ObjectiveTo observe the changes in the levels of different subtypes of epidermal growth factor receptor （ErbB）， namely ErbB1， ErbB2， ErbB3， and ErbB4， in the spinal dorsal horn of inflammatory pain model rats， and to explore their mechanism of mediating hyperalgesia as well as the intervention mechanism of electroacupuncture at "Zusanli （ST 36）" and "Kunlun （BL 60）". MethodsThe study was divided into five parts. In experiment 1， 14 Sprague Dawley （SD） rats were randomly divided into control and inflammatory pain group （7 rats each group） to observe the pain behavior and the protein expression of different ErbB receptor subtypes in the spinal dorsal horn. In experiment 2， 30 rats were randomly divided into control group 1， inflammatory pain group 1， and low-， medium-， and high-concentration TX1-85-1 groups， with 6 rats in each group， to observe the effect of inhibiting spinal ErbB3 on inflammatory pain. In experiment 3， 12 rats were randomly divided into control virus group and ErbB3 knockdown virus group， with 6 rats in each group， to observe the effect of knocking down ErbB3 in the spinal dorsal horn on inflammatory pain. In experiment 4， 44 rats were randomly divided into control group 2， inflammatory pain group 2， electroacupuncture group， and sham electroacupuncture group， with 11 rats in each group， to observe the effect of electroacupuncture. In experiment 5， 40 rats were randomly divided into control group 3， inflammatory pain group 3， electroacupuncture group 1， and electroacupuncture + NRG1 group， with 10 rats in each group， to observe the effect of activating ErbB3 on electroacupuncture. A rat model of inflammatory pain was established by subcutaneous injection of 100 μl of complete Freund's adjuvant into the sole of the unilateral hind foot of SD rats. Rats in the low-， medium-， and high-concentration TX1-85-1 groups were intrathecally injected with ErbB3 inhibitor TX1-85-1 on day 5 to day 7 after modeling. Rats in the ErbB3 knockdown virus group were injected with ErbB3 knockdown virus packaged with adenovirus vector-based short hairpin RNA （shRNA） into the spinal dorsal horn in situ 3 weeks before modeling. Rats in each electroacupuncture group received electroacupuncture at bilateral "Zusanli （ST 36）" and "Kunlun （BL 60）" from day 1 to day 7 after modeling， with dense-sparse waves at a frequency of 2 Hz/100 Hz and a current of 0.5-1.5 mA for 30 minutes once a day. Rats in the electroacupuncture + NRG1 group were intrathecally injected with ErbB3 ligand recombinant human neuregulin-1 （NRG1） after electroacupuncture intervention from day 5 to day 7 after modeling. The mechanical withdrawal threshold and thermal withdrawal latency of rats were measured on day 1， 3， 5， and 7 after modeling to evaluate behavior， and Western Blot was used to detect the protein and phosphorylation levels of each ErbB subtype in the spinal dorsal horn. ResultsCompared with the control group， rats in the inflammatory pain group showed decreased mechanical withdrawal threshold and thermal withdrawal latency of rats， and increased expression of phosphorylated ErbB3 （p-ErbB3） protein in the spinal dorsal horn on days 1， 3， 5， and 7 after modeling （P＜0.01）. On day 5 and day 7 after modeling， compared with the inflammatory pain group 1， the mecha-nical withdrawal threshold and thermal withdrawal latency of rats in the medium- and high-concentration TX1-85-1 groups increased， and the expression of p-ErbB3 protein decreased （P＜0.05）. On day 1， 3， 5， and 7 after modeling， compared with the control virus group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the ErbB3 knockdown virus group increased （P＜0.05）. On day 5 and day 7 after modeling， compared with the inflammatory pain group 2 and the sham electroacupuncture group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the electroacupuncture group increased， and the expression of p-ErbB3 protein decreased （P＜0.05）. On day 5 and day 7 after modeling， compared with the electroacupuncture + NRG1 group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the electroacupuncture group 1 increased （P＜0.05）. ConclusionThe p-ErbB3 in the spinal dorsal horn involved in hyperalgesia in rats with inflammatory pain， and electroacupuncture at "Zusanli （ST 36）" and "Kunlun （BL 60）" can alleviate inflammatory pain by inhibiting the expression of p-ErbB3 protein in the spinal dorsal horn of rats.

