Pancreatic cancer is a highly malignant solid tumor of the digestive system with extremely poor treatment prognosis. Although its incidence rate is low， its mortality rate is extremely high. In recent years， the number of diagnosed cases worldwide has continued to rise， making pancreatic cancer the sixth leading cause of cancer-related deaths globally. Currently， clinical treatment primarily relies on operation and chemotherapy to suppress tumors. However， these approaches face challenges such as suboptimal efficacy， high postoperative recurrence rates， and severe adverse reactions. Therefore， identifying safe and effective treatment modalities remains a pressing challenge for the medical community. In recent years， research on traditional Chinese medicine （TCM） interventions for pancreatic cancer has increased significantly. Multiple studies have shown that single-herb TCM， TCM formulas， and their derived single compounds can regulate the levels of tumor cell signaling pathways through multiple action targets. They inhibit the development and progression of pancreatic cancer by inhibiting cancer cell proliferation， promoting cell apoptosis， inhibiting tumor angiogenesis， reducing cancer cell invasion and migration capabilities， regulating the cell cycle， and modulating the tumor microenvironment. Additionally， TCM has the advantages of significantly enhancing the anticancer efficacy of chemotherapy drugs and causing fewer adverse reactions. However， the specific action mechanisms by which TCM intervenes in pancreatic cancer remain unclear. Further extensive research is still needed to validate the role of regulating classical signaling pathways such as phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， Wnt/β-catenin， nuclear transcription factor-κB （NF-κB）， notch， and hedgehog in the treatment of pancreatic cancer. Therefore， this paper reviewed Chinese and international studies on TCM intervention in pancreatic cancer through relevant signaling pathways in recent years， summarized the potential action mechanisms of TCM in the treatment of pancreatic cancer， and provided references for related research in the future.

Obesity， a global chronic disease， is associated with adipose tissue dysfunction， which is one of the contributing factors to obesity. The cyclic adenosine monophosphate （cAMP） signaling pathway， a key regulator of lipid metabolism， plays a pivotal role in obesity development. Various of traditional Chinese medicine monomers， such as flavonoids， lignans， phenols， and terpenoids， as well as traditional Chinese medicine compound formulas like Xiaoyao powder， Shengmai powder， and Zexie decoction， can maintain energy homeostasis， balance adipose tissue function， regulate glucose metabolism， improve insulin resistance， and suppress inflammatory responses through cAMP signaling pathway regulation， thereby intervening in lipid metabolism for obesity treatment. Although a substantial amount of basic research has preliminarily elucidated the potential mechanisms by which traditional Chinese medicine intervenes in obesity through the cAMP signaling pathway， clinical translational research remains inadequate. There is an urgent need for large-sample， high-quality randomized controlled trials to validate these findings.

Objective: To explore the network structure of middle school students basic psychological needs and psychological behavioral problems, and identify the core nodes within the network, as well as examine demographic subgroup differences, so as to provide support for targeted mental health interventions for adolescents. Methods: In September and October of 2023, a total of 2 000 junior and senior high school students were selected with multistage cluster random sampling from 8 schools in Jiaojiang District and Tiantai County, Taizhou City. An online self administered questionnaire was used to assess emotional and behavioral problems, perceived autonomy, self awareness, loneliness, and social support. The instruments included the Strengths and Difficulties Questionnaire (SDQ), Perceived Choice and Awareness of Self Scale (PCASS), Mental Health Literacy Questionnaire (MHLQ), University of California,Los Angeles Loneliness Scale (UCLA-LS), and the Multidimensional Scale of Perceived Social Support (MSPSS). A network analysis approach was employed to construct a network representing adolescents basic psychological needs and psychological behavioral problems, focusing on centrality measures and demographic subgroup differences. Results: A total of 418 students (20.9%) reported abnormal emotional and behavioral problems. Perceived autonomy and competence were negatively correlated with emotional problems (weights: 0.12, 0.14) and hyperactivity (weights: 0.10, 0.16). Social support showed negative correlation with peer relationship issues, hyperactivity, and conduct problems (weights: 0.16, 0.13, 0.10). Loneliness was positively correlated with emotional symptoms and peer relationship problems (weights: 0.28, 0.18). In the overall network, perceived relationships (social support and loneliness), emotional symptoms, and hyperactivity emerged as central nodes. Significant differences in network structure were observed between gender subgroups ( P =0.02). Girls internalizing issues were more influenced by loneliness and perceived autonomy frustration, while social support exhibited higher centrality in boys. Conclusions Perceived relationships, emotional problems, and hyperactivity are key nodes in the network of adolescents basic psychological needs and psychological behavioral problems. Loneliness demonstrates a prominent influence within the network, and the overall network exhibits gender differences.

Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Tuberculosis (TB), a chronic infectious disease caused by Mycobacterium tuberculosis, is primarily airborne and remains a global health problem, especially in resource-limited countries and regions. The emergence of drug resistance in M. tuberculosis has rendered the existing means ineffective in the treatment of TB. Therefore, research in new therapeutic directions has become imperative. In this review, we outline functional peptides in terms of the mechanisms of action, anti-TB attempts, advantages and disadvantages, and latest advances, aiming to analyze the research progress in anti-TB peptides. Furthermore, we investigate the potential applications of bioactive compounds found in traditional Chinese Medicine within the context of peptides.

Background Lead smelting workers are exposed to mixed heavy metals such as lead (Pb) and cadmium (Cd). However, the specific associations and molecular mechanisms by which their combined exposure induces genetic damage remain unclear. Objective To clarify the association between combined Pb-Cd exposure and genetic damage and to explore the possible biological mechanisms through occupational epidemiological investigations and animal experiments. Methods (1) Population study: A cross-sectional study was conducted on 374 lead smelting workers in northern China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect urinary levels of 8 metals including Pb and Cd, and graphite furnace atomic absorption spectroscopy (GFAAS) was used to quantify blood levels of Pb and Cd. The cytokinesis-block micronucleus assay (CBMN) was used to assess genetic damage. Poisson regression was used to analyze the association between metal exposure and micronucleus rates. (2) In vivo experiment: Thirty SD rats were randomly assigned to five groups: control (pure water), Pb (300 mg·L⁻¹ lead acetate), Cd (50 mg·L⁻¹ cadmium chloride), combined exposure (Pb + Cd), and resveratrol intervention (Pb + Cd + 50 mg·L⁻¹ resveratrol). After 8 weeks of ad libitum drinking water exposure, liver pathology, oxidative stress indicators [reactive oxygen species (ROS), reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)], genetic damage (Comet assay and γ-H2AX) were evaluated. Furthermore, cell cycle distribution, apoptosis rates, and mRNA expression of DNA damage response (DDR), DNA repair, and apoptosis-related genes were measured. Results (1) The geometric mean (GM, 95%CI) of urinary Pb and Cd were 14.69 (13.14, 16.51) µg·L⁻¹ and 2.11 (1.90, 2.33) µg·L⁻¹, respectively; the blood Pb and Cd levels were 117.10 (105.59, 129.87) µg·L⁻¹ and 4.55 (4.23, 4.89) µg·L⁻¹, respectively among the 374 workers. The mean micronucleus rate was (1.64±0.081) ‰, with significantly higher rates in males (1.65±0.083) ‰ than females (1.53±0.334) ‰ (U=4.166, P=0.041). All Pb and Cd biomarkers were positively correlated with micronucleus rate (FR>1, P<0.05), with a significant interaction effect observed between Pb and Cd (FR>1, P<0.05). (2) In rats, co-exposure to Pb and Cd caused liver tissue damage and inflammatory infiltration. Significant increases were observed in lymphocyte ROS; GSSG and MDA in lung tissue increased, while GSH and CAT activity decreased. Comet assay indicators and γ-H2AX levels were significantly elevated. Co-exposure induced S-phase arrest and increased apoptosis. mRNA levels of DDR (ATM, ATR, Chk2, and P53) and pro-apoptotic genes (Bax and Caspase-3) were upregulated, while the anti-apoptotic gene Bcl-2 and DNA repair genes (BRCA1, BRCA2, RAD51, RAD52, and CtIP) were downregulated. Two-way ANOVA confirmed synergistic effects on GSSG, Comet assay indicators, and ATR/Chk2 mRNA expression. Conclusion Occupational co-exposure to Pb and Cd synergistically induces genetic damage. This damage is mediated by oxidative stress and DNA damage, which activates the DDR pathway and inhibits the expression of DNA repair genes, ultimately leading to cell cycle arrest and apoptosis.

Background Lead smelting workers are exposed to mixed heavy metals such as lead (Pb) and cadmium (Cd). However, the specific associations and molecular mechanisms by which their combined exposure induces genetic damage remain unclear. Objective To clarify the association between combined Pb-Cd exposure and genetic damage and to explore the possible biological mechanisms through occupational epidemiological investigations and animal experiments. Methods (1) Population study: A cross-sectional study was conducted on 374 lead smelting workers in northern China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect urinary levels of 8 metals including Pb and Cd, and graphite furnace atomic absorption spectroscopy (GFAAS) was used to quantify blood levels of Pb and Cd. The cytokinesis-block micronucleus assay (CBMN) was used to assess genetic damage. Poisson regression was used to analyze the association between metal exposure and micronucleus rates. (2) In vivo experiment: Thirty SD rats were randomly assigned to five groups: control (pure water), Pb (300 mg·L⁻¹ lead acetate), Cd (50 mg·L⁻¹ cadmium chloride), combined exposure (Pb + Cd), and resveratrol intervention (Pb + Cd + 50 mg·L⁻¹ resveratrol). After 8 weeks of ad libitum drinking water exposure, liver pathology, oxidative stress indicators [reactive oxygen species (ROS), reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)], genetic damage (Comet assay and γ-H2AX) were evaluated. Furthermore, cell cycle distribution, apoptosis rates, and mRNA expression of DNA damage response (DDR), DNA repair, and apoptosis-related genes were measured. Results (1) The geometric mean (GM, 95%CI) of urinary Pb and Cd were 14.69 (13.14, 16.51) µg·L⁻¹ and 2.11 (1.90, 2.33) µg·L⁻¹, respectively; the blood Pb and Cd levels were 117.10 (105.59, 129.87) µg·L⁻¹ and 4.55 (4.23, 4.89) µg·L⁻¹, respectively among the 374 workers. The mean micronucleus rate was (1.64±0.081) ‰, with significantly higher rates in males (1.65±0.083) ‰ than females (1.53±0.334) ‰ (U=4.166, P=0.041). All Pb and Cd biomarkers were positively correlated with micronucleus rate (FR>1, P<0.05), with a significant interaction effect observed between Pb and Cd (FR>1, P<0.05). (2) In rats, co-exposure to Pb and Cd caused liver tissue damage and inflammatory infiltration. Significant increases were observed in lymphocyte ROS; GSSG and MDA in lung tissue increased, while GSH and CAT activity decreased. Comet assay indicators and γ-H2AX levels were significantly elevated. Co-exposure induced S-phase arrest and increased apoptosis. mRNA levels of DDR (ATM, ATR, Chk2, and P53) and pro-apoptotic genes (Bax and Caspase-3) were upregulated, while the anti-apoptotic gene Bcl-2 and DNA repair genes (BRCA1, BRCA2, RAD51, RAD52, and CtIP) were downregulated. Two-way ANOVA confirmed synergistic effects on GSSG, Comet assay indicators, and ATR/Chk2 mRNA expression. Conclusion Occupational co-exposure to Pb and Cd synergistically induces genetic damage. This damage is mediated by oxidative stress and DNA damage, which activates the DDR pathway and inhibits the expression of DNA repair genes, ultimately leading to cell cycle arrest and apoptosis.

