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.

ObjectiveTo investigate the effects of Qizhujianwei granules （QZJW） on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia （GIN） and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine （MNNG）， ranitidine， irregular feeding patterns， and sodium salicylate. Except for the normal group， after successful modeling， the rats were randomly divided according to body weight into a model group， a Moluodan group （0.55 g·kg^-1）， and a QZJW group （7.34 g·kg^-1）， with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pepsinogenⅠ （PGⅠ）， pepsinogenⅡ （PGⅡ）， and gastrin （G-17）， as well as the expression level of transforming growth factor-β₁ （TGF-β₁） in gastric mucosal tissue， and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry （IHC） was used to detect the localization and expression levels of proliferating cell nuclear antigen （Ki-67） and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A （Wnt3a）， β-catenin， CyclinD₁， proto-oncogene Cmyc， transforming growth factor-β receptor Ⅰ （TGFβRⅠ）， intracellular signaling transducers Smad2/3， phosphorylated （p）-Smad2/3， twist family transcription factor （Twist1）， and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group， the model group showed characteristic changes including dim eyes， pale ears and claws， dark-red tongue， and reduced luster of the tail. The gastric mucosa appeared pale， with surface congestion and erosion. The gastric mucosal glands were disordered， the nuclear-to-cytoplasmic ratio increased， and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased （P<0.01）， while the level of G-17 was significantly increased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly increased （P<0.05， P<0.01）， whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased （P<0.05）. Compared with the model group， the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased （P<0.05， P<0.01）， while the level of G-17 was significantly decreased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly decreased （P<0.05， P<0.01）. ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile， it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β₁/Smad/Twist1 signaling pathway， thereby blocking the malignant progression of GIN.

ObjectiveTo investigate the effects of Qizhujianwei granules （QZJW） on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia （GIN） and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine （MNNG）， ranitidine， irregular feeding patterns， and sodium salicylate. Except for the normal group， after successful modeling， the rats were randomly divided according to body weight into a model group， a Moluodan group （0.55 g·kg^-1）， and a QZJW group （7.34 g·kg^-1）， with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pepsinogenⅠ （PGⅠ）， pepsinogenⅡ （PGⅡ）， and gastrin （G-17）， as well as the expression level of transforming growth factor-β₁ （TGF-β₁） in gastric mucosal tissue， and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry （IHC） was used to detect the localization and expression levels of proliferating cell nuclear antigen （Ki-67） and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A （Wnt3a）， β-catenin， CyclinD₁， proto-oncogene Cmyc， transforming growth factor-β receptor Ⅰ （TGFβRⅠ）， intracellular signaling transducers Smad2/3， phosphorylated （p）-Smad2/3， twist family transcription factor （Twist1）， and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group， the model group showed characteristic changes including dim eyes， pale ears and claws， dark-red tongue， and reduced luster of the tail. The gastric mucosa appeared pale， with surface congestion and erosion. The gastric mucosal glands were disordered， the nuclear-to-cytoplasmic ratio increased， and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased （P<0.01）， while the level of G-17 was significantly increased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly increased （P<0.05， P<0.01）， whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased （P<0.05）. Compared with the model group， the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased （P<0.05， P<0.01）， while the level of G-17 was significantly decreased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly decreased （P<0.05， P<0.01）. ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile， it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β₁/Smad/Twist1 signaling pathway， thereby blocking the malignant progression of GIN.

Neuropathic pain （NP） is a chronic pain syndrome resulting from injury， inflammation， or dysfunction of the somatosensory nervous system. Its pathogenesis is complex and intimately associated with peripheral sensitization and maladaptive neuroplasticity within the central nervous system. The core clinical manifestations， including spontaneous pain， allodynia， and paresthesia， severely compromise patients’ quality of life and pose substantial challenges to clinical management. Endoplasmic reticulum stress （ERS）， a critical cellular defense mechanism against disrupted intracellular homeostasis， is primarily initiated and modulated through three canonical branches of the unfolded protein response （UPR）： the protein kinase RNA-like endoplasmic reticulum kinase （PERK） pathway， the inositol-requiring transmembrane kinase/endonuclease 1α （IRE1α） pathway， and the activating transcription factor 6 （ATF6） pathway. These signaling cascades play a pivotal role in the pathological progression of NP. Traditional Chinese medicine （TCM） exhibits unique advantages in the treatment of NP. Leveraging its hallmark characteristics of multi-target， multi-pathway， and holistic regulation， TCM can systematically modulate the ERS signaling network to inhibit neuronal apoptosis， attenuate neuroinflammatory infiltration， and rectify autophagic dysfunction， ultimately promoting the repair and regeneration of damaged neural tissue. This review systematically summarizes the core role of ERS in the occurrence and development of NP. It focuses on the latest research progress regarding ERS pathway modulation in NP amelioration by representative TCM interventions， including potential core bioactive components （e.g.， tanshinoneⅡ_A， catalpol， and formononetin）， classic and empirical compound formulas （e.g.， Huangqi Guizhi Wuwu decoction， Compound Qiying granules， and Tangluoning）， and TCM external therapies （e.g.， electroacupuncture， moxibustion with seed-sized moxa cone， and acupotomy）. Through an in-depth analysis of the functional characteristics and mechanisms of these TCM interventions， particularly their bidirectional regulation and multi-target synergy， this review aims to provide a solid theoretical foundation for further optimizing TCM-based strategies for NP prevention and treatment and to delineate future directions for clinical translation of related research achievements and targeted drug development.

Factorial design is an important method for optimizing complex strategies in implementation science. This paper systematically elucidates the origin, types, and core concepts of the factorial design, and then use a brief smoking cessation intervention project as an example to illustrate its specific applications in identifying key factors and testing interactions. Factorial design has the following typical advantages: it can test synergistic and antagonistic effects between factors, provide effect estimates that are broadly valid across the experimental conditions, and offer high statistical efficiency. At the same time, it also has certain limitations, including that its complexity is positively correlated with the number of factors, the need for large sample sizes to detect interactions, the potential for insufficient acceptability of some strategy combinations due to ethical concerns or participant burden, and the complexity of the analytical methods required. In future research, its application should be further optimized by appropriately controlling the number of factors, clearly defining research objectives, and evaluating intervention acceptability, in order to promote the development of precision implementation science.

Antibody-drug conjugates (ADCs) have emerged as a standard treatment modality for previously treated driver gene-positive advanced non-small cell lung cancer (NSCLC). Sacituzumab tirumotecan (sac-TMT), a novel TROP-2-targeting ADC, has been the focus of the phase Ⅲ clinical trial OptiTROP-Lung04. This trial demonstrated, for the first time, that single-agent sac-TMT significantly improves progression-free survival and overall survival compared with conventional platinum-based chemotherapy in patients with epidermal growth factor receptor (EGFR) mutant advanced NSCLC following resistance to EGFR tyrosine kinase inhibitors. This review combines existing consensus from literature with the latest research evidence to systematically analyze OptiTROP-Lung04 from multiple perspectives, including molecular mechanisms, study design, clinical significance, and safety management. Furthermore, it explores future development directions in an effort to provide new insights into precision therapy for advanced NSCLC.

ObjectiveTo investigate the risk factors for rebleeding after endoscopic therapy for esophageal and gastric varices in liver cirrhosis patients， to construct a clinical predictive model， and to provide a reference for predicting rebleeding in the early stage， reducing the incidence rate of rebleeding， and improving the clinical outcome of patients. MethodsA retrospective analysis was performed for the clinical data of 194 liver cirrhosis patients with gastroesophageal variceal bleeding who received initial endoscopic therapy at Department of Gastroenterology， The Second People’s Hospital of Lanzhou， from January 1， 2021 to May 31， 2025. According to whether rebleeding occurred within 1 year after endoscopic therapy， the patients were divided into rebleeding group and non-rebleeding group. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The patients enrolled were randomly divided into a training set and a validation set at a ratio of 7∶3. In the training set， the Lasso regression analysis was used to obtain optimal predictive variables， and the factors that might affect prognosis were included in the univariate and multivariate Logistic regression analyses to identify independent predictive factors for rebleeding after endoscopic therapy for esophageal and gastric varices in liver cirrhosis patients， which were used to construct a nomogram model. In both the training set and the validation set， the receiver operating characteristic （ROC） curve and the calibration curve were used to assess the discriminatory ability and calibration of the model， and decision curve analysis and the clinical impact curve were used to assess the clinical practicability of the model. ResultsAmong the 194 liver cirrhosis patients with esophageal and gastric varices， 116 （59.79%） experienced rebleeding within 1 year after endoscopic therapy， with 76 patients in the training set and 40 patients in the validation set. In the training set， the Lasso regression analysis and the univariate and multivariate Logistic regression analyses showed that etiology of liver cirrhosis （odds ratio ［OR］=3.540， 95% confidence interval ［CI］： 1.520 — 7.150， P<0.001）， Child-Pugh class （OR=3.560， 95%CI： 1.380 — 9.500， P=0.019）， severity of esophageal and gastric varices （OR=8.190， 95%CI： 3.568 — 17.850， P=0.026）， and main portal vein diameter （OR=2.954， 95%CI： 1.349 — 15.030， P=0.044） were independent predictive factors for rebleeding of esophageal and gastric varices in liver cirrhosis patients. A nomogram model was constructed based on the above independent predictive factors. The ROC curve analysis showed that this model had an area under the ROC curve of 0.845 （95%CI： 0.778 — 0.912） in the training set and 0.801 （95%CI： 0.798 — 0.868） in the validation set. The model had an index of concordance of 0.832 in the training set and 0.820 in the validation set， suggesting that the model had a good discriminatory ability. The Hosmer-Lemeshow test showed P values of 0.320 and 0.550 in the training set and validation set， respectively， the calibration curve indicated that the predicted probabilities of the nomogram model were in good concordance with the actual observed probabilities， suggesting that the model had good calibration. The decision curve analysis and the clinical impact curve showed that the model had good clinical utility. ConclusionThe nomogram model based on etiology of liver cirrhosis， Child-Pugh class， severity of esophageal and gastric varices， and main portal vein diameter has a certain clinical value in predicting the risk of rebleeding from esophageal and gastric varices in liver cirrhosis.

Objective To investigate the relationship between platelet to lymphocyte ratio(PLR)and low-density lipoprotein cholesterol(LDL-C)/high-density lipoprotein cholesterol(HDL-C)ratio with the degree of carotid artery stenosis,neurological deficits,and prognosis in elderly pa-tients with ischemic stroke and carotid artery stenosis.Methods A total of 186 elderly patients diagnosed with ischemic stroke and carotid artery stenosis admitted in our hospital from June 2021 to June 2024 were enrolled in this study.The PLR and LDL-C/HDL-C ratio were collected,and then with median split,they were divided into high and low PLR groups(both 93 cases),and high and low LDL-C/HDL-C groups(both 93 cases).General clinical data were compared between the two pairs of groups.Multivariate logistic regression analysis was used to identify the factors influencing the severity of carotid artery stenosis,neurological deficits,and prognosis.Kendall's Tau-b correlation analysis was employed to assess the relationship of PLR and LDL-C/HDL-C with the degree of carotid artery stenosis and prognosis.Pearson correlation analysis was conduc-ted to evaluate the association of PLR and LDL-C/HDL-C with neurological deficits.Results Sta-tistically differences were observed in the degree of carotid artery stenosis and prognosis between the high and low PLR groups(P＜0.01).The NIHSS score was significantly higher in the high PLR group(P＜0.01).Similar differences were noted between the high and low LDL-C/HDL-C groups in terms of degree of carotid artery stenosis and prognosis(P＜0.01).The NIHSS score was obviously higher in the high LDL-C/HDL-C group(P＜0.01).Multivariate logistic regression analysis showed that PLR and LDL-C/HDL-C were risk factors for the degree of carotid artery stenosis,neurological deficits and prognosis in elderly patients with carotid artery stenosis after ischemic stroke(OR=3.842,95％CI:2.551-5.328,P=0.000;OR=3.604,95％CI:2.402-5.407,P=0.000;OR=2.956,95％CI:1.955-4.471,P=0.000;OR=3.463,95％CI:2.506-4.785,P=0.000;OR=2.878,95％CI:1.991-4.160,P=0.000;OR=3.785,95％CI:2.483-5.768,P=0.000).Kendall's Tau-b correlation analysis showed that PLR and LDL-C/HDL-C were positively correlated with the degree of carotid artery stenosis and the prognosis in these eld-erly patients(P＜0.05).Pearson correlation analysis indicated that PLR and LDL-C/HDL-C were positively correlated with the NIHSS score in the patients(P＜0.05).Conclusion For the elderly ischemic stroke patients with carotid artery stenosis,PLR and LDL-C/HDL-C are related to the prognosis,and can be used to help assess the severities of carotid artery stenosis and neurological deficits.

The use of immune checkpoint inhibitors(ICIs)has dramatically changed the treatment landscape of advanced non-small cell lung cancer (NSCLC), and have improved the survival outcomes of advanced patients while offering better overall safety compared to chemotherapy.However, due to immune senescence, the efficacy and safety of immunotherapy in elderly patients are different from those in non-elderly patients.Moreover, most clinical trials have limited data on elderly patients, and immunotherapy in the elderly population lacks high-level evidence-based medical support.This article introduces the theoretical basis of immunotherapy in the elderly population, summarizes clinical data on the efficacy and safety of immunotherapy for advanced NSCLC in the elderly, and analyses the immunotherapy for special subgroups of elderly patients, aiming to provide a reference basis for treating this population.The results showed that single-agent immunotherapy had good efficacy and safety in elderly patients with advanced NSCLC in the age group of 65-74 years, obtaining long-term survival benefits, However, the benefits of immunotherapy in the elderly population ≥75 years old remian unclear, and the outcomes of immunotherapy in the elderly ≥80 years old were poor.In addition, the performance status (PS) score of ≥2 was a significant factor in reducing the efficacy of single-agent immunotherapy in elderly patients.In addition, a pre-treatment PS score of ≥2 was an independent risk factor for reducing the efficacy of immunotherapy alone.Immunotherapy in combination with chemotherapy in the elderly has shown efficacy comparable to the overall population.However, there is an increased incidence of treatment-related adverse events(TRAEs)in patients ≥75 years of age.Dual-immunity combination therapies are not currently recommended for the treatment of advanced NSCLC in the elderly.Elderly patients with brain metastases have poor prognosis, and treatment may consider ICIs in combination with local radiotherapy.Basic research on how to improve the benefit of immunotherapy in elderly patients is also ongoing.In conclusion, the therapeutic prospect of immunotherapy in advanced NSCLC in the elderly is promising, and more exploration is needed in the future.

Tunnel peripherally inserted central catheter (TPICC) catheterization technology is a new type of PICC catheterization that applies subcutaneous tunnel technology to traditional PICC catheterization. It has significant advantages in reducing catheter-related complications and improving patient comfort. According to the different methods of creating subcutaneous tunnels, it can be divided into one-needle TPICC catheterization technology and two-needle TPICC catheterization technology. This article reviews the overview, clinical application status and application effects of two TPICC catheterization techniques, and puts forward existing problems and prospects, in order to provide reference for clinical practice and related research of the two.