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*

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

The accurate and timely detection of biochemical coagulation indicators is pivotal in pulmonary and critical care medicine. Despite their reliability, traditional laboratories often lag in terms of rapid diagnosis. Point-of-care testing (POCT) has emerged as a promising alternative, which is awaiting rigorous validation. We assessed 226 samples from patients at the First Affiliated Hospital of Guangzhou Medical University using a Beckman Coulter AU5821 and a PUSHKANG POCT Biochemistry Analyzer MS100. Furthermore, 350 samples were evaluated with a Stago coagulation analyzer STAR MAX and a PUSHKANG POCT Coagulation Analyzer MC100. Metrics included thirteen biochemical indexes, such as albumin, and five coagulation indices, such as prothrombin time. Comparisons were drawn against the PUSHKANG POCT analyzer. Bland-Altman plots (MS100: 0.8206‒0.9995; MC100: 0.8318‒0.9911) evinced significant consistency between methodologies. Spearman correlation pinpointed a potent linear association between conventional devices and the PUSHKANG POCT analyzer, further underscored by a robust correlation coefficient (MS100: 0.713‒0.949; MC100: 0.593‒0.950). The PUSHKANG POCT was validated as a dependable tool for serum and whole blood biochemical and coagulation diagnostics. This emphasizes its prospective clinical efficacy, offering clinicians a swift diagnostic tool and heralding a new era of enhanced patient care outcomes.
Humans ; Point-of-Care Testing ; Critical Care ; Blood Coagulation Tests/methods* ; Male ; Blood Coagulation ; Female ; Middle Aged ; Reproducibility of Results ; Prothrombin Time ; Aged ; Adult ; Point-of-Care Systems

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the effect of miR-22-3p on pyroptosis of vascular smooth muscle cells(VSMCs)induced by homocysteine(Hcy).Methods Human VSMCs were cultured in vitro and divided into a Control group(0 μmol/L Hey)and a Hey group(100 μmol/L Hey).After intervention,expression levels of pro Caspase-1,gasdermin D(GSDMD),N-GSDMD,and NLR family pyrin domain containing 3(NLRP3)were detected by Western blot.MiR-22-3p expression was determined by quantitative real-time reverse-transcription polymerase chain reaction.Interleukin(IL)-1 β and IL-18 levels in the supernatant were measured by enzyme-linked immunosorbent assay.Cells were also transfected with control miR-22-3p(miR-22-3p-NC),miR-22-3p-mimic,and miR-22-3p-inhibitor,to observe the effects on VSMC pyroptosis induced by Hcy.Results Expression levels of pro Caspase-1,GSDMD,N-GSDMD,and NLRP3 in VSMCs were increased(P＜0.05),IL-1 β and IL-18 levels were increased(P＜0.01),and the relative expression level of miR-22-3p was reduced(P＜0.01)in the Hcy group compared with the Control group.Transfection with miR-22-3p-mimic significantly decreased the expression levels of pro Caspase-1,GSDMD,N-GSDMD,and NLRP3 in VSMCs(P＜0.01),and significantly decreased levels of IL-1β and IL-18(P＜0.01),while transfection with miR-22-3p-inhibitor significantly increased the expression levels of pro Caspase-1,GSDMD,N-GSDMD,and NLRP3 in VSMCs(P＜0.01)and significantly increased the levels of IL-1β and IL-18(P＜0.05).Conclusions MiR-22-3p may delay Hcy-induced VSMC pyroptosis.