Objective: The impact of prophylactic salpingectomy on the prevention of epithelial ovarian cancer (EOC) remains unclear, particularly in Asian populations where data is lacking. In this systematic review and meta-analysis study, we sought to assess whether prophylactic salpingectomy could reduce the incidence of ovarian cancer in the general population of multiple ethnicities. Methods: A systematic review and meta-analysis were conducted using PubMed/MEDLINE, EMBASE, the Cochrane Library, and Web of Science to assess the effectiveness of salpingectomy, bilateral salpingectomy (BS), and unilateral salpingectomy (US) in reducing the risk of EOC and evaluating postoperative outcomes. Results: The final analyses included 6 eligible trials (5,747,056 patients), including 1 cohort study and 5 case-control studies. The analyses of these studies demonstrated that women who underwent salpingectomy had a significantly reduced risk of EOC compared to those who did not receive salpingectomy (odds ratio [OR]=0.63; 95% confidence interval [CI]=0.45–0.89; p=0.007). Five studies (5,746,469 patients) indicated a significant reduction in EOC risk among patients who underwent BS (OR=0.48; 95% CI=0.33–0.69; p<0.001).On the other hand, in the analysis of 4 studies (5,745,887 patients) that examined US, the association with EOC risk was not significant despite the protective trend (OR=0.82; 95% CI=0.64–1.06; p=0.12). Conclusion Our results indicate BS is an effective strategy for reducing the risk of sporadic EOC, but the results did not lead to the same conclusion for patients who underwent US. When a candidate or patient is undergoing a hysterectomy or has other benign diseases, prophylactic BS may be a safe surgical procedure that carries future benefits in terms of EOC risk.

OBJECTIVES: To investigate the molecular mechanism by which He's Yangchao Decoction (HSYC) improves ovarian function in a mouse model of premature ovarian insufficiency (POI). METHODS: Forty ICR mice were used to establish a POI model via intraperitoneal injection of cyclophosphamide and were randomly assigned to four groups: model control group, low-dose HSYC group, high-dose HSYC group, and estradiol group (positive control). Additionally, 10 age-matched ICR mice were selected as the blank control group. After intragastric intervention, the ovarian index, serum follicle-stimulating hormone (FSH) levels, and ovarian tissue expression of the FSH receptor (FSHR) were measured. A POI cell model was established by treating the human granulosa tumor cell line (KGN) with 4-hydroxycyclophosphamide. The cells were divided into four groups: solvent control group, HSYC group, inhibitor control group, and inhibitor+HSYC group, which were respectively treated with TH5487 (an OGG1 inhibitor) and HSYC-containing serum. The expressions of OGG1, mitochondrial DNA (mtDNA) oxidative damage markers, and pyroptosis-related proteins were detected by molecular docking, Western blotting, and immunofluorescence. RESULTS: Compared with the blank control group, the model control group showed a decreased ovarian index (P<0.05) and increased serum FSH levels (P<0.01). The ovarian index was higher in both the low- and high-dose HSYC groups compared with the model control group (both P<0.05). FSHR expression in ovarian tissue was lower in the model control group than that in the blank control group, but was higher in the high-dose HSYC group compared with the model control group (P<0.05 or P<0.01). Molecular docking confirmed strong binding affinity between the active components of HSYC and OGG1 (binding energy: －6.3 to －8.3 kcal/mol). Western blotting analysis revealed that OGG1 protein expression in the ovaries of the model control group was significantly reduced compared with the blank control group, while it was increased in the low-dose HSYC group and the estradiol group (P<0.05 or P<0.01). Immunofluorescence results demonstrated that the expression levels of mito-chondrial transcription factor A (TFAM) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) were decreased in the model control group compared with the blank control group (P<0.01), whereas their expressions were significantly elevated in the high-dose HSYC group and the estradiol group (all P<0.01). Cell experiments showed that TH5487 intervention increased the expression of 8-oxoguanine (8-OxoG) (P<0.01), while HSYC-containing serum intervention reduced 8-OxoG expression and increased TFAM expression (P<0.01). The expression of pyroptosis-related proteins (GSDMD, N-GSDMD, caspase-1, IL-1β) increased after TH5487 intervention (P<0.05), whereas HSYC-containing serum suppressed their expression (all P<0.05). CONCLUSIONS HSYC improves POI by upregulating OGG1 expression, mitigating mtDNA oxidative damage, and inhibiting granulosa cell pyroptosis.