Objective To investigate the safety and feasibility of the domestic SA-1000 single-port single-arm robot-assisted laparoscopic system in total hysterectomy.Methods Data from 16 patients who underwent total hysterectomy using the SA-1000 system at the Department of Obstetrics and Gynecology,The Second Affiliated Hospital of Naval Medical University,between Mar.2023 and Jan.2024 were retrospectively collected.Surgical parameters were analyzed.Postoperative pain was assessed using the visual analogue scale(VAS)at 24 h after surgery and before discharge.Incision cosmesis was evaluated 3-5 weeks postoperatively using the body image questionnaire(BIQ,score range 3-24).Results All 16 procedures were successfully completed using the SA-1000 system without conversion to open surgery,achieving a 100.0%procedural success rate.The mean whole surgery time was(234.40±56.24)min.The median robotic arm setup time was 8.0(4.0,13.5)min,and the median console operating time was 128.0(100.0,151.0)min.The median intraoperative blood loss was 100.0(100.0,200.0)mL.No perioperative complications,such as hemorrhage,infection,injury to adjacent organs(ureters,bladder,bowel),poor wound healing,or incisional hernia,were observed.The mean wound pain score at 24 h postoperatively was 3.81±1.64,decreasing to a median of 3.0(2.0,4.0)before discharge.The BIQ score assessed at 3-5 weeks postoperatively was 21.88±1.15.Conclusion The application of the domestic SA-1000 single-port single-arm robot-assisted laparoscopic system for total hysterectomy is safe and feasible,demonstrating favorable surgical outcomes.It holds promise for broader implementation and promotion in domestic medical centers.

Objective:In order to explore the changes of vascular endothelial function parameters and their correlation with prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH) after intracranial aneurysm embolization.Methods:A retrospective cohort study was conducted to select 126 patients diagnosed with aSAH in the Department of Neurointerventional of Beijing Fengtai You′anmen Hospital from August 2021 to August 2023. There were 69 males and 57 females, with an age of (52.27±3.34) years, aged 45-62 years. The patients were grouped according to the glasgow prognostic score (GOS) at three months after the prognosis of intracranial aneurysm embolization, including 81 cases in the good prognosis group and 45 cases in the poor prognosis group. The main indexes were calcitonin gene-related peptide (CGRP), endothelin-1, vascular endothelial growth factor (VEGF), S100β, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and the secondary indicators were the Hunt and Hess Scale (Hunt-Hess), the National Institutes of Health Stroke Scale (NIHSS), and the Glasgow coma scale (Glasgow), coma scale (GCS), Immunoglobulin A (IgA), Immunoglobulin M (IgM) and Immunoglobulin G (IgG). A generalized mixed-effect model was established to analyze the effect of vascular endothelial function on adverse prognosis, and ROC curve was used to analyze the impact of changes in vascular endothelial function on adverse prognosis. The restriction cubic spline model was used to analyze the dose-response relationship between the changes of postoperative endothelial function indexes and the poor prognosis of intracranial aneurysm embolization in aSAH patients. The Log-rank test was used for Kaplan-Meiker survival analysis. The mean ± standard deviation ( ± s) was used for the normally distributed continuous data, and the independent samples t-test was used for comparison between groups. The chi-square test was used for comparison of enumerated data between groups. Results:There were statistically significant levels of Hunt-Hess, NIHSS, GCS, cerebral vasospasm (CVS) and shunt dependence in the two groups ( P<0.05), and the CGRP of the two groups increased significantly after surgery, and after 2 weeks of treatment, the CGRP of the patients in the good prognosis group was (58.36±3.84) pg/mL, which was significantly higher than that in the poor prognosis group (49.36±4.55) pg/mL. After 2 weeks of treatment, endothelin-1 and VEGF in the good prognosis group were (62.74±27.46) pg/mL and (110.55±34.82) ng/mL, respectively, which were significantly lower than those in the poor prognosis group (92.64±28.44) pg/mL and (145.45±32.19) ng/mL, respectively, and the differences between the two groups were statistically significant ( P<0.05), The neurological indexes of the two groups were significantly decreased, and the S100β, GFAP and NSE in the good prognosis group were (6.75±2.73) ng/L, (6.85±1.54) mg/L and (8.24±4.51) ng/L after 2 weeks of treatment, which were significantly lower than those in the poor prognosis group (8.76±2.44) ng/L, (8.63±1.63) mg/L and (13.84±3.19) ng/L, respectively. There was a statistically significant difference between the two groups ( P<0.05).Before and after the correction factors, the vascular endothelial function indexes of aSAH patients at different time points were significantly correlated with their neurological function indicators. The 14-day change of vascular endothelial function index was significantly correlated with poor prognosis ( P<0.05). The results of subgroup analysis showed that vascular endothelial function indicators and poor prognosis were statistically significant in the range of Hunt-Hess≥2 points, NIHSS≥14 points, GCS≥11 points, CVS, shunt dependence, S100β<10.81 ng/L, GFAP≥9.93 mg/L, NSE≥29.00 ng/L, IgA<2.46 g/L, IgM≥1.70 g/L, and IgG<11.50 g/L ( P<0.05). The results of ROC curve showed that the area under the curve (AUC) of CGRP, endothelin-1 and VEGF were 0.869, 0.834 and 0.874, respectively. There was a nonlinear dose-response relationship between CGRP, endothelin-1 and VEGF and the poor prognosis of intracranial aneurysm embolization in aSAH patients. Conclusion:The vascular endothelial function of aSAH patients with aSAH can be improved after intracranial aneurysm embolization, and it is related to neurological function, and the better the endothelial function index, the higher the probability.