Objective To investigate the species of sandflies and the prevalence of Leishmania infections in sandflies from selected areas of northern and northwestern China, so as to provide insights into identification of leishmaniasis vectors and assessment of epidemiological trends of leishmaniasis in China. Methods Sandfly samples were collected from Mentougou District of Beijing Municipality, Xiangning County in Linfen City of Shanxi Province, Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, and Payzawat County of Karamay District of Karamay City, Gaochang District of Turpan City in Xinjiang Uygur Autonomous Region from July 2023 to July 2024. Approximately 100 intact female sandfly samples were randomly selected from each site and the species of sandflies was identified according to morphological characteristics and molecular assays. Female sandflies originating from the same habitat were grouped into pools of 10 individuals. Leishmania infection was detected using polymerase chain reaction (PCR) assay targeting the internal transcribed spacer 1 (ITS-1) gene, and the prevalence of Leishmania infection was calculated in sandflies from different sampling sites using the minimum infection rate (MIR) method. In addition, positive amplicons were sequenced and subjected to phylogenetic analysis. Results A total of 6 155 sandflies were collected from different environments at sampling sites across the six aforementioned regions from July 2023 to July 2024. Phlebotomus chinensis (96.00%) was the dominant sandfly species in Mentougou District, Beijing Municipality, with a small proportion of Ph. sergenti (4.00%), and only Ph. chinensis was found in Xiangning County, Linfen City, Shanxi Province. Ph. wui was the only sandfly species detected in Ejin Banner, Alxa League, Inner Mongolia Autonomous Region, and Payzawat County, Kashgar City, Xinjiang Uygur Autonomous Region, and Ph. caucasicus (97.70%) was the dominant sandfly species in Karamay District, Karamay City, Xinjiang Uygur Autonomous Region, with a small proportion of Ph. wui (2.30%), while Ph. alexandri was the only species in Gaochang District, Turpan City, Xinjiang Uygur Autonomous Region. A total of 40, 60, 34, 18, 18, and 22 pools of sandfly samples were tested from Mentougou District in Beijing Municipality, Xiangning County in Linfen City of Shanxi Province, Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, Payzawat County in Kashgar City, Karamay District in Karamay City, and Gaochang District in Turpan City of Xinjiang Uygur Autonomous Region, respectively. L. infantum was detected in Ph. chinensis samples from Mentougou District in Beijing Municipality, and Xiangning County of Linfen City in Shanxi Province, with MIR of 0.25% to 1.00%, and L. donovani was detected in Ph. wui from Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, and Payzawat County in Kashgar City of Xinjiang Uygur Autonomous Region, with MIR of 0.56% to 0.88%; however, no Leishmania infection was detected in Ph. caucasicus from Karamay District in Karamay City or Ph. alexandri from Gaochang District in Turpan City of Xinjiang Uygur Autonomous Region. Phylogenetic analysis showed that the Leishmania ITS-1 gene sequences obtained from Mentougou District in Beijing Municipality and Xiangning County in Linfen City of Shanxi Province were clustered into the same clade with the reference sequences of L. infantum ITS-1 gene, while the Leishmania ITS-1 gene sequences obtained from Ejin Banner in Alxa League of Inner Mongolia Autonomous Region and Payzawat County in Kashgar City of Xinjiang Uygur Autonomous Region were clustered into the same clade with the reference sequences of L. donovani ITS-1 gene. Conclusions There are variations in sandfly species in selected areas of northern and northwestern China, and variations in the species of Leishmania infecting sandflies. Improved surveillance of sandfly vectors and targeted control strategies with adaptations to geographical features and leishmaniasis vectors are recommended.

Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

The abnormal accumulation, structural change, and spread of tau protein in the brain are now considered important factors in the progression of Alzheimer’s disease (AD) and many other tau-related neurodegenerative diseases. Clinical and pathological studies have shown that the amount and distribution of abnormal tau protein are closely related to synaptic damage, neuronal loss, and cognitive decline. Therefore, tau protein has become an important target for disease-modifying therapy. However, tau is difficult to target because it has no fixed structure, lacks a clear active site, undergoes many post-translational modifications, and forms different abnormal structures in different diseases and disease stages. Therefore, the effective and selective removal of harmful tau species is both a major opportunity and a major challenge in drug discovery for neurodegenerative diseases. Proteolysis-targeting chimeras (PROTACs) offer a new strategy to deal with this problem. Unlike traditional inhibitors, PROTACs do not simply block protein function. Instead, they bring the target protein close to an E3 ubiquitin ligase, which leads to ubiquitination and degradation of the target protein by the proteasome. This event-driven mechanism may be especially useful for disease-related proteins such as tau protein, which are hard to inhibit with traditional small molecules. In recent years, tau protein-targeting PROTACs and related degradation strategies have shown promising effects in cell and animal models. These effects include reducing abnormal tau protein levels, lowering synaptic toxicity, regulating disease-related signaling pathways, and improving behavioral or cognitive outcomes. These studies support targeted tau protein degradation as a promising therapeutic approach, although many problems still need to be solved before clinical use. In this review, we summarize recent progress in the development of tau protein-targeting PROTACs and discuss the main factors that affect their design and activity. We focus on the choice of tau protein-binding ligands, their binding sites, and their ability to recognize abnormal tau protein rather than normal tau protein. We also discuss the selection of E3 ligase recruiters, linker length and structure, ternary complex formation, and structure-activity relationships that influence degradation potency and selectivity. In addition, we introduce new strategies beyond traditional proteasomal degradation, including the regulation of tau protein phosphorylation and autophagy-based clearance. These approaches may be more suitable for different tau species or different stages of disease. A major challenge for tau protein-targeting PROTACs is delivery to the central nervous system. Many PROTACs have high molecular mass, large polar surface area, flexible structures, and may be removed by efflux transporters. As a result, they often have poor ability to cross the blood-brain barrier and may not reach enough free drug levels in the brain. Therefore, the therapeutic potential of tau protein-targeting PROTACs depends not only on their ability to degrade tau protein in vitro, but also on whether they can achieve long-lasting, selective, and safe target engagement in important brain regions after practical administration. Future studies should focus on improving selectivity for abnormal tau protein, understanding E3 ligase function in neural cells, designing brain-penetrant molecules, developing better delivery methods, and testing these drugs in models that better reflect human disease. Overall, tau protein-targeting PROTACs are a promising and fast-developing strategy for treating tau-related diseases. However, their successful clinical translation will require progress in chemical biology, medicinal chemistry, neuroscience, drug delivery, and translational medicine.

Helicobacter pylori （H. pylori） infection is not only associated with gastrointestinal diseases， but also potentially links with neuropsychiatric disorders revealed by recent studies. Through a systematic review of the existing literature， this review summarizes epidemiological evidence for the association between H. pylori infection and diseases such as Parkinson′s disease （PD）， Alzheimer′s disease （AD）， multiple sclerosis （MS）， migraine， depression， and anxiety disorders， and further explores potential mechanisms by which it affects central nervous system function， including neural pathways mediated by the enteric nervous system and the vagus nerve， immune pathways mediated by inflammatory cytokines， and endocrine pathways mediated by gut microbial metabolites. Additionally， the current challenges facing H. pylori eradication therapy and the prospects for emerging adjuvant strategies such as probiotics and fecal microbiota transplantation are discussed. Finally， future research directions are outlined， emphasizing the need for prospective cohort studies based on standardized diagnostic methods and further investigation using animal models to elucidate the pathophysiological mechanisms， with the aim of providing new perspectives for the prevention， treatment， and early intervention of related neuropsychiatric disorders.

