ObjectiveThis paper aims to investigate the potential molecular biological mechanism of Buyang Huanwu Tongfeng decoction in treating hyperuricemia and gouty arthritis by network pharmacology and molecular docking technology and preliminarily verify the mechanism through animal experiments. MethodsThe active ingredients and targets in the Buyang Huanwu Tongfeng decoction were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and ETCM databases. The DisGeNET and GeneCards databases were utilized to acquire disease targets associated with hyperuricemia and gouty arthritis. These disease targets were then intersected with drug targets to identify key targets. The R language ClusterProfiler package and Python were employed for conducting gene ontology（GO） enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） enrichment analysis. The regulatory network diagram of the drug-key target-function-pathway was visualized using Cytoscape 3.9.1 software， and the protein-protein interaction （PPI） network for key targets was depicted. Finally， the hub gene was determined through topological analysis. Auto Dock， PyMOL， and other software were used for molecular docking to explore the possible therapeutic mechanism of Buyang Huanwu Tongfeng decoction for hyperuricemia and gouty arthritis. In animal experiments， a composite rat model of hyperuricemia induced by intraperitoneal injection of oteracil potassium combined with gouty arthritis induced by the modified Coderre method was established. Through hematoxylin-eosin（HE） staining， uric acid test， enzyme linked immunosorbent assay（ELISA）， Western blot， and real-time polymerase chain reaction（Real-time PCR）， the molecular mechanism and key targets of Buyang Huanwu Tongfeng decoction for treating hyperuricemia and gouty arthritis were observed. ResultsAfter screening and removing duplicate values， 76 active ingredients and 15 key targets were finally obtained. GO enrichment analysis yielded that the treatment of hyperuricemia and gouty arthritis with Buyang Huanwu Tongfeng decoction was significantly associated with acute inflammatory response， astrocyte activation， regulation of interleukin （IL）-8 production， nuclear receptor activity， and binding of growth factor receptor. KEGG pathway enrichment analysis obtained that the key target genes were significantly associated with the IL-17 signaling pathway， advanced glycosylation end/receptor of advanced glycation endproducts（AGE/RAGE） signaling pathway， anti-inflammatory， and other pathways. PPI network indicated that albumin（ALB）， peroxisome proliferator-activated receptor-γ （PPAR-γ）， IL-6， IL-1β， and C-reactive protein（CRP） were the key protein targets. The molecular docking results showed that ALB had the strongest binding force with beta-carotene （β-carotene）. Biochemical results showed that blood uric acid decreased in the Buyang Huanwu Tongfeng decoction groups. HE staining results showed that the low-dose （7.76 g·kg^-1·d^-1）， medium-dose （15.53 g·kg^-1·d^-1）， and high-dose （31.05 g·kg^-1·d^-1） groups of Buyang Huanwu Tongfeng decoction had different degrees of remission， and the remission of the high-dose group was the most obvious. Fibroblastic tissue hyperplasia in synovial joints accompanied with inflammatory cell infiltration， as well as inflammatory cell infiltration in renal tissue of the high-dose group was significantly reduced， followed by the medium-dose and low-dose groups， and the expression of ALB， PPAR-γ， IL-6， IL-1β， and CRP was down-regulated to different degrees. ConclusionBy regulating the targets such as ALB， PPAR-γ， IL-6， IL-1β， and CRP， inhibiting the PPAR-γ/nuclear transcription factor （NF）-κB pathway， and reducing AGEs/RAGE-mediated inflammation， Buyang Huanwu Tongfeng decoction exerts anti-inflammatory and analgesic effects and activates blood circulation and diuresis in the treatment of hyperuricemia and gouty arthritis.

Objective: To improve the efficiency and standardization of preoperative anemia diagnosis and treatment by establishing a systematic intelligent management platform for preoperative anemia. Methods: A multidisciplinary collaborative model was adopted to develop a preoperative anemia management system that integrates intelligent early warning, standardized treatment pathways, and quality control. The system utilizes natural language processing technology to automatically capture laboratory data and establish evidence-based medical decision support functions. A pre-post study design was employed to compare changes in preoperative anemia screening rates, preoperative anemia intervention rates, reasonable use of iron supplements, and perioperative red blood cell transfusion rates before and after system implementation. Results: After system implementation, the standardization of anemia diagnosis and treatment significantly improved: 1) Screening effectiveness: The anemia screening rate increased to 50.00% (an increase of 27.24%); 2) Intervention effectiveness: The anemia treatment rate rose to 56.30% (an increase of 14.02%); 3) Treatment standardization: The reasonable use rate of iron supplements increased to 55.33% (an increase of 21.02%); the red blood cell transfusion rate decreased to 18.29% (a decrease of 4.07%), and the amount of red blood cell transfusions was reduced by 291 units. Conclusion: This system achieves full-process management of preoperative anemia through information technology, significantly enhancing the standardization of diagnosis and treatment as well as intervention effectiveness, providing an effective solution for perioperative anemia management.

