ObjectiveTo investigate the effects of targeted silencing of Runt-related Transcription Factor 3 （RUNX3） on the proliferation and migration of Mouse Hepatic Stellate Cells （HSCs）， as well as subsequent collagen deposition. MethodsMouse hepatic stellate cell line （JS-1） was selected and then morphologically observed and identified under a microscope. After the cells had fully adhered， they were treated with 5 ng/mL of transforming growth factor beta 1 （TGF-β₁） for 24 hours to induce hepatic stellate cell activation. Furthermore， a RUNX3 silencing model was established using RUNX3 lentiviral infection. The experiment was divided into four groups： Control group， TGF-β₁ group， TGF-β₁+siRNA-NC group， and TGF-β₁+siRNA-RUNX3 group. Protein expression changes of RUNX3， alpha-smooth muscle actin （α-SMA）， and Alpha 1 type I collagen （Collagen I） were detected using Western blot method. Cellular immunofluorescence assays were employed to investigate the deposition changes of α-SMA and RUNX3 in hepatic stellate cells. RT-qPCR was utilized to examine the mRNA expression changes of RUNX3， α-SMA， and Collagen I. The proliferative capacity of hepatic stellate cells was assessed using Edu staining. The migratory ability of hepatic stellate cells was evaluated through wound healing assays and Transwell migration experiments. ResultsCompared with Control group， a significant elevation in RUNX3 was observed in the TGF-β₁-induced activated HSCs （P<0.01）. Meanwhile， the protein and mRNA levels of fibrosis-related markers and α-SMA and Collagen I were significantly upregulated （P<0.001）. Additionally， the proliferation and migration capabilities of HSCs were significantly enhanced （P<0.001）. In contrast， when compared to TGF-β₁+siRNA-NC group， TGF-β₁+siRNA-RUNX3 group exhibited a notable decrease in RUNX3 and other related indicators， such as the protein and mRNA levels of α-SMA and Collagen I （P<0.05）. Concurrently， the proliferation and migration capabilities of HSCs were significantly inhibited in TGF-β₁+siRNA-RUNX3 group （P<0.01）. ConclusionSilencing RUNX3 can inhibit the deposition of collagen and the proliferation and migration of hepatic stellate cells. Conversely， RUNX3 promotes the proliferation and migration capabilities of HSCs， thereby facilitating the activation of HSC.

ObjectiveTo investigate the role of runt-related transcription factor 3 （RUNX3） in transforming growth factor-β₁ （TGF-β₁）-induced activation of mouse primary pulmonary fibroblasts （PFs）， and its effects on fibroblast activation protein （FAP） expression， cell proliferation， and collagen synthesis. MethodsPFs were isolated from C57BL/6 mice and cultured. A RUNX3 knockdown model was established using small interfering RNA （siRNA）. Cells were assigned to the control group （Control）， TGF-β₁-treated group （TGF-β₁）， negative control group （TGF-β₁+siRNA-NC）， and RUNX3-silenced group （TGF-β₁+si-RUNX3）. In addition， a RUNX3 overexpression rescue experiment was performed based on TGF-β₁ stimulation. Protein and mRNA levels of RUNX3， FAP， and typeⅠcollagen （COL1A1） were measured by Western blot and reverse transcription quantitative real-time PCR （RT-qPCR）. Cell proliferation was assessed using CCK-8 and EdU assays. Co-expression of COL1A1 and FAP was examined by double immunofluorescence staining. ResultsCompared with the Control group， RUNX3， FAP， and COL1A1 expression levels were upregulated in PFs in the TGF-β₁ group （P<0.01）. The CCK-8 assay showed that the absorbance value was reduced in the RUNX3 knockdown group compared with the negative control group （P<0.01）. Consistently， the EdU assay demonstrated a lower proportion of EdU-positive cells in the RUNX3 knockdown group than in the negative control group （P<0.01）. Immunofluorescence double staining revealed decreased fluorescence intensities of COL1A1 and FAP in the RUNX3 knockdown group relative to the negative control. Under RUNX3 overexpression conditions， these fluorescence signals exhibited a partial rebound （P<0.01）. ConclusionRUNX3 in TGF-β1-induced PFs may promote cell proliferation and collagen synthesis by positively regulating FAP expression. Targeting the RUNX3/FAP axis may represent a potential therapeutic strategy for pulmonary fibrosis.

