Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective To investigate the impact of anti-reflux modified duodenal exclusion surgery on glucose metabolism in rats with type 2 diabetes mellitus (T2DM), and to elucidate the role of the duodenum in maintaining glucose homeostasis. MethodsForty male Sprague-Dawley rats aged 5 weeks were fed a high-fat diet and induced with T2DM using low-dose streptozotocin. Thirty-six rats that met the T2DM model criteria were randomly divided into three groups: the simple duodenal exclusion surgery group (DE group), the anti-reflux modified duodenal exclusion group (MDE group), and the sham operation group (SO group), with 12 rats in each group. Gastroenterography was performed 4 weeks after surgery, and the body weight, fasting blood glucose levels, and serum glucagon-like peptide-1 (GLP-1) concentrations were measured before surgery and at 1, 2, 4, and 8 weeks post-surgery. Eight weeks post-surgery, the rats were euthanized, and a 1 cm segment of the biliopancreatic loop was collected from each group for pathological sectioning and HE staining to observe the intestinal mucosal villus length under an optical microscope. Results Gastroenterography showed that there was significant reflux of the contrast agent into the duodenal lumen in the DE group, while no reflux was observed in the MDE group. At one week post-surgery, the body weights of rats in all three groups significantly decreased compared to before surgery (P<0.05), and then the body weights of all groups increased over time, with no significant differences between the groups (P>0.05). Compared with the SO group, the fasting blood glucose levels in the MDE and DE groups significantly decreased at all time points post-surgery (P<0.05), while GLP-1 concentrations significantly increased (P<0.05). The fasting blood glucose levels in the MDE group were lower than those in the DE group at all time points post-surgery (P<0.05), but there were no significant differences in serum GLP-1 concentrations between the MDE and DE groups (P>0.05). Regarding intestinal mucosal morphology, the villus lengths of the biliopancreatic loops in the MDE group were significantly shorter than those in the DE and SO groups (P<0.05). Conclusion Anti-reflux modified duodenal exclusion surgery effectively improves glucose metabolism in T2DM rats by preventing the reflux of chyme into the diverted duodenum, thereby enhancing its hypoglycemic effect.

Background::Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury.Methods::This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed. Results::The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH.Conclusions::The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

Noxious mechanical information is transmitted through molecularly distinct nociceptors, with pinprick-evoked sharp sensitivity via A-fiber nociceptors marked by developmental expression of the neuropeptide Y receptor 2 (Npy2r) and von Frey filament-evoked punctate pressure information via unmyelinated C fiber nociceptors marked by MrgprD. However, the molecular programs controlling their development are only beginning to be understood. Here we demonstrate that Npy2r-expressing sensory neurons are in fact divided into two groups, based on transient or persistent Npy2r expression. Npy2r-transient neurons are myelinated, likely including A-fiber nociceptors, whereas Npy2r-persistent ones belong to unmyelinated pruriceptors that co-express Nppb. We then showed that the transcription factors NFIA and Runx1 are necessary for the development of Npy2r-transient A-fiber nociceptors and MrgprD C-fiber nociceptors, respectively. Behaviorally, mice with conditional knockout of Nfia, but not Runx1 showed a marked attenuation of pinprick-evoked nocifensive responses. Our studies therefore identify a transcription factor controlling the development of myelinated nociceptors.

OBJECTIVE:To evaluate the efficacy and safety of Qianlie shutong capsule combined with Quinolone antibiotics in the treatment of chronic prostatitis, and provide evidence-based reference for clinical treatment. METHODS:Retrieved from PubMed,EMBase,Cochrane Library,CBM,CJFD,VIP Database and Wanfang Database,randomized clinical trials(RCT)about the efficacy and safety of Qianlie shutong capsule combined with Quinolone antibiotics(test group)versus only Quinolone antibiot-ics(control group)in the treatment of chronic prostatitis were collected,Meta-analysis was performed by using Rev Man 5.3 soft-ware after data extracting and quality evaluating by modified Jadad. RESULTS:Totally 16 RCTs were enrolled,involving 2 368 pa-tients. Results of Meta-analysis showed the total effective rate [RR=1.56,95% CI(1.29,1.88),P<0.001],US National Institutes of Health Chronic Prostatitis Symptom Index scores(NIH-CPSI scores)[MD=-6.97,95% CI(-8.67,-5.26),P<0.001],pain symptom scores[MD=-3.18,95%CI(-3.92,-2.44),P<0.001)],voiding dysfunction scores [MD=-1.62,95%CI(-1.85,-1.38), P<0.001],life quality scores[MD=-2.16,95% CI(-2.89,-1.43),P<0.001],EPS leukocyte count [MD=-8.90,95% CI (-11.79,-6.02),P<0.001] and recurrence rate[RR=0.22,95%CI(0.12,0.42),P<0.001] in test group were significantly better than control group,there were statistically significant differences between 2 groups;and there was no significant difference in the incidence of adverse reactions between 2 groups [RR=0.49,95%CI(0.11,2.13),P=0.34]. CONCLUSIONS:The efficacy of Qian-lie shutong capsule combined with Quinolone antibiotics is better than only Qianlie shutong capsule or Quinolone antibiotics in the treatment of chronic prostatitis,with similar safety.

Objective To investigate the expression of cyclooxgenase 2 (COX-2) and vascular endothelial growth factor (VEGF) in clear cell renal cell carcinoma (CCRCC) and their correlation with Prognosis. Methods EnVision immunohistochemistry was used to determine the expression of COX-2 and VEGF in 80 CCRCC tissues and 20 normal kidney tissues .The relationship between the above marks and prognosis were analyzed. Results The positive rates of COX-2[65.00 % (52/80) vs 10.00 % (2/20), x2= 7.760, P= 0.021]and VEGF[61.25 % (49/20) vs 20.00 (4/80),x2 = 8.870, P= 0.012]were much higher in CCRCC than those in normal kidney. The expression of COX-2 was correlated with TNM stage (x2 = 8.200,P =0.005), histological grade (x2 = 13.860, P = 0.000) and lymph node metastasis (x2 = 6.050, P = 0.001) in CCRCC, but not with age (x2 = 0.560, P = 0.663) and diameter of tumor (x2 = 0.700, P = 0.528). Both COX-2 expression and VEGF expression were associated significantly with prognosis in CCRCC (x2 = 18.280,P = 0.038;x2 = 6.420, P= 0.042, respectively). There was a positive correlation between COX-2 and VEGF in CCRCC (r =0.485, P < 0.01). Conclusion COX-2 is related to prognosis in CCRCC and can be used as prognostic indicators in patients.

0.05 ),and the recurrence rate in Group Ⅲ was highest,the difference beingsiedcant as compared with Group Ⅰ(P