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*

Burkitt lymphoma is a highly aggressive B-cell lymphoma and the fastest proliferating human malignant tumor.If the disease is found in the early stage,the patient could have a high possibility to be cured successfully,whereas the prognosis is poor in the late stage.Burkitt lymphoma can occur in children and adults,and it is categorized as local(Africa),sporadic,and immunodeficiency associated type.Sporadic Burkitt lymphoma mainly affects children and ado-lescents,and the most common initial sites are abdominal organs and lymph nodes.Sporadic Burkitt lymphoma manifested by initial oral and maxillofacial lesions is rela-tively rare.Here,a case of pediatric sporadic Burkitt lym-phoma,with oral and maxillofacial lesions as the first symptoms,was reported.The patient was treated in the Department of Periodontology,Shandong University School and Hospital of Stomatology.After timely checkup was pro-vided,the patient was transferred to another hospital and had good results.In this article,an incidence of Burkitt lympho-ma,with oral and maxillofacial lesions as the first symptom,was reviewed to provide reference for oral clinicians to achieve early diagnosis and treatment of patients with Burkitt lymphoma with oral diseases and improve the success rate of treatment.

Objective To compare the efficacy and safety of endoscopic ligation treatment and endoscopic tissue glue injection for secondary prevention of gastric variceal bleeding.Methods Patients with cirrhosis and esophagogastric variceal bleeding treated with gastric variceal ligation in Zhongshan Hospital,Fudan University,from January 2017 to December 2019 were screened(ligation group).And during the same period,patients underwent endoscopic cyanoacrylate treatment were also screened(tissue glue group).59 patients were included in the two groups after propensity score matching.Univariate and multivariate Cox proportional hazard regression models were used to anslyze risk factors for re-bleeding.Kaplan-Meier curves were plotted to analyze re-bleeding rate and mortality of the two treatment groups.Results There was no statistically significant difference in the eradication rate of esophagogastric varices between the ligation group and the tissue glue group(83.05％vs 79.66％,P=0.778);the ligation group required fewer median endoscopic treatments for variceal eradication(2 vs 3,P=0.017)and a lower average dosage of cyanoacrylate(0.70 mL vs 2.67 mL,P＜0.001).Multivariate Cox regression analysis showed that portal shunt was a risk factor for esophagogastric varices re-bleeding(HR=3.14,95％CI 1.02-9.68,P=0.046),endoscopic variceal ligation was a protective factor against re-bleeding(HR=0.25,95％CI 0.08-0.71,P=0.010).Compared with endoscopic cyanoacrylate injection,endoscopic ligation treatment did not significantly increase the 2-year risk of esophagogastric variceal re-bleeding(18.69％vs 36.29％,P=0.067)or risk of death(1.69％vs 3.39％,P=1.000);patients with GOV1 type had a significantly lower risk of re-bleeding after endoscopic ligation treatment(0 vs 40.27％,P=0.012)and there was a trend towards a lower re-bleeding risk in patients with GOV2 type after endoscopic ligation treatment(13.27％vs 34.16％,P=0.056).Conclusions Endoscopic ligation treatment has higher eradication rate for esophagogastric varices,and does not increase the risk of re-bleeding,death,or other adverse events.Therefore,it can be considered an effective secondary prevention way for patients with gastric varices.

Objective To investigate the current status,obstacles,and specific needs associated with the application of transradial access(TRA)in peripheral interventions in Chinese hospitals,with the aim of promoting the broader adoption of TRA in interventional procedures.Methods The Committee of Interventional Oncology of China Anti-Cancer Association conducted a cross-sectional questionnaire survey to investigate and analyze the nationwide situation of TRA in peripheral interventional surgeries in 2022.Results Personnel from 60 hospitals participated in the questionnaire.The results showed that the number of peripheral interventionals performed using TRA was significantly lower than that performed using transfemoral access(TFA),with considerable variability among hospitals.The primary obstacles to the adoption of TRA were the lack of suitable catheters and the difficulty of radial artery puncture.Approximately 86.67％of the institutions expressed a high expectation for the innovation of new TRA-specific devices,particularly catheters,microcatheters,and guidewires.60.00％of medical institutions indicated a strong desire for systematic training and participation in multi-center clinical trials.Conclusions TRA peripheral intervention is feasible in many hospitals in China,however,systematic training and further promotion of TRA are essential.The innovation of new TRA-specific devices and TRA in peripheral intervention is urgent.

Objective:To explore the differences of gene expression profiles of precursors of exhausted T cells (Tpex) and terminal exhausted T cells (Tex) in the peripheral blood of patients with active pulmonary tuberculosis (ATB).Methods:Twenty-five cases of ATB, 13 cases of latent tuberculosis infection (LTBI) and 10 health controls were enrolled from January 2021 to October 2022 in the Fifth People′s Hospital of Wuxi. The proportions of Tpex and Tex in the peripheral blood mononuclear cells (PBMCs) of the three groups were detected by flowcytometry. PBMCs of ATB were separated into Tpex and Tex by fluorescence-activated cell sorting. RNA-sequencing was performed and up-regulated and down-regulated genes were screended. Differently expressed genes were analyzed by gene set enrichment analysis of gene ontology (GO) to find regulatory pathways affecting cell metabolism and function. Wilcoxon matched-pairs signed rank test, Kruskal-Wallis test and Dunn multiple comparsion test were used for statistical analysis.Results:The proportion of Tpex in ATB group was 2.86%(1.74%), which was lower than 7.93%(6.16%) of Tex, and the difference was statistically significant ( Z=-3.91, P<0.001). The proportions of Tpex and Tex in LTBI group were 9.47%(6.26%) and 7.43%(5.48%), respectively, and the difference was not statistically significant ( Z=-0.93, P=0.345). The proportions of Tpex and Tex in healthy control group were 8.42%(2.69%) and 6.49%(5.14%), respectively, with no statistical significance ( Z=-1.36, P=0.170). There was statistical difference of the proportion of Tpex among the three groups ( H=21.93, P<0.001), and the proportion of Tpex in ATB group was lower than those in LTBI and heathy control groups, and the differences were both statistically significant ( Z=4.16, P<0.001 and Z=3.34, P=0.003, respectively), while the proportions of Tex in these three groups were not statistically different ( H=2.17, P=0.338). Compared with Tex, the gene expressions of memory markers, such as B-cell lymphoma 2 of Tpex were up-regulated, and the gene expressions of exhausted markers, such as lymphocyte activation gene 3 were down-regulated. In terms of cellular metabolism, the gene expressions of mitochondrial protein complex, mitochondrial matrix and oxidative phosphorylation of Tpex were up-regulated, and the gene expressions of glycolysis were down-regulated. The gene expressions of pyruvate metabolism in Tex were up-regulated, and the gene expressions of CD4 + T lymphocyte activation and differentiation and glycolytic process in Tpex were down-regulated. Conclusions:Tpex in ATB express more characteristics of memory cells and less features of exhausted markers compared with Tex, and the function of mitochondria of Tpex preserves well.

Background In the Global Burden of Disease research, it has been found that atmospheric fine particulate matter (PM_2.5) pollution significantly harms human health. Currently, there is limited research on polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) that exhibit high toxicity effects in PM_2.5 . Objective By studying the spatiotemporal distribution and variation characteristics of PCDD/Fs in PM_2.5 in Pudong area of Shanghai, to assess the associated population health risk. Methods This study set up 28 sampling points in Pudong area. One sample of PM_2.5 was collected during winter (February 2022) and summer (July 2022) at each site, with a sampling period lasting 24 h. The concentration of PM_2.5 was measured by membrane filter method, and the content of 17 kinds of 2,3,7,8-substituted chlorinated PCDD/Fs in the samples was analyzed using isotope dilution. Seasonal variations (winter and summer) in the concentrations of PM_2.5 and PCDD/Fs were evaluated, sources of PCDD/Fs pollution were tracing by principal component analysis, and health risks to the population from respiratory exposure to PCDD/Fs were estimated by VLIER-HUMAAN model. Results The PM_2.5 concentrations in the 28 samples ranged from 10 to 126 μg·m⁻³, while the concentrations of PCDD/Fs in PM_2.5 ranged from 58 to 2625 fg·m⁻³. The concentration of PM_2.5 during winter (11-126 μg·m⁻³) was higher than that during summer (10-60 μg·m⁻³). The concentration range of PCDD/Fs in winter was from 58 to 2625 fg·m⁻³, which corresponded to a range of toxic equivalent quantity (WHO-TEQ) concentration from 2.99 to 40.97 fg·m⁻³ when taking World Health Organization's toxic equivalency factor (WHO-TEQ); the concentration range of PCDD/Fs in summer was from 72 to 446 fg·m⁻³, which corresponded to a range of WHO-TEQ concentration from 2.66 to 16.61 fg·m⁻³. This range in summer was significantly lower than that observed in winter. The results of principal component analysis revealed that waste incineration was the primary source of PCDD/Fs in winter PM_2.5 in the area, whereas traffic emissions emerged as the main source in summer. The assessment of Pudong residents' respiratory exposure to PCDD/Fs in PM_2.5 showed significantly higher exposure of children in summer and winter than that of adults, indicating higher susceptibility of children to air pollutants. Both the hazard ratios (HR) for children and adults were below 1, while the cancer risks (CR) ranged from 8.41×10⁻⁸ to 2.35×10⁻⁶. Notably, during winter, the CR at 4 locations slightly exceeds 1×10⁻⁶, indicating a potential carcinogenic risk. Conclusion The overall pollution level of PCDD/Fs in PM_2.5 in Pudong area is relatively low, but it shows clear seasonal patterns. Waste incineration and traffic are the main sources of PCDD/Fs in PM_2.5 in the area. Although the cancer risk of exposure to PCDD/Fs in PM_2.5 for children or adults is relatively low, there is a certain risk at some locations in winter, necessitating additional monitoring and control.

Objective To investigate the distribution and antimicrobial resistance of clinical isolates in the First Affiliated Hospital of Xi'an Jiaotong University in 2022 for rational use of antibiotics in clinical practice.Methods Nonduplicate clinical isolates were collected from January 1,2022 to December 31,2022.Antimicrobial susceptibility testing was carried out using Kirby-Bauer method and automated systems.The data were analyzed using WHONET 5.6 software and interpreted according to the Clinical and Laboratory Standards Institute(CLSI)breakpoints(2021 Edition).Results Of the 8 638 clinical isolates,gram negative bacteria and gram positive bacteria accounted for 60.8％(5 253/8 638)and 39.2％(3 385/8 638),respectively.The prevalence of methicillin-resistant strains was 33.0％in S.aureus(MRSA),75.8％in S.epidermidis(MRSE),and 51.9％in other coagulase-negative Staphylococcus(MRCNS).No staphylococcal strains were found resistant to vancomycin.The prevalence of vancomycin-resistant E.faecium was 0.6％,and no vancomycin-resistant E.faecalis was found.E.faecalis strains showed higher resistance rate to linezolid(5.2％)than E.faecium(0.7％).The prevalence of carbapenem-resistant Enterobacterales(CRE)was 7.9％,specifically 12.1％for carbapenem-resistant K.pneumoniae(CRKP)and 1.6％for carbapenem-resistant E.coli(CREC).The prevalence of carbapenem-resistant P.aeruginosa(CRPA)and carbapenem-resistant A.baumannii(CRAB)was 30.9％and 77.0％,respectively.Conclusions Clinical microbiology laboratories should strengthen the collection and testing of clinical specimens from the sites of infection in order to improve pathogenic diagnosis and antimicrobial resistance surveillance.This is conducive to the rational use of antibiotics and reduce the further spread of multidrug-resistant bacteria.

Objective:To investigate the application of phase angle by bioelectrical impedance in the assessment of malnutrition and its correlation with nutrtition status as measured by several different screening tools in patients on maintenance hemodialysis (MHD).Methods:This was a cross-sectional study, including 151 patients on MHD. Bioelectrical impedance analysis was used to detect body composition in hemodialysis patients. Nutritional Risk Screening 2002 (NRS 2002) scores, body mass index (BMI) and the Global Leadership Initiative on Malnutrition (GLIM) criteria were used to investigate the prevalence of malnutrition in MHD patients. The correlation between phase angle and nutrition-related indicators such as visceral fat area, body weight, skeletal muscle, and serum albumin in MHD patients was analyzed, and the consistency between phase angle and the three screening tools was examined.Results:In a total of 151 patients on MHD, the malnutrition prevalence as measured by BMI, NRS 2002 score and GLIM criteria was 9.27%, 27.81% and 54.97%, respectively. Phase angle in MHD patients was positively correlated with BMI( P<0.01), negatively correlated with impaired nutrition score of NRS 2002( P<0.01), and also associated with nutrition screening results as measured by GLIM criteria( P<0.001). Further study showed that phase angle was positively correlated with body weight, skeletal muscle and serum albumin( P<0.01), but negatively with visceral fat area and extracellular water/total body water( P<0.01). Conclusions:Malnutrition is highly prevalent in MHD patients. Phase angle showed good consistency with BMI, NRS 2002 and GLIM criteria in terms of malnutrition screening, implying the potential application in the assessment of malnutrition in MHD patients. However, the clinical relevance still needs corroboration with future large-scale researches.

