Traditional Chinese medicine （TCM）， through its multi-target and systematic regulatory effects， has demonstrated unique advantages in the treatment of gastric precancerous lesions （GPL）. At present， TCM theoretical research on GPL is mainly reflected in three aspects， the integration of macroscopic syndrome differentiation， the inflammation-carcinoma transformation mechanism， as well as the systematization and scientization of theoretical inheritance from famous TCM practitioners. High-quality evidence-based research findings serve as the foundation for clinical practice guidelines on GPL， and TCM has gained international academic recognition in the field of GPL prevention and treatment. Research on TCM mechanisms has yielded a series of important outcomes in the aspects of signaling pathways， gene expression regulation， cellular epigenetics， histone modification， and intestinal microecology. It is proposed that future research on GPL should focus on four key directions， establishing multi-omics data， exploring targeted intervention strategies on key regulatory nodes， advancing the standardization process of integrated traditional Chinese and western medicine prevention and treatment technologies， and constructing stratified screening and intervention platforms. The in-depth integration of TCM microcosmic mechanism of action with its macroscopic syndrome differentiation and treatment system， coupled with interdisciplinary research， will provide valuable references for the clinical treatment and scientific research of GPL.

ObjectiveA middle cerebral artery occlusion (MCAO) mouse model is established by electrocoagulation of the middle cerebral artery. The study examines the mechanism by which exosomes (EXO) derived from human amniotic mesenchymal stem cells (hAMSCs) improve ischemic stroke and regulate neural ferroptosis-related injury. MethodsThirty-two SPF-grade male C57BL/6J mice aged 6 - 8 weeks were randomly divided into four groups (n=8 per group): sham group (Sham), model group (MCAO), MCAO plus normal saline group (MCAO+NaCl), and MCAO plus exosome group (MCAO+EXO). The mouse MCAO model was established by electrocoagulation of the middle cerebral artery. Mice in the Sham group underwent exposure of the middle cerebral artery without electrocoagulation. Twenty-four hours before MCAO induction, mice in the MCAO+EXO group received a tail vein injection of 100 μL of exosomes derived from the culture supernatant of hAMSCs at a concentration of 9.5×10¹¹ particles/mL. Mice in the MCAO+NaCl group were injected with an equal volume of normal saline via the tail vein. Twenty-four hours after model establishment, neurological deficits were evaluated using the Longa neurological deficit scoring system. Cerebral infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Hematoxylin and eosin (HE) staining was performed to evaluate morphological changes of neurons in the ischemic brain regions. The contents of ferrous iron (Fe²⁺), malondialdehyde (MDA), total glutathione (total GSH), oxidized glutathione (GSSG), and reduced glutathione (GSH) in the infarct core and peri-infarct regions were determined using microcolorimetric assays to evaluate differences among groups. The mRNA expression levels of ferroptosis-related factors, including nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in the infarct core and peri-infarct regions were measured by real-time quantitative PCR. Protein expression levels of NRF2, SLC7A11, and GPX4 in the infarct and peri-infarct regions of each group were analyzed by Western blotting. ResultsCompared with the MCAO group, the Longa neurological deficit score was significantly reduced in the MCAO+EXO group (P<0.01). Prominent cerebral infarction was observed in the MCAO group, whereas the infarct volume ratio was markedly decreased in the MCAO+EXO group compared with the MCAO group (P<0.001). Histopathological analysis revealed that mice in the MCAO group exhibited obvious neuronal damage, including cytoplasmic vacuolar degeneration, nuclear pyknosis and fragmentation, unclear nuclear structure, and disorganized neuronal arrangement, compared with the Sham group. In contrast, neurons in the MCAO+EXO group showed relatively preserved morphology, with intact cellular structures and large, regular nuclei located centrally within the cells. Biochemical analysis demonstrated that Fe²⁺ and MDA levels in the infarct core and peri-infarct regions were significantly increased in the MCAO group compared with the Sham group (P<0.001). These levels were significantly reduced in the MCAO+EXO group compared with the MCAO group (P<0.01). In addition, total glutathione (total GSH), oxidized glutathione (GSSG), and reduced glutathione (GSH) levels were markedly decreased in the MCAO group relative to the Sham group (P<0.01). Compared with the MCAO group, the MCAO+EXO group exhibited significantly increased levels of total GSH and GSH (P<0.001), while no significant change was observed in GSSG levels (P>0.05). Furthermore, both mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) were significantly downregulated in the MCAO group compared with the Sham group (P<0.01, P<0.001). In contrast, both mRNA and protein expression levels of NRF2, SLC7A11, and GPX4 were significantly upregulated in the MCAO+EXO group compared with the MCAO group (P<0.05). ConclusionIn the mouse MCAO model, tail vein injection of exosomes derived from hAMSCs can improve motor function, reduce infarct area, protect neuronal cell morphology, and reduce the degree of nerve injury. Exosomes may exert a protective effect by activating the NRF2/SLC7A11/GPX4 pathway and reducing ferroptosis in neuronal cells of MCAO model mice.

