Rheumatoid arthritis （RA） is a common autoimmune disease characterised clinically by symmetrical joint pain， swelling， and stiffness. Long-term chronic synovial inflammation can lead to severe joint damage and even disability， thereby affecting quality of life for patients. Current clinical treatment of RA emphasises an integrated approach combining traditional Chinese and Western medicine， with traditional Chinese medicine offering certain advantages in reducing disease activity of RA， preventing relapses， and other aspects. Modern clinical evidence confirms that Guizhi Shaoyao Zhimutang （GSZT） is effective in improving symptoms such as immune metabolism， joint stiffness， and joint pain in RA patients. Pharmacological studies have revealed that GSZT primarily contains components such as cinnamaldehyde， total glucosides of paeony， total alkaloids of Aconiti Lateralis Radix Praeparata， glycyrrhetinic acid， zingiberone， isoimperatorin， ephedra polysaccharides， and cedrol. It improves RA symptoms via multiple mechanisms and targets， including enhancing immune responses， exerting anti-inflammatory and analgesic effects， regulating relevant signalling pathways， inhibiting cell apoptosis， and suppressing bone destruction. This paper reviewed the syndrome patterns and pharmacological basis of GSZT in the treatment of RA， as well as its clinical applications and related mechanisms， thereby providing a theoretical basis and reference for the further development and utilisation of GSZT in the treatment of RA.

Rheumatoid arthritis （RA） is a common autoimmune disease characterised clinically by symmetrical joint pain， swelling， and stiffness. Long-term chronic synovial inflammation can lead to severe joint damage and even disability， thereby affecting quality of life for patients. Current clinical treatment of RA emphasises an integrated approach combining traditional Chinese and Western medicine， with traditional Chinese medicine offering certain advantages in reducing disease activity of RA， preventing relapses， and other aspects. Modern clinical evidence confirms that Guizhi Shaoyao Zhimutang （GSZT） is effective in improving symptoms such as immune metabolism， joint stiffness， and joint pain in RA patients. Pharmacological studies have revealed that GSZT primarily contains components such as cinnamaldehyde， total glucosides of paeony， total alkaloids of Aconiti Lateralis Radix Praeparata， glycyrrhetinic acid， zingiberone， isoimperatorin， ephedra polysaccharides， and cedrol. It improves RA symptoms via multiple mechanisms and targets， including enhancing immune responses， exerting anti-inflammatory and analgesic effects， regulating relevant signalling pathways， inhibiting cell apoptosis， and suppressing bone destruction. This paper reviewed the syndrome patterns and pharmacological basis of GSZT in the treatment of RA， as well as its clinical applications and related mechanisms， thereby providing a theoretical basis and reference for the further development and utilisation of GSZT in the treatment of RA.

ObjectiveTo investigate the effect of solute carrier family 7 member 5 (SLC7A5) inhibitor JPH203 on renal fibrosis induced by unilateral ureteral obstruction in mice. MethodsSixteen SPF male C57BL/6 mice were randomly divided into the control group and the experimental group, with 8 mice in each group. The mouse model of renal fibrosis was established by unilateral ureteral obstruction. From the third day after surgery, the mice in the control group were intraperitoneally injected with phosphate-buffered saline (PBS) for 11 consecutive days, and the injection dose was 200 μL/d. Mice in the experimental group received intraperitoneal injection of JPH203 (50 mg/kg) every day for 11 days. On day 14, the mice were euthanized, then the kidney tissues were obtained. Hematoxylin and eosin (HE) staining was used to assess renal tissue damage, Masson staining was used to evaluate collagen fiber deposition in the extracellular matrix, and immunohistochemistry was used to detect the levels of fibroblast activation markers α-smooth muscle actin (α-SMA) and collagen type Ⅰ (COL-Ⅰ) in kidney tissues. Western blotting was further performed to measure the expression levels of SLC7A5 and transforming growth factor-β1 (TGF-β1), as well as the phosphorylation levels of mammalian target of rapamycin complex 1 (mTORC1) signaling pathway-related molecules. Real-time quantitative PCR was used to verify changes in the mRNA levels of SLC7A5, α-SMA, and COL-Ⅰ in kidney tissues. ResultsCompared with the control group, the experimental group showed reduced destruction of renal tissue structure and a significantly lower pathological injury score (P<0.05). Additionally, collagen deposition in the extracellular matrix was decreased, and the percentage of collagen fiber area was significantly reduced (P<0.001) in the experimental group. The levels of fibroblast activation markers α-SMA and COL-Ⅰ were significantly lower in the experimental group (both P<0.001). The expression levels of SLC7A5 and TGF-β1 were also significantly decreased (P<0.001), and the phosphorylation levels of mTORC1 signaling pathway-related proteins 4E-BP1 and mTORC1 were significantly reduced (P<0.001). Real-time quantitative PCR confirmed that the mRNA levels of SLC7A5, α- SMA, and COL-Ⅰ in kidney tissues were significantly lower in the experimental group (P<0.001). ConclusionJPH203 may inhibit the progression of renal fibrosis in mice by suppressing SLC7A5 expression, regulating the mTORC1 signaling pathway, and altering fibroblast activation status.

ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

Recent studies have shown that an imbalance in iron metabolism can affect the composition and microstructural changes of bone, disrupting bone homeostasis and leading to osteoporosis(OP). The imbalance in iron metabolism, along with its induced local abnormal microenvironment and cellular iron death, has become a new focal point in OP research, drawing increasing attention from the academic community regarding the regulation of iron metabolism to prevent and manage OP. From the perspective of traditional Chinese medicine(TCM), iron metabolism imbalance has potential connections to TCM theories regarding internal organs, as well as treatments aimed at tonifying the kidney, strengthening the spleen, and activating blood circulation. Evidence is continually emerging that TCMs and effective components that tonify the kidney, strengthen the spleen, and activate blood circulation can prevent and manage OP by regulating iron metabolism. This article analyzes the relationship between iron and bone, as well as the effects of TCM formulations on improving iron metabolism and influencing bone metabolism, from the perspectives of iron metabolism mechanisms and TCM interventions, aiming to broaden existing clinical strategies for prevention and treatment and inject new momentum into the field of OP as it moves into a new era.
Osteoporosis/drug therapy* ; Humans ; Iron/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Medicine, Chinese Traditional ; Bone and Bones/drug effects*

This study aims to investigate the scientificity and efficacy of the compatibility of Jinlingzi San from pharmacokinetics. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was utilized to determine the plasma concentrations of the active components: toosendanin, tetrahydropalmatine A, and tetrahydropalmatine B at various time points following the gavage of Jinlingzi San and its single medicines in rats. Subsequently, WinNonlin was employed to calculate pertinent pharmacokinetic parameters. The pharmacokinetic parameters in rat plasma were compared between the single medicines and the compound formula of Jinlingzi San. It was discovered that the area under the curve(AUC_(all)) and peak concentrations(C_(max)) of tetrahydropalmatine A, and tetrahydropalmatine B were significantly elevated in the compound formula group compared with the single medicine groups. Conversely, the AUC_(all )and C_(max) of toosendanin notably decreased. Furthermore, the compound formula group had longer mean residence time(MRT) and lower apparent clearance(CL/F) of all three active ingredients than the single medicine groups(P<0.05). These findings indicated that Jinlingzi San enhanced the absorption of tetrahydropalmatine A and tetrahydropalmatine B in vivo, facilitating their pharmacological actions. Concurrently, it inhibited the absorption of toosendanin, thereby preventing potential toxic reactions. Moreover, the compatibility prolonged the residence time of the active ingredients in the body. This study provides a reference for exploring the compatibility rationality of Jinlingzi San.
Animals ; Rats ; Tandem Mass Spectrometry/methods* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Chromatography, Liquid/methods* ; Berberine Alkaloids/blood* ; Liquid Chromatography-Mass Spectrometry

Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*

OBJECTIVES: To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students. METHODS: This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia. RESULTS: The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081). CONCLUSIONS Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans ; Myopia/etiology* ; Male ; Female ; Depression/physiopathology* ; Cross-Sectional Studies ; Sleep ; Adolescent ; Students ; Child ; Time Factors ; Sleep Duration