Objective Orosomucoid1 （ORM1） is a novel target in the quest for anti-fatigue pharmacotherapy. Preliminary investigations have illuminated oleuropein （OLE） as a promising candidate molecule, poised to enhance ORM1 expression. To elucidate the influence of OLE on ORM1 protein expression and assess its ramifications on muscle endurance. Methods The impact of OLE on ORM1 protein expressions within hepatocytes and liver tissue was meticulously quantified through Western blotting; the effects of OLE on muscle endurance were evaluated via the rotarod and forced swimming tests; glycogen content within liver and muscle tissues was determined utilizing a specialized kit; and PAS staining was employed to visualize glycogen deposition in the gastrocnemius muscle. Results OLE demonstrated a capacity to elevate ORM1 protein expression in hepatocytes in a time- and dose-dependent manner, concurrently prolonging the duration of swimming and rotarod performance in mice, also in a time- and dose-dependent manner. Furthermore, OLE augmented ORM1 expression in liver tissue, elevated serum ORM1 levels, and enhanced glycogen reserves within the liver and muscle. Conclusion OLE may serve to amplify muscle endurance by elevating ORM1 levels in vivo and augmenting glycogen stores within skeletal muscle.

Objective:To review drug clinical trial development in Shaanxi province and to understand the effectiveness of the implementation of a record system in promoting drug clinical trial development.Methods:Based on the data of drug clinical trials in Shaanxi province released on the official website of the National Medical Products Administration, this study made a statistical analysis of the number of drug clinical trial institutions, regional distribution, registered majors and principal investigators, and the development of drug clinical trial projects.Results:After implementing drug clinical trial institution registration, the drug clinical trial institutions in Shaanxi Province developed rapidly, increasing from 20 in the qualification period to 46, with a growth rate of 130%. A total of 113 specialties were recorded, of which the highest number of professional records were for endocrinology and oncology. 46 institutions recorded 1, 094 principal investigators and participated in 3803 drug clinical trial projects. However, only 8 institutions had undertaken drug clinical trial projects as group leaders.Conclusions:The number of drug clinical trial institutions in Shaanxi province increased significantly, reflecting a good overall development status. However, issues still exist, such as unbalanced development of clinical trial resources within the region, insufficient researchers with the ability to conduct clinical trials, relatively concentrated drug clinical trial projects, and lack of experience in undertaking clinical trials as a group leader.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Objective To analyze the innovative model and effectiveness of the four-level prevention of stroke in Nantong Medical and Prevention Collaborative Center for Cardiovascular and Cerebrovascular Disease,so as to provide new practical experience for the prevention and treatment of cerebrovascular disease.Methods In practice,Nantong city has explored the"53343"mode of collaborative treatment and prevention of cardiovascular and cerebrovascular diseases,and innovatively integrated this mode into four-level prevention to form a practice mode of zero-level guidance,first-level monitoring,second-level coordination and three-level leading.Data from the China Health Statistics Yearbook from 2011 to 2022 and the monitoring data of cardiovascular and cerebrovascular events in Nantong City on the Jiangsu Provincial Chronic Disease Management Information Platform from 2017 to 2023 were collected and processed by using Excel and SPSS 24.0,to analyze the changes of stroke surveillance data and effectiveness in Nantong City after applying the model.Results According to the monitoring data of cardiovascular and cerebrovascular events in Nantong City from the Jiangsu Provincial Chronic Disease Management Information Platform,despite the continuous increase in the number of monitored individuals over five years,the monitoring data for stroke from the Nantong Medical and Prevention Collaborative Center for Cardiovascular and Cerebrovascular Disease witnessed a decline in the number of monitored individuals for the first time in 2022.The stroke monitoring data from the same monitoring agency showed a more stable fluctuation trend compared to the number of national stroke patients discharged from 2017 to 2021.We established a coherent health service operation mechanism,cultivated 14 interdisciplinary talents,held a special continuing education class on stroke,strengthened the in-depth collaboration between clinical and public health,and provided a practical and innovative model for effective prevention and treatment of stroke.Conclusions The four-level prevention based on the medical and preventive collaboration center for cardiovascular and cerebrovascular diseases can achieve process and cycle health management,effectively slow down the upward trend of stroke,and improve the ability and level of scientific research and teaching.