Objective To analyze the situation of insecticide-treated nets (ITNs) ownership in malaria-endemic African countries from 2010 to 2023, so as to provide insights into China’s deeper participation in malaria control in Africa. Methods The study period from 2010 to 2023 was divided into three phases: the baseline phase (from 2010 to 2015), the middle phase (from 2016 to 2019), and the final phase (from 2020 to 2023), a total of 11 African countries with at least one Demographic and Health Survey (DHS) in each phase were included. Data pertaining to ITNs in 33 surveys of the above 11 African counties from 2010 to 2023 were captured from the DHS database, and the proportions of sources of ITNs and ITN ownership in each phase (number of ITNs ownership per person, overall ownership rate, and ownership rate per two residents) were calculated. The differences in numbers of ITNs per person between urban and rural areas and specified by socioeconomic status were analyzed. Results The proportions of ITNs from distribution campaigns were 60.24% to 94.01% and 50.46% to 85.04% in 11 African countries in the middle and final phases, respectively. The median numbers (interquartile range) of INTs ownership per person were 0.22 (0.50), 0.33 (0.50) and 0.33 (0.50) in the baseline, middle, and final phases, and the overall ownership rates [95% confidence interval (CI)] were 59.77% (59.50%, 60.05%), 70.32% (70.06%, 70.57%), and 69.21% (68.95%, 69.47%), while the ownership rates per two residents were 26.91% (26.66%, 27.16%), 38.07% (37.80%, 38.34%), and 36.56% (36.29%, 36.84%), respectively. The number of ITNs per person showed a significant increase followed by a significant decrease in 7 countries during all three phases (H = 102.518 to 2 327.440, all P < 0.05; Z = -48.886 to -4.653, all P < 0.016 7 after Bonferroni correction). In 33 surveys, there were 31 (Z = -26.719 to -2.472, P < 0.05) and 28 surveys (Z = -27.316 to -4.068, P < 0.001) with significant differences in numbers of ITNs ownership per person between households in urban and rural areas and with different socioeconomic status, including 20 surveys with a significantly higher number of ITNs ownership per person in households in rural areas than in urban areas, and 17 surveys with a significantly higher number of ITNs ownership per person among the poorest households than among the richest households. Conclusions There are substantial disparities in ITNs ownership in 11 African countries. Intensified co-operation on malaria prevention and control measures, such as ITNs, is recommended between China and African countries to build a global community of health for all.

Objective To identify inflammation-related genes in atrial fibrillation(AF)and explore the possible role and mechanism of these genes and infiltrating immune cells in the development of AF.Methods A series of bioinformatics analysis combined with machine learning algorithms to identify biomarkers of AF,the receiver operating characteristic(ROC)curves were used to verify the prediction and diagnostic value of key genes,and Spearman correlation analysis was used to clarify the correlation between key genes and infiltrating immune cells.Results 593 differential genes(| log2(fold change,FC)|>1,P<0.05),7 immune cell subtypes(P<0.05)were selected,190 immune-related differential genes were obtained,3 biomarkers(IGF1,PTGS 2 and PPARG),and the correlation analysis showed that 3 markers were significantly associated with infiltrating immune cells(P<0.05).Conclusion IGF1,PTGS2 and PPARG are inflammation-related genes of AF,which are speculated to be closely related to the process and pathway of immune cell infiltration.

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demon-strated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel anti-angiogenic therapy for endometriosis.

