Objective To explore the feasibility and reference value of allogeneic lung transplantation and postoperative monitoring in miniature pigs for lung transplantation research. Methods Two miniature pigs (R1 and R2) underwent left lung allogeneic transplantation. Complement-dependent cytotoxicity tests and blood cross-matching were performed before surgery. The main operative times and partial pressure of arterial oxygen (PaO₂) after opening the pulmonary artery were recorded during surgery. Postoperatively, routine blood tests, biochemical blood indicators and inflammatory factors were detected, and pathological examinations of multiple organs were conducted. Results The complement-dependent cytotoxicity test showed that the survival rate of lymphocytes between donors and recipients was 42.5%-47.3%, and no agglutination reaction occurred in the cross-matching. The first warm ischemia times of D1 and D2 were 17 min and 10 min, respectively, and the cold ischemia times were 246 min and 216 min, respectively. Ultimately, R1 and R2 survived for 1.5 h and 104 h, respectively. Postoperatively, in R1, albumin (ALB) and globulin (GLB) decreased, and alanine aminotransferase increased; in R2, ALB, GLB and aspartate aminotransferase all increased. Urea nitrogen and serum creatinine increased in both recipients. Pathological results showed that in R1, the transplanted lung had partial consolidation with inflammatory cell infiltration, and multiple organs were congested and damaged. In R2, the transplanted lung had severe necrosis with fibrosis, and multiple organs had mild to moderate damage. The expression levels of interleukin-1β and interleukin-6 increased in the transplanted lungs. Conclusions The allogeneic lung transplantation model in miniature pigs may systematically evaluate immunological compatibility, intraoperative function and postoperative organ damage. The data obtained may provide technical references for subsequent lung transplantation research.

OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

OBJECTIVE To analyze the safety and efficacy of vonoprazan （VPZ） in the treatment of peptic ulcer （PU） and post-endoscopic submucosal dissection （ESD） ulcers， providing evidence-based pharmaceutical evidence for clinical practice and medical decision-making. METHODS Retrieved from CNKI， Wanfang， VIP， CBM， PubMed， Embase， Web of Science， and the Cochrane Library， meta-analyses/systematic reviews related to VPZ in the treatment of PU and post-ESD ulcers were collected. Two researchers independently performed literature screening， data extraction， quality assessment of included studies， and evaluation of literature overlap. By employing the umbrella review analysis， a fresh meta-analysis was conducted on all relevant raw research data when a high degree of overlap was identified among the included studies. RESULTS A total of 17 meta-analyses were included， with quality ranging from high to very low； all outcome measures involved showed a very high level of overlap in the included meta-analyses （corrected covered area： 22.22%-100%）. In the treatment of post-ESD ulcers， compared to proton pump inhibitor （PPI）， VPZ significantly improved the ulcer healing rate at 4 weeks post-ESD [RR＝1.27， 95%CI （1.03， 1.56）， Z＝2.21， P＝ 0.027] and the ulcer contraction rate post-ESD [MD＝0.08， 95%CI （0.00， 0.16）， Z＝2.09， P＝0.037]， while significantly reducing the ulcer recurrence rate in patients with a history of PU [RR＝0.49， 95%CI （0.32， 0.73）， Z＝3.49， P＝0.001]； the delayed bleeding rate in the VPZ group was significantly lower than that in the lansoprazole subgroup [RR＝0.47， 95%CI （0.25， 0.90）， Z＝2.28， P＝0.02]. In the treatment of PU， the incidence of adverse events with VPZ was significantly higher than that with PPI in the duodenal ulcer subgroup [RR＝1.13， 95%CI （1.02， 1.26）， Z＝2.38， P＝0.017]. CONCLUSIONS For post-ESD ulcers， VPZ demonstrates superior therapeutic efficacy compared to PPI and can reduce ulcer recurrence rates in patients with a history of PU. However， it does not offer advantages in terms of safety for duodenal ulcer treatment.

ObjectiveTo study the mechanism of Yinchenhao Tang on the improvement of cholestatic liver injury （CLI） by inhibiting toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor-κB （NF-κB） pathway via regulating farnesol X receptor （FXR）. MethodsA total of 40 Wistar male rats were randomly selected， with 10 as a blank group，and the remaining rats were subjected to the CLI model induced by alpha-naphthalene isothiocyanate （ANIT）. After modeling，they were randomly divided into the model group， the ursodeoxycholic acid （0.1 g·kg^-1） group and the Yinchenhao Tang （9.23 g·kg^-1） group，with 10 animals in each group. Each administration group was given the corresponding drug by intragastric administration for three consecutive days. Alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），γ-glutamyl transpeptidase （γ-GT），total bile acid （TBA），total bilirubin （TBil） and direct bilirubin （DBil） levels in serum were detected. Tumor necrosis factor-α （TNF-α），interleukin-1β （IL-1β），and interleukin-6 （IL-6） levels in liver tissue were detected. Real-time PCR was used to detect the mRNA expression of FXR，TLR4，MyD88，NF-κB，F4/80，TNF-α，IL-1β and IL-6 in liver tissue. Western blot was used to detect protein expression of FXR，TLR4，MyD88 and NF-κB in liver tissue. The histopathological changes of the liver were observed by hematoxylin-eosin （HE） staining. ResultsCompared with those in the blank group，ALT，AST，ALP，γ-GT，TBA，TBil and DBil levels in serum of rats in the model group were significantly increased （P<0.01）. The levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were significantly increased （P<0.01），and the mRNA and protein expressions of FXR in liver tissue were decreased （P<0.01）. The mRNA and protein expressions of TLR4，MyD88 and NF-κB and the mRNA expression of F4/80 were obviously increased （P<0.05，P<0.01）. Hepatic histopathology showed inflammatory cell infiltration and proliferative changes of bile duct epithelial cells. Compared with those in the model group，ALT，ALP，γ-GT，TBA，TBil and DBil levels in serum of rats in the ursodeoxycholic acid group were obviously decreased （P<0.05，P<0.01），and the levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were obviously decreased （P<0.05，P<0.01）. The mRNA and protein expressions of TLR4，MyD88 and NF-κB and the mRNA expression of F4/80 in liver tissue were obviously decreased （P<0.05，P<0.01）. ALT，AST，ALP，γ-GT，TBA，TBil and DBil levels in the serum of rats in the Yinchenhao Tang group were obviously decreased （P<0.05，P<0.01），and the levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were obviously decreased （P<0.01）. The mRNA and protein expressions of FXR in liver tissue were significantly increased，and the mRNA expressions of TLR4，MyD88，NF-κB，and F4/80， as well as the protein expressions of TLR4 and NF-κB were obviously decreased （P<0.05，P<0.01）. The inflammatory cell infiltration of liver tissue and the proliferation of bile duct epithelial cells decreased. ConclusionYinchenhao Tang has an obvious protective effect on CLI，and its mechanism may be related to regulating FXR to inhibit TLR4/MyD88/NF-κB pathway-mediated inflammatory response.

This paper has constructed a traditional Chinese medicine （TCM） specialized disease dataset platform for mixed hemorrhoids based on a multimodal large model， and the preliminary application has been validated. The platform uses StarRocks to establish a four-level data warehouse system， enabling the aggregation， cleaning， and standardization of multi-source heterogeneous data. Using DeepSeek-R1-Distill-Qwen-7B as the base model， domain fine-tuning is performed through low-rank adaptation （LoRA） technology. Combined with LLaMA-3.3 natural language processing and reasoning chain techniques， the platform enables intelligent parsing and structured extraction of unstructured TCM medical records. It accurately identifies six major categories and 28 subcategories of entities， including symptoms and syndromes， with a fine-tuned model F1 score of 93.8%. The platform has established a high-quality specialized disease dataset containing more than 50,000 medical records and has been applied in a real-world study involving 17,831 patients， preliminarily verifying the efficacy of TCM heritage surgery.

ObjectiveTo establish a regional risk assessment system for hospital-acquired infections in neurosurgery department of general hospital, and to evaluate its prevention and control effectiveness. MethodsFailure mode and effect analysis (FMEA) was used to identify the core risk factors for infections in neurosurgery department. The risk priority number (RPN) of each risk factor was calculated to determine the priority intervention targets. Targeted interventions were developed and continuously refined through the plan-do-check-act (PDCA) cycles. Data from January to June 2023 (control group) and July to December 2023 (intervention group) were collected to compare the differences in environmental hygiene monitoring qualification rate, incidence rate of hospital-acquired infections among inpatients, and detection rate of bacterial antimicrobial resistance. ResultsHigh-risk factors for hospital-acquired infections in neurosurgery department included patient-related risk factors, inadequate implementation of isolation measures for special infections, and poor compliance with surgical site infection (SSI) prevention protocols. After intervention, the environmental hygiene qualification rate significantly increased from 81.55% to 100.00% (χ²=120.49, P<0.001). The overall hospital-acquired infection rate among inpatients decreased from 2.62% to 2.45%, the infection rate of per case declined from 3.12% to 2.84%, and the detection rate of multidrug-resistant organism infections reduced from 43.72% to 36.79%. Additionally, antimicrobial utilization rate decreased from 48.75% to 42.53% (χ²=34.09, P<0.001). ConclusionThe FMEA-based risk assessment system can effectively identify critical infection risks in neurosurgery department, and targeted interventions can significantly improve infection prevention and control performance.

This paper comprehensively discusses on the potential neurobiological mechanisms of acupuncture in the treatment of tobacco dependence， focusing on three important aspects， including acupuncture's regulation of tobacco dependence behavior， effects of acupuncture on withdrawal syndrome， and the role of acupuncture in preventing relapse. It is found that acupuncture can inhibit drug-seeking behavior by regulating the reward pathway and related neurons， such as dopamine， thus modulating tobacco dependence behavior. It also alleviates withdrawal symptoms by improving the oral environment of smokers and reducing negative emotions after quitting. Furthermore， acupuncture can prevent relapse by decreasing brain network activity related to smoking cravings and improving cognitive brain functions like addiction memory. Currently， research on the specific neurobiological mechanism of acupuncture in treating tobacco dependence and the involved neural circuits is limited. Future research directions are proposed， including the evaluation of clinical effects， exploration of specific therapeutic mechanisms， investigation of brain pathology， and strengthening the exploration of brain functions. Additionally， combining modern technologies to clarify the neural circuits involved in acupuncture intervention will provide a basis for acupuncture treatment of tobacco addiction.

ObjectiveTo investigate the effect of laminin subunit α3 （LAMA3） on the epithelial-mesenchymal transition （EMT）， invasion， and metastasis abilities of pancreatic cancer （PC）. MethodsA comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC， especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines； immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells； Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. ResultsThe analysis of the TCGA database identified 3 EMT-related oncogenes for PC， i.e.， LAMA3， AREG， and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC （risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG）. The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC （hazard ratio=1.32， 95% confidence interval： 1.07‍ ‍—‍ 1.62， P<0.01）. Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line， there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1， BxPC-3， PANC-1， MIA PaCa-2， and SW1990 cell lines， with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT， collagen metabolism， extracellular matrix degradation， the TGF-β pathway， and the PI3K pathway. After the knockdown of LAMA3， there were significant reductions in the expression levels of N-Cadherin， Vimentin， and Snail， while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. ConclusionLAMA3 is highly expressed in PC and can promote the EMT， invasion， and migration of PC cells， and therefore， LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.

ObjectiveTo investigate the effect and mechanism of polysaccharide in water extract of Cyclocarya paliurus （CPWP） in inhibiting benign prostatic hyperplasia （BPH）. MethodsCPWP was obtained by heating reflux， aqueous extraction， alcohol precipitation， and freeze drying. The chemical composition and structural properties of CPWP were analyzed by high performance liquid chromatography with 1-pheny-3-methyl-5-pyrazolone pre-column derivatization and infrared spectroscopy. Male SD rats were randomly assigned into control， model， finasteride （ig 5 mg·kg^-1）， and low-， medium-， and high-dose （ig 50， 75， 100 mg·kg^-1） CPWP groups， with 8 rats in each group. The BPH model was established by subcutaneously injecting propionate testosterone in castrated rats. The rats in the drug intervention groups were administrated with corresponding drugs， and those in the control group were administrated with an equal volume of normal saline each day. After 30 consecutive days， the rats were sacrificed， and the prostate tissue was separated and weighed. The effects of drug interventions on the body weight， prostate wet weight， and prostate index of rats were examined. The prostate tissue was stained with hematoxylin-eosin （HE） for observation of pathological changes. Enzyme-linked immunosorbent assay was employed to measure the level of dihydrotestosterone （DHT）， and immunohistochemical staining was used to detect the expression of steroid 5 alpha-reductase 2 （SRD5A2） and Ki67 in the prostate tissue. ResultsCPWP was identified as a saccharide， with characteristic absorption peaks of saccharides. CPWP showed the total sugar content of 44.15% and molecular weight within the range of 5.5-78.8 kDa， being composed of mannose， rhamnose， galacturonic acid， glucose， galactose， xylose， and arabinose. Compared with the control group， the model group had significantly increased prostate wet weight and prostate index （P<0.01）， thick and tall prostate epithelial cells， increased internal wrinkles， papillary expansion into the cavity， an elevation in DHT level in the serum， and up-regulated expression of SRD5A2 and Ki67 in the prostate tissue （P<0.05， P<0.01）. Compared with the model group， both the finasteride and CPWP groups showed decreases in prostate wet weight and prostate index （P<0.05， P<0.01）， thinned prostate epithelial cells， with only a small portion of internal wrinkles and papillary expansion into the cavity， shortened papillary protrusions， lowered DHT level in the serum， and down-regulated expression of SRD5A2 and Ki67 in the prostate tissue （P<0.01）. Moreover， CPWP exerted effects in a dose-dependent manner. ConclusionCPWP inhibits BPH by regulating the expression of SRD5A2.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.