ObjectiveTo optimize and validate the optimal sequential alcohol-water extraction process of modified Banxia Xiexintang（MBXT） based on pharmacodynamic evaluation， combined with the G1-entropy weight method and Box-Behnken response surface methodology， and to systematically and comprehensively analyze the material basis of this formula， providing a scientific basis for its quality control and industrial production. MethodsRats were randomly divided into the normal group， model group， metformin group， and MBXT water extraction， water extraction and ethanol precipitation， sequential ethanol-water extraction groups. Except for the normal group， a polycystic ovary syndrome with insulin resistance（PCOS-IR） model was established in all rats via a high-fat diet combined with letrozole induction. Enzyme-linked immunosorbent assay（ELISA） biochemical assay kits and hematoxylin-eosin（HE） staining were used to compare sex hormone levels in serum and ovarian histopathology， thereby screening extraction process routes. Based on this， a comprehensive score was constructed using the G1-entropy weight method based on the transfer rates of index components（berberine hydrochloride and baicalin） and the dry extract rate. Box-Behnken response surface methodology was then utilized to optimize the extraction process parameters. Finally， the chemical constituents of the sample from the optimal process were qualitatively analyzed by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap mass spectrometry（UPLC-Q-Orbitrap-MS）. ResultsPharmacodynamic findings revealed that compared with the normal group， serum testosterone（T） and luteinizing hormone（LH） levels were significantly elevated in the model group， while estradiol（E₂） and follicle-stimulating hormone（FSH） levels were significantly decreased（P<0.01）， with polycystic changes observed in ovarian tissues. Compared with the model group， all treatment groups significantly reversed the changes in sex hormone levels， with the sequential ethanol-water extraction group showing the optimal effect in improving the aforementioned indicators and pathological morphology， followed by subsequent process optimization. The optimized process involved adding 12 times the amount of 70% ethanol for extracting twice， each lasting 120 min， and adding 12 times the amount of water for extracting thrice， each lasting 90 min. Validation test results showed that under optimal process conditions， the average transfer rates of berberine hydrochloride and baicalin were 76.05% and 93.38%， respectively. MS analysis identified a total of 377 compounds， including 112 flavonoids， 41 terpenoids， 28 organic acids， 22 coumarins， and 8 alkaloids， while elucidating the cleavage patterns of key components. ConclusionThe optimized sequential ethanol-water extraction process is stable and feasible， effectively preserving the material basis of MBXT for treating PCOS-IR. It further clarifies the main chemical composition of this formula， providing a scientific basis for the development and quality control of its preparations.