Objective:To learn about the monitoring indicators and patient management in coal-burning-borne endemic arsenic poisoning areas in Shaanxi Province, and provide a basis for consolidating and improving the prevention and control achievements.Methods:From March to December 2023, in accordance with the requirements of the "Notice of the Office of Shaanxi Provincial Health Commission on Issuing of the Monitoring Plan for Key Endemic Diseases Such as Kashin-Beck Disease" and "The Monitoring Plan for Endemic Fluorosis and Arsenic Poisoning in Shaanxi Province", a basic situation investigation was conducted in the affected villages of all counties (districts) with coal-burning-borne endemic arsenic poisoning in Shaanxi Province, and on-site visits were conducted to check the management of high arsenic coal mines. Using the simple random sampling method, 30 families in each village were selected to investigate the use of stoves and the formation of health-related behaviors. A survey on arsenic poisoning was carried out among all populations in the affected villages. According to the requirements of the provincial monitoring program, 720 people were randomly selected from 12 affected villages in 3 monitoring counties to measure their urinary arsenic level. The determination was based on the "Guidelines for the Safety of Urinary Arsenic in Population" (WS/T 665-2019). The evaluation for elimination of disease areas was carried out in accordance with the "National Health Commission Issued the Evaluation Approach for Control and Elimination of Priority Endemic Diseases (2019 edition)".Results:A total of 2 cities, 8 counties (districts), 99 townships, and 1 414 affected villages were monitored. All 53 high arsenic coal mines had stopped mining. The rate of qualified improved stoves was 99.97%; the correct utilization rate of qualified improved stoves, and the correct drying rate of corn and chili peppers provided for human consumption in the affected villages were 100.00%. A total of 2 064 138 people were examined, and 2 682 cases of arsenic poisoning were detected, all of whom were historical patients. There were no new cases of arsenic poisoning or skin cancer. There were currently 2 682 arsenic poisoning patients who had received family doctor contract services and implemented follow-up management. The geometric mean of urinary arsenic was 0.016 7 mg/L, which was lower than the safety guideline value for human urinary arsenic (0.032 mg/L).Conclusions:The monitoring indicators in the coal-burning-borne endemic arsenic poisoning areas in Shaanxi Province have reached the elimination standards. In the future, we should continue to strengthen the management of high arsenic coal mines, implement comprehensive prevention and control measures mainly focused on furnace and stove renovation and health promotion, and do a good job in patient management to continuously consolidate and improve the prevention and control achievements.

Objective:To investigate the clinical features of nontuberculous mycobacteria (NTM) disease patients with positive anti-interferon γ (IFN-γ) autoantibody.Methods:Forty-three adult human immunodeficiency virus-uninfected patients with NTM disease hospitalized in Huashan Hospital, Fudan University and Jing′an Branch, Huashan Hospital, Fudan University from July 2021 to August 2023 were included. Clinical data and NTM strain information of the patients were collected. The plasma levels of anti-IFN-γ autoantibodies were detected by enzyme-linked immunosorbent assay, and the patients were divided into antibody positive group and antibody negative group. The clinical characteristics and laboratory examination results between the two groups were compared. The independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Multivariate logistic regression analysis was used to determine the correlation factors of positive anti-IFN-γ autoantibodies. Results:Among the 43 patients, 13 cases (30.2%) were positive for anti-IFN-γ autoantibodies and 30 cases (69.8%) were negative. The proportions of patients with NTM disseminated infection (9/13 vs 30.0%(9/30))and combined bacterial infection (5/13 vs 6.7%(2/30)) in antibody positive group were both higher than those in antibody negative group, and the differences were both statistically significant ( χ2=5.74 and 6.73, respectively, both P<0.05). The white blood cell count, platelet count, the proportion of platelet count >350×10 9/L of antibody positive patients were all higher than those of antibody negative group, while the white sphere ratio was lower than that of antibody negative group, with statistical significance ( t=2.42, 3.02, χ2=9.77 and t=3.66, respectively, all P<0.05). Erythrocyte sedimentation rate, C-reactive protein, procalcitonin, globulin, immunoglobulin G, immunoglobulin A and immunoglobulin M in antibody positive patients were all higher than those in antibody negative group, and the differences were all statistically significant ( U=99.50, 112.00, 115.50, 61.50, 76.50, 99.00 and 83.00, respectively, all P<0.05). Mycobacterium abscessus complex (seven cases and 11 cases, respectively) and Mycobacterium avium complex (five cases and 13 cases, respectively) were the main isolated strains in antibody positive and antibody negative patients. Multivariate logistic regression analysis showed that combined with bacterial infection (odds ratio ( OR)=21.83, 95% confidence interval ( CI) 1.94 to 245.71), NTM disseminated infection ( OR=7.64, 95% CI 1.10 to 53.26), platelet count>350×10 9/L ( OR=14.31, 95% CI 1.91 to 107.04) were risk factors for anti-IFN-γ autoantibodies positive (all P<0.05). Conclusions:Patients with positive anti-IFN-γ autoantibodies have higher probability of having elevated levels of systemic inflammation. Anti-IFN-γ autoantibody test is recommended for patients with NTM disease who present with co-bacterial infection, NTM disseminated infection, or elevated platelet count (>350×10 9/L).