This article summarized the current status and challenges of manipulation therapy for musculoskeletal pain and its placebo effect in clinical trials, analyzing the impact of the placebo effect on the evaluation of therapeutic efficacy. The efficacy of different manual manipulation techniques remains uncertain, and the degree of blinding and patient expectations play a crucial role in efficacy assessment. The article suggested improving trial design through standardized placebo intervention design, comprehensive investigation of patient expectations and psychological states, rigorous training of practitioners, and optimized diagnostic and treatment scenarios and doctor-patient relationship, to ensure consistency between intervention and placebo groups. Specific measures include the application of the DITTO (Deconstruct, Identify, Take out, Think, Optimize) framework, the use of standardized questionnaire tools, and multi-center, large-sample randomized controlled trials to enhance the external validity and statistical power of research results, thereby providing more scientifically reliable evidence for clinical practice.

The liver has diverse functions such as metabolism， detoxification， and immune defense， and the maintenance of hepatic microenvironment homeostasis is crucial for overall bodily health. The hepatic microenvironment consists of the components such as parenchymal cells， non-parenchymal cells， and non-cellular components. Chronic inflammatory responses induced by various etiological factors may promote the formation and progression of liver fibrosis. During the dynamic progression of liver fibrosis， from the early to advanced stages， various components within the hepatic microenvironment undergo a series of changes， which can promote the malignant progression of liver fibrosis. An in-depth exploration of the mechanisms underlying such changes in each component of the liver fibrosis microenvironment is of great significance for understanding the pathogenesis of liver fibrosis and discovering potential treatment strategies.

OBJECTIVE To assess the correlation between the steady-state minimal concentration （cmin） and 24 h area under the drug concentration-time curve （AUC24）/minimal inhibitory concentration （MIC） ratio （AUC24/MIC） of vancomycin in pediatric patients， and analyze independent risk factors for treatment failure. METHODS Data of hospitalized children treated with vancomycin and receiving therapeutic drug monitoring in our hospital from January 2021 to July 2024 were retrospectively collected and divided into success group and failure group according to whether the treatment was successful or not. Spearman correlation analysis was used to analyze the correlation between cmin and AUC24/MIC of vancomycin， and one-way and multifactorial Logistic regression analyses were used to screen the independent risk factors for vancomycin treatment failure. RESULTS A total of 59 children were included， with 41 in the success group and 18 in the failure group. Compared with the failure group， AUC24/MIC of vancomycin was significantly higher in the success group （P＝0.038）， but there was no statistically significant difference in the cmin of the two groups （P＞0.05）； cmin of vancomycin was significantly positively correlated with AUC24/MIC （r＝0.499， P＜0.001）， but it has a certain efficacy in predicting the achievement of the AUC24/MIC standard （≥400） （area under the receiver operator characteristic curve＝0.696）， with an optimal cutoff value of 6.05 mg/L determined by the Youden index. The efficacy of AUC24/ MIC in predicting treatment failure was superior to cmin （areas under the receiver operator characteristic curve were 0.671 vs. 0.523， P were 0.038 vs. 0.684）， with higher sensitivity （83.3% vs. 66.7%）. Hypoproteinemia and AUC24/MIC≤369.1 were independent risk factors for vancomycin treatment failure （P＜0.05）. The incidence of nephrotoxicity was 3.4%. CONCLUSIONS There is a significant positive correlation between cmin and AUC24/MIC of vancomycin in pediatric patients； hypoproteinemia and AUC24/MIC≤369.1 are independent risk factors for vancomycin treatment failure in children.

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

OBJECTIVES: To assess the effectiveness of the comparison between pit and fissure sealants and fluoride varnishes, as well as various types of sealants, in preventing caries on the occlusal surface of children's first permanent molars (FPM). METHODS: Conduct a comprehensive search of literature published between January 1, 1988, and May 30, 2024, in the following databases: China National Knowledge Infrastructure, Web of Science, Cochrane Library, Embase, PubMed, China Science Periodical Database and China Biology Medicine database. Meta-analysis and subgroup analyses were performed on the literature that met the inclusion criteria. RESULTS: A total of 5 618 pieces of literature were retrieved, resulting in the inclusion of 14 in the study. Meta-analysis showed that there was no statistically significant difference in the efficacy between varies pit and fissure sealants compared to fluoride varnishes, and between varies types of sealants in preventing caries on the occlusal surface of children's first permanent molars within 24 months post-surgery (P>0.05). CONCLUSIONS Within 24 months, there was no significant difference in the effectiveness of using resin-based or glass iomomer pit and fissure sealants compared with fluoride varnishes in preventing occlusal caries in FPM in children; within 24 months, there was no significant difference in the effectiveness of using resin-based sealants compared with ART sealants in preventing occlusal caries in FPM in children. ART sealants are recommended over resin-based sealers for children who have no conditions for chair-side manipulation or who are poorly co-operative.
Humans ; Pit and Fissure Sealants/therapeutic use* ; Dental Caries/prevention & control* ; Molar ; Child ; Fluorides, Topical/therapeutic use* ; Dentition, Permanent

Objective: To investigate the effects of “Three Methods and Three Acupoints” (TMTP) Tuina therapy on spinal microcirculation in sciatic nerve injury (SNI). Methods: Thirty-six Sprague–Dawley rats were randomly assigned to four groups: normal, sham operation, model, and TMTP Tuina. Successful model induction was confirmed by observable hind limb lameness. After 20 sessions, hind limb grip strength and motor nerve conduction velocity (MNCV) were measured at baseline and following the 10th and 20th intervention. CD31 and α-SMA in the ventral horn of SNI model rats were detected using immunofluorescence. Motor neurons in the ventral horn were detected by Nissl staining. PTEN levels in the ventral horn were measured by ELISA, and PI3K, Akt, BDNF, VEGF, and HIF-1α expression was determined by RT-PCR. Spinal cord microcirculation was evaluated by western blotting analysis of the levels of Akt, p-Akt, BDNF, and VEGF. Results: Hind limb grip strength and MNCV significantly improved in the TMTP Tuina group compared to the model group (both P < .001). Morphology of ventral horn motor neurons in the TMTP Tuina group improved compared to the model group, with increased expressions of α-SMA (P = .002) and CD31 (P = .006). Western blot analysis indicated increased expression of VEGF (P = .005), p-Akt (P < .001), and BDNF (P = .008) in the ventral horn following Tuina treatment. RT-PCR analysis revealed increased expression of PI3K, Akt, BDNF, VEGF and HIF-1α (all P < .05). In contrast, expression of PTEN decreased compared to the model group (P < .001). Conclusion TMTP Tuina therapy may restore motor function in rats, enhance ventral horn motor neuron morphology, and promote angiogenesis and vascular smooth muscle proliferation. The mechanism may involve the activation of the PI3K/Akt signaling pathway.

OBJECTIVES: To explore the therapeutic mechanism of compound Centella asiatica formula (CCA) for alleviating Schistosoma japonicum (Sj)-induced liver fibrosis in mice. METHODS: The active components and targets of CCA were identified using the TCMSP database with cross-analysis of Sj-related liver fibrosis targets. A "drug-component-target-pathway-disease" network was constructed using Cytoscape 3.9.1. Functional enrichment analysis (GO/KEGG) was performed using DAVID. Molecular docking study was carried out to validate interactions between the core targets and the key compounds. For experimental validation of the results, 36 mice were divided into control group, Sj-infected model group, and CCA-treated groups. In the latter two groups, liver fibrosis was induced via abdominal infection with Sj cercariae for 8 weeks, followed by 8 weeks of daily treatment with CCA decoction or saline. Hepatic pathology of the mice was assessedwith HE and Masson staining, and hepatic expressions of collagen-I and collagen-III were detected using immunohistochemistry; serum IL-6 and TNF-α levels were determined with ELISA. Hepatic expressions of TLR4 and MyD88 proteins were analyzed with Western blotting. RESULTS: We identified a total of 107 bioactive CCA components and 791 targets, including 37 intersection targets linked to Sj-induced fibrosis. The core targets included TNF, TP53, JUN, MMP9, and CXCL8, involving the IL-17 signaling, lipid metabolism, TLR4/MyD88 axis, and cancer pathways. Molecular docking study confirmed strong binding affinity between quercetin (a primary CCA component) and TNF/TP53/JUN/MMP9. In Sj-infected mouse models, CCA treatment significantly attenuated hepatic inflammatory cell infiltration, reduced collagen-I and collagen-III deposition, improved tissue architecture, reduced serum IL-6 and TNF-α levels, and downregulated TLR4 and MyD88 expressions in the liver. CONCLUSIONS CCA mitigates Sj-induced liver fibrosis by targeting TNF, TP53, JUN, and MMP9 to modulate the TLR4/MyD88 pathway, thereby suppressing pro-inflammatory cytokine release, inhibiting hepatic stellate cell activation, reducing collagen deposition, and preventing granuloma formation in the liver.
Animals ; Toll-Like Receptor 4/metabolism* ; Mice ; Myeloid Differentiation Factor 88/metabolism* ; Schistosoma japonicum ; Liver Cirrhosis/parasitology* ; Schistosomiasis japonica ; Signal Transduction ; Molecular Docking Simulation ; Inflammation ; Centella/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

AIM:To observe the effects of Huangqi-Danggui mixture(HQDG)on the pyroptosis of brain tis-sues in rats with middle cerebral artery occlusion/reperfusion(MCAO/R),and to explore the mechanism of neuroprotec-tion provided by HQDG.METHODS:Sixty-four SD rats were randomly divided into 4 groups:sham group,model group,HQDG group,and Xuesaitong(XST)group.The infarct volume of brain tissues was observed by 2,3,5-triphenyl-tetrazolium chloride staining,while hematoxylin-eosin staining was used to observe the pathological changes of brain tis-sues.Immunofluorescence was employed to assess the expression of nucleotide-binding oligomerization domain-like recep-tor protein 3(NLRP3),cleaved caspase-1 and gasdermin D(GSDMD)in the ischemic penumbra of brain tissues.The se-rum levels of interleukin-1β(IL-1β)and IL-18 were measured using ELISA.Western blot was used to detect NLRP3,cleaved caspase-1,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),IL-1β and IL-18 in brain tissues.RESULTS:Compared with sham group,the neurological deficit scores of the rats in model group were significantly increased(P<0.01),while those in HQDG and XST groups were significantly reduced compared with model group(P<0.01).The cerebral infarct volume ratio was significantly reduced in HQDG and XST groups compared with model group(P<0.01).The pathological damage of brain tissue in HQDG and XST groups was significantly reduced compared with model group.The positive rates of NLRP3,cleaved caspase-1 and GSDMD in the ischemic penumbra of brain tissues were significantly decreased in HQDG group compared with model group(P<0.01).The expression of pyrop-tosis-related proteins,NLRP3,cleaved caspase-1 and ASC,in the ischemic penumbra of brain tissues was significantly el-evated in model group compared with sham group(P<0.01),and significantly decreased in HQDG group compared with model group(P<0.01).The serum levels of IL-1β and IL-18 were significantly increased in model group compared with sham group(P<0.01),and significantly reduced in HQDG group compared with model group(P<0.01).CONCLU-SION:The HQDG effectively attenuates brain tissue injury in rats with MCAO/R,and its mechanism may be related to the inhibition of neural cell pyroptosis.