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*

This article introduces a recent paper published in JAMA titled " Tirzepatide for weight reduction in Chinese adults with obesity: The SURMOUNT-CN randomised clinical trial". The paper details the design, results, and implications of a randomized controlled clinical study of the efficacy and safety of tirzepatide in overweight/obese adults in China(SURMOUNT-CN). This study represents the first Chinese evidence supporting tirzepatide for the treatment of obesity, offering a potent therapeutic option for the prevention and treatment of obesity and weight-related comorbidity.

Objective To explore the core genes related to the diagnosis and prognosis of gastric cancer(GC)based on Gene Expression Omnibus(GEO)database and screen the molecular targets involved in the occurrence and development of GC.Methods GC microarray data GSE118916,GSE54129 and GSE79973 were downloaded from GEO database,and the differentially expressed genes(DEGs)were screened.Enrichment analysis of the signaling pathways and molecular functions were preformed and protein-protein interaction networks(PPI)were constructed to identify the hub genes,whose expression levels and diagnostic and prognostic values were verifies based on gastric adenocarcinoma data from TCGA.The expression levels of these core genes were also detected in different GC cell lines using qRT-PCR.Results Seventy-seven DEGs were identified,which encodes proteins located mainly in the extracellular matrix and basement membrane with activities of oxidoreductase and extracellular matrix receptor and ligand,involving the biological processes of digestion and hormone metabolism and the signaling pathways in retinol metabolism and gastric acid secretion.Nine hub genes were obtained,among which SPARC,TIMP1,THBS2,COL6A3 and THY1 were significantly up-regulated and TFF1,GKN1,TFF2 and PGC were significantly down-regulated in GC.The abnormal expressions of SPARC,TIMP1,THBS2,COL6A3,TFF2 and THY1 were significantly correlated with the survival time of GC patients.ROC curve analysis showed that aberrant expression of TIMP1,SPARC,THY1 and THBS2 had high diagnostic value for GC.High expressions of SPARC,TIMP1,THBS2 and COL6A3 were detected in GC tissues.In the GC cell lines,qRT-PCR revealed different expression patterns of these hub genes,but their expressions were largely consistent with those found in bioinformatics analyses.Conclusion SPARC,TIMP1,THBS2 and other DEGs are probably involved in GC occurrence and progression and may serve as potential candidate molecular markers for early diagnosis and prognostic evaluation of GC.

Objective To explore the core genes related to the diagnosis and prognosis of gastric cancer(GC)based on Gene Expression Omnibus(GEO)database and screen the molecular targets involved in the occurrence and development of GC.Methods GC microarray data GSE118916,GSE54129 and GSE79973 were downloaded from GEO database,and the differentially expressed genes(DEGs)were screened.Enrichment analysis of the signaling pathways and molecular functions were preformed and protein-protein interaction networks(PPI)were constructed to identify the hub genes,whose expression levels and diagnostic and prognostic values were verifies based on gastric adenocarcinoma data from TCGA.The expression levels of these core genes were also detected in different GC cell lines using qRT-PCR.Results Seventy-seven DEGs were identified,which encodes proteins located mainly in the extracellular matrix and basement membrane with activities of oxidoreductase and extracellular matrix receptor and ligand,involving the biological processes of digestion and hormone metabolism and the signaling pathways in retinol metabolism and gastric acid secretion.Nine hub genes were obtained,among which SPARC,TIMP1,THBS2,COL6A3 and THY1 were significantly up-regulated and TFF1,GKN1,TFF2 and PGC were significantly down-regulated in GC.The abnormal expressions of SPARC,TIMP1,THBS2,COL6A3,TFF2 and THY1 were significantly correlated with the survival time of GC patients.ROC curve analysis showed that aberrant expression of TIMP1,SPARC,THY1 and THBS2 had high diagnostic value for GC.High expressions of SPARC,TIMP1,THBS2 and COL6A3 were detected in GC tissues.In the GC cell lines,qRT-PCR revealed different expression patterns of these hub genes,but their expressions were largely consistent with those found in bioinformatics analyses.Conclusion SPARC,TIMP1,THBS2 and other DEGs are probably involved in GC occurrence and progression and may serve as potential candidate molecular markers for early diagnosis and prognostic evaluation of GC.

Objective To explore the causal relationship between ischemic stroke and different types of epilepsy so as to provide genetic evidence for the risk of epilepsy after ischemic stroke.Methods Based on the summary data of genome-wide association study,Mendelian randomization (MR ) analysis was performed with MR-Egger regression,weighted median and inverse-variance weighting.Sensitivity analysis was conducted by using MR-Egger regression test,MR-PRESSO test and leave-one-out method.Results Two-sample MR analysis showed that there was a causal relationship between ischemic stroke and the risk of epilepsy (OR=1.10,P=0.036)and generalized epilepsy (OR=1.25,P=0.001 ),but no such relationship was observed with the risk of focal epilepsy (OR=1.06,P=0.360).In addition,diastolic blood pressure (OR=1.12,P=0.002)and BMI (OR=1.08,P=0.015)also had a causal relationship with the risk of epilepsy. After adjusting confounding factors,multivariate MR analysis revealed that only ischemic stroke (OR=1.18,P=3.770×10-6)and epilepsy risk had a causal relationship.Conclusion There is a causal relationship between ischemic stroke and the risk of generalized epilepsy,which can be used to stratify the risk of post-stroke epilepsy.

This case report described the sucussful treatment of a male infant born at 21 weeks and 4 days through assisted reproductive technology. After prenatal consultation and with the strong desire of the parents, active resuscitation and treatment were performed. The infant received 52 days of mechanical ventilation and was extubated to non-invasive ventilation at a corrected gestational age of 28 weeks and 6 days. During hospitalization, no vasoactive drugs were used, and necrotizing enterocolitis did not occur. The gastric tube was removed at a corrected gestational age of 37 weeks and 4 days. At a corrected gestational age of 40 weeks, cranial MRI showed no abnormalities. The infant was discharged at a corrected gestational age of 42 weeks after 143 days of treatment, without the need for any respiratory support. Follow-up until a corrected age of 6 months showed good growth and development.

Objective For patient-specific open-wedge high tibial osteotomy(OWHTO),a novel anatomical fixation plate was designed,and the effects of geometric parameters and material selection on biomechanical fixation were studied.Methods A patient-specific OWHTO anatomical fixation plate was designed and constructed,and the effects of design parameters(thickness,width,and length of the fixation plate)and four different materials(stainless steel,titanium alloy,magnesium alloy,and PEEK)on the biomechanics of the OWHTO fixation system were studied using finite element analysis.The biomechanical differences between the anatomical fixation plate and TomoFix fixation plate were also compared.Results The thickness had a greater effect on the micromotion of the osteotomy space than the length and width of the fixation plate did.Titanium alloy or magnesium alloy fixation plates were more conducive than stainless steel and PEEK materials in obtaining reasonable stability and mechanical transfer simultaneously.Compared with that of the TomoFix plate,the maximum von Mises stress of the anatomical fixation plate was reduced by 13.5%;the maximum von Mises stress of the screws and tibia was increased by 9.8%and 18.4%,respectively;and the micromotion at the maximum osteotomy space cc was increased by 49.3%.Conclusions Anatomical fixation plates have a positive effect on reducing the stress-shielding effect and improving biomechanical properties under the premise of ensuring stability.This study provides a reference for the development of OWHTO anatomical fixation plates.

Objective To prepare specific mouse monoclonal antibody (mAb) against human adenovirus type 55 Hexon protein (HAdV55 Hexon). Methods The Hexon genes of HAdV55, 3, 4, 7, 16 and 21 were chemically synthesized as templates for PCR amplification. The prokaryotic expression plasmids pET28a-HAdV55 Hexon and eukaryotic expression plasmids pCAGGS-HAdV3, 4, 7, 16, 21 and 55 Hexon were constructed respectively. The pET28a-HAdV55 Hexon plasmid was transformed into E. coli competent cell BL21 (DE3) and was induced by IPTG. After the purified inclusion body was denatured and renatured, Hexon55 protein was purified by tangential flow filtration system. pCAGGS-HAdV55 Hexon was used to immunize BALB/c mice by cupping, and HAdV55 Hexon protein was used to booster immunization. The anti-HAdV55 Hexon mAb was prepared by hybridoma technique and the titer and subclass were determined. The specificity of antibody was identified by Western blot using HEK293T cells transfected with pCAGGS-HAdV55 Hexon and by immunofluorescence assay (IFA) using BHK cells transfected with pCAGGS-HAdV55 Hexon. Both clones with high titer were selected, and the cross-reactivity of pCAGGS-HAdV3, 4, 7, 16, 21 and 55 Hexon transfected cells were analyzed by Western blot analysis and IFA. Results PET28a-HAdV55 Hexon and pCAGGS-HAdV55 Hexon, 3, 4, 7, 16 and 21 expression plasmids were successfully constructed. BL21 transformed with pET28a-HAdV55 Hexon was induced by IPTG. The HAdV55 Hexon protein was mainly expressed in the form of inclusion body. After denaturation and renaturation, the purified HAdV55 Hexon protein was obtained by ultrafiltration. Six hybridoma cell lines secreting HAdV55 Hexon mAb were obtained. The antibody subclass analysis showed that 2 strains were IgG2a subtypes and 4 strains were IgG2b. Two specific HAdV55 Hexon antibodies with high titer were obtained, and there was no cross-reactivity with HAdV3, 4, 7, 16, 21 Hexon. Conclusion The specific mice mAb against HAdV55 Hexon provides an experimental basis for establishing its antigen detection method.
Animals ; Mice ; Humans ; Adenoviruses, Human/genetics* ; Escherichia coli/genetics* ; HEK293 Cells ; Isopropyl Thiogalactoside ; Blotting, Western ; Immunoglobulin G ; Antibodies, Monoclonal ; Antibody Specificity ; Mice, Inbred BALB C

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Objective:To analyze the situation of influenza vaccination among primary healthcare workers, find out the problems, and explore the strategies and measures to promote influenza vaccination among grass-roots medical staff.Methods:From April to May 2021, key insider interviews and literature research were carried out based on the perspectives of influenza vaccine suppliers (influenza vaccine manufacturers), consumers (primary medical institutions and primary healthcare workers), and managers (governments at all levels, health administrative departments and disease prevention and control departments). The SWOT (strengths, weaknesses, opportunities, and threats) analysis technique was used to comprehensively evaluate the current situation of influenza vaccination among grass-roots healthcare workers, and a SWOT analysis matrix was established.Results:Influenza vaccination of grass-roots healthcare workers have advantages and opportunities, including primary medical and health institutions' vital influenza vaccination accessibility, influenza vaccine safety is higher, COVID-19 outbreak improves the public awareness of respiratory infectious diseases and vaccine production enthusiasm, coronavirus vaccination has strengthened the capacity of the vaccine distribution system. There are also disadvantages and threats such as the high price of influenza vaccine, insufficient supply, low awareness of influenza vaccine vaccination among grass-roots healthcare workers, lack of demand assessment mechanism on influenza vaccine, poor vaccine deployment, structural imbalance in vaccine supply in different areas, and severe vaccine waste. SWOT analysis matrix of the influenza vaccination status of grass-roots healthcare workers was established, forming dominant opportunity (SO) strategy, dominant threat (ST) strategy, inferior opportunity (WO) strategy, and inferior threat (WT) strategy.Conclusion:Measures should be taken by the supplier, the demand—side, and the management side to improve the influenza vaccine coverage rate of primary healthcare workers, but the emphasis should be on the coordination and management of the management side.