Precancerous lesions of gastric cancer （PLGC） are a group of pathological changes caused by abnormalities in the structure， morphology， and differentiation of gastric mucosal epithelial cells. Since the early symptoms are hidden and non-specific， PLGC is not easy to be diagnosed and it has often developed into intermediate or advanced gastric cancer once being diagnosed and missed the best time for treatment. Accordingly， the incidence of this disease is increasing year by year， which lifts a heavy burden on the patients. The pathogenesis of PLGC is complex， involving inflammatory microenvironment， bile reflux， glycolysis， autophagy， and apoptosis. Currently， PLGC is mainly treated with anti-inflammatory and endoscopic therapies， which are difficult to curb the development of PLGC. Therefore， seeking a safe and effective therapy is an important topic of modern research. Traditional Chinese medicine （TCM）， characterized by treatment based on syndrome differentiation and a holistic view， exerts effects via multiple pathways， mechanisms， and targets. Recent studies have confirmed that TCM can regulate the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）， Wnt/β-catenin， Sonic Hedgehog， nuclear factor-κB （NF-κB）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， hypoxia-inducible factor-1α （HIF-1α）， neurogenic locus notch homolog protein （Notch）， nuclear factor E₂-related factor 2 （Nrf2） and other signaling pathways. By targeting these pathways， TCM can inhibit aerobic glycolysis， reduce oxidative stress， repair the inflammatory microenvironment， regulate cellular autophagy， and promote vascular normalization， thereby delaying or reversing PLGC. However， few researchers have systematically summarized the TCM regulation of PLGC-associated pathways. By reviewing the relevant articles at home and abroad， this paper summarized the roles of the above signaling pathways in the development of PLGC and the research progress in the regulation of signaling pathways by TCM in the treatment of PLGC， with a view to providing a new theoretical basis for the clinical research on PLGC and the drug development for this disease.

BACKGROUND:A large number of studies have confirmed that the therapeutic effectiveness of mesenchymal stem cell secretome is comparable to that of mesenchymal stem cells,but the mechanism of its action is still unclear. OBJECTIVE:To summarize the research progress of mesenchymal stem cell secretome in recent years,to investigate the molecular mechanism of its therapeutic effect,to analyze the current problems and to look forward to the future development. METHODS:The terms"exosomes,mesenchymal stem cells secrete,extracellular vesicles,mesenchymal stem cells,mechanism"were used as English search terms in the PubMed database.Articles that were not related to the research purpose of the article and duplicated articles were excluded.At the same time,we combined the method of literature tracking.Finally,109 articles that met the criteria were incuded for the review. RESULTS AND CONCLUSION:(1)The mesenchymal stem cell secretome promotes tissue repair and regeneration through delivering genetic material,immunomodulatory factors,growth factors,etc.to target cells,by activating anti-apoptotic,regulating angiogenesis,modulating fibrosis and pro-survival pathways in target cells.(2)The potential of mesenchymal stem cell secretome in disease therapy has also been confirmed.Numerous research results have shown that mesenchymal stem cell secretome can be used as a new cell-free treatment for inflammatory and degenerative diseases.(3)Mesenchymal stem cell secretome has been engineered to have more efficient therapeutic effects in recent years.However,due to the heterogeneity of the mesenchymal stem cell secretome and the complexity of its components,the exact mechanism of its therapeutic effect is still unclear.(4)At present,further research is needed to identify the key targets of mesenchymal stem cell secretome,and innovative specific and enhanced mesenchymal stem cell secretome should be developed by combining with engineering and genetic engineering technologies in the future.

Parkinson’s disease （PD） is a common chronic neurodegenerative disease with movement disorders as the main clinical manifestation. The nuclear factor-erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway is closely associated with the occurrence and progression of PD. TCM flavonoid monomers （luteolin， rutin， etc.）， alkaloids （camptothecin， sinomenine， and alkaloids extracted from Uncaria rhynchophylla）， terpenes （tanshinone ⅡA， carvacrol， paeoniflorin）， phenols （ellagic acid， rosmarinic acid）， saponins （ginsenoside RK1）， and traditional Chinese medicine compounds （Wuzi yanzong pill and PD formula-2） can resist oxidative stress damage， inhibit inflammatory responses and abnormal aggregation of α-synuclein， and regulate neurotrophic factors by activating the Nrf2/HO-1 signaling pathway， thereby alleviating dopaminergic neuronal damage.

