ObjectiveTo reveal the mechanism of Zuogui Jiangtang Jieyu prescription against damage to hippocampal synaptic microenvironment via suppressing glutamate receptor 2 （GluR2）/Parkin signal-mediated mitophagy in rats with diabetes-related depression （DD）. MethodsEighty male SD rats underwent adaptive feeding for 5 days before the study. Ten rats were randomly assigned to the normal group. The model of DD rats was established with the rest by 2-week high-fat diet + streptozotocin （STZ） tail intravenous injection + 28 days of chronic unpredictable mild stress （CUMS） combined with isolation. The rats were randomly divided into a normal group， a model group， a GluR2 blocker group （5 μg·kg^-1）， a GluR2 agonist group （10 μg·kg^-1）， a metformin + fluoxetine group （0.18 g·kg^-1 metformin + 1.8 mg·kg^-1 fluoxetine）， and high- and low-dose Zuogui Jiangtang Jieyu prescription groups （20.52 and 10.26 g·kg^-1， respectively）. The rats in the GluR2 blocker group and the GluR2 agonist group were continuously injected with CNQX and Cl-HIBO in the dentate gyrus of the hippocampus once a week starting from stress modeling， respectively， while the metformin + fluoxetine group and the high- and low-dose Zuogui Jiangtang Jieyu prescription groups were continuously given intragastric administration for 28 d at the same time of stress modeling. Depression-like behavior was evaluated by open field and forced swimming experiments. The levels of serum insulin and adenosine triphosphate （ATP） in hippocampus were detected by biochemical analysis. The levels of 5-hydroxytryptamine （5-HT） and dopamine （DA） in hippocampus were detected by enzyme-linked immunosorbent assay （ELISA）. The autophagosomes of hippocampal neurons were observed by transmission electron microscopy. The morphology and structure of dendrites and spines of hippocampal neurons were evaluated by Golgi staining. Western blot detected the expression levels of GluR2 and Parkin proteins in hippocampus. The expression levels of GluR2， Parkin， regulating synaptic membrane exocytosis protein 3 （RIMS3）， and postsynaptic density protein 95 （PSD95） in the dentate gyrus of the hippocampus were detected by immunofluorescence. ResultsCompared with the normal group， the model group exhibited reduced total activity distance in the open field and increased immobility time in forced swimming （P<0.01）， lowered levels of serum insulin and ATP， 5-HT， and DA in hippocampus （P<0.01）， increased autophagosomes of hippocampal neurons， significantly damaged morphology and structure of dendrites and spines of hippocampal neurons， decreased expression levels of GluR2， RIMS3， and PSD95 in hippocampus， and an increased Parkin expression level （P<0.05， P<0.01）. Compared with the model group， the GluR2 blocker group and the GluR2 agonist group showed aggravation and alleviation of the above abnormal changes， respectively （P<0.05， P<0.01）. The above depression-like behavior was significantly improved in the high- and low-dose Zuogui Jiangtang Jieyu prescription groups to different degrees. Specifically， the two groups saw elevated levels of serum insulin and ATP， 5-HT， and DA in hippocampus （P<0.05， P<0.01）， restrained increase in autophagosomes and damage to morphology and structure of dendrites and spines of hippocampal neurons， up-regulated protein expression levels of GluR2， RIMS3， and PSD95， and down-regulated Parkin expression level （P<0.05， P<0.01）. ConclusionZuogui Jiangtong Jieyu prescription can ameliorate the mitophagy-mediated damage to hippocampal synaptic microenvironment in DD rats， the mechanism of which might be related to the regulation of GluR2/Parkin signaling pathway.

ObjectiveTo explore the mechanism by which the ethanol extract of Epimedium brevicornu （EEBM） intervenes in mesenchymal adipose-derived stem cells （ADSCs） to delay aging in castrated rats. MethodsForty-five 3-month-old SPF female SD rats were ovariectomized and randomly divided into model group， ADSCs treatment group， and ADSCs groups treated with low， medium， and high concentrations of EEBM （1， 50， 100 μg·L^-1）， referred to as the AE low， medium， and high concentration groups， with 9 rats in each group. After tail vein injection of 200 μL of the corresponding stem cell suspension， aging-related indicators including cyclin-dependent kinase inhibitor （p21）， tumor suppressor gene （p53）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， superoxide dismutase （SOD）， malondialdehyde （MDA）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cysteine-aspartic acid protease-3 （Caspase-3）， and lipofuscin were measured using enzyme-linked immunosorbent assay （ELISA） and Western blot. ResultsCompared with the model group， the IL-6 content in the AE low， medium， and high concentration groups was significantly decreased （P<0.05）. Lipofuscin， MDA， and IL-8 levels in the ADSCs treatment group and AE low， medium， and high concentration groups were significantly reduced （P<0.01）， while SOD content was significantly increased （P<0.05， P<0.01）. Compared with the ADSCs treatment group， lipofuscin and IL-8 levels in the AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）. The MDA content was significantly decreased in the AE medium concentration group （P<0.01）. Compared with the model group， protein levels of p21， p53， Bax， and Caspase-3 in the ADSCs treatment group and AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）， while the Bcl-2 protein level was significantly increased （P<0.01）. Compared with the ADSCs treatment group， protein levels of p21， p53， Bax， and Caspase-3 in the AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）， and the Bcl-2 protein level in the AE low concentration group was significantly increased （P<0.01）. ConclusionThe results of this experiment show that EEBM-treated ADSCs or ADSCs may delay aging in castrated rats by inhibiting cell apoptosis， reducing cell cycle inhibitors and pro-inflammatory factors， enhancing antioxidant capacity， and reducing oxidative reactions. Moreover， EEBM-treated ADSCs demonstrate stronger anti-aging effects than ADSCs alone. This study provides experimental evidence supporting the clinical use of EEBM to intervene in ADSCs and delay aging.

ObjectiveTo analyze the incidence rate and mortality of acute myocardial infarction (AMI) and their changing trends among the registered residents in Xiaoshan District, Hangzhou City from 2017 to 2023, so as to provide references for formulating policies related to AMI prevention. MethodsThe morbidity and mortality data of AMI among the registered residents in Xiaoshan District from 2017 to 2023 were collected through the Hangzhou Chronic Disease and Death Cause Monitoring System. Software such as Excel 2019, SPSS 25.0 and Joinpoint 4.9.1.0 were used to calculate the incidence rate, mortality, and average annual percentage change (AAPC) of AMI. ResultsFrom 2017 to 2023, the average annual crude incidence rate, age-standardized incidence rate using China standard population (ASIRC), and the age-standardized incidence rate using World standard population (ASIRW) of AMI in Xiaoshan District were 48.25/100 000, 29.14/100 000, and 21.64/100 000, respectively, and, from which the AAPCs were 5.495%, 6.010%, and 6.533%, respectively, all showing an upward trend. The average annual crude mortality rate, the age-standardized mortality rate using China standard population (ASMRC), and the age-standardized mortality rate using World standard population (ASMRW) were 11.76/100 000, 6.52/100 000, and 4.71/100 000, respectively, from which the AAPCs were -9.669%, -10.433% and -9.615%, respectively, all showing a downward trend. The average annual crude incidence rate of AMI was higher in males (65.87/100 000) than that in females (31.31/100 000). Moreover, the average annual crude mortality rate of AMI was higher in males (14.08/100 000) than that in females (9.52/100 000), and the difference was statistically significant (all P<0.001) .After age grouping, the crude incidence rate of AMI among the residents aged 35-, 45-, 55-, and 65- years in Xiaoshan District from 2017 to 2023 showed an upward trend over time, with AAPCs of 16.993%, 17.149%, 8.523%, and 5.002%, respectively. While the crude mortality rate in residents aged 35-, 75-, and 85-102 years showed an decreasing trend over time, with AAPCs of -23.977%, -15.467%, and -17.415%, respectively, but there was no statistically significant difference in the trends in incidence rate and mortality of other age groups (all P>0.05). ConclusionThe situation of AMI prevention and control among the registered residents in Xiaoshan District is not optimistic, and targeted measures should be strengthened for the male residents aged ≥35 years old.