The prelimbic cortex (PL) plays a critical role in processing both the sensory and affective components of pain. However, the underlying molecular mechanisms remain poorly understood. In this study, we observed a reduction in hyperpolarization-activated cation current (I_h) in layer V pyramidal neurons of the contralateral PL in a mouse model of spared nerve injury (SNI). The expression of hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) channels was also decreased in the contralateral PL. Conversely, microinjection of fisetin, a partial agonist of HCN2, produced both analgesic and anxiolytic effects. Additionally, we found that cyclin-dependent kinase 5 (CDK5) was activated in the contralateral PL, where it formed a complex with HCN2 and phosphorylated its C-terminus. Knockdown of CDK5 restored HCN2 expression and alleviated both pain hypersensitivity and anxiety-like behaviors. Collectively, these results indicate that CDK5-mediated dysfunction of HCN2 in the PL underlies nerve injury-induced mechanical hypersensitivity and anxiety.
Animals ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism* ; Hyperalgesia/metabolism* ; Cyclin-Dependent Kinase 5/metabolism* ; Neuralgia/metabolism* ; Male ; Anxiety/metabolism* ; Mice ; Potassium Channels/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Pyramidal Cells/metabolism*

Bronchiectasis(BE) is the third major chronic airway disease, and its incidence rate shows a continuously increasing trend. Bronchiectasis is a highly heterogeneous chronic airway disease. Due to structural alterations, airflow limitation, and mucus hypersecretion, clinical treatment faces many challenges. Particularly, problems including Pseudomonas aeruginosa-dominant drug-resistant bacterial colonization, recurrent infections, airway mucus hypersecretion, and impaired lung function are the most urgent, requiring long-term and personalized treatment and management integrating traditional Chinese and western medicine to prevent the recurrence and continuous progression of the disease. In recent years, both traditional Chinese medicine and western medicine have made certain progress in pathogenesis theories, clinical studies, and basic research regarding the therapeutic challenges of bronchiectasis. Therefore, this paper summarized relevant research from the past 10 years and explored future directions and potential advantages of integrated traditional Chinese and western medicine treatment, providing references for optimizing the clinical management strategies for bronchiectasis.
Bronchiectasis/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Animals

Chronic kidney disease (CKD) is a significant global public health issue. In recent years, several new drugs have shown substantial efficacy in CKD treatment. Sodium-glucose cotransporter 2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists improve renal outcomes in CKD patients through various mechanisms, and also demonstrate favorable effects on cardiovascular outcomes. Novel agents, including endothelin receptor antagonists, are accumulating clinical evidence for delaying kidney disease progression, with ongoing development of new therapeutic targets. This article reviewed the latest research progress of these drugs in CKD treatment, offering new perspectives and reference points for comprehensive CKD management.

Objective:To investigate the overall drug resistance, drug resistance trend and distribution of drug resistance mutation sites in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients with antiviral therapy failure in Yunnan Province.Methods:The demographic data and genotype drug resistance of HIV/AIDS population with antiviral therapy failure in Yunnan Province from January 2021 to December 2023 were collected and analyzed by cross-sectional investigation. Statistical analyses were performed using chi-square test.Results:Among 15 159 HIV/AIDS patients, 12 215 cases tested positive by amplification. The circulating recombinant form (CRF) 08_BC was the predominant genetic subtype, accounting for 54.97%(6 714/12 215), followed by CRF01_AE (16.14%(1 972/12 215)) and CRF07_BC (14.48% (1 769/12 215)). When the viral load was ≥200 to <1 000 copies/mL, the incidence of drug resistance was 21.48%(99/461). When it was ≥1 000 to <10 000 copies/mL, the incidence was 51.29%(2 867/5 590). When it was ≥10 000 to <100 000 copies/mL, the incidence was 69.39% (3 979/5 734). When it was ≥100 000 copies/mL, the incidence was 81.86%(352/430). A total of 7 297 drug resistant cases were detected, with a drug resistance rate of 59.74% (7 297/12 215), thus the estimated drug resistance incidence rate among the antiviral treated population in Yunnan Province was 2.00% (7 297/364 238). From 2021 to 2023, the annual drug resistance rates among patients were 60.71%(2 554/4 207), 60.28%(1 671/2 772), and 58.67% (3 072/5 236), respectively, with no statistically significant difference ( χ2=4.47, P=0.107). Among the population with antiviral therapy failure, the drug resistance rates of non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), and protease inhibitor (PI) were 93.70%(6 837/7 297), 44.10%(3 218/7 297) and 5.15%(376/7 297), respectively. The mutation sites with the highest frequencies among the three classes of drugs including NRTI, NNRTI and PI were M184V/I (46.13%(2 123/4 602)), K103N/S (37.14%(2 648/7 129)), L33F (15.50%(82/529)) and M46I/L (15.50%(82/529)), respectively. Analysis of the degree of drug resistance showed that among NNRTI drugs, nevirapine (49.01%(5 987/12 215)) and efavirenz (48.00%(5 863/12 215)) had the highest drug resistance rates, followed by emtricitabine (23.59%(2 882/12 215)) and lamivudine (23.58%(2 881/12 215)) among NRTI drugs. Conclusions:Among HIV/AIDS patients with antiviral therapy failure in Yunnan Province from 2021 to 2023, CRF08_BC is the main genetic subtype. The drug resistance rate of patients increases with the increase of HIV-1 viral load. There is no significant change in the drug resistance rate from 2021 to 2023. NNRTI has the highest drug resistance rate, followed by NRTI, and PI has the lowest. The main mutation sites are M184V/I for NRTI, K103N/S for NNRTI, and M46I/L and L33F for PI. The drug resistance rates of nevirapine, efavirenz, emtricitabine and lamivudine are relatively high.