Objective:To understand the current status and characteristics of clinical trials for oral diseases in China, for the purpose of providing a reference for the research and development of oral diseases in China.Methods:Retrieving the information on clinical trials related to oral diseases registered on the "Platforms for drug clinical trial registration and information" of the National Medical Products Administration from the date of the database establishment to December 31, 2024. The number of clinical trials, type of drugs, trial phases, indication, trial scope, design types were statistically analyzed.Results:As of December 31, 2024, a total of 578 drug clinical trials for oral disease were registered, accounting for 2.1% (578/27 905) of the clinical trials disclosed on the platform during the same period. Bioequivalence clinical trials accounted for the highest proportion [73.9% (427/578)], followed by Phase Ⅰ [9.0% (52/578)], Phase Ⅱ [8.0% (46/578)], and Phase Ⅲ [4.5% (26/578)]. The 578 clinical trials involved 149 types of trial drugs, mainly chemical drugs, among which 127 were developed by domestic pharmaceutical enterprises and 27 by international pharmaceutical enterprises (the five investigational drugs have undergone clinical trials by both domestic and international pharmaceutical companies). The project leader units of the 578 drug clinical trials were distributed in 27 provinces, autonomous regions, municipalities, and Hong Kong Special Administrative Region. Excluding 427 bioequivalence clinical trials, the project leader units of 151 new drug clinical trials showed a significant aggregation phenomenon, and only three specialized oral hospitals have served as project leader units for drug clinical trials.Conclusions:The number of drug clinical trials for oral disease in China has generally shown an increasing trend, but there are still problems such as small number of clinical trials, low proportion of investment in new drug development and international multicenter trials, concentrated indications of clinical trials and insufficient clinical trial experience in specialized oral medical institutions. Enhancing the enthusiasm and innovation capabilities of domestic pharmaceutical enterprises in the research and development of oral diseases drugs, exploring the advantages of traditional Chinese medicine/natural medicine resources for oral diseases, and establishing a clinical research system in specialized oral medical institutions are of great significance for the development of oral drugs.

Objective:To evaluate the diagnostic efficacy of serum anti-deamidated gliadin peptide antibody immunoglobulin A (DGP-IgA) in adult celiac disease.Methods:A retrospective case-control study was conducted. Clinical data of 80 adult celiac disease patients (celiac disease group) treated in the Department of Gastroenterology of the People's Hospital of Xinjiang Uygur Autonomous Region from September 2020 to December 2023 were collected. Meanwhile, 40 healthy individuals who underwent physical examinations were selected as the healthy control group. According to the Oslo definition of celiac disease, 80 celiac disease patients were classified into classical type (52 patients), non-classical type (21 patients), and subclinical type (7 patients). Serum DGP-IgA and anti-tissue transglutaminase antibody immunoglobulin A (tTG-IgA) were measured in both celiac disease and healthy control groups by using the ELISA method. The degree of intestinal mucosal damage in celiac disease patients was assessed by the Marsh Oberhuber histopathological grading system (Marsh grading for short) using the small intestinal biopsy pathological results. Statistical analysis was performed to compare the differences in serum DGP-IgA and tTG-IgA between the two groups, as well as the differences in antibodies among different clinical phenotypes. Spearman's rank correlation analysis was used to evaluate the correlation between serum DGP-IgA level and Marsh grading. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic efficacy of DGP-IgA, tTG-IgA, and the combination of DGP-IgA and tTG-IgA for celiac disease.Results:Among the 80 celiac disease patients, there were 19 males and 61 females, with a mean age of 45.31 ± 14.96 years. In the healthy control group, there were 15 males and 25 females, with a mean age of 47.03 ± 11.86 years. There were no statistically significant differences in age and gender between the two groups (both P > 0.05). The level of DGP-IgA and tTG-IgA in the celiac disease group were significantly higher than those in the healthy control group [DGP-IgA: 308.31 (279.86, 349.92) U/ml vs. 269.85 (251.42, 290.40) U/ml, P < 0.01; tTG-IgA: 261.05 (79.23, 2 542.30) U/ml vs. 1.90 (1.90, 2.40) U/ml, P < 0.01]. Further subtype analysis revealed that DGP-IgA level in classical celiac disease patients was higher than that in subclinical celiac disease patients [314.63 (289.35, 357.30) U/ml vs. 275.65 (260.90, 296.72) U/ml, P < 0.05], with statistically significant difference. Serum DGP-IgA level in celiac disease patients was positively correlated with Marsh grading ( r = 0.343, P < 0.01). The ROC curve results showed that the area under curve (AUC) for serum DGP-IgA in diagnosing celiac disease was 0.768, with an optimal cutoff value of 292.51 U/ml, sensitivity of 66.3%, and specificity of 77.5%; AUC for serum tTG-IgA was 0.974, with an optimal cutoff value of 20.1 U/ml, sensitivity of 92.5%, and specificity of 95.0%; AUC for the combination of DGP-IgA and tTG-IgA was 0.991, with a sensitivity of 98.8% and specificity of 97.5%. Conclusions:Serum DGP-IgA alone has limited clinical significance in diagnosing adult celiac disease. The diagnostic efficacy can be improved only when combined with tTG-IgA detection.