Objective To explore the role of E1A binding protein p300 (EP300)-mediated crotonylation (Kcr) modification of malic enzyme 1 (ME1) in ferroptosis of renal tubular epithelial cells. Methods C57BL/6 mice were divided into Sham operation group (Sham group), DMSO vehicle control + ischemia-reperfusion (IR) injury group (Vehi + IR group), and EP300 inhibitor C646 + IR injury group (C646 + IR group), with 12 mice in each group. Pathological changes in renal tissues were evaluated in each group, and indicators of renal function, ferroptosis, and fibrosis were assessed. Another 24 mice were used to establish the IR injury model to analyze changes in Kcr modification levels and EP300 expression over the 14-day course of IR injury. The in vitro HK-2 cell experimental model was established and divided into control group, hypoxia/reoxygenation (H/R) group, and C646 + H/R group. Corresponding HK-2 cells were transfected with the ME1-K337R plasmid, in which lysine 337 (K) was mutated to arginine (R) to mimic the de-Kcr modification. Small interfering RNA was used to target EP300 and transfect the cells in order to obtain EP300 knockdown cells (siEP300). The expression of ferroptosis-related proteins and fibrosis phenotypes was detected. Results At 14 d after IR injury, the protein Kcr level and EP300 expression were increased in mice. Compared with the Sham group, the Vehi+IR group showed markedly disrupted renal tissue structure, extensive red collagen deposition in the renal interstitium, decreased expression levels of glutathione, reduced nicotinamide adenine dinucleotide phosphate (NADPH), and glutathione peroxidase 4 (GPX4, P＜0.01), increased malondialdehyde and serum creatinine levels (P＜0.01), decreased ME1 enzymatic activity (P＜0.001), and increased expression of fibronectin 1 and smooth muscle actin-α (P＜0.001). Compared with the Vehi+IR group, the C646+IR group showed alleviated renal pathological injury, improved renal function, and reduced ferroptosis and fibrosis (P＜0.05). Compared with the control group, HK-2 cells subjected to H/R treatment exhibited aggravated ferroptosis and fibrosis (P＜0.05); compared with the H/R group, the C646+H/R group showed reduced ferroptosis and fibrosis (P＜0.05). Transfection with the ME1-K337R plasmid and siEP300 showed reduced ME1 Kcr, ferroptosis, and fibrosis. Conclusions EP300 contributes to ferroptosis in renal tubular epithelial cells by mediating ME1 crotonylation, and inhibition of EP300 may help alleviate the chronic progression following IR injury.

Objective:To analyze the efficacy of combination of peginterferon α-2b（Peg-IFN α-2b）with nucleos（t）ide analogues（NAs）on antiviral therapy in children with chronic hepatitis B（CHB）and to provide an optimized clinical treatment strategies for CHB children.Methods:A retrospective analysis was conducted on 30 CHB children treated in The First Affiliated Hospital of the Army Medical University（Southwest Hospital）from January 2022 to January 2025 with treatment duration at least 48 weeks. The enrolled children were aged between 2 and 17 years and divided into the NAs combined with Peg-IFN α-2b（NPI）group（n=13）and NAs group（n=17）by their therapy regimens. The characteristics of baseline，week 12，week 24，week 48 and week 96 were compared between groups，as well as the differences in response to biochemical，immune and viral indicators at each observation point. Logistic regression analysis and receiver operating characteristic（ROC）curve analysis were performed to identify factors influencing the HBsAg seroclearance. Results:At baseline of treatment，the proportion of HBeAg positivity in the NPI group and the NAs group was high（76.9% vs 86.6%， χ2=0.679， P=0.628），and the alanine aminotransferase（ALT）and aspartate aminotransferase（AST）in the NPI group were significantly lower than those in the NAs group（ P<0.001）. At 24 weeks，the decrease in HBsAg in the NPI group was also significantly higher than that in the NAs group（ Z=-3.161， P=0.002）. Finally，the cumulative seroclearance rate of HBsAg at 96 weeks in the NPI group was significantly higher than that in the NAs group（46.15% vs 5.88%， χ2=0.679， P=0.025）. Mulitivariate Logistic regression analysis showed that treatment regimen and gender were risk factors affecting the outcome of HBsAg（ P<0.05）. ROC curve analysis showed that the increase in ALT at 12 weeks compared with baseline（AUC=0.857，Cutoff value=3.615 IU/L），the decrease in ALT at 24 weeks（AUC=0.870，Cutoff value=47.85 IU/L），and the decrease in HBsAg at 12 weeks and especially at 24 weeks（AUC=0.885，Cutoff value=0.97log IU/ml）were effective predictors of HBsAg prognosis at 96 weeks. Conclusion:In CHB children，antiviral regimen Peg-IFN α-2b combined with NAs was more effective than NAs alone in improving the HBsAg seroclearance rate of CHB，and the effects in female were better than in male. The decline of HBsAg and the fluctuation of ALT in the early treatment period are valid predictors of HBsAg clearance.