Objective To compare the efficacy and safety of video-assisted thoracoscopic surgery (VATS) thymectomy for the treatment of thymoma through subxiphoid uniportal approach using double sternum retractors, and subxiphoid and subcostal arch approach. Methods We retrospectively analyzed the clinical data of the patients diagnosed with thymoma who underwent VATS thymectomy from June 2023 to June 2024 in West China Hospital. Patients were categorized based on the surgical approach into two groups: a subxiphoid uniportal VATS thymectomy (SUVT) group and a subxiphoid and subcostal arch VATS thymectomy (SASAT) group. Comparisons were made between the two groups regarding surgical duration, intraoperative blood loss, postoperative drainage, thymoma size and location, and postoperative pain assessed using the visual analogue scale (VAS). Results The SUVT group consisted of 20 patients, including 11 males and 9 females, with an average age of (51.5±14.3) years. The SASAT group comprised 40 patients, including 26 males and 14 females, with an average age of (50.0±13.0) years. Compared to the SASAT group, the SUVT group had significantly larger thymomas [ (5.9±2.7) cm vs. (4.2±2.1) cm, P=0.010] and a higher proportion of neoplasms located in the superior mediastinum (30.0% vs. 2.5%, P=0.007). Additionally, the VAS pain scores on postoperative days 3, 7, and 30 were significantly lower in the SUVT group compared to the SASAT group (P<0.05). There were no statistical differences between the two groups in demographic characteristics, operative time, intraoperative blood loss, duration and volume of postoperative drainage, length of postoperative hospital stay, or the VAS pain score on the first postoperative day. Conclusion SUVT using double sternum retractors significantly reduces postoperative pain and provides superior efficacy in the resection of larger thymomas or those situated in the superior mediastinum.

Exercise-induced metabolic remodeling is a fundamental adaptive process whereby the body reorganizes systemic and cellular metabolism to meet the dynamic energy demands posed by physical activity. Emerging evidence reveals that such remodeling not only enhances energy homeostasis but also profoundly influences immune function through complex molecular interactions involving glucose, lipid, and protein metabolism. This review presents an in-depth synthesis of recent advances, elucidating how exercise modulates immune regulation via metabolic reprogramming, highlighting key molecular mechanisms, immune-metabolic signaling axes, and the authors’ academic perspective on the integrated “exercise-metabolism-immunity” network. In the domain of glucose metabolism, regular exercise improves insulin sensitivity and reduces hyperglycemia, thereby attenuating glucose toxicity-induced immune dysfunction. It suppresses the formation of advanced glycation end-products (AGEs) and interrupts the AGEs-RAGE-inflammation positive feedback loop in innate and adaptive immune cells. Importantly, exercise-induced lactate, traditionally viewed as a metabolic byproduct, is now recognized as an active immunomodulatory molecule. At high concentrations, lactate can suppress immune function through pH-mediated effects and GPR81 receptor activation. At physiological levels, it supports regulatory T cell survival, promotes macrophage M2 polarization, and modulates gene expression via histone lactylation. Additionally, key metabolic regulators such as AMPK and mTOR coordinate immune cell energy balance and phenotype; exercise activates the AMPK-mTOR axis to favor anti-inflammatory immune cell profiles. Simultaneously, hypoxia-inducible factor-1α (HIF-1α) is transiently activated during exercise, driving glycolytic reprogramming in T cells and macrophages, and shaping the immune landscape. In lipid metabolism, exercise alleviates adipose tissue inflammation by reducing fat mass and reshaping the immune microenvironment. It promotes the polarization of adipose tissue macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. Moreover, exercise alters the secretion profile of adipokines—raising adiponectin levels while reducing leptin and resistin—thereby influencing systemic immune balance. At the circulatory level, exercise improves lipid profiles by lowering pro-inflammatory free fatty acids (particularly saturated fatty acids) and triglycerides, while enhancing high-density lipoprotein (HDL) function, which has immunoregulatory properties such as endotoxin neutralization and macrophage cholesterol efflux. Regarding protein metabolism, exercise triggers the expression of heat shock proteins (HSPs) that act as intracellular chaperones and extracellular immune signals. Exercise also promotes the secretion of myokines (e.g., IL-6, IL-15, irisin, FGF21) from skeletal muscle, which modulate immune responses, facilitate T cell and macrophage function, and support immunological memory. Furthermore, exercise reshapes amino acid metabolism, particularly of glutamine, arginine, and branched-chain amino acids (BCAAs), thereby influencing immune cell proliferation, biosynthesis, and signaling. Leucine-mTORC1 signaling plays a key role in T cell fate, while arginine metabolism governs macrophage polarization and T cell activation. In summary, this review underscores the complex, bidirectional relationship between exercise and immune function, orchestrated through metabolic remodeling. Future research should focus on causative links among specific metabolites, signaling pathways, and immune phenotypes, as well as explore the epigenetic consequences of exercise-induced metabolic shifts. This integrated perspective advances understanding of exercise as a non-pharmacological intervention for immune regulation and offers theoretical foundations for individualized exercise prescriptions in health and disease contexts.

ObjectiveTo explore the effects of astragalin （AST） on autophagy and apoptosis of astrocytes in the L_4-5 dorsal horn of the spinal cord in mice with inflammatory pain induced by complete Freund's adjuvant （CFA）. MethodsTwenty-four male C57BL/6 mice， aged six months， were randomly assigned to four groups： control group， saline group， CFA model group， and CFA+AST group， six mice in each group. The inflammatory pain model was established by injection of 10 µL CFA into the right lateral malleolus fossa. The saline group were injected with an equal amount of normal saline at the same site. The inflammatory pain mice in CFA+AST group were further treated with AST （60 mg/kg） intraperitoneally once a day for 21 consecutive days. Multiplex immunofluorescence staining was used to detect the coexpression of autophagy-related factors including ATG 12 and Beclin-1， apoptosis-related factors including Cleaved-Caspase3 and Caspase9， and the astrocyte marker such as GFAP in the L_4-5 spinal dorsal horn of the mice in each group. Western blot was used to examine the protein expression levels of autophagy-related proteins（ATG12， Beclin-1） and apoptosis-related proteins（Caspase 3， Caspase 9） in the L_4-5 spinal dorsal horn of mice. ResultsImmunofluorescent staining showed that in the L_4-5 dorsal horn of the spinal cord， the fluorescence intensity of ATG12 （P<0.000 1） and Beclin-1 （P<0.000 1） was significantly increased， while that of Cleaved-Caspase 3 （P<0.001） and Caspase 9 （P<0.000 1） was decreased in the CFA+AST group when compared to the CFA model group. Furthermore， AST could inhibit the activation of astrocytes. Western blot further confirmed that AST significantly upregulated the expression of ATG12 （P<0.000 1） and Beclin-1 （P<0.000 1） in the L_4-5 spinal cord of CFA mice， and downregulated the expression of Caspase 3 （P<0.01） and Caspase 9 （P<0.001）. ConclusionsAST promotes autophagy of astrocytes and inhibits their apoptosis in the L_4-5 spinal dorsal horn of CFA mice.