Objective:To understand the current status and characteristics of clinical trials for oral diseases in China, for the purpose of providing a reference for the research and development of oral diseases in China.Methods:Retrieving the information on clinical trials related to oral diseases registered on the "Platforms for drug clinical trial registration and information" of the National Medical Products Administration from the date of the database establishment to December 31, 2024. The number of clinical trials, type of drugs, trial phases, indication, trial scope, design types were statistically analyzed.Results:As of December 31, 2024, a total of 578 drug clinical trials for oral disease were registered, accounting for 2.1% (578/27 905) of the clinical trials disclosed on the platform during the same period. Bioequivalence clinical trials accounted for the highest proportion [73.9% (427/578)], followed by Phase Ⅰ [9.0% (52/578)], Phase Ⅱ [8.0% (46/578)], and Phase Ⅲ [4.5% (26/578)]. The 578 clinical trials involved 149 types of trial drugs, mainly chemical drugs, among which 127 were developed by domestic pharmaceutical enterprises and 27 by international pharmaceutical enterprises (the five investigational drugs have undergone clinical trials by both domestic and international pharmaceutical companies). The project leader units of the 578 drug clinical trials were distributed in 27 provinces, autonomous regions, municipalities, and Hong Kong Special Administrative Region. Excluding 427 bioequivalence clinical trials, the project leader units of 151 new drug clinical trials showed a significant aggregation phenomenon, and only three specialized oral hospitals have served as project leader units for drug clinical trials.Conclusions:The number of drug clinical trials for oral disease in China has generally shown an increasing trend, but there are still problems such as small number of clinical trials, low proportion of investment in new drug development and international multicenter trials, concentrated indications of clinical trials and insufficient clinical trial experience in specialized oral medical institutions. Enhancing the enthusiasm and innovation capabilities of domestic pharmaceutical enterprises in the research and development of oral diseases drugs, exploring the advantages of traditional Chinese medicine/natural medicine resources for oral diseases, and establishing a clinical research system in specialized oral medical institutions are of great significance for the development of oral drugs.

Objective This study aims to develop an early in-hospital temperature management protocol for heat stroke patients and assess its effectiveness,providing guidance for rapid cooling and precise target temperature control.Methods The protocol was developed through a Delphi expert consultation combined with expert panel meetings.A multi-center,non-randomized,historical control study was conducted,utilizing convenience sampling to select heat stroke patients from the emergency departments of 7 tertiary hospitals in Zhejiang Province,China,between June and August 2024 as an experimental group.The protocol was implemented in this group,while the control group consisted of heat stroke patients treated between June and August 2022,prior to protocol implementation.Cooling rates,target temperature attainment rates,and clinical outcomes were compared between the 2 groups.Results The final protocol included 6 primary indicators,23 secondary indicators,and 56 tertiary indicators.After protocol implementation,the experimental group achieved a cooling rate of 0.08(0.05～0.09)℃/min within 0.5 hours,significantly higher than the control group,which had a rate of 0.04(0.02～0.06)℃/min(P＜0.001).The target temperature attainment rates at 0.5 hours and 2.0 hours were 55.93％and 98.31％,respectively,significantly higher than the rates of 15.87％and 61.11％in the control group(P＜0.001).The mechanical ventilation rate,hospitalization rate,ICU admission rate,and mortality rate in the experimental group were 25.42％,61.02％,44.07％,and 8.47％,respectively.Logistic regression analysis revealed that the early in-hospital temperature management protocol significantly reduced the risk of mechanical ventilation and hospitalization in heat stroke patients,with odds ratios(ORs)of 0.294 and 0.300,respectively(both P＜0.05).Conclusion The developed protocol for early in-hospital temperature management in heat stroke patients is scientific,systematic,and practical.It improves cooling rates and target temperature attainment,thereby enhancing the prognosis of heat stroke patients.

OBJECTIVE: This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China. METHODS: Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site. RESULTS: Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL. CONCLUSION The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans ; HIV Infections/virology* ; China/epidemiology* ; Drug Resistance, Viral ; Male ; Adult ; Female ; Middle Aged ; HIV-1/genetics* ; Anti-HIV Agents/therapeutic use* ; Myanmar/epidemiology* ; Young Adult ; Prevalence ; Adolescent ; Mutation

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major health concern in northwest China; however, the impact of particulate matter (PM) exposure during sand-dust storms (SDS) remains poorly understood. Therefore, this study aimed to investigate the association between PM exposure on SDS days and COPD hospitalization risk in arid regions. METHODS: Data on daily COPD hospitalizations were collected from 323 hospitals from 2018 to 2022, along with the corresponding air pollutant and meteorological data for each city in Gansu Province. Employing a space-time-stratified case-crossover design and conditional Poisson regression, we analyzed 265,379 COPD hospitalizations. RESULTS: PM exposure during SDS days significantly increased COPD hospitalization risk [relative risk ( RR) for PM _2.5, lag 3:1.028, 95% confidence interval ( CI): 1.021-1.034], particularly among men and the elderly, and during the cold season. The burden of PM exposure on COPD hospitalization was substantially high in Northwest China, especially in the arid and semi-arid regions. CONCLUSION Our findings revealed a positive correlation between PM exposure during SDS episodes and elevated hospitalization rates for COPD in arid and semi-arid zones in China. This highlights the urgency of developing region-specific public health strategies to address adverse respiratory outcomes associated with SDS-related air quality deterioration.
Humans ; China/epidemiology* ; Pulmonary Disease, Chronic Obstructive/chemically induced* ; Particulate Matter/analysis* ; Hospitalization/statistics & numerical data* ; Male ; Female ; Middle Aged ; Aged ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Spatio-Temporal Analysis ; Adult ; Sand ; Air Pollution