ObjectiveTo evaluate the therapeutic effects of modified Banxia Xiexintang（MBXT） on polycystic ovary syndrome with insulin resistance（PCOS-IR） rats and reveal its potential mechanisms based on the integrated analysis of transcriptomics and metabolomics. MethodsFemale SD rats were selected， and a PCOS-IR model was established by intragastric administration of letrozole combined with a high-fat diet for 21 days. The modeled rats were randomly divided into the model group， MBXT low-， medium-， and high-dose groups（6.62， 13.23， 26.46 g·kg^-1）， and metformin group（0.158 g·kg^-1）， with a normal group set up separately. After 14 days of administration， the estrous cycle was observed， ovarian morphology was examined by hematoxylin-eosin（HE） staining， and the levels of testosterone（T）， estradiol（E₂）， follicle-stimulating hormone（FSH）， and luteinizing hormone（LH） in serum were detected by enzyme-linked immunosorbent assay（ELISA）. Serum metabolites and ovarian tissue gene expression were detected using ultra-performance liquid chromatography-quadrupole-electrostatic orbitrap mass spectrometry（UPLC-Q-Orbitrap-MS） and RNA-Seq technology， respectively， followed by multi-omics integrated analysis. ResultsPharmacodynamic findings revealed that all MBXT dose groups could reversed abnormal estrous cycles in PCOS-IR rats， improve polycystic ovarian lesions， and normalize dysregulated serum hormone levels（T， LH， E₂， FS， P<0.05， P<0.01）. Metabolomic analysis revealed that compared with the model group， MBXT reversed 278 differential metabolites such as estrone and S-formylglutathione， mainly involving pathways such as steroid hormone biosynthesis， glutathione metabolism， and lipid peroxidation regulation. Transcriptomic analysis identified 434 differentially expressed genes， and enrichment analysis revealed that MBXT significantly regulated lipid peroxidation defense systems， including glutathione metabolism， peroxisome function， and fatty acid metabolism， thereby intervening in ferroptosis processes. It also engaged in inflammation-related pathways such as the chemokine signaling pathway. Integrated analysis revealed that both metabolomics and transcriptomics co-enriched metabolic pathways associated with ferroptosis and fatty acid metabolism. And key Hub genes［such as Ras-related C3 botulinum toxin substrate 2 gene（Rac2） and Fas ligand gene（Faslg）］ showed significant correlations with differential metabolites. ConclusionMBXT can effectively ameliorate reproductive dysfunction and metabolic disorders in PCOS-IR rats. Its mechanism may be related to remodeling the immune-metabolism network， particularly by regulating MHC-mediated immune responses， inhibiting local ovarian ferroptosis， and enhancing steroid hormone synthesis pathways.

ObjectiveTo investigate the mechanism of modified Banxia Xiexintang（MBXT） in improving ovarian dysfunction in polycystic ovary syndrome with insulin resistance（PCOS-IR） rats by inhibiting ferroptosis through the adenosine monophosphate（AMP）-activated protein kinase（AMPK）/fatty acid synthase（FASN）/glutathione peroxidase 4（GPX4） signaling pathway. MethodsSeventy-six female SD rats were randomly divided into a normal group（n=13） and a modeling group（n=63）. The modeling group established a PCOS-IR model by intragastric administration of letrozole combined with a high-fat diet for 21 days. After successful modeling， these rats were randomly divided into the model group， MBXT low-， medium-， and high-dose groups（6.62， 13.23， 26.46 g·kg^-1）， metformin group（0.158 g·kg^-1）， and high-dose of MBXT combined with ferroptosis inducer Erastin group（15 mg·kg^-1）， with 10 rats in each group. After 14 days of intervention， ovarian pathological morphology was observed by hematoxylin-eosin（HE） staining， the mitochondrial ultrastructure of granulosa cells was observed by transmission electron microscopy（TEM）， ovarian reactive oxygen species（ROS） levels were detected by dihydroethidium（DHE） probe， biochemical methods were used to detect Fe²⁺， malondialdehyde（MDA）， glutathione（GSH） and other indicators in ovarian tissues， serum sex hormone and insulin levels were measured by enzyme-linked immunosorbent assay（ELISA）， and the protein expressions of AMPK， FASN， acyl-CoA synthetase long-chain family member 4（ACSL4）， GPX4， and solute carrier family 7 member 11（SLC7A11） in ovarian tissues were detected by Western blot. ResultsCompared with the normal group， the model group showed polycystic changes in the ovaries， with atrophy of mitochondria in granulosa cells and increased membrane density. Serum levels of testosterone（T）， luteinizing hormone（LH）， and insulin were significantly increased（P<0.01）. The levels of ROS， MDA， 4-hydroxynonenal（4-HNE）， and Fe²⁺ in ovarian tissues were significantly elevated（P<0.01）， while adenosine triphosphate（ATP）， GSH， and reduced nicotinamide adenine dinucleotide phosphate （NADPH） levels were significantly decreased（P<0.01）. The phosphorylation levels of AMPK and acetyl-CoA carboxylase （ACC）， as well as the protein expressions of SLC7A11， GPX4， and ferroptosis suppressor protein 1（FSP1） were significantly downregulated（P<0.01）， whereas the expressions of FASN， ACSL4， and nuclear receptor coactivator 4（NCOA4） were significantly upregulated（P<0.01）. Compared with the model group， MBXT intervention at various doses improved the above pathological changes and biochemical indicators in a dose-dependent manner， with the high-dose group showing the most significant effect（P<0.01）. Compared with the MBXT high-dose group， the high-dose of MBXT combined with ferroptosis inducer Erastin group restored ovarian ferroptosis characteristics in rats， with increased ROS and lipid peroxidation products， and altered expressions of key proteins（P<0.05， P<0.01）. ConclusionMBXT can effectively improve ovarian function and metabolic disorders in PCOS-IR rats. Its mechanism may be related to activating the AMPK/ACC signaling pathway， downregulating FASN and ACSL4 to reduce lipid peroxidation substrates， and restoring glucose-6-phosphate dehydrogenase/phosphoglycerate dehydrogenase（G6PD/PHGDH） metabolic flux to enhance the GPX4/FSP1 antioxidant defense system， thereby inhibiting ferroptosis in ovarian granulosa cells.

