ObjectiveTo investigate the effects of modified Buyang Huanwu Tang on cerebral ischemia-reperfusion injury （CI/RI） in mice via the PTEN-induced putative kinase 1/E3 ubiquitin ligase （PINK1/Parkin） signaling pathway-mediated mitophagy， and to explore the underlying mechanism by which modified Buyang Huanwu Tang improves CI/RI. MethodsSeventy-two male C57BL/6J mice were randomly divided into six groups （n = 12 per group）： Sham-operated group， middle cerebral artery occlusion/reperfusion （MCAO/R） model group， low-， medium-， and high-dose modified Buyang Huanwu Tang groups （8.84， 17.68， 35.36 g·kg^-1·d^-1）， and an aspirin group （13.00 mg·kg^-1·d^-1）. Neurological deficit scores were assessed using the Zea-Longa method. Cerebral infarct volume ratio was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Histopathological changes and neuronal injury in brain tissues were observed using hematoxylin-eosin （HE） staining and Nissl staining. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） assay. Mitochondrial ultrastructure in brain tissue was observed by transmission electron microscopy （TEM）. Serum levels of superoxide dismutase （SOD） and malondialdehyde （MDA） were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of PINK1， Parkin， microtubule-associated protein 1 light chain 3B （LC3B， LC3Ⅱ/Ⅰ）， and p62 in brain tissues were detected by real-time quantitative reverse transcription PCR （Real-time PCR） and Western blot， respectively. ResultsCompared with the sham-operated group， the MCAO/R model group showed significantly increased neurological deficit scores and cerebral infarct volume ratios （P<0.01）. Severe cortical injury on the infarct side was observed， characterized by decreased neuronal density， cytoplasmic vacuolation， nuclear pyknosis， a marked reduction in Nissl bodies， dissolution of Nissl bodies in the cytoplasm of some pyramidal neurons， and blurred cellular boundaries. The number of TUNEL-positive cells increased significantly （P<0.01）. Mitochondria exhibited cristae membrane rupture and matrix vacuolation， with rupture of the outer mitochondrial membrane and formation of autophagosomes， the number of which increased significantly. Serum SOD activity decreased significantly （P<0.01）， while MDA content increased significantly （P<0.01）. In infarcted brain tissues of model mice， the relative mRNA expression and protein levels of PINK1， Parkin and LC3B were significantly increased （P<0.05， P<0.01）， whereas p62 mRNA and protein expression were significantly decreased （P<0.05， P<0.01）， showing statistical significance. Compared with the model group， all treatment groups showed significantly decreased neurological deficit scores and cerebral infarct volume ratios （P<0.01）. Neuronal density increased significantly， cytoplasmic vacuolation was alleviated， nuclear morphology tended to be more regular and clearer， Nissl body density increased significantly with reduced dissolution and improved contour clarity. The mitochondrial cristae structure was partially restored， with some mitochondria showing autophagosome encapsulation， and the degree of mitochondrial damage was alleviated. Serum SOD activity increased significantly （P<0.01）， while MDA content decreased significantly. The mRNA and protein expression levels of PINK1， Parkin， and LC3Ⅱ/Ⅰ were significantly increased （P<0.05， P<0.01）， while p62 mRNA and protein expression in the low- and medium-dose modified Buyang Huanwu Tang groups were significantly decreased （P<0.05， P<0.01）， showing statistical significance. ConclusionModified Buyang Huanwu Tang can upregulate the protein expression levels of PINK1， Parkin， and LC3Ⅱ/Ⅰ and downregulate p62 protein expression， suggesting that it may improve CI/RI by regulating the expression of proteins related to the PINK1/Parkin signaling pathway. Regulation of the mitophagy pathway may be one of the mechanisms by which modified Buyang Huanwu Tang alleviates CI/RI in mice.