Osteoarthritis （OA） and stroke are common clinical diseases that reduce patients' quality of life and place a burden on families and society. Ruyi Zhenbaowan， a classic prescription in Tibetan medicine， have the functions of clearing heat， awakening the brain and opening orifices， relaxing tendons and promoting meridian circulation， and eliminating yellow water. Clinically， they are used to treat osteoarthritis， post-stroke sequelae， neuropathic pain， and other related conditions. Modern pharmacological studies have demonstrated their anti-inflammatory， analgesic， and nerve-repairing effects. However， current research remains insufficient regarding the appropriate indications， timing， and efficacy of this medicine in treating relevant diseases. To enhance clinicians' understanding of this medicine and promote its standardized and rational clinical use， a panel of national experts， including clinical specialists， Tibetan medicine practitioners， pharmacologists， and methodologists， formulated this consensus based on clinical experience and evidence-based practice. The Cochrane systematic review framework， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system， and the nominal group method were employed to generate seven graded recommendations and 19 consensus-based suggestions. These recommendations clearly define the key points in the clinical application of Ruyi Zhenbaowan， including therapeutic indications， dosage and administration， treatment duration， and medication safety. The consensus specifically addresses the clinical efficacy， appropriate timing of administration， dosage strategies， treatment cycles， and combination medication strategies for treating osteoarthritis and stroke and provides an overview of safety considerations. The aim is to provide standardized guidance for hospitals and healthcare institutions nationwide to ensure the rational application of Ruyi Zhenbaowan in the treatment of osteoarthritis and stroke， reduce medication-related risks， and further leverage its clinical advantages. This consensus has been approved and issued by the China Association of Chinese Medicine， with the standard number GS/CACM 369-2024.

The pathogenesis of ankylosing spondylitis （AS） is usually insidious and has not been fully elucidated. Non-steroidal anti-inflammatory drugs （NSAIDs） and anti-rheumatic drugs （ARDs） are usually given to improve the condition. however, some patients still have poor results or adverse reactions from conventional treatments. Biological agents have significantly changed therapeutic strategies in the field of rheumatology since their clinical application was initiated and are gradually becoming the main therapeutic option for patients with AS. The current research progress on biologics in the treatment of AS in terms of the current treatment status, clinical problems, and solution strategies were reviewed, which could provide theoretical basis and reference with clinical value, and promote the precise treatment of AS in the future.

ObjectiveTo investigate the effects of mitotically-associated long non-coding RNA （lncRNA MANCR） on the proliferation，migration， and epithelial mesenchymal transition （EMT） of gastric cancer （GC） cells by regulating the microRNA-50-5p （miR-150-5p）/non-metastatic melanoprotein B （GPNMB） axis. MethodsThe mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in 42 cases of GC tissue and adjacent tissue resected during surgery in the First Hospital of Hebei Medical University from June 2022 to September 2023 were detected by Real-time PCR. Human gastric mucosal epithelial cells GES-1 and human GC cells BGC-823 were cultured in vitro， and their lncRNA MANCR expression was detected. BGC-823 cells were randomly separated into control group （routine culture），sh-NC group （with sh-NC transfected），sh-MANCR group （with sh-MANCR transfected），sh-MANCR + anti-NC group （with sh-MANCR and anti-NC both transfected），and sh-MANCR + anti-miR-150-5p group （with sh-MANCR and anti-miR-150-5p both transfected）. The mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in the BGC-823 cells of all groups were analyzed. EdU staining was used to detect the proliferation of BGC-823 cells. Transwell assay was used to detect the migration and invasion of BGC-823 cells. The expressions of EMT-related proteins E-cadherin，N-cadherin，Vimentin， and GPNMB were detected by Western blot. The interactions between lncRNA MANCR and miR-150-5p and between miR-150-5p and GPNMB were analyzed by dual luciferase reporter assay. ResultsThe mRNA expressions of lncRNA MANCR and GPNMB in GC tissue were higher than those in adjacent tissue，and the expression of miR-150-5p was lower than that in adjacent tissue （P<0.05）. Compared with that in GES-1，lncRNA MANCR expression in BGC-823 cells was increased （P<0.05）. Compared with those in the sh-NC group and control group，the EdU-positive cell rate，migration number，invasion number，the mRNA expressions of lncRNA MANCR and GPNMB， and the expressions of protein，N-cadherin protein， and Vimentin protein in the BGC-823 cells in the sh-MANCR group were lower ，and the protein expressions of miR-150-5p and E-cadherin were higher （P<0.05）. Compared with those in the sh-MANCR group and the sh-MANCR + anti-NC group，the protein expressions of miR-150-5p and E-cadherin in the sh-MANCR + anti-miR-150-5p group were decreased. The EdU-positive cell rate，migration number，invasion number，mRNA expressions of GPNMB， and expressions of protein，N-cadherin protein， and Vimentin protein were increased （P<0.05）. lncRNA MANCR could target the negative regulation of miR-150-5p，and miR-150-5p could target the negative regulation of GPNMB. ConclusionKnockout of lncRNA MANCR can inhibit the proliferation，migration， and EMT of GC cells by regulating the miR-150-5p/GPNMB axis.