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 assess the differences in multidimensional clinical manifestations between patients with irritable bowel syndrome (IBS) matching the Rome Ⅲ criteria but not matching Rome Ⅳ and IBS patients matching the Rome Ⅳ criteria, among patients diagnosed with IBS according to Rome Ⅲ criteria.Methods:From November 2016 to October 2017, a total of 472 IBS patients admitted to six hospitals were selected, which included Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology (139 cases), Sir Run Run Shaw Hospital, School of Medicine of Zhejiang University (95 cases), the First Affiliated Hospital of Dalian Medical University (96 cases), the Affiliated Hospital of Guizhou Medical University (90 cases), the People′s Hospital of Guangxi Zhuang Autonomous Region (20 cases), and the Second Affiliated Hospital of Xi′an Jiaotong University (32 cases). The 472 IBS patients were divided into the group that matching the Rome Ⅳ criteria (Rome Ⅳ group), and the group that matching the Rome Ⅲ criteria but not matching the Rome Ⅳ criteria (Rome Ⅲ group). The basic characteristics (IBS course, post-infectious IBS, history of smoking or drinking, etc.), abdominal symptoms, and defecation-related symptoms of two groups were compared and analyzed by face-to-face questionnaires. Multi-dimensional clinical manifestations assessment was completed by questionnaires, which included gastrointestinal symptom rating scale (GSRS), irritable bowel syndrome-severity scoring system (IBS-SSS), irritable bowel syndrome-quality of life (IBS-QOL), and hospital anxiety and depression scale (HADS). Independent sample t-test, rank sum test, and chi-square test were used for statistical analysis. Results:There were 344 patients (72.9%) in Rome Ⅳ group and 128 patients (27.1%) in Rome Ⅲ group. The IBS course of patients in Rome Ⅳ group was longer than that in Rome Ⅲ group (3.0 years (7.0 years) vs. 2.0 years (5.7 years)), and the difference was statistically significant ( Z=-2.73, P=0.006). The GSRS scores of loose stools and abdominal pain of IBS patients in Rome Ⅳ group were higher than those in Rome Ⅲ group, and the GSRS scores of increased exhaust and abdominal distension of IBS patients in Rome Ⅳ group were lower than those in Rome Ⅲ group (3.0(2.0) vs. 2.0(4.0), 3.0(2.0) vs.1.0(2.0), 1.5(3.0) vs. 2.0(3.0), 1.0 (3.0) vs. 2.0(3.0)), and the differences were statistically significant ( Z=-2.48, -9.90, -2.11 and -2.06, P=0.013, <0.001, =0.035 and =0.040). The proportions of fatigue and dizziness of IBS patients in Rome Ⅳ group were higher than those in Rome Ⅲ group (58.4% (201/344) vs. 43.0% (55/128), 30.8% (106/344) vs. 29.7% (38/128)), and the differences were statistically significant ( χ2=8.37 and 12.36, P=0.004 and <0.001). The scores of anxiety and depression subscales of the HADS of IBS patients in Rome Ⅳ group were higher than those in Rome Ⅲ group (6.5 (6.8) vs. 6.0 (6.0), 5.0 (6.0) vs. 3.0 (5.0)), and the differences were statistically significant ( Z=-2.58 and -2.40, P=0.010 and 0.017). The scores of IBS-SSS scale, abdominal pain severity, abdominal pain frequency, and impact on quality of life of IBS patients in Rome Ⅳ group were all higher than those in Rome Ⅲ group (249.5 (108.0) vs. 177.0 (111.8), 50.0 (25.0) vs. 20.0 (30.0), 50.0 (70.0) vs. 10.0 (30.0), 66.0 (42.0) vs. 42.5 (34.0)), and the differences were statistically significant ( Z=-7.79, -9.64, -10.65 and -2.48, P<0.001, <0.001, <0.001 and =0.013). The score of IBS-QOL for behavioral disorder of IBS patients in Rome Ⅳ group was lower than that in Rome Ⅲ group (74.5±21.6 vs. 79.2±17.7), and the difference was statistically significant ( t=-2.22, P=0.027). Conclusion:The clinical symptoms of patients mathching the Rome Ⅳ criteria are more typical and severe, as compared with those of IBS patients matching the Rome Ⅲ criteria but not matching the Rome Ⅳ criteria.

Objective:To understand the current status of foreign dual-degree programs of Medical Doctor (MD) and Master of Public Health (MPH) and provide evidence-based decision-making reference for promoting the education of high-level applied public health talents in China.Methods:The list of involved institutions and information of foreign MD-MPH dual-degree programs was collected through literature retrieval, online information searching, and additional survey of key figures. We extracted the details of each project regarding professional fields, core competence, length of schooling, teaching and learning arrangement, internship eligibility, and graduation assessment. Python 3.8.0 was used for data cleaning, and the occurrence frequency of related items in each dimension was calculated.Results:A total of 99 MD-MPH programs from 104 foreign institutions were included, among which 97.1% of them were implemented in universities from the United States. The School of Public Health provided 42.4% (42/99) of the programs. Epidemiology was the major discipline set up among most programs, accounting for 12.0% (29/241) of all the specialties involved. Epidemiological research methods, health policy management and practice, and public health practice were the top 3 core competencies to be mastered. Of the 99 programs, 87 gave information on the length of the program, of which 74.7% (65/87) were five years, 6.9% (6/87) were four years, and 18.4% (16/87) included both 4-year and 5-year programs.Conclusions:The international MD-MPH programs were sophisticated and mainly organized by the School of Public Health alone or in conjunction with the School of Medicine. Epidemiology is the core course and competence objective, with a length of 4-5 years. Through learning experience from international MD-MPH programs and the Chinese unique medical development background, China should optimize its medical education system to develop a suitable talent training strategy for MD-MPH dual-degree programs in the new era.

Objective:To investigate the efficacy of Zhongjiefeng dispersible tablets combined with ranitidine in the treatment of recurrent oral ulcer and its effec on inflammatory factors. Methods:Eighty-six patients who received recurrent oral ulcer in Yiwu Hospital of Traditional Chinese Medicine from January 2019 to January 2020 were included in this study. They were randomly assigned to receive treatment with either ranitidine (control group, n = 43) or Zhongjiefeng dispersible tablets combined with ranitidine (observation group, n = 43) for 4 weeks. Before and after treatment, visual analogue scale score and inflammatory factor were compared between the control and observation groups. Change in main symptom score after treatment relative to before treatment and the curative effect were also compared between the two groups. Results:After treatment, the visual analogue scale score in the observation group was significantly lower than that in the control group [(1.32 ± 0.37) vs. (3.06 ± 0.54), t = 17.430, P < 0.05]. After treatment, serum interleukin-2 [(16.42 ± 3.18) μg/L], interleukin-6 [(6.56 ± 1.28) ng/L], tumor necrosis factor-α [(7.69 ± 1.34) μg/L] levels in the observation group were significantly lower than those in the control group [(25.97 ± 5.24) μg/L, (9.84 ± 1.62) ng/L and (11.86 ± 1.83) μg/L, t = 10.217, 10.4617 and 12.056, all P < 0.05]. After treatment, ulcer area score [(0.76 ± 0.14) points] and ulcer number score [(0.68 ± 0.19) points] in the observation group were significantly lower than those in the control group [(1.21 ± 0.20) points and (1.24 ± 0.30) points, t = 12.087, 10.341, both P < 0.05]. Total effective rate in the observation group was significantly higher than that in the control group [93.02% (40/43) vs. 72.09% (31/43), χ 2 = 6.541, P < 0.05]. Conclusion:Zhongjiefeng dispersible tablets combined with ranitidine exhibits obvious curative effect on recurrent oral ulcer in patients through reducing pain and inflammatory reaction.

PURPOSE: Vascular endothelial growth factor (VEGF) signal transduction mainly depends on its binding to VEGF receptor 2 (VEGFR-2). VEGF downstream signaling proteins mediate several of its effects in cancer progression, including those on tumor growth, metastasis, and blood vessel formation. The activation of VEGFR-2 signaling is a hallmark of and is considered a therapeutic target for breast cancer. Here, we report a study of the regulation of the VEGFR-2 signaling pathway by a small molecule, isomangiferin. METHODS: A human breast cancer xenograft mouse model was used to investigate the efficacy of isomangiferin in vivo. The inhibitory effect of isomangiferin on breast cancer cells and the underlying mechanism were examined in vitro. RESULTS: Isomangiferin suppressed tumor growth in xenografts. In vitro, isomangiferin treatment inhibited cancer cell proliferation, migration, invasion, and adhesion. The effect of isomangiferin on breast cancer growth was well coordinated with its suppression of angiogenesis. A rat aortic ring assay revealed that isomangiferin significantly inhibited blood vessel formation during VEGF-induced microvessel sprouting. Furthermore, isomangiferin treatment inhibited VEGF-induced proliferation of human umbilical vein endothelial cells and the formation of capillary-like structures. Mechanistically, isomangiferin induced caspase-dependent apoptosis of breast cancer cells. Furthermore, VEGF-induced activation of the VEGFR-2 kinase pathway was down-regulated by isomangiferin. CONCLUSION: Our findings demonstrate that isomangiferin exerts anti-breast cancer effects via the functional inhibition of VEGFR-2. Pharmaceutically targeting VEGFR-2 by isomangiferin could be an effective therapeutic strategy for breast cancer.
Angiogenesis Inhibitors ; Animals ; Apoptosis ; Blood Vessels ; Breast Neoplasms ; Cell Proliferation ; Heterografts ; Human Umbilical Vein Endothelial Cells ; Humans ; In Vitro Techniques ; Mice ; Microvessels ; Neoplasm Metastasis ; Phosphotransferases ; Rats ; Receptors, Vascular Endothelial Growth Factor* ; Signal Transduction ; Vascular Endothelial Growth Factor A* ; Vascular Endothelial Growth Factor Receptor-2*