients in the MS-AF group, including 6 males and 2 females, with an average age of (43.12±5.30) years. The left atrial volume load was higher in MR-AF patients, while the left atrial pressure load was higher in MS-AF patients. In MS-AF patients, the relative expression levels of MAPK9, JUN, CASP3, BAX, and BCL2 mRNA in left atrial tissues were significantly upregulated. The serum TGF-β1 protein level and the relative expression levels of p-JNK, p-c-Jun, and Caspase-3 proteins in the left atrial tissues of the MR-AF group were higher. Myocardial cell damage was more severe in the MS-AF group, and the protein expression level of Bcl-2 was higher. Conclusion Different MVD have distinct hemodynamic characteristics. The myocardium of the left atrium in MR-AF patients is more prone to apoptosis, possibly through the activation of the TGF-β1/JNK signaling pathway.

BACKGROUND: G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present work, we explored how paroxetine, a GRK2 inhibitor, modulates the differentiation and activation of immune cells in rheumatoid arthritis (RA). METHODS: The blood samples of healthy individuals and RA patients were collected between July 2021 and March 2022 from the First Affiliated Hospital of Anhui Medical University. C57BL/6 mice were used to induce the collagen-induced arthritis (CIA) model. Flow cytometry analysis was used to characterize the differentiation and function of dendritic cells (DCs)/T cells. Co-immunoprecipitation was used to explore the specific molecular mechanism. RESULTS: In patients with RA, high expression of GRK2 in peripheral blood lymphocytes, accompanied by the increases of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR). In animal model, a decrease in regulatory T cells (T regs ), an increase in the cluster of differentiation 8 positive (CD8 + ) T cells, and maturation of DCs were observed. Paroxetine, when used in vitro and in CIA mice, restrained the maturation of DCs and the differentiation of CD8 + T cells, and induced the proportion of T regs . Paroxetine inhibited the secretion of pro-inflammatory cytokines, the expression of C-C motif chemokine receptor 7 in DCs and T cells. Simultaneously, paroxetine upregulated the expression of programmed death ligand 1, and anti-inflammatory cytokines. Additionally, paroxetine inhibited the PI3K-AKT-mTOR metabolic pathway in both DCs and T cells. This was associated with a reduction in mitochondrial membrane potential and changes in the utilization of glucose and lipids, particularly in DCs. Paroxetine reversed PI3K-AKT pathway activation induced by 740 Y-P (a PI3K agonist) through inhibiting the interaction between GRK2 and PI3K in DCs and T cells. CONCLUSION Paroxetine exerts an immunosuppressive effect by targeting GRK2, which subsequently inhibits the metabolism-related PI3K-AKT-mTOR pathway of DCs and T cells in RA.
G-Protein-Coupled Receptor Kinase 2/metabolism* ; Arthritis, Rheumatoid/immunology* ; Animals ; Dendritic Cells/metabolism* ; Paroxetine/therapeutic use* ; Proto-Oncogene Proteins c-akt/metabolism* ; Mice ; Humans ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Male ; Phosphatidylinositol 3-Kinases/metabolism* ; Lymphocyte Activation/drug effects* ; Female ; T-Lymphocytes/metabolism* ; Middle Aged

This article systematically reviews the characteristics and trends of the writing, editing, publication and promotion of physiology textbooks in China from the late 19th century to the present, focusing on the introduction, development and innovation of Chinese physiology textbooks. The development of physiology textbooks in China is divided into four main stages: the introduction and initial development of physiology textbooks from the late 19th century to 1925; the localization and diversification of textbooks from 1926 to 1949, after the establishment of the Chinese Physiological Society; the exploratory phase of textbook construction after the founding of the People's Republic of China from 1949 to 1976; the formation and innovation of the textbook development process from 1977 to the present, following the restoration of the college entrance examination. For each phase, the article not only records the historical development of physiology textbooks, but also analyzes the evolution of their content, writing styles and the interaction with the social and political contexts. The article summarizes the characteristics and experiences of all these four phases. Special attention is given to the comprehensive statistical analysis of physiology textbooks published since the restoration of the college entrance examination and Economic Reform and Opening-up in 1977, revealing the changes in the number, publication trends and academic features of textbooks during this period. Finally, the article presets the future development of physiology textbooks in China, proposing that textbook writing should integrate aspects such as ideological and political education, medical humanities, basic and clinical medicine, health education, scientific research and international exchange and collaboration. The article also advocates for the application of new technologies and methods, such as artificial intelligence, virtual teaching models and knowledge graphs, to support "personalized learning". This research provides a systematic reference for the study of the history of medical education and offers theoretical support for the future innovation of physiology textbook in China.