Polycystic ovary syndrome （PCOS） with insulin resistance （IR） represents a common complex endocrine-metabolic disorder in reproductive-aged women，posing substantial threats to their reproductive and long-term health. The networked characteristics of pathological mechanisms pose severe challenges in the diagnosis and treatment modes with a single medical system. Western medicine identifies it as a pathological axis with the core of "IR-hyperinsulinemia-hyperandrogenemia" and offers effective symptomatic treatments，it is often faced with limitations such as insufficient overall regulation and drug side effects. Traditional Chinese medicine is characterized by a holistic concept centered on the dysfunction of "kidney-spleen-liver" and syndrome differentiation and treatment，yet its microscopic action mechanisms remain to be fully elucidated. An integrative diagnosis and treatment mode of traditional Chinese medicine and western medicine provides a vital approach to overcoming these challenges. This review systematically sorted out the understanding of polycystic ovary syndrome with insulin resistance （PCOS-IR） pathogenesis from both Chinese and western medicine perspectives. An explainable mapping relation potentially existing between the molecular pathological networks defined by western medicine and the macroscopic dialectical system of traditional Chinese medicine was hypothesized. The synergistic potentiation mechanisms of integrative strategies of traditional Chinese medicine and western medicine were analyzed，with a focus on clarifying the recent progress of integrative diagnosis and treatment strategies. The paper aims to provide a more comprehensive and profound reference for research and clinical practice in this field，advance the further development of the prevention and treatment of PCOS-IR with integrated traditional Chinese medicine and western medicine，and explore the establishment of a more precise，individualized diagnosis and treatment system to make optimal clinical decisions.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Background/Aims: Chronic constipation is prevalent yet under-diagnosed across Asia, compromising quality of life and burdening healthcare systems. Cultural stigma, varied diets, and limited access to standardized diagnostic tools delay timely care. Methods: The Bali Chronic Constipation Roundtable in November 2024, brought together experts from 11 Asian countries. The group reviewed epidemiological data, analyzed multinational questionnaire on clinical practice pattern, and conducted structured discussions to identify key barriers and propose region-specific recommendations. Results: Chronic constipation prevalence varies across Asia, ranging from 1.8% in India to 16.6% in Japan, with women and the elderly disproportionately affected. Under-reporting persists owing to cultural taboos and widespread self treatment with laxatives and traditional medications. Although the Rome IV criteria remains the global standard, they may not fully reflect Asian symptom profiles, and diagnosis is limited by scarce motility laboratories. First line therapies such as dietary-fiber optimization and osmotic laxatives are widely available, but newer pharmacotherapies (prucalopride, linaclotide, lubiprostone, and elobixibat) remain costly and unevenly accessible. Biofeedback for dyssynergic defecation is underutilized due to limited availability. Experts recommend expanded regional research on to refine diagnostic criteria, coupled with enhanced physician education and public awareness. They advocate accessibility to second-line and novel therapies that incorporate culturally attuned regional guidelines, and improved access to gastrointestinal motility testing. Conclusions The Bali Chronic Constipation Roundtable highlighted Asia’s need for region specific diagnostics and management. Addressing diagnostic and treatment gaps will improve outcomes, while ongoing researcher clinician policy collaboration must standardize guidelines, advance research, and ensure equitable care across Asia.