ObjectiveTo investigate the effects of mitotically-associated long non-coding RNA （lncRNA MANCR） on the proliferation，migration， and epithelial mesenchymal transition （EMT） of gastric cancer （GC） cells by regulating the microRNA-50-5p （miR-150-5p）/non-metastatic melanoprotein B （GPNMB） axis. MethodsThe mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in 42 cases of GC tissue and adjacent tissue resected during surgery in the First Hospital of Hebei Medical University from June 2022 to September 2023 were detected by Real-time PCR. Human gastric mucosal epithelial cells GES-1 and human GC cells BGC-823 were cultured in vitro， and their lncRNA MANCR expression was detected. BGC-823 cells were randomly separated into control group （routine culture），sh-NC group （with sh-NC transfected），sh-MANCR group （with sh-MANCR transfected），sh-MANCR + anti-NC group （with sh-MANCR and anti-NC both transfected），and sh-MANCR + anti-miR-150-5p group （with sh-MANCR and anti-miR-150-5p both transfected）. The mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in the BGC-823 cells of all groups were analyzed. EdU staining was used to detect the proliferation of BGC-823 cells. Transwell assay was used to detect the migration and invasion of BGC-823 cells. The expressions of EMT-related proteins E-cadherin，N-cadherin，Vimentin， and GPNMB were detected by Western blot. The interactions between lncRNA MANCR and miR-150-5p and between miR-150-5p and GPNMB were analyzed by dual luciferase reporter assay. ResultsThe mRNA expressions of lncRNA MANCR and GPNMB in GC tissue were higher than those in adjacent tissue，and the expression of miR-150-5p was lower than that in adjacent tissue （P<0.05）. Compared with that in GES-1，lncRNA MANCR expression in BGC-823 cells was increased （P<0.05）. Compared with those in the sh-NC group and control group，the EdU-positive cell rate，migration number，invasion number，the mRNA expressions of lncRNA MANCR and GPNMB， and the expressions of protein，N-cadherin protein， and Vimentin protein in the BGC-823 cells in the sh-MANCR group were lower ，and the protein expressions of miR-150-5p and E-cadherin were higher （P<0.05）. Compared with those in the sh-MANCR group and the sh-MANCR + anti-NC group，the protein expressions of miR-150-5p and E-cadherin in the sh-MANCR + anti-miR-150-5p group were decreased. The EdU-positive cell rate，migration number，invasion number，mRNA expressions of GPNMB， and expressions of protein，N-cadherin protein， and Vimentin protein were increased （P<0.05）. lncRNA MANCR could target the negative regulation of miR-150-5p，and miR-150-5p could target the negative regulation of GPNMB. ConclusionKnockout of lncRNA MANCR can inhibit the proliferation，migration， and EMT of GC cells by regulating the miR-150-5p/GPNMB axis.