Objective:To evaluate the effect of hydrogen on lipopolysaccharide (LPS) and nigericin-induced pyroptosis in macrophages and the role of long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1).Methods:Human monocyte-derived macrophages THP-1 cells were cultured in vitro and divided into 4 groups ( n=25 each) using a random number table method: control group (group C), LPS and nigericin group (group LN), hydrogen-rich medium+ LPS and nigericin group (group H+ LN), and lentiviral transfection+ hydrogen-rich medium+ LPS-nigericin group (group LV+ H+ LN). THP-1 cells were cultured in the common culture medium for 24 h in group C. LPS at a final concentration of 100 ng/ml and nigericin 10 μmol/L were added to the culture medium, and the cells were incubated for 24 h in group LN. In group H+ LN, the culture medium was replaced with 0.6 mmol/L hydrogen-rich medium, then LPS at a final concentration of 100 ng/ml and nigericin 10 μmol/L were immediately added, and the cells were incubated for 24 h. In group LV+ H+ LN, THP-1 cells over-expressing NEAT1 stably after being transfected with lentivirus were used, then LPS at a final concentration of 100 ng/ml and nigericin 10 μmol/L were immediately added, and the cells were incubated for 24 h. Cell viability was detected by CCK-8 assay. Lactic dehydrogenase (LDH) release was assessed by colorimetric method. The amount of LDH released was measured by colorimetry. The concentrations of interleukin-1beta (IL-1β) and IL-18 in culture medium were measured by enzyme-linked immunosorbent assay. The pyroptotic rate was detected by flow cytometry. The expression of nucleotide-binding oligomerization domain-like receptor-containing pyrin domain 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1 and gasdermin D (GSDMD) was detected by Western blot. The expression of NEAT1 gene was determined by quantitative real-time polymerase chain reaction. Results:Compared with group C, the cell viability was significantly decreased, the amount of LDH released, concentrations of IL-1β and IL-18, and pyroptotic rate were increased, and the expression of NEAT1 gene, NLRP3, ASC, caspase-1 and GSDMD was up-regulated in group LN ( P<0.05). Compared with group LN, the cell viability was significantly increased, the amount of LDH released, concentrations of IL-1β and IL-18, and pyroptotic rate were decreased, and the expression of NEAT1 gene, NLRP3, ASC, caspase-1 and GSDMD was down-regulated in group H+ LN ( P<0.05). Compared with group H+ LN, the cell viability was significantly decreased, the amount of LDH released, concentrations of IL-1β and IL-18, and pyroptotic rate were increased, and the expression of NEAT1 gene, NLRP3, ASC, caspase-1 and GSDMD was up-regulated in group LV+ H+ LN ( P<0.05). Conclusions:Hydrogen can ameliorate LPS and nigericin-induced pyroptosis in macrophages, and the mechanism may be associated with down-regulating the expression of lncRNA NEAT1.

Objective:To explore the bioaccessibility of the main metal components in welding fume welding fume in simulated lung fluid, and to evaluate the exposure level of each metal component in combination with the EPA inhalation exposure risk assessment model.Methods:In November 2022, the microscopic morphology characteristics of welding fumes were analyzed by scanning electron microscopy, the bioaccessibility of each metal component in lung fluid simulated normal and lung inflammatory states was analyzed by in vitro simulation method, and the exposure level of each metal component was calculated in combination with the EPA inhalation exposure risk assessment model.Results:The main metal components in carbon dioxide gas shielded welding fumes were Fe, Mn, Zn, Ti, Al, Cu, Cr, Cd, Ni and As, and the bioaccessibility in simulated normal lung interstitial fluid was 0.82%-1.84%, 5.07%-9.41%, 4.52%-7.23%, 5.10%-8.67%, 20.48%-29.60%, 5.27%-9.83%, 4.80%-7.56%, 0.07%-1.08%, 6.48%-13.84% and 33.02%-42.81%. The bioaccessibility of the above metal components in the lung fluid under simulated lung inflammation was 14.79%-27.45%, 34.53%-46.11%, 35.31%-59.13%, 16.45%-22.51%, 60.78%-76.51%, 26.58%-34.12%, 15.32%-25.87%, 2.0%-5.7%, 34.77%-43.33% and 71.34%-88.36%, respectively. Compared with the simulated lurg interstitial fluid, the bioaccessibility of metal components in the lung fluid under the simulated inflammatory state was increased, and the difference was statistically significant ( P<0.05). The average daily exposure dose Mn in the two simulated lung fluids exceeded the inhalation reference limit (>50 times), and the average daily exposure dose Ti and Cr in the simulated lung inflammation exceeded the reference limit (>1.3 times) . Conclusion:Attention should be paid to the bioaccessibility characteristics of metal components in the exposure level and hazard assessment of welding fumes.

Objective:To explore the bioaccessibility of the main metal components in welding fume welding fume in simulated lung fluid, and to evaluate the exposure level of each metal component in combination with the EPA inhalation exposure risk assessment model.Methods:In November 2022, the microscopic morphology characteristics of welding fumes were analyzed by scanning electron microscopy, the bioaccessibility of each metal component in lung fluid simulated normal and lung inflammatory states was analyzed by in vitro simulation method, and the exposure level of each metal component was calculated in combination with the EPA inhalation exposure risk assessment model.Results:The main metal components in carbon dioxide gas shielded welding fumes were Fe, Mn, Zn, Ti, Al, Cu, Cr, Cd, Ni and As, and the bioaccessibility in simulated normal lung interstitial fluid was 0.82%-1.84%, 5.07%-9.41%, 4.52%-7.23%, 5.10%-8.67%, 20.48%-29.60%, 5.27%-9.83%, 4.80%-7.56%, 0.07%-1.08%, 6.48%-13.84% and 33.02%-42.81%. The bioaccessibility of the above metal components in the lung fluid under simulated lung inflammation was 14.79%-27.45%, 34.53%-46.11%, 35.31%-59.13%, 16.45%-22.51%, 60.78%-76.51%, 26.58%-34.12%, 15.32%-25.87%, 2.0%-5.7%, 34.77%-43.33% and 71.34%-88.36%, respectively. Compared with the simulated lurg interstitial fluid, the bioaccessibility of metal components in the lung fluid under the simulated inflammatory state was increased, and the difference was statistically significant ( P<0.05). The average daily exposure dose Mn in the two simulated lung fluids exceeded the inhalation reference limit (>50 times), and the average daily exposure dose Ti and Cr in the simulated lung inflammation exceeded the reference limit (>1.3 times) . Conclusion:Attention should be paid to the bioaccessibility characteristics of metal components in the exposure level and hazard assessment of welding fumes.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective:To compare the efficacy of maxillary distraction osteogenesis (DO) and Le FortⅠ osteotomy (LFⅠ) in patients with complex cleft lip and palate.Methods:A retrospective study was conducted, clinical data were collected involving patients with complex cleft lip and palate who required combined orthodontic and orthognathic treatment and were treated at the Stomatological Hospital of Chongqing Medical University from January 2015 to December 2022. Patients were divided into three groups based on the surgical method used for the maxilla: total maxillary distraction (TMD, group A), anterior maxillary distraction (AMD, group B), and Le Fort Ⅰ osteotomy (LFⅠ, group C). Cone-beam CT scans and lateral cephalograms were obtained preoperatively and at 3 months postoperatively. Three-dimensional reconstructions were performed using Mimics 21.0 and Dolphin Imaging 11.9 software to evaluate changes in craniofacial morphology and airway. Data analysis was conducted using SPSS 25.0. Intragroup comparisons before and after surgery were performed using the Wilcoxon rank sum test, and intergroup comparisons among the three groups were conducted using the Kruskal-Wallis H test. Results:A total of 15 patients were included, with 5 patients in each group. The cohort comprised 8 males and 7 females, aged between 15 and 21 years. There were no statistically significant differences in the distribution of gender, age, or cleft lip and palate classification among the three groups ( P>0.05). Postoperatively, all three groups showed improvement in maxillary hypoplasia. Compared to preoperative measurements, the angle formed by the points A (subspinale), N (nasion), and B (supramentale) (ANB angle) increased in all three groups (all P<0.05). The vertical distance from point A to the nasion perpendicular (A-Nperp) increased in groups A and B ( P<0.05 for both) but not in group C ( P>0.05). The area of the alveolar gap showed an increasing trend in all three groups ( P>0.05). The mandibular plane angle (FMA) decreased postoperatively in group B but showed an increasing trend in the other two groups, though the differences were not statistically significant ( P>0.05). Postoperative airway volume increased or showed an increasing trend in groups A ( P<0.05) and B ( P>0.05) but decreased in group C ( P>0.05). Intergroup comparisons showed significant differences in the angle formed by the sella (S), nasion (N), and point A (SNA angle) and the vertical distance from the anterior nasal spine to the coronal plane (ANS-CP) ( P<0.05). Group A had significantly larger SNA angles and ANS-CP values than group B, and the ANS-CP value in group A was significantly larger than in group C (all P<0.05). There were no other statistically significant differences among the groups ( P>0.05). Conclusion:For patients with severe maxillary hypoplasia due to complex cleft lip and palate, TMD can correct sagittal discrepancies between the upper and lower jaws, increase upper airway volume, but may potentially enlarge the alveolar gap area and increase vertical height of the maxilla. AMD result in less change in maxillary position compared to TMD and is mainly used for patients with severe maxillary dental crowding, needing increased arch length, having minor sagittal discrepancies, or with preexisting velopharyngeal dysfunction. LFⅠ result in changes in maxillary position similar to AMD but less than TMD, making it suitable for patients with moderate maxillary hypoplasia and mild maxillary dental crowding. The advantage of LFⅠ lies in its precise postoperative occlusal design and accurate three-dimensional movement of the jaw.