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.

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

OBJECTIVE: To investigate the effects of low-dose irradiated autologous peripheral blood reinfusion (LDIAPBR) on a rat model of radiation-induced leukopenia. METHODS: The rats were randomly divided into four groups. In the LDIAPBR group, LDIAPBR was performed 1 day before modeling (10% of the total circulating blood volume was withdrawn, irradiated with 100 mGy ex vivo, and completely reinfused). Meanwhile, the normal group and model group only underwent blood withdrawal and reinfusion of the same proportion without blood irradiation. Except for the normal group, all groups were subjected to 1 Gy X-ray whole-body irradiation to establish a radiation-induced leukopenia rat model. The positive drug group received subcutaneous injection of rhG-CSF after modeling. It was monitored that the general condition of the rats, peripheral blood cell counts, immune organ indices, bone marrow nucleated cell counts and viability, and the pathological analysis of bone marrow sections was conducted. RESULTS: The LDIAPBR group exhibited significant improvements in overall condition compared to the model group. Notably, compared with the model group, peripheral blood leukocyte and lymphocyte counts were markedly higher in the LDIAPBR group. Furthermore, there was a significant increase in both the number and viability of nucleated cells in the bone marrow. Pathological examination of bone marrow sections revealed increased nucleated cell density and reduced cavity area in the LDIAPBR group. CONCLUSION LDIAPBR can effectively improve hematological parameters and bone marrow hematopoietic function in a rat model of radiation-induced leukopenia, providing a new approach for the prevention and treatment of radiation-related injuries.
Animals ; Leukopenia/prevention & control* ; Rats ; Blood Transfusion, Autologous ; Whole-Body Irradiation ; Radiation Injuries, Experimental/therapy*

OBJECTIVE: To investigate the effect of irradiation dose rate of ⁶⁰Co γ-ray on hematopoietic and immune cells in total body irradiation (TBI) mice. METHODS: After TBI with 8 Gy ⁶⁰Co γ-ray at three irradiation dose rates of 0.027, 0.256 and 0.597 Gy/min, the survival and change of body weight of C57BL/6J mice were observed within 30 days. The peripheral blood parameters were examined at each time point within 30 days post-irradiation. The hematopoietic stem/progenitor cell counts of mice were examined on the 10^th and 30^th day post-irradiation by flow cytometry, as well as the proportions of immune cells in peripheral blood, bone marrow and spleen of mice on the 30^th day post-irradiation. RESULTS: After TBI with 8 Gy ⁶⁰Co γ-ray, the 30-day survival rate of high dose-rate group was 0, which was significantly lower than 90% of medium dose-rate group and 100% of low dose-rate group (both P < 0.001). The peripheral blood parameters of all three groups showed a sharp decline → low value → gradually recovering trend. The count of white blood cell, neutrophil, lymphocyte, red blood cell, platelet and hemoglobin level in the high dose-rate and medium dose-rate groups were significantly lower than those in the low dose-rate group on day 7-18 post-irradiation (all P < 0.05), but there were no significant differences between the high dose-rate and medium dose-rate groups (P >0.05). On the 10^th day after irradiation, the proportion and number of bone marrow hematopoietic stem/progenitor cells (including LK, LSK, LT-HSC, ST-HSC, and MPP cells) in the low dose-rate and medium dose-rate groups were significantly decreased compared to those in the normal group (all P < 0.05), but there were no significant differences between the two groups (P >0.05). On the 30^th day after irradiation, LSK, LT-HSC, ST-HSC and MPP cells in the low dose-rate group recovered to normal levels, while those in the medium dose-rate group were still significantly lower than those in the low dose-rate group (all P < 0.001). The results of bone marrow and peripheral immune cell tests on the 30^th day after irradiation showed that the ratios of T and B lymphocytes in the low dose-rate and medium dose-rate groups were reduced compared to that in the normal group (both P < 0.05), while the ratio of neutrophils was increased (P < 0.01). The trend of changes in the spleen and peripheral blood was consistent. CONCLUSION The degree of hematopoietic and immune cell damage in mice after TBI with 8 Gy ⁶⁰Co γ-ray is related to the dose rate, and low dose-rate irradiation can reduce the damage in the animal model. Therefore, choosing the appropriate dose rate of irradiation is a key factor in establishing an objective and reliable experimental animal model of irradiation.
Animals ; Mice ; Whole-Body Irradiation ; Gamma Rays ; Mice, Inbred C57BL ; Hematopoietic Stem Cells/radiation effects* ; Cobalt Radioisotopes ; Dose-Response Relationship, Radiation ; Male

OBJECTIVE: To screen anti-tumor drugs that improve antigen processing and presentation in acute myeloid leukemia (AML) cells. METHODS: A TCR-like or TCR mimic antibody that can specifically recognize HLA-A*0201:WT1_126-134 ( RMFPNAPYL) complex (hereafter referred to as HLA-A2:WT1) was synthesized to evaluate the function of antigen processing and presentation machinery (APM) in AML cells. AML cell line THP1 was incubated with increasing concentrations of IFN-γ, hypomethylating agents (HMA), immunomodulatory drugs (IMiD), proteasome inhibitors (PI) and γ-secretase inhibitors (GSI), followed by measuring of HLA-ABC, HLA-A2 and HLA-A2:WT1 levels by flow cytometry at consecutive time points. RESULTS: The TCR-like antibody we generated only binds to HLA-A*0201⁺WT1⁺ cells, indicating the specificity of the antibody. HLA-A2:WT1 level of THP-1 cells detected with the TCR-like antibody was increased significantly after co-incubation with IFN-γ, showing that the HLA-A2:WT1 TCR like antibody could evaluate the function of APM. Among the anti-tumor agents screened in this study, GSI (LY-411575) and HMA (decitabine and azacitidine) could significantly increase the HLA-A2:WT1 level. The IMiD lenalidomide and pomalidomide could aslo upregulate the expression of HLA-A2:WT1 complex under certain concentrations of the drugs and incubation time. As proteasome inhibitors, carfilzomib could significantly decreased the expression of HLA-A2:WT1, while bortezomib had no significant effect on HLA-A2:WT1 expression. CONCLUSION HLA-A2:WT1 TCR-like antibody can effectively reflect the APM function. Some of the anti-tumor drugs can affect the APM function and immunogenicity of tumor cells.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Antineoplastic Agents/pharmacology* ; Antigen Presentation/drug effects* ; HLA-A2 Antigen/immunology* ; Receptors, Antigen, T-Cell/immunology* ; Cell Line, Tumor ; Interferon-gamma

OBJECTIVE: To investigate the role of MK2 inhibitor MMI-0100 on inflammatory response after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and related mechanisms. METHODS: An allo-HSCT mouse model was established. Recipient rats were randomly divided into BMT+NaCl group and BMT+MMI-0100 group, and were injected with NaCl and MMI-0100 every day after transplantation, respectively. Samples of the two groups were collected on d 7 and 14, femur paraffin sections were stained with HE, and pathological changes in the bone marrow cavity were observed under the light microscope. The gene and protein expression levels of pro-inflammatory cytokines IL-1β and IL-18 were detected by qPCR and Western blot. Macrophage typing was detected by flow cytometry. The expression levels of NLRP3 and Caspase-1 were detected by Western blot. RESULTS: Inflammatory cell infiltration in the bone marrow cavity was significantly reduced in the BMT+MMI-0100 group. Western blot results showed that the protein expression levels of IL-1β and IL-18 in the BMT+MMI-0100 group were decreased compared to the BMT+NaCl group on day 7 and day 14 (all P <0.01). The qPCR results showed that compared to the BMT+NaCl group, the IL-18 gene expression levels in the BMT+MMI-0100 group were significantly reduced on day 7 and day 14 (both P <0.01). In the BMT+MMI-0100 group, the expression level of IL-1β gene decreased on day 7 (P <0.05), but increased and was higher than that in the BMT+NaCl group on day 14 (P <0.05). Flow cytometry results showed that the expression of M1 macrophages and M1/M2 ratio decreased in the BMT+MMI-0100 group compared to BMT+NaCl group (all P <0.05). Western blot results showed that the protein expression levels of NLRP3 and Caspase-1 in the BMT+MMI-0100 group were lower than those in the BMT+NaCl group (all P <0.05). CONCLUSION MMI-0100 can ameliorate bone marrow inflammatory injury after allo-HSCT and may act by reducing NLRP3 expression to promote M2 polarization.
Animals ; Interleukin-1beta/metabolism* ; Rats ; Interleukin-18/metabolism* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammation ; Bone Marrow/pathology* ; Protein Serine-Threonine Kinases/metabolism* ; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors* ; Caspase 1/metabolism* ; Macrophages ; Transplantation, Homologous

OBJECTIVE: To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome