[摘 要] 目的：探究甘氨胆酸（GCA）对肺腺癌A549细胞移植瘤小鼠放射治疗敏感性的影响及其机制。方法：建立A549人肺腺癌细胞裸鼠移植瘤模型，随机分为移植瘤对照组（对照组）、GCA组、放疗组（RT组）和GCA + 放疗组（GCA + RT组）。RT组和GCA + RT组接受单次10  Gy照射，GCA组及GCA + RT组连续7 d每日灌胃GCA 280  mg/kg。间隔2 d测量1次移植瘤体积，末次给药后处死小鼠并取移植瘤组织，检测移植瘤组织中超氧化物歧化酶（SOD）与谷胱甘肽过氧化物酶（GSH-Px）活性，qPCR法和WB法分别检测放疗关键基因（MCM6、ITGA6、CASP3等）mRNA和蛋白表达水平，H-E染色观察移植瘤组织的形态变化。通过GEO（GSE276500、GSE294906、GSE218171）及TCGA数据库数据验证放疗关键基因。结果：GCA单用对瘤体生长有一定抑制作用，但联合放疗的GCA + RT组相比单纯放疗组表现出放疗抵抗的效应（P < 0.05）。GCA处理显著提高移植瘤组织SOD活性（P < 0.01）、降低GSH-Px活性（P < 0.01），提示GCA可改变移植瘤抗氧化酶平衡，减弱放疗诱导的氧化应激。GCA干预上调移植瘤组织中MCM6与ITGA6 mRNA表达、下调CASP3 mRNA表达（均P < 0.05）。GCA + RT组移植瘤组织中的MCM6蛋白表达显著高于对照组（P < 0.05）。H-E染色显示，GCA组部分瘤组织坏死，而GCA + RT组坏死组织面积较RT组有所缩小。GEO和TCGA数据库验证支持MCM6、ITGA6高表达与放疗抵抗和预后不良相关。结论：GCA通过增强SOD活性、降低GSH-Px活性并上调ITGA6、MCM6的表达改变氧化应激与关键信号网络，从而削弱A549移植瘤对放疗的敏感性。

Purpose: Metastatic rectal cancer (mRC) is a highly lethal and complex disease that demands a multidisciplinary treatment approach. However, the clinical effectiveness of radiotherapy (RT) for de novo mRC remains controversial and uncertain. Methods: This retrospective cohort study examined medical records from Kaohsiung Chang Gung Memorial Hospital for patients with histologically confirmed de novo mRC diagnosed between January 2015 and December 2020. All patients received standard systemic therapy and radical surgery when feasible. The primary outcome, overall survival (OS), was assessed using the Kaplan-Meier method. Multivariable analysis was performed using a Cox regression model. Results: Among 271 patients included in the analysis, 117 received RT and 154 did not. The median OS was significantly longer in the RT group compared with the non-RT group (27.8 months vs. 21.9 months; P=0.046). Multivariate analysis identified several independent predictors of OS: age ≥65 years (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.26–2.27; P=0.001), primary tumor resection (HR, 2.62; 95% CI, 1.90–3.61; P<0.001), M1b or M1c disease (HR, 1.97; 95% CI, 1.44–2.69; P<0.001), and receipt of RT (HR, 1.41; 95% CI, 1.02–1.94; P=0.036). Conclusion RT significantly improves OS in patients with mRC, underscoring its role in treatment strategies. These findings support its inclusion in therapeutic protocols and highlight the need for larger, multicenter trials to confirm and extend these results.

Objective To explore the efficacy and safety of blue laser vaporization in the treatment of large-volume (＞80 mL) benign prostatic hyperplasia (BPH). Methods A retrospective analysis was conducted on the clinical data of 149 BPH patients with prostate volume＞80 mL who underwent blue laser vaporization at our hospital during Aug. 2023 and Aug. 2025. The 1-month postoperative maximum urinary flow rate (Qmax) and international prostate symptom score (IPSS), operation time, postoperative hemoglobin drop, bladder irrigation volume, catheter indwelling time, and incidence of postoperative complications were recorded and analyzed. Results All operations were successfully completed, without conversion to other approaches. The operation time was (41.47±11.05) minutes, postoperative hemoglobin drop (2.78±1.19) g/L, bladder irrigation volume (9.97±1.49) bags, and catheter indwelling time (3.30±1.85) days. One month after surgery, the Qmax was significantly higher than the preoperative value [(20.19±3.39) mL/s vs. (2.39±2.17) mL/s], while the IPSS was significantly lower [(4.46±0.87) vs. (27.69±2.06)], with statistically significant differences (P＜0.001). Postoperative complications included 1 case of incontinence (0.67%), 2 cases of urethral stricture/bladder neck contracture (1.34%), and 1 case of secondary bleeding (0.67%), all of which improved with symptomatic treatment. Conclusion Blue laser vaporization is effective for treating large-volume BPH, with advantages such as minimal bleeding risk, short operation time, fast recovery and safety.

This study aimed to investigate the effect of Dahuang Zhechong Pills(DHZCP) in delaying heart aging(HA) and explore the potential mechanism. Network pharmacology and molecular docking were employed to explore the targets and potential mechanisms of DHZCP in delaying HA. Furthermore, in vitro experiments were conducted with the DHZCP-containing serum to verify key targets and pathways in D-galactose(D-gal)-induced aging of cardiomyocytes. Active components of DHZCP were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCSMP), and relevant targets were predicted. HA-related targets were screened from the GeneCards, Online Mendelian Inheritance in Man(OMIM), and DisGeNET. The common targets shared by the active components of DHZCP and HA were used to construct a protein-protein interaction network in STRING 12.0, and core targets were screened based on degree in Cytoscape 3.9.1. Metaspace was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of the core targets to predict the mechanisms. Molecular docking was performed in AutoDock Vina. The results indicated that a total of 774 targets of the active components of DHZCP and 4 520 targets related to HA were screened out, including 510 common targets. Core targets included B-cell lymphoma 2(BCL-2), serine/threonine kinase 1(AKT1), and hypoxia-inducible factor 1 subunit A(HIF1A). The GO and KEGG enrichment analyses suggested that DHZCP mainly exerted its effects via the phosphatidylinositol 3-kinase(PI3K)/AKT signaling pathway, HIF-1α signaling pathway, longevity signaling pathway, and apoptosis signaling pathway. Among the pathways predicted by GO and KEGG enrichment analyses, the PI3K/AKT/HIF-1α signaling pathway was selected for verification. The cell-counting kit 8(CCK-8) assay showed that D-gal significantly inhibited the proliferation of H9c2 cells, while DHZCP-containing serum increased the viability of H9c2 cells. SA-β-gal staining revealed a significant increase in the number of blue-green positive cells in the D-gal group, which was reduced by DHZCP-containing serum. TUNEL staining showed that DHZCP-containing serum decreased the number of apoptotic cells. After treatment with DHZCP-containing serum, the protein levels of Klotho, BCL-2, p-PI3K/PI3K, p-AKT1/AKT1, and HIF-1α were up-regulated, while those of P21, P16, BCL-2 associated X protein(Bax), and cleaved caspase-3 were down-regulated. The results indicated that DHZCP delayed HA via multiple components, targets, and pathways. Specifically, DHZCP may delay HA by reducing apoptosis via activating the PI3K/AKT/HIF-1α signaling pathway.
Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Signal Transduction/drug effects* ; Apoptosis/drug effects* ; Myocytes, Cardiac/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Animals ; Rats ; Humans ; Molecular Docking Simulation ; Aging/metabolism* ; Protein Interaction Maps/drug effects* ; Heart/drug effects* ; Network Pharmacology

The medicinal materials of Bawei Chenxiang Pills(BCPs) were extracted via three methods: reflux extraction by water, reflux extraction by 70% ethanol, and extraction by pure water following reflux extraction by 70% ethanol, yielding three extracts of ST, CT, and CST. The efficacy of ST(760 mg·kg~(-1)), CT(620 mg·kg~(-1)), and CST(1 040 mg·kg~(-1)) were evaluated by acute myocardial ischemia(AMI) and p-chlorophenylalanine(PCPA)-induced insomnia in mice, respectively. Western blot was further utilized to investigate their hypnosis mechanisms. The main chemical components of different extracts were identified by the UPLC-Q-Exactive-MS technique. The results showed that CT and CST significantly increased the ejection fraction(EF) and fractional shortening(FS) of myocardial infarction mice, reduced left ventricular internal dimension at end-diastole(LVIDd) and left ventricular internal dimension at end-systole(LVIDs). In contrast, ST did not exhibit significant effects on these parameters. In the insomnia model, CT significantly reduced sleep latency and prolonged sleep duration, whereas ST only prolonged sleep duration without shortening sleep latency. CST showed no significant effects on either sleep latency or sleep duration. Additionally, both CT and ST upregulated glutamic acid decarboxylase 67(GAD67) protein expression in brain tissue. A total of 15 main chemical components were identified from CT, including 2-(2-phenylethyl) chromone and 6-methoxy-2-(2-phenylethyl) chromone. Six chemical components including chebulidic acid were identified from ST. The results suggested that chromones and terpenes were potential anti-myocardial ischemia drugs of BCPs, and tannin and phenolic acids were potential hypnosis drugs. This study enriches the pharmacological and chemical research of BCPs, providing a basis and reference for their secondary development, quality standard improvement, and clinical application.
Animals ; Drugs, Chinese Herbal/isolation & purification* ; Mice ; Male ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Humans ; Myocardial Infarction/drug therapy* ; Myocardial Ischemia/drug therapy*

Objective To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.

Objective To analyze the diagnostic value of serum miR-181b and long noncoding RNA(lncRNA)myocardial infarction association transcript(MIAT)for hypertensive nephropathy.Methods A total of 120 patients with essential hypertension admitted to Jinhua People's Hospital from October 2022 to October 2024 were selected as research subjects.According to urinealbumin-to-creatinine ratio,they were divided into hypertensive nephropathy group(68 cases)and simple hypertension group(52 cases),and another 60 healthy individuals undergoing physical examinations during the same period were selected as control group.The serum miR-181b,lncRNA MIAT,hypersensitive C-reaction protein(hs-CRP),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in each group were compared.Results There were statistically significant differences in hs-CRP,TNF-α,IL-6,miR-181b and lncRNA MIAT among three groups(P＜0.05).Among them,the levels of hs-CRP,TNF-α,IL-6 and lncRNA MIAT in hypertensive nephropathy group＞simple hypertension group＞control group,and miR-181b level was in hypertensive nephropathy group＜simple hypertension group＜control group.The results of Pearson correlation analysis showed that expression of serum miR-181b in patients with hypertensive nephropathy was negatively correlated with the levels of lncRNA MIAT,hs-CRP,TNF-α,and IL-6(P＜0.05),while expression of lncRNA MIAT was positively correlated with the levels of hs-CRP,TNF-α,and IL-6(P＜0.05).The sensitivity of miR-181b and lncRNA MIAT in the diagnosis of hypertensive nephropathy evaluated by receiver operating characteristic curve was 97.1％and 73.5％respectively,the specificity was 68.7％and 92.1％respectively,and area under the curve were 0.819 and 0.951 respectively.Conclusion miR-181b and lncRNA MIAT are abnormally expressed in the serum of patients with hypertensive nephropathy and are expected to become potential markers for early diagnosis of hypertensive nephropathy.

Objective To investigate the effect of polymorphism at the-94ins/del ATTG(rs28362491)site in the promoter region of nuclear transcription factor-κB(NF-κB)1 on the lipid-lowering and anti-inflammatory efficacy of atorvastatin in patients with coronary heart disease(CHD).Methods A total of 180 patients with CHD in Jinhua People's Hospital from June 2022 to June 2024 were selected as the research objects.The genotypes of rs28362491 locus of NF-κB1 gene were detected.The levels of blood lipids and inflammatory factors before treatment,1 month and 6 months after treatment were analyzed,and the incidence of adverse reactions during treatment were observed.Results A total of 180 CHD patients underwent genetic testing and were divided into DD genotypes 46 cases,ID genotypes 76 cases,and II genotypes 58 cases.The levels of total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),interleukin(IL)-6,IL-8,and tumor necrosis factor-α(TNF-α)in DD genotypes were higher than those in ID genotypes and Ⅱ genotypes(P<0.05).After 1month and 6 months treatment,the levels of TC,LDL-C,IL-6,IL-8,and TNF-α in three groups of patients decreased significantly compared to before treatment(P<0.05).At the same time point,the change rates of TC,LDL-C,IL-6,IL-8,and TNF-α levels in ID genotypes and Ⅱgenotypes were higher than those in DD genotypes(P<0.05).Conclusion The efficacy of atorvastatin in CHD patients is associated with the rs28362491 polymorphism of the NF-κB1 gene,with II genotypes and ID genotypes showing better efficacy than DD genotypes.

Objective To establish a high-throughput non-targeted screening and prioritization method for emerging pollutants(EPs)in sewage using direct injection high-resolution mass spectrometry(HRMS).Methods The sewage samples were filtered by membrane filter and directly subjected to the liquid chromatography-time-of-flight mass spectrometer based on a method modified from our previous study.A C18 chromatographic column was applied for a gradient elution separation,and accurate mass and mass spectral fragment information were obtained through the MS full scan mode and MS/MS DIA data collection mode.After peak detection and alignment,the features from the raw data through open source software MZmine 3,and then high-throughput screening strategies such as MassBank and PubChem databases were used for compound annotation.Finally,the candidate features were confirmed with chemical standards by compared their retention time and mass spectrum fragmentation ion peaks.Results 13 EPs were identified,including 7 industrial chemicals,4 pharmaceuticals,1 pesticide and 1 metabolite.High detection rates were observed for metformin(86.2％),2-hydroxybenzothiazole(79.3％),1,2-benzisothiazole-3-one(72.4％),and 1,2-benzisothiazole-3-one(72.4％).The quantitative concentration range of EPs was 1.37～19.05 ng/mL,with the high concentrations observed for melamine(19.05 ng/mL)and furosemide(18.49 ng/mL).Ecological risk assessment identified 1,2-benzisothiazol-3-one,4-aminoacetophenone,creatinine,2-hydroxybenzothiazole,and furosemide as key pollutants.Conclusion This direct injection coupled with HRMS workflow enables efficient non-targeted screening and prioritization of emerging EPs in sewage samples,highlighting five ecotoxicologically critical EPs.The methodology enhances environmental monitoring capabilities and provide critical technical support for interdisciplinary research such as environmental forensics and health risk assessment.

Hepatocellular carcinoma(HCC)