Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

ObjectiveTo observe the clinical effectiveness and potential mechanism of combined tongue three-needle acupuncture and acupoint application on Lianquan （CV 23） for patients with dysphagia after ischemic stroke. MethodsA prospective study was conducted on 160 patients with post-stroke dysphagia， who were randomly divided into a treatment group and a control group， with 80 cases in each group. The control group received conventional rehabilitation training， while the treatment group received tongue three-needle acupuncture combined with acupoint application on Lianquan （CV 23） on the basis of conventional rehabilitation training， for 4 weeks in both groups. We compared the clinical effectivenss of both groups after treatment， and assessed the swallowing function including videofluoroscopic swallowing study （VFSS）， standardized swallowing assessment （SSA） and functional oral intake scale （FIOS）， swallowing contrast test including hyoid maximum displacement （HmaxD）， pharyngeal transit time （PTT）， and upper esophageal sphincter （UES） opening， surface electromyography （sEMG） test including maximum amplitude and swallowing duration as well as swallowing quality of life questionnaire （SWAL-QOL） score of the patients in both groups before treatment， after 2 weeks and 4 weeks of treatment， respectively. ResultsThe total effective rate in treatment group was 82.50% （66/80）， significantly higher than 66.25% （53/80） in control group （P＜0.05）. The VFSS， and FOIS scores， UES opening rate and HmaxD， sEMG maximal amplitude values， and SWAL-QOL scores were increased in both groups after 2 weeks and 4 weeks of treatment compared with the values before treatment （P＜0.05）， while SSA scores， PTT， and swallowing duration were decreased compared within group before treatment （P＜0.05）. VFSS and FOIS scores， UES opening rate and HmaxD， sEMG maximal amplitude values， and SWAL-QOL scores after 2 and 4 weeks of treatment in the treatment group were higher （P＜0.05）， while SSA scores， PTT， and swallowing duration were lower （P＜0.05） than those in the control group at the same time. ConclusionCombined tongue three-needle acupuncture and acupoint application on Lianquan （CV 23） for patients with dysphagia after ischemic stroke can significantly improve swallowing activities， and its mechanism of action may be related to the improvement of the contraction ability and coordination of swallowing-related muscle groups.

This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified＿f＿Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Lung/metabolism* ; Mice, Inbred C57BL ; Capsules ; Orthomyxoviridae Infections/virology* ; Gastrointestinal Microbiome/drug effects* ; Male ; Humans ; Female ; Influenza A virus/physiology* ; Influenza, Human/virology*

This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

Objective:To investigate the diagnostic value of plasma cytokines such as interleukin (IL)-2, IL-6 and interferon (IFN)-γ in non-Hodgkin lymphoma (NHL).Methods:A retrospective case-control study was conducted. A total of 48 NHL patients admitted to the Second Affiliated Hospital of Xuzhou Medical University between January 2020 and December 2022 were selected as NHL group, and another 34 healthy people who underwent physical examimation during the same period were selected as the healthy control group. The levels of IL-2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF) - α and IFN-γ in the plasma of patients at first admission and healthy subjects during physical examination were detected by using flow cytometry. The differences in general data and all cytokines levels of both groups were compared. The collinearity stepwise screening was made in 7 cytokines levels, and the screened variables were included in multivariate binary logistic regression model. Plasma cytokines with independent effects on the pathogenesis of NHL were screened. Taking local biopsy, histopathological examination or immunohistochemical examination as the gold standard, the receiver operating characteristic (ROC) curves of individual and combined diagnosis of NHL based on the selected cytokines were drawn to judge the diagnostic effect of all indicators on NHL.Results:There were 32 males (66.7%) and 16 females (33.3%) in NHL group, with the median age [ M ( Q1, Q3)] of 56.50 (45.75, 67.50) years; there were 28 males (82.4%) and 6 females (17.6%) in the healthy control group, with the median age of 52.00 (47.50, 55.50) years. There were no statistically significant differences in age and gender composition between the 2 groups (all P > 0.05). The levels of IL-2 [1.44 (1.36, 1.85) pg/ml vs. 1.19 (0.86, 1.68) pg/ml] and TNF-α [3.46 (2.68, 4.06) pg/ml vs. 2.23 (1.52, 3.46) pg/ml] in NHL group were higher than those in the healthy control group, and the differences were statistically significant (all P < 0.05). There were no statistically significant differences in IL-4, IL-6, IL-10, IL-17, IFN-γ levels (all P > 0.05). According to collinear stepwise screening of independent variables, IL-4 and TNF-α were excluded from 7 cytokines, and the other 5 cytokines were included in multivariate logistic regression model, and the result showed that the decreased level of IL-2 ( OR = 0.20, 95% CI: 0.08-0.53, P = 0.001) and the increased levels of IL-6 ( OR = 1.18, 95% CI: 1.04-1.33, P = 0.009) and IFN-γ ( OR = 1.26, 95% CI: 1.08-1.46, P = 0.003) were independent risk factors for the onset of NHL. The results showed that the area under the curve of IL-2, IL-6, IFN-γ and the combination of 3 indexes for the diagnosis of NHL was 0.760 (95% CI: 0.651-0.870), 0.595 (95% CI: 0.468-0.722), 0.508 (95% CI: 0.373-0.642), 0.847 (95% CI: 0.763-0.930), and the optimal cut-off value of the combination of 3 indexes was 0.730 which was calculated by logistic regression model formula; the corresponding sensitivity and specificity were 70.2% and 94.1%, respectively. Conclusions:The decreased level of IL-2 and increased levels of IL-6 and IFN-γ at initial diagnosis are risk factors for the onset of NHL. The combined detection of the 3 indexes shows a good value in the diagnosis of NHL.