Abstract Family is the primary living place of children and adolescents, which has important impacts on children and adolescents physical activity. The article systematically reviews the research progress on potential mechanisms of family influence on physical activities of children and adolescents, focusing on the theoretical mechanism of intergenerational transmission on parent-child physical activities,which includes family s role in children s motivation and achievement for exercise behaviors, the integrative model of parental socialization influence and integrated model of physical activity parenting. It provides new perspectives for future research in related fields and gives more suggestions and reference for subsequent development of family enhancement programs and family-school collaborative programs.

ObjectiveTo explore the possible mechanism of the Yiqi Jiedu formula （YQ） in treating ischemic stroke （IS） from the perspective of the microbial-gut-brain axis （MGBA）. MethodRats were randomly divided into five groups， with six in each group， including sham surgery group， model group， and low， medium， and high dose YQ groups （1， 5， and 25 mg·kg^-1）. Except for the sham surgery group， all other groups were established with a middle cerebral artery occlusion （MCAO） model using the thread occlusion method. The success of modeling was determined through neurobehavioral scoring， and the protective effect of YQ on IS was evaluated. Then， the changes in gut microbiota before and after MCAO modeling and YQ administration were compared using 16S rDNA sequencing technology， and the possible biological pathways related to the effect of this formula were analyzed. The expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-17A （IL-17A）， and interleukin-10 （IL-10） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression of tight junction proteins ZO-1 and Occludin in brain and intestinal tissue， and hematoxylin-eosin staining （HE） was used to observe pathological changes in the cerebral cortex and colon， so as to validate the possible mechanism of action. ResultYQ significantly improved the neurobehavioral score of MCAO rats （P<0.01） and played a good regulatory role in intestinal microbial disorders caused by enriched pathogens and opportunistic pathogens during the acute phase. Among them， significantly changed microorganisms include Morgentia， Escherichia Shigella， Adlercreutzia， and Androbacter. Bioinformatics analysis found that these bacteria may be related to the regulation of inflammation in the brain. Compared with the blank group， the detection of inflammatory factors in the serum of IS model rats showed an increase in inflammatory factors IL-6 and IL-17A （P<0.01） and a decrease in the content of anti-inflammatory factor IL-10 （P<0.01）. Compared with the model group， the content of inflammatory factors IL-6 and IL-17A in the serum of the treatment group decreased （P<0.05）， and that of anti-inflammatory factor IL-10 increased （P<0.01）. The expression results of barrier proteins ZO-1 and Occludin in brain and intestinal tissue showed that the expression levels of both decreased in IS model rats （P<0.05）， while the expression levels of both increased in the treatment group （P<0.05）. ConclusionAcute cerebral ischemia can lead to an imbalance of intestinal microbiota and damage to the intestinal barrier， and it can increase intestinal permeability. YQ can regulate intestinal microbiota imbalance caused by ischemia， inhibit systemic inflammatory response， and improve the disruption of the gut-blood brain barrier， preventing secondary cascade damage to brain tissue caused by inflammation. The MGBA may be an important mechanism against the IS.

Objective To investigate the clinical effect and hearing loss of endolymphatic sac decompression(ESD)combined with one or two semicircular canal obstruction(SCO)in treating the patient with stage Ⅲ or stageⅣ Meniere disease.Methods Forty-three patients with stage Ⅲ or stage Ⅳ Meniere disease,who failed to respond to conventional conservative treatment and had the expectation of preserving residual hearing function,were enrolled in the study.They were divided into three groups according to the operation they underwent:ESD combined with lateral and posterior semicircular canal obstruction(ESD+LPSCO)13 cases,ESD combined with lateral semicircu-lar canal obstruction(ESD+LPSCO)14 cases,and ESD only 16 cases.Data of vertigo,ear fullness and tinnitus be-fore and after operation was collected,analyzed and compared.Hearing function before and after the operation was also evaluated.Results The number of vertigo attacks in the three groups(ESD+LPSCO,ESD+LSCO,and ESD)were all significantly reduced after operation.The vertigo control rate were 92.3％,78.6％and 62.5％re-spectively.Compared with pre-operation,the vertigo severity post-operation in the three groups were also signifi-cantly reduced.And the improvement rate of vertigo severity after ESD+LPSCO and ESD+LSCO were both 100％,which were significantly higher than that of ESD(68.8％).The discomfort of tinnitus and ear fullness in the three groups were significantly improved compared with that of pre-operation.The improvement rates of tinnitus in the three groups were 46.2％,50.0％and 43.8％respectively,with no significant difference.The improvement rate of ear fullness in the three groups were 61.5％,57.1％and 50.0％respectively,with no significant difference either.The proportion of patients with decreased hearing after operation in the three groups was 15.4％,7.1％and 18.8％,respectively,and the differences were insignificant.Conclusion ESD combined with one or two SCO can effectively control vertigo and other symptoms of patients with stage Ⅲ or Ⅳ Meniere's disease who had failure to conventional conservative treatment,and can preserve the residual hearing function in considerable extent.