Objective:To investigate the efficacy and safety of sintilimab combined with the SOX regimen for adjuvant treatment of stage Ⅲgastric cancer after D2 radical resection and to provide a reference for individualized clinical treatment.Methods:The clinical data of 245 pa-tients with stage III gastric cancer who underwent D2 radical resection at the 940th Hospital of the Joint Support Force of the People's Liber-ation Army from June 2019 to May 2022 were retrospectively analyzed.The 180 patients who received only the SOX regimen were desig-nated the control group,and the 65 patients who received sintilimab combined with the SOX regimen were designated the experimental group.The 3-year disease-free survival(DFS)rate,overall survival(OS)rate,and adverse reactions among the two groups and different sub-groups(HER-2 positive,dMMR,CPS≥5)were compared.Results:The 3-year DFS(81.5%vs.59.4%)and OS(84.6%vs.70.6%)rates in the experimental group were significantly higher than those in the control group(both P<0.05).Group analysis showed that in patients with CPS≥5,the 3-year DFS(91.5%vs.67.0%)and OS(95.7%vs.71.6%)rates within the experimental group were significantly better than those in the control group(both P<0.05).Intra-group analysis within the experimental group showed that the 3-year DFS rate(91.5%vs.55.6%)and OS rate(95.7%vs.55.6%)of patients with CPS≥5 were significantly better than those of patients with CPS<5(both P<0.05).The overall and grade≥3 incidences of liver and kidney function damage,thyroid dysfunction,colitis,pneumonia,and rash in the experimental group were higher than those in the control group(all P<0.05),while the differences in other adverse reactions,including leukopenia were not statistic-ally significant(all P>0.05).Conclusions:Sintilimab combined with the SOX regimen can significantly improve 3-year DFS and OS rates in pa-tients with stage Ⅲ gastric cancer after surgery,especially in the CPS≥5 subgroup,with significant benefits and controllable safety.

Objective To construct the respiratory rehabilitation calisthenics for school-age children with asthma,and evaluate its effects,in order to provide a guidance for the scientific and effective implementation of respiratory rehabilitation in clinical work.Methods By convenience sampling method,the school-age children with asthma treated in the respiratory outpatient department of a tertiary specialized children's hospital in Chongqing from De-cember 2023 to February 2024 were selected.The children were randomly divided into an experimental group and the control group(25 of each group)by a random number table.Both groups were given routine asthma drug in-halation treatment and health education.Additionally,the experimental group received respiratory rehabilitation calis-thenics training and the control group received conventional aerobic exercise training.After 3-month intervention,the effects of adherence to respiratory rehabilitation training,lung functions,exercise capacity,inspiratory muscle strength and occurrence of adverse events were evaluated between 2 groups.Results 24 children of each group completed the study.After 3-month intervention,the adherence to respiratory rehabilitation training,exercise capacity and in-spiratory muscle strength were improved in the experimental group compared with those in the control group,and all differences were statistically significant(P＜0.05).There were no adverse events in both groups.Conclusion The respiratory rehabilitation calisthenics for school-age children with asthma constructed in this study was scientif-ic,feasible and safe,and could improve exercise capacity and inspiratory muscle strength for children with asthma.