Humans ; China ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Physiology/education* ; Textbooks as Topic/history*

This study aims to explore the protective effect of Chaihu Jia Longgu Muli Decoction on rats with heart failure after myocardial infarction, and to clarify its possible mechanisms, providing a new basis for basic research on the mechanism of classic Chinese medicinal formula-mediated inflammatory response in preventing and treating heart failure induced by apoptosis after myocardial infarction. A heart failure model after myocardial infarction was established in rats by coronary artery ligation. The rats were divided into sham group, model group, and low, medium, and high-dose groups of Chaihu Jia Longgu Muli Decoction, with 10 rats in each group. The low-dose, medium-dose, and high-dose groups of Chaihu Jia Longgu Muli Decoction were given 6.3, 12.6, and 25.2 g·kg~(-1) doses by gavage, respectively. The sham group and model group were given an equal volume of distilled water by gavage once daily for four consecutive weeks. Cardiac function was assessed using color Doppler echocardiography. Myocardial pathology was detected by hematoxylin-eosin(HE) staining, apoptosis was measured by TUNEL assay, and mitophagy was observed by transmission electron microscopy. The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and N-terminal pro-B-type natriuretic peptide(NT-proBNP) in serum were detected by enzyme-linked immunosorbent assay(ELISA). The expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), and cleaved caspase-3 was detected by Western blot. Additionally, the expression of phosphorylated nuclear transcription factor-κB(NF-κB) p65(p-NF-κB p65)(upstream) and nuclear factor kappa B inhibitor alpha(IκBα)(downstream) in the NF-κB signaling pathway was assessed by Western blot. The results showed that compared with the sham group, left ventricular ejection fraction(LVEF) and left ventricular short axis shortening(LVFS) in the model group were significantly reduced, while left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD) increased significantly. Myocardial tissue damage was severe, with widened intercellular spaces and disorganized cell arrangement. The apoptosis rate was increased, and mitochondria were enlarged with increased vacuoles. Levels of TNF-α, IL-1β, and NT-proBNP were elevated, indicating an obvious inflammatory response. The expression of pro-apoptotic factors Bax and cleaved caspase-3 increased, while the anti-apoptotic factor Bcl-2 decreased. The expression of p-NF-κB p65 was upregulated, and the expression of IκBα was downregulated. In contrast, the Chaihu Jia Longgu Muli Decoction groups showed significantly improved of LVEF, LVFS and decreased LVEDD, LVESD compared to the model group. Myocardial tissue damage was alleviated, and intercellular spaces were reduced. The apoptosis rate decreased, mitochondrial volume decreased, and the levels of TNF-α, IL-1β, and NT-proBNP were lower. The expression of pro-apoptotic factors Bax and cleaved caspase-3 decreased, while the expression of the anti-apoptotic factor Bcl-2 increased. Additionally, the expression of p-NF-κB p65 decreased, while IκBα expression increased. In summary, this experimental study shows that Chaihu Jia Longgu Muli Decoction can reduce the inflammatory response and apoptosis rate in rats with heart failure after myocardial infarction, which may be related to the regulation of the IκBα/NF-κB signaling pathway.
Animals ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Myocardial Infarction/physiopathology* ; Male ; NF-kappa B/genetics* ; Heart Failure/etiology* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; NF-KappaB Inhibitor alpha/genetics* ; Humans ; Tumor Necrosis Factor-alpha/genetics*

OBJECTIVES: To evaluate the efficacy and safety of avatrombopag in promoting platelet engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, compared with recombinant human thrombopoietin (rhTPO). METHODS: A retrospective analysis was conducted on 53 pediatric patients who underwent allo-HSCT at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from April 2023 to August 2024. Based on medications used during the periengraftment period, patients were divided into two groups: the avatrombopag group (n=15) and the rhTPO group (n=38). RESULTS: At days 14, 30, and 60 post-transplant, platelet engraftment was achieved in 20% (3/15), 60% (9/15), and 93% (14/15) of patients in the avatrombopag group, and in 39% (15/38), 82% (31/38), and 97% (37/38) in the rhTPO group, respectively. There were no significant differences between the two groups in platelet engraftment rates at each time point, cumulative incidence of platelet engraftment, overall survival, and relapse-free survival (all P>0.05). Multivariable Cox proportional hazards analysis indicated that acute graft-versus-host disease was an independent risk factor for delayed platelet engraftment (P=0.043). CONCLUSIONS In children undergoing allo-HSCT, avatrombopag effectively promotes platelet engraftment, with efficacy and safety comparable to rhTPO, and represents a viable therapeutic option.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Transplantation, Homologous ; Blood Platelets/drug effects* ; Thiazoles/therapeutic use* ; Thrombopoietin/therapeutic use* ; Thiophenes

OBJECTIVE: To evaluate the protective effects of gentiopicroside (GPS) against reactive oxygen species (ROS)-induced NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in endothelial cells, aiming to reduce atherosclerosis. METHODS: Eight-week-old male ApoE-deficient mice were randomly divided into 2 groups (n=10 per group): the vehicle group and the GPS treatment group. Both groups were fed a high-fat diet for 16 weeks. GPS (40 mg/kg per day) was administered by oral gavage to the GPS group, while the vehicle group received an equivalent volume of the vehicle solution. At the end of the treatment, blood and aortic tissues were collected for assessments of atherosclerosis, lipid profiles, oxidative stress, and molecular expressions related to NLRP3 inflammasome activation, ROS production, and apoptosis. Additionally, in vitro experiments on human aortic endothelial cells treated with oxidized low-density lipoprotein (ox-LDL) were conducted to evaluate the effects of GPS on NLRP3 inflammasome activation, pyroptosis, apoptosis, and ROS production, specifically examining the role of the sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. SIRT1 and Nrf2 inhibitors were used to confirm the pathway's role. RESULTS: GPS treatment significantly reduced atherosclerotic lesions in the en face aorta (P<0.01), as well as in the thoracic and abdominal aortic regions, and markedly decreased sinus lesions within the aortic root (P<0.05 or P<0.01). Additionally, GPS reduced oxidative stress markers and proinflammatory cytokines, including interleukin (IL)-1 β and IL-18, in lesion areas (P<0.05, P<0.01). In vitro, GPS inhibited ox-LDL-induced NLRP3 activation, as evidenced by reduced NLRP3 (P<0.01), apoptosis-associated speck-like protein containing a CARD, cleaved-caspase-1, and cleaved-gasdermin D expressions (all P<0.01). GPS also decreased ROS production, apoptosis, and pyroptosis, with the beneficial effects being significantly reversed by SIRT1 or Nrf2 inhibitors. CONCLUSION GPS exerts an antiatherogenic effect by inhibiting ROS-dependent NLRP3 inflammasome activation via the SIRT1/Nrf2 pathway.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Reactive Oxygen Species/metabolism* ; Iridoid Glucosides/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Animals ; Atherosclerosis/metabolism* ; Inflammasomes/drug effects* ; Male ; Sirtuin 1/metabolism* ; Signal Transduction/drug effects* ; Humans ; Endothelial Cells/pathology* ; Mice ; Oxidative Stress/drug effects* ; Apoptosis/drug effects* ; Lipoproteins, LDL ; Mice, Inbred C57BL

OBJECTIVE: To explore the association between acupuncture during controlled ovarian hyperstimulation (COH) and the live birth rate (LBR) using different propensity score methods. METHODS: In this retrospective cohort study, eligible women who underwent a COH were divided into acupuncture and non-acupuncture groups. The primary outcome was LBR, as determined by propensity score matching (PSM). LBR was defined as the delivery of one or more living infants that reached a gestational age over 28 weeks after embryo transfer. The propensity score model encompassed 16 confounding variables. To validate the results, sensitivity analyses were conducted using three additional propensity score methods: propensity score adjustment, inverse probability weighting (IPW), and IPW with a "doubly robust" estimator. RESULTS: The primary cohort encompassed 9751 patients (1830 [18.76%] in the acupuncture group and 7921 [81.23%] in the non-acupuncture group). Following 1:1 PSM, a higher LBR was found in the acupuncture cohort (41.4% [755/1824] vs 36.4% [664/1824], with an odds ratio of 1.23 [95% confidence interval, 1.08-1.41]). Three additional propensity score methods produced essentially similar results. The risk of serious adverse events did not significantly differ between the two groups. CONCLUSION This retrospective study revealed an association between acupuncture and an increased LBR among patients undergoing COH, and that acupuncture is a safe and valuable treatment option. Please cite this article as: Zheng XY, Jiang ZY, Li YT, Li CL, Zhu H, Yu Z, Yu SY, Yang LL, Tang SY, Lü XY, Liang FR, Yang J. Association between acupuncture and live birth rates after fresh embryo transfer: A cohort study based on different propensity score methods. J Integr Med. 2025; 23(5):528-536.
Humans ; Female ; Propensity Score ; Embryo Transfer ; Adult ; Acupuncture Therapy ; Retrospective Studies ; Pregnancy ; Live Birth ; Birth Rate ; Cohort Studies

Objective:To analyze the current status and trends in the clinical management and outcomes of respiratory distress syndrome (RDS) in preterm infants <32 weeks′ gestation admitted to the Chinese Neonatal Network (CHNN) from 2019 to 2023.Methods:A cross-sectional study was conducted from November 2024 to January 2025 using the CHNN cohort of very preterm and extremely preterm infants. A total of 30 869 RDS infants with gestational age <32 weeks were admitted within 1 day after birth to CHNN centers from 2019 to 2023. Data on demographics, perinatal management, early complications within 7 days of age, and in-hospital outcomes were collected. Yearly groups were defined by admission year. Trends by year were evaluated by Cochran-Armitage trend test, linear regression model and median regression model.Results:The gestational age at birth of 30 869 RDS infant was 28.9 (27.1, 30.7) weeks and the birth weight was 1 259 (932, 1 586) g. Males account for 56.5% (17 363/30 757). From 2019 to 2023, the prevalence of RDS was 73.8% (5 503/7 461), 74.5% (5 490/7 368), 79.8% (5 884/7 372), 81.6% (6 435/7 889), and 86.0% (7 557/8 789), respectively, showing an increasing trend year by year ( P<0.001). The overall rate of pulmonary surfactant administration was 72.4% (22 359/30 869), fluctuating between 71.2% (5 381/7 557) and 74.3% (4 089/5 503) over the 5-year period. Antenatal corticosteroids were administered to 82.3% (24 357/29 597) mothers of RDS infants and 23.6% (7 218/30 565) RDS infants received noninvasive positive end-expiratory pressure support in the delivery room, both showing a increasing trend over the 5 years (both P<0.001). The incidence of pneumothorax and the use rate of inhaled nitric oxide within 7 days of age were 1.3% (393/30 846) and 1.4% (436/30 869), respectively, both showing increasing trends over the 5 years (both P<0.001). The rate of complete course of antenatal corticosteroids administration was 64.6% (14 458/22 382), the rates of discharge against medical advice and mortality within 7 days of age were 5.3% (1 635/30 869) and 2.7% (724/26 803), respectively, all showing a decreasing trend over time (all P<0.05). Regarding in-hospital outcomes, mortality rate of RDS infants was 4.6% (1 228/26 803), showing a downward trend year by year ( P=0.005). The incidence of bronchopulmonary dysplasia (BPD) was 35.0% (9 417/26 919), and the combined incidence of death or BPD was 36.4% (9 763/26 803), both showing an increasing trend year by year (both P<0.001). Conclusions:RDS prevalence increased annually in preterm infants <32 weeks′ gestation from 2019 to 2023, with declining mortality but rising BPD rates. While antenatal steroid use and noninvasive positive end-expiratory pressure support application improved, full-course antenatal steroid compliance decreased. These findings highlight the need for standardized perinatal management protocols to improve the clinical management of RDS.

Objective:To evaluate the efficacy and safety of endoscopic injection sclerotherapy (EIS) and endoscopic rubber band ligation (ERBL) for the treatment of grade Ⅰ-Ⅲ internal hemorrhoids.Methods:A prospective study was conducted on patients with grade Ⅰ-Ⅲ internal hemorrhoids who sought treatment at Renmin Hospital of Wuhan University or the NO.2 People's Hospital of Fuyang City from November 2021 to November 2022. Eligible patients were continuously enrolled based on inclusion and exclusion criteria and randomized into 2 groups using a central randomization system: the EIS group and the ERBL group. The primary outcomes included symptom improvement rate, recurrence rate, incidence of adverse events (bleeding, anal distension, pain, urinary retention, etc.), surgical costs, patient satisfaction, hemorrhoidal disease symptom score (HDSS), European quality of life 5-dimensions (EQ-5D) score, and self-rated health status score.Results:A total of 203 patients were enrolled (86 from Renmin Hospital of Wuhan University and 117 from the NO.2 People's Hospital of Fuyang City), with 103 in the EIS group and 100 in the ERBL group. Both groups successfully completed endoscopic treatment for internal hemorrhoids. The surgical cost in the EIS group was significantly lower than that in the ERBL group (1 044.77±522.77 yuan VS 2 538.44±465.63 yuan, t=-21.660, P<0.001). The incidence of perioperative pain and moderate-to-severe pain in the EIS group was significantly lower than that in the ERBL group [2.91% (3/103) VS 25.00% (25/100), χ2=20.817, P<0.001; 0.97% (1/103) VS 18.00% (18/100), χ2=17.344, P<0.001]. There were no significant differences in the incidence of perioperative bleeding, anal distension, or urinary retention between the two groups [0.97% (1/103) VS 1.00% (1/100), 11.65% (12/103) VS 19.00% (19/100), 0.00% (0/103) VS 2.00% (2/100), P>0.05]. During the 12-week follow-up, 4 patients were lost to follow-up (all from the EIS group). There were no significant differences in symptom improvement rate, recurrence rate, or patient satisfaction rate between the two groups [96.97% (96/99) VS 96.00% (96/100), 3.03% (3/99) VS 5.00% (5/100), 97.98% (97/99) VS 95.00% (95/100), P>0.05]. At 12 weeks postoperatively, the HDSS in the EIS group significantly decreased compared to preoperative levels [0.0 (0.0, 1.0) VS 5.0 (3.0, 7.0), Z=-18.270, P<0.010], the EQ-5D score in the ERBL group significantly increased compared to preoperative levels (1.00±0.01 VS 0.98±0.03, F=27.527, P<0.010), and self-rated health status score in the ERBL group significantly increased compared to preoperative levels (92.31±6.89 VS 82.62±10.98, F=115.025, P<0.010). At 12 weeks postoperatively, the HDSS in the ERBL group significantly decreased compared to preoperative levels [0.0 (0.0, 1.0) VS 5.0 (4.0, 8.0), Z=-16.110, P<0.010], the EQ-5D score in the ERBL group significantly increased compared to preoperative levels (1.00±0.00 VS 0.98±0.05, F=13.718, P<0.010), and self-rated health status score in the ERBL group significantly increased compared to preoperative levels (93.46±6.35 VS 84.15±10.71, F=123.695, P<0.010). Conclusion:Both EIS and ERBL are safe and effective treatments for grade Ⅰ-Ⅲ internal hemorrhoids, with high patient satisfaction. Comparatively, EIS demonstrates lower surgical costs and a reduced incidence and severity of perioperative pain.