Mediastinal lymph node metastasis is a common metastasis pathway of non-small cell lung cancer (NSCLC), and its occurrence is closely related to lymphatic drainage pattern. NSCLC in different pulmonary lobes requires different lymphatic drainage patterns, which poses a challenge for the formulation of individualized treatment strategies. Accurate staging is the prerequisite for precision treatment of NSCLC. Computed tomography (CT) examination is an important tool for evaluating mediastinal lymph node metastasis, which is crucial for making treatment plan and evaluating patient prognosis. However, it is difficult to diagnose metastatic lymph nodes with insignificant imaging features, especially metastatic lymph nodes in zone 4 and zone 7, which are hot spots for mediastinal lymph node metastasis. However, clinical guidelines do not make clear provisions on lymph node dissection in zone 4, which makes preoperative clinical staging and prognosis evaluation of patients with NSCLC particularly important. By integrating and analyzing a large amount of data in CT images, the emerging CT radiomics technology captures subtle features that may be overlooked in conventional CT scans, showing great application prospects in improving the accuracy of non-invasive diagnosis of lymph node metastasis. This review aims to explore the mediastinal drainage pattern and the role of CT in evaluating mediastinal lymph node metastasis, in order to provide valuable imaging evidence for accurately judging mediastinal lymph node metastasis of NSCLC, formulating appropriate lymph node dissection scope, optimizing treatment strategy, and improving patient prognosis.

Acquired cerebral amyloid angiopathy,as a cerebrovascular disease discovered in recent years,mainly spreads through iatrogenic factors.This paper focuses on acquired cerebral amyloid angiopathy and delves into the new applications and profound implications of the"toxins damaging brain collaterals"theory proposed by academician WANG Yongyan in stroke research.Starting from the perspective of"toxins damaging brain collaterals",it comprehensively analyzes the causes and pathological mechanisms of acquired cerebral amyloid angiopathy,emphasizing the importance of external toxins,latent toxins,and turbid toxins in understanding the pathogenesis of the disease.It reveals that"toxins damaging brain collaterals"is the core mechanism of acquired cerebral amyloid angiopathy.On this basis,it proposes a new connotation of"toxins damaging brain collaterals":first,"toxin"includes both internal and external toxins;second,the organic integration of"external wind theory"and"toxins damaging brain collaterals"guides the improvement of theoretical research,clinical treatment,and prevention strategies for stroke,and promotes a deeper understanding of the disease.This approach to understanding acquired cerebral amyloid angiopathy from the perspective of"toxins damaging brain collaterals"not only demonstrates the effective integration of traditional Chinese medicine theory and modern biomedical science,but also provides insights and references for the clinical diagnosis and treatment of the disease.

AIM: To investigate the pathogenic bacteria, drug resistance, therapy and prognosis of infectious endophthalmitis secondary to different ophthalmic surgeries.METHODS:A retrospective analysis was conducted on the clinical data of 37 patients(37 eyes)with infectious endophthalmitis secondary to different ophthalmic surgeries. All these patients were treated in the Ophthalmology Department of Hebei General Hospital between January 2009 and June 2023. The pathogenic bacteria, drug resistance and therapeutic effects of early intravitreal injection of antibiotics or vitrectomy combined with silicone oil filling were analyzed.RESULTS:There were 24 eyes following cataract phacoemulsification combined with intraocular lens implantation, 4 eyes following vitrectomy, 2 eyes following combination surgery for glaucoma and cataract, 2 eyes following anti-glaucoma surgery, 2 eyes following corneal transplantation, 2 eyes following anterior chamber puncture, and 1 eye following intravitreal injection among the 37 eyes with infectious endophthalmitis. Totally 37 samples of intraocular fluid were submitted for bacterial and fungal culture, and 20 strains of pathogenic bacteria were identified, including 17 Gram-positive bacteria, 2 Gram-negative bacteria, 1 fusarium, and 12 cases were staphylococcus epidermidis. According to the final therapy, 7 eyes only treated by intravitreal injection, 11 eyes treated by intravitreal injection and vitrectomy, and 19 eyes only treated by vitrectomy. At the last follow-up, the best corrected visual acuity(BCVA)was ≤0.05 in 15 eyes, 0.06-0.3 in 15 eyes, and 0.4-1.0 in 7 eyes. Compared to before treatment(no light perception - hand movement in 31 eyes, counting fingers -0.05 in 3 eyes, 0.06-0.3 in 3 eyes), the difference was statistically significant(P<0.001).CONCLUSION: For infectious endophthalmitis patients with relatively mild ocular manifestation and good initial visual acuity, intravitreal injection of antibiotics remains an economically viable and effective therapy option. Early vitrectomy may effectively prevent the progression of infectious endophthalmitis, reduce the number of surgeries, and significantly improve the vision outcomes.