Objective:To establish 30-day of age transcutaneous bilirubin (TcB) reference curves for healthy neonates, and to investigate regional variations in bilirubin dynamics.Methods:A multicenter retrospective cohort study was conducted. A total of 220 950 healthy neonates born at a gestational age of 35-<42 weeks, with a birth weight ≥2 000 g, who did not receive phototherapy within 60 h after birth were recruited. All of them underwent remote TcB monitoring using the Bilibaby remote jaundice monitoring system between August 1 st, 2020 and December 31 st, 2024 in 426 hospitals. TcB data were collected within the period from birth to 30-day of age. The P40, P75, and P95 of TcB values were calculated, and dynamic TcB curves for 30-day of age were constructed. Patterns of bilirubin change, rates of change, and transition outcomes were described. Regional comparisons between South and North were conducted using linear mixed-effects models for TcB trajectories and Pearson′s chi-square test for outcome differences. Results:A total of 220 950 neonates were included, of whom 101 711 (46.03%) were female. Gestational age at birth was (38.75±1.12) weeks, and birth weight was (3 272±417) g. TcB levels increased rapidly within 3-day of age, peaked at 4-6-day of age, with peak values at P40, P75, and P95 of 200.6, 239.7 and 275.4 μmol/L (11.8, 14.1 and 16.2 mg/dl), respectively. TcB levels gradually declined thereafter and stabilized after 13-day of age, with values at P40, P75, and P95 fluctuating between 147.9-159.8, 190.4-200.6, and 231.2-239.7 μmol/L (8.7-9.4, 11.2-11.8, 13.6-14.1 mg/dl), respectively. Notably, among neonates categorized as low-or low-intermediate-risk within 3-day of age, 6 700 (12.76%) progressed to intermediate-high or high risk between 4 and 30 days of age. Before 13-day of age, TcB levels in the southern regions were consistently higher than those in the northern regions ( P=0.039); from 14 to 30 days of age, the overall TcB levels had no statistically difference, but the temporal changes in TcB still showed regional differences (degrees of freedom=3, all interaction P<0.05). Among neonates classified as low-or low-intermediate risk within 3-day of age, 25 326 were from southern regions, of whom 4 254 (16.80%) progressed to intermediate-high or high risk between 4 and 30 days of age. In northern regions, 27 193 neonates were classified as low-or low-intermediate risk within 3-day of age, among whom 2 446 (8.99%) progressed to intermediate-high or high risk. The risk progression between the 2 regions had statistically difference ( χ2=716.49, P<0.001). Conclusions:A TcB percentile curve for neonates within 30-day of age was established, revealing that both the overall TcB level and its temporal trend were higher in southern than in northern newborns. These findings provide baseline data to support continuous management of neonatal jaundice.

This study aims to analyze the screening results and epidemiological characteristics of prostate cancer (PCa) among elderly males in the rural areas of Songjiang, Shanghai City, through the implementation of a preliminary prostate-specific antigen (PSA) screening based on a community-linkage model, and to explore an effective screening approach. A retrospective observational study design was employed to collect data from residents who underwent PSA screening at Songjiang Hospital affiliated to Shanghai Jiao Tong University School of Medicine, in collaboration with multiple community health service centers in Songjiang District, Shanghai City, between June 2022 and June 2024, through free clinics and annual health examinations. Prostate biopsy was recommended for individuals with total PSA (tPSA) levels >10 ng/ml and those with 4 ng/ml≤tPSA≤10 ng/ml and abnormal free-to-total PSA (f/tPSA) ratios. Clinical characteristics of detected PCa patients were analyzed. Follow-up was conducted through phone calls and home visits by family doctors, coupled with enhanced health education. The results indicated that a total of 17 198 residents participated in the screening, among which 2 234 (12.99%) had tPSA levels between 4 ng/ml and 10 ng/ml, and 257 (1.49%) had tPSA levels >10 ng/ml. Ultimately, 417 residents underwent prostate biopsy, with 171 being diagnosed with PCa, yielding a positive biopsy rate of 41.00% and a PCa detection rate of 0.99%. The predominant pathological subtype among PCa patients was adenocarcinoma (168 cases, 98.24%). Of the 146 PCa patients who received treatment, the majority were classified as intermediate or high-risk (124 cases, 84.93%). Furthermore, with the optimization of the screening model, there was a significant increase in the proportion of subsequent outpatient visits. In conclusion, the community-linkage-based PSA screening model demonstrated high effectiveness in screening for PCa among elderly males in the rural areas of Songjiang, Shanghai City. Epidemiological findings revealed that PCa patients in this region are primarily composed of intermediate and high-risk groups, highlighting the need for intensified early screening and health education.

Objective:To observe the effect of moxibustion on angiogenesis-related indicators in knee joint synovial tissue of adjuvant arthritis model rats,and to explore the mechanism of moxibustion in inhibiting vascular endothelial growth factor(VEGF)expression in synovial tissue and further limiting the activation of Rho family proteins Rac1 and Cdc42,thereby inhibiting angiogenesis during rheumatoid arthritis(RA)treatment.Methods:Forty-eight male Sprague-Dawley rats were equally divided into a normal group,a model group,a moxibustion group,and a moxibustion+VEGF agonist group according to the random principle.The complete Freund's adjuvant method was used for modeling.On the 12th day after modeling,the moxibustion group and the moxibustion+VEGF agonist group were subjected to suspended moxibustion at bilateral Zusanli(ST36),Guanyuan(CV4),and Ashi points for 20 min each time,once a day,for a total of 15 times.The moxibustion+VEGF agonist group received VEGF agonist(tirofiban hydrochloride hydrate)injection in the knee joint cavity at the same time.Hematoxylin-eosin staining was used to evaluate the pathological changes of rat synovial tissue in each group.Immunohistochemistry was used to observe the CD31 expression level in rat synovial tissue.Western blotting was used to detect the levels of VEGF,Rac1,and Cdc42 protein in rat synovial tissue,and polymerase chain reaction(PCR)was used to detect the VEGF mRNA expression.Results:Compared to the normal group,the expression levels of CD31 protein and VEGF mRNA and protein in rat synovial tissue in the model group increased significantly(P<0.01),and the expression levels of phospho-Rac1 and phospho-Cdc42 proteins also increased significantly(P<0.01).After moxibustion intervention,the expression levels of CD31 protein and VEGF mRNA and protein in the moxibustion group were significantly lower than those in the model group(P<0.01),while the differences in each indicator between the moxibustion+VEGF agonist group and the model group were not statistically significant(P>0.05).Compared to the moxibustion group,the expression levels of CD31 protein,VEGF mRNA and protein,phospho-Cdc42,and phospho-Rac1 in the moxibustion+VEGF agonist group increased significantly(P<0.01).Conclusion:Moxibustion improved synovial inflammation in RA by inhibiting angiogenesis.The mechanism may be to regulate angiogenesis-related VEGF,restrict the activation of Rac1 and Cdc42,and inhibit pseudopodia formation in vascular endothelial cells,thereby reducing angiogenesis.