Objective To investigate the epidemiological characteristics and risk factors of non-alcoholic fatty liver disease in Jincheng between 2015 and 2020. Methods Clinical data of 8,578 medical check-ups at Physical Examination Center of ou hospital from January 2015 to December 2020 were retrospectively selected. The prevalence of non-alcoholic fatty liver disease in the last 5 years was recorded, and Logistic regression was utilized to identify the risk factors for the development of non-alcoholic fatty liver disease. Results The overall prevalence of non-alcoholic fatty liver disease in Jincheng was 14.57% in 2015-2020. The prevalence of non-alcoholic fatty liver disease was higher in men than in women (16.99% vs 10.98%) and highest in the 40-59 age group (18.76%). No statistical difference was reported in blood urea nitrogen (BUN) and serum creatinine (Scr) between groups (P>0.05), while statistical difference was found in diabetes, hypertension, body mass index (BMI), waist circumference, weekly exercise frequency, daily vegetable intake, triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT) and uric acid (UA) between two groups (P<0.05). Multivariate Logistic regression analysis denoted that BMI (OR=2.794, 95% CI: 1.745-4.550), waist circumference (OR=2.586, 95% CI: 1.585-4.299), diabetes (OR=0.644, 95% CI: 1.425-2.781), hypertension (OR=1.479, 95% CI: 1.121-2.290), weekly exercise ≥6h (OR=0.617, 95% CI: 0.519-0.709), daily vegetable intake ≥300g (OR=0.590, 95% CI: 0.467-0.652), TG (OR=1.481, 95% CI: 1.122-1.996), TC (OR=1.562, 95% CI:1.143-2.135), LDL-C (OR=1.440, 95% CI: 1.139-2.048), HDL-C (OR=0.656 , 95% CI: 0.587-0.783) , ALT (OR=1.591, 95% CI: 1.056-2.183), and UA (OR=1.412, 95% CI: 1.009-1.887) were risk factors for non-alcoholic fatty liver disease (P<0.05) . Conclusion The prevalence of non-alcoholic fatty liver disease in Jincheng City from 2015 to 2020 is 14.57%, the prevalence of males is higher than that of females, and the prevalence rate is the highest in the 40-59 age group. Moreover , diabetes mellitus , hypertension , BMI , waist circumference , weekly exercise , daily vegetable intake , serum TG, TC, LDL-C, HDL-C, ALT, and UA are all associated with the risk of the disease.

Objective: To investigate the effect of targeted silencing of DNA methyltransferase 3A(DNMT3A) on collagen deposition, proliferation and migration activity of mouse lung fibroblasts(PFs). Methods: In order to ensure the proliferation and migration activity of primary fibroblasts, the lung tissues of neonatal C57 suckling mice were taken, PFs were extracted after being sheared, and the morphology was observed and identified under the microscope. PFs cells were activated by 5 ng/ml TGF-β1for 24 h after cell attachment, and DNMT3A silencing model was constructed by small interfering RNA; The experiment was divided into control group, TGF-β1group, TGF-β1+ siRNA-NC group and TGF-β1+ siRNA-DNMT3A group. The protein expressions of DNMT3A, α-smooth muscle actin(α-SMA) and Collagen Ⅰ were detected by Western blot; Real time quantitative reverse transcription polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression changes ofDNMT3A,α-SMAandCollagenⅠ. The proliferation ability of PFs was detected by CCK-8 and EdU staining; the migration ability of PFs was detected by scratch test and Transwell migration test. Results: Compared with the control group, TGF-β1induced the increase of DNMT3A in the activated PFs cell group(P<0.01), the protein and mRNA levels of fibrosis and proliferation related indicators α-SMA and Collagen Ⅰ also increased(allP<0.05), and the proliferation and migration ability of PFs increased(allP<0.000 1). Compared with the siRNA-NC group, the protein expression levels of DNMT3A(P<0.000 1) and related indicators α-SMA(P<0.01) and Collagen Ⅰ(P<0.01) significantly decreased in the DNMT3A silencing group by Western blot, and the mRNA levels ofDNMT3A,α-SMAandCollagenⅠby RT-qPCR also decreased(allP<0.001), and the proliferation(P<0.01) and migration ability(P<0.05) of PFs cells decreased compared with the control group. Conclusion Silencing DNMT3A can inhibit the deposition of collagen and the proliferation of PFs. DNMT3A can promote the proliferation and migration of PFs, and then promote the activation of PFs and the development of pulmonary fibrosis. This process may be regulated by DNA methylation modification.