ObjectiveTo investigate the mechanism of neferine（Nef） in promoting vascular regeneration against cerebral ischemia through modulation of mitochondrial calcium uniporter（MCU） ion channel. MethodTaking the area of subintestinal vessels in microvascular deficiency zebrafish as an index， the vascular regenerative efficacy of Nef was evaluated， and the median effective concentration（EC₅₀） was calculated. Rats were randomly divided into a sham operation group， a model group， a positive drug group（butylphthalide， 6 mg·kg^-1）， and Nef low， medium， and high dose groups（0.125， 0.625， 3.125 μg·kg^-1）. Except for the sham operation group， the middle cerebral artery occlusion（MCAO） model was established in other groups. After modeling， the groups were administered the corresponding dose of drugs by gavage， while the sham operation and model groups received equal volumes of saline， once a day for 7 consecutive days. Neurobehavioral scores were assessed for each group of rats， and the infarct rate of ischemic brain tissue was calculated by 2，3，5-triphenyltetrazolium chloride（TTC） staining. The regional cerebral blood flow（rCBF） of each group was measured using a speckle contrast imaging. Immunofluorescence and Western blot were conducted to detect the expression of vascular endothelial growth factor（VEGF）， platelet endothelial cell adhesion molecule-1（CD31）， and hypoxia-inducible factor-1α（HIF-1α） proteins in each group. Human umbilical vein endothelial cells（HUVECs） were divided into the normal group， model group， positive drug group（astragaloside Ⅳ， 10 μmol·L^-1）， and Nef group （32 nmol·L^-1）. In the verification of mitochondrial protection of Nef and its mechanism in promoting vascular regeneration， the spermine（MCU agonist） and Nef+spermine group were added. HUVECs model of oxygen-glucose deprivation（OGD） was established in all groups except the normal group， the cell viability was assessed using 3-（4，5-dimethylthiazol-2-yl）-2，5-diphenyltetrazolium bromide（MTT） assay， and cell migration ability was evaluated through scratch and tube formation assays. Fluorescent probes（Rhod-2 AM， Fluo-3 AM， JC-1， Calcein AM） and a cellular energy metabolism analyzer were used to analyze the mitochondrial protective effects of Nef. Molecular docking was performed to predict the binding ability of Nef with MCU and HIF-1α， and Western blot was used to detect the effects of Nef on the protein expressions of MCU， B-cell lymphoma-2 associated X protein（Bax）， Caspase-3 and HIF-1α in the OGD model HUVECs. ResultThe results of vascular regeneration in microvascular deficiency zebrafish showed that compared to the normal group， the area of subintestinal vessels in the model group significantly decreased（P<0.01）. Compared to the model group， different concentrations of Nef could significantly increase the area of subintestinal vessels（P<0.01）， with the maximum tolerated concentration of 10.24 μmol·L^-1 and the EC₅₀ of 0.23 μmol·L^-1. Anti-cerebral ischemia results on MCAO rats showed that compared to the sham operation group， the model group had a significant decrease in rCBF and a significant increase in infarct rate， while CD31 expression significantly decreased（P<0.01）， and VEGF and HIF-1α protein expressions significantly increased（P<0.05）. Compared to the model group， the treated groups showed significant increases in rCBF， significant reductions in infarct volume， and significant increases in CD31， VEGF， and HIF-1α protein expression（P<0.01）. Cell experiment results showed that compared to the normal group， the model group had decreased cell viability and migration ability， increased intracellular Ca²⁺ and mitochondrial Ca²⁺ levels， reduced mitochondrial permeability transition pore（MPTP） opening， and decreased mitochondrial energy metabolism capability， with increased expressions of MCU， Bax， Caspase-3 and HIF-1α proteins（P<0.05， P<0.01）. Compared to the model group， the Nef group showed increased cell viability and migration ability， decreased intracellular Ca²⁺ and mitochondrial Ca²⁺ levels， increased MPTP opening， enhanced mitochondrial energy metabolism capability， decreased expressions of MCU， Bax and Caspase-3 proteins， and increased HIF-1α protein expression（P<0.05， P<0.01）. ConclusionNef can stabilize mitochondrial membrane potential and inhibit mitochondrial apoptosis. By down-regulating the expression of MCU， it suppresses the activation of intracellular Bax and Caspase-3 while activating the HIF-1α signaling pathway， enhancing the expression of VEGF and CD31， thereby promoting vascular regeneration to treat ischemic brain injury.