Objective To explore the effect of endoscopic ultrasonography(EUS)with different probes on the measurement of gastrointestinal submucosal tumor(SMT)diameter.Methods The clinical data of 356 patients(with a total of 372 lesions)initially diagnosed as SMT by EUS at the Second Affiliated Hospital of Army Medical University from January 2023 to June 2024 were analyzed retrospectively.The basic characteristics of the origin layers and pathological distribution of SMT were analyzed.The differences between the EUS-measured diameters and the actual diameters of SMT at different diameter ranges of lesions were compared.Taking the postoperative pathological diagnosis results as the gold standard,the effects of different clinicopathological features and probe types on the relative error in EUS-measured diameters of SMT were analyzed.Results Among the 372 gastrointestinal SMT lesions,lesions were more frequent in female patients,gastric lesions was the most common,and leiomyoma was the predominant pathological type.The accuracy of EUS in diagnosing SMT was 94.4%.A statistically significant difference was observed between the EUS-measured diameters and the actual diameters of SMT(P<0.05).There were significantly differences in various ranges of lesions between the EUS-measured diameters and the actual diameters(P<0.05).The gender,age,lesion location,and pathological type had no significant effect on the relative error of EUS-measured diameters(P>0.05);while probe types had a significant effect on the relative error of EUS-measured diameters(P<0.05).For lesions with an actual diameter of 2.0 to 3.9 cm,the relative error of SMT diameters measured by small-probe EUS was significantly greater than that by large-probe EUS(P<0.05).Conclusion Large-probe EUS exhibits a smaller relative error in measuring the diameter of SMT with a diameter of≥2.0 cm.Therefore,large-probe EUS is recommended for the examination of SMT with an estimated diameter exceeding 2.0 cm.

Background and Aims:The incidence of intrahepatic cholangiocarcinoma(ICC)has been increasing in recent years.Due to its insidious onset and low rate of early diagnosis,radical resection remains the only potential curative treatment.Lymph node metastasis is a major adverse prognostic factor in ICC,but the scope and therapeutic value of lymphadenectomy remain controversial.Previous studies suggest that patients with central ICC may derive greater survival benefit from lymphadenectomy than those with peripheral ICC.Preoperative assessment of lymph node status mainly relies on imaging,but its accuracy is limited.This study aimed to investigate the prognostic impact of lymphadenectomy in ICC patients at different anatomical sites to inform surgical decision-making.Methods:A retrospective analysis was conducted on 220 ICC patients who underwent radical resection at the 904th Hospital of the Joint Logistic Support Force of the PLA from May 2016 to May 2021.The cohort included 126 males and 94 females,with a mean age of(56.76±13.15)years.Patients were categorized into peripheral ICC(n=144)and central ICC(n=76)groups.Clinical characteristics,albumin-bilirubin(ALBI)grade,preoperative risk of lymph node metastasis,number of lymph nodes dissected,lymph node metastasis status,and postoperative survival outcomes were compared.Subgroup analyses were conducted to assess the prognostic value of the number of lymph nodes dissected under different risk stratifications.Results:Significant differences were observed between peripheral and central ICC in ALBI grade(x2=9.952,P=0.002),preoperative lymph node metastasis risk(x2=6.166,P=0.014),number of lymph nodes dissected(x2=4.167,P=0.042),and lymph node metastasis rate(x2=7.331,P=0.007).The 3-year overall survival(OS)rate was higher in peripheral ICC(31.94％)than in central ICC(15.79％)(x2=13.890,P＜0.001).Among central ICC patients,those with ≥6 lymph nodes dissected had better 3-year OS than those with＜6(16.89％vs.13.04％,x2=3.894,P=0.048).In the high-risk subgroup of central ICC,≥6 lymph nodes dissected was also associated with improved 3-year OS compared with＜6(15.62％vs.11.11％,x2=3.962,P=0.047).In contrast,the number of lymph node dissections had no significant prognostic impact in peripheral ICC or in patients classified as low risk.Conclusion:Patients with peripheral ICC had a better prognosis than those with central ICC.Adequate lymphadenectomy(≥6 nodes)improved survival and enhanced staging accuracy in central ICC patients at high risk of lymph node metastasis,highlighting the importance of preoperative risk assessment for optimizing surgical strategies.