Flap transplantation is a critical surgical strategy for the reconstruction of tissue defects caused by trauma, tumor resection, and congenital malformations, and its survival rate directly determines surgical efficacy and patient prognosis. Following transplantation, flaps inevitably undergo ischemia-reperfusion (I/R) injury, during which oxidative stress, inflammatory responses, and metabolic disturbances are intricately intertwined, ultimately leading to cellular injury and tissue necrosis. Recent studies have demonstrated that multiple forms of programmed cell death—including apoptosis, pyroptosis, ferroptosis, necroptosis, and PANoptosis—play central roles in flap I/R injury. The extensive crosstalk and molecular interactions among these pathways form a highly complex cell death network. Specifically, apoptosis is mediated by the imbalance of Bcl-2 family proteins and the activation of cysteine-dependent aspartate-specific protease (caspase) cascades; pyroptosis is driven by the NLRP3-caspase-1-GSDMD axis, resulting in membrane pore formation and the release of pro-inflammatory cytokines; ferroptosis is characterized by iron-dependent lipid peroxidation and dysfunction of glutathione peroxidase 4 (GPX4); necroptosis is triggered by the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3-MLKL signaling complex, leading to membrane rupture; and PANoptosis represents an integrated form of inflammatory cell death that coordinates multiple death pathways. Importantly, these forms of programmed cell death are not independent but are interconnected through extensive signaling crosstalk. Key regulatory molecules, including caspase-8, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2), collectively modulate the dynamic balance among these pathways. Therefore, the multidimensional interplay and spatiotemporal dynamics of programmed cell death constitute a fundamental pathological basis of flap I/R injury. This review systematically summarizes the latest advances in the mechanisms and interactions of various programmed cell death pathways in flap I/R injury, aiming to elucidate the underlying regulatory network. These insights may provide novel theoretical foundations for optimizing flap protection strategies, improving flap survival, and promoting tissue repair.

OBJECTIVE To optimize the forming process of Yindan huoxue tongyu granules， and evaluate the quality of the granules. METHODS Taking forming rate， angle of repose， moisture， moisture absorption rate and dissolution rate as indexes， single factor experiment combined with Plackett-Burman design was adopted to screen key process parameters； analytic hierarchy process combined with entropy weight method and Box-Behnken response surface method were used to optimize the molding process of Yindan huoxue tongyu granules， and the forming process was verified. The relative homogeneity index， bulk density， vibration density， Hausner ratio， angle of repose， moisture and hygroscopicity were used as secondary physical indexes to establish the physical fingerprints of 10 batches of Yindan huoxue tongyu granules to evaluate particle quality consistency. RESULTS The optimal molding process of Yindan huoxue tongyu granules was as follows： mannitol as the fixed excipient， the drug-assisted ratio was 1∶1（m/m） and the drying time was 1 h； 90% ethanol was used as wetting agent and the amount of it was 32%， the drying temperature was 70 ℃. The results of validation tests showed that the average comprehensive score was 97.45， which was close to the predicted value of 97.18. The similarities between the physical fingerprints of 10 batches of Yindan huoxue tongyu granules prepared by the optimal molding process and the reference physical fingerprint were all higher than 0.99. CONCLUSIONS The molding process is stable and feasible， and the quality of Yindan huoxue tongyu granules produced is stable and controllable.

Synovium is the target organ of rheumatoid arthritis.The excessive proliferation of synovial cells and insufficient apoptosis lead to synovial hyperplasia,which in turn causes damage to the surrounding tissues of the joint and bone destruction."Yang transforming qi and yin forming elements"is derived from Su Wen and is a highly summarized description of the functions of yin and yang,which runs through the entire course of the disease.This article elucidated the theoretical connotation of"yang transforming qi and yin forming elements"and its connection with synovial hyperplasia,proposing that the insufficiency of"yang transforming qi"is the root of synovial hyperplasia,while the excess of"yin forming elements"is the manifestation of synovial hyperplasia.Based on this,it put forward that"assisting yang qi as the priority,and according to the bias of pathogenic factors of yin,supplementing the method of reducing yin forming elements"is an important principle for treating this disease,which could provide new ideas for the treatment of the disease.

Objectives:To investigate the effect and mechanism of mitochondrial targeting peptide SS-31 on senescence and pyroptosis of nucleus pulposus(NP)cells induced by inflammation.Methods:NP cells were isolated and cultured in vitro from 6-week-old male SD rats,and were divided into control group,lipopolysaccharide(LPS)group,and LPS+SS-31 group;And the control group of cells received no treatment,LPS group of cells were treated with 100μg/mL LPS for 24h,and LPS+SS-31 group of cells were pre-treated with SS-31 30min before LPS intervention.The levels of cellular senescence and pyroptosis were assessed in each group using β-galactosidase(SA-β-Gal)staining and westem blot(WB)assay;Transmission electron mi-croscopy and oxygen consumption rate(OCR)assay were used to analyze the mitochondrial function of NP cells in each group;The expressions of phosphorylated nuclear factor-κB-p65(p-NF-κB-p65),cyclic GMP-AMP synthase(cGAS),and interferon stimulating gene(STING)in each group were detected by WB and im-munofluorescence;Hematoxylin-eosin(HE)staining,immunohistochemistry(IHC)staining and WB assay were performed to analyze the effects of in vivo injection of SS-31 on intervertebral disc degeneration,senescence,and pyroptosis.Results:The positive SA-β-Gal staining of NP cells,expression of senescence marker pro-teins(p53,p21),and pyroptosis-related molecules(NLRP3,Caspase-1 p20)were significantly lower in the LPS+SS-31 group compared with the LPS group(P＜0.05);Transmission electron microscopy(TEM)showed that the mitochondrial swelling of NP cells was round,the matrix was translucent,and the interstitial lumen of the mitochondrial cristae was dilated in the LPS group,while the mitochondrial swelling was subsided,and the morphology of mitochondria tended to be normalized in the LPS+SS-31 group.Meanwhile,the maximum respi-ration level of NP cells was significantly enhanced in the LPS+SS-31 group compared with the LPS group(P＜0.05).The results of WB and immunofluorescence showed that LPS significantly up-regulated the expression of p-NF-κB-p65,cGAS,and STING(P＜0.05),while SS-31 pretreatment significantly inhibited the expression of p-NF-κB-p65,cGAS and STING in NP cells induced by LPS(P＜0.05).Finally,in vivo experiments con-firmed that local injection of SS-31 reduced the senescence and pyroptosis of NP cells,and alleviated the degeneration of intervertebral disc induced by annulus fibropuncture.Conclusions:SS-31 alleviates inflamma-tion-induced senescence and pyroptosis of NP cells,which is related to the inhibition of NF-κB signaling pathway and cGAS/STING signaling pathway.

Objective:To analyze the risk factors associated with future exacerbations in patients with chronic obstructive pulmonary disease (COPD) who have no history of exacerbation in the past year.Methods:COPD patients with no exacerbation history in the past year, registered in the RealDTC study from January 2018 to December 2023, were enrolled. Demographic data, COPD Assessment Test (CAT) scores, modified Medical Research Council (mMRC) dyspnea questionnaire scores, forced expiratory volume in the first second predicted of percentage (FEV 1%pred), forced expiratory volume in one second (FEV 1) to forced vital capacity (FVC), Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, GOLD groups, and inhaled medication regimens were collected. All patients were followed up for one year, and the number of exacerbations was recorded. Patients were divided into an exacerbation group and a non-exacerbation group based on the occurrence of exacerbations during the follow-up period. Logistic regression analysis was used to screen the influencing factors for exacerbations in COPD patients. Results:A total of 2 901 COPD patients were included, among which 633 patients (21.8%) experienced exacerbations during the follow-up period. Compared with the non-exacerbation group, patients in the exacerbation group were older, with higher CAT and mMRC scores, lower body mass index (BMI), FEV 1%pred, and FEV 1/FVC. The proportions of patients with high school education or above and those using long-acting β 2-agonist (LABA) + long-acting muscarinic antagonist (LAMA) medications were also lower (all P<0.05). Logistic regression analysis showed that age ( OR=1.010, 95% CI: 1.000-1.021), CAT score ≥20 ( OR=1.415, 95% CI: 1.074-1.865), education level of junior high school or below ( OR=1.243, 95% CI: 1.003-1.540), LABA + LAMA inhalation ( OR=0.605, 95% CI: 0.432-0.848), and BMI ( OR=0.969, 95% CI: 0.943-0.995) were independent risk factors for future exacerbations in COPD patients with no exacerbation history in the past year (all P<0.05). Conclusions:The risk of future exacerbations remains high in COPD patients with no exacerbation history in the past year. High CAT scores, low education levels, and low BMI are associated with future exacerbations. Clinicians should pay close attention to the management of such patients and implement appropriate interventions.

OBJECTIVE To investigate the time-effect relationship of ginger-partitioned moxibustion in treating fecal inconti-nence in patients with mild to moderate active Crohn's disease so as to optimize moxibustion duration and provide a basis for clinical application.METHODS A total of 128 patients with Crohn's disease complicated by fecal incontinence who met the inclusion crite-ria were selected as the study subjects.They were divided into a control group and three experimental groups(experimental group Ⅰ,Ⅱ,and Ⅲ)of 32 patients each using a stratified random method(with 1 dropout in experimental group Ⅰ).Patients in the control group received routine anti-tumor necrosis factor-α monoclonal antibody(adalimumab)treatment,while patients in the experimental groups received ginger moxibustion therapy in addition to the treatment provided to the control group.Among them,experimental groupⅠ received treatment for 20 minutes,experimental group Ⅱ for 40 minutes,and experimental group Ⅲ for 60 minutes.The course of treatment for all four groups was 3 months.Changes in TCM syndrome scores were compared before and after treatment in the four groups to assess clinical efficacy.The cleveland clinic incontinence score(CCIS)was used to assess the severity of fecal incontinence,the Crohn's disease activity index(CDAI)was used to assess the degree of disease activity,and the inflammatory bowel disease ques-tionnaire(IBDQ)was used to evaluate the quality of life.Anal pressure index and peripheral blood CRP and ESR levels were mea-sured,and the relationship between moxibustion time and effect was analyzed.RESULTS After 3 months of treatment,the total TCM syndrome scores of all four groups improved to varying degrees(P<0.05,P<0.01).The total scores of groups Ⅰ,Ⅱ,and Ⅲ were supe-rior to those of the control group(P<0.05,P<0.01),while group Ⅱ had the lowest total TCM syndrome score.Group Ⅱ had the high-est overall clinical effective rate,significantly better than both the control and group Ⅰ(P<0.05,P<0.01).CCIS scores,IBDQ scores and total scores,and peripheral blood ESR levels were significantly reduced in all four groups(P<0.01),with group Ⅱ having the low-est score,lower than both the control and group Ⅰ(P<0.05,P<0.01).CRP levels were significantly reduced in groups Ⅱ and Ⅲ(P<0.05,P<0.01),both lower than the control group(P<0.05,P<0.01),with group Ⅱ lower than group Ⅰ(P<0.01).Intestinal symptom scores in the IBDQ of groups Ⅱ and Ⅲ were significantly higher than those in the control group and group Ⅰ(P<0.05,P<0.01).The maximum resting pressure of the anal canal,rectal defecation threshold,and maximum tolerance capacity all increased significantly in the four groups(P<0.05,P<0.01),but there were no significant differences among the groups(P>0.05).During the treatment,two cases of mild skin redness occurred in group Ⅲ,which resolved after treatment,with no serious adverse reactions.CONCLUSION Ginger moxibustion in the treatment of Crohn's disease complicated by fecal incontinence exhibits a time-effect relationship,with 40 minutes as the optimal duration.It can effectively improve symptoms,control inflammation,enhance quality of life,and has good safety.

Objective:To develop a rapid assessment scale for healthy aging suitable for the Chinese population.Methods:Based on existing healthy aging assessment scales, national standards, and expert consensus, an initial Healthy Aging Rapid Assessment Scale was drafted through two rounds of expert consultation. A pre-survey was conducted with 3 220 subjects recruited from Guangzhou between July 2023 and July 2024. Items were screened through item analysis and exploratory factor analysis to form the final scale. Reliability and validity of the final scale were validated across five cities: Guangzhou, Dongguan, Shenzhen, Baoding, and Chuxiong.Results:The initial version comprised 36 items, while the finalized scale contained 18 items across three dimensions: metabolic health, mental health, and cognitive health. Test-retest reliability ranged from 0.71 to 0.81 across all study sites. The Spearman-Brown coefficient varied between 0.91-0.96, Cronbach′s α between 0.77-0.83, comparative fit index (CFI) between 0.90-0.98, goodness-of-fit index (GFI) between 0.90-0.99, and root-mean-square error of approximation (RMSEA) between 0.03-0.09. For the three dimensions, reliability and validity metrics demonstrated consistency: Spearman-Brown coefficients 0.87-0.99, Cronbach′s α 0.77-0.83, CFI 0.90-0.98, GFI 0.90-0.99, and RMSEA 0.03-0.09 across four regions.Conclusion:The developed Healthy Aging Rapid Assessment Scale for the Chinese population exhibits robust reliability and validity.

The patient,male,42 years old,was given 1.5 mg·kg-1·h-1 sodium valproate via intravenous infusion due to epilepsy,resulting in multiple organ failure.The diagnosis and treatment process of the patient was retrospectively analyzed.The relevance evaluation was carried out using Naranjo's ADR evaluation probability scale,and the relevant literatures were reviewed to provide a reference for the clinical safety of sodium valproate.

BACKGROUND:Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects,but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury.Therefore,it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE:To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024.The search terms used were"flap,ischemia-reperfusion injury,inflammatory response,oxidative stress,Ca2+overload,apoptosis,mesenchymal stem cells,platelet-rich plasma,signaling pathways,shock wave,pretreatment"in Chinese and English.After elimination of irrelevant literature,poor quality and obsolete literature,77 documents were finally included for review. RESULTS AND CONCLUSION:Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response,oxidative stress response,Ca2+overload,and apoptosis,which can cause apoptosis of vascular endothelial cells,vascular damage and microcirculation disorders in the flap,and eventually lead to flap necrosis.Studies have found that mesenchymal stem cell transplantation,platelet-rich plasma,signaling pathway modulators,shock waves,and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees,and reduce the necrosis rate and necrosis area of the grafted flap.Although there are many therapeutic methods for skin flap ischemia/reperfusion injury,a unified and effective therapeutic method has not yet been developed in the clinic,and the advantages and disadvantages of various therapeutic methods have not yet been compared.Most of the studies remain in the stage of animal experiments,rarely involving clinical observations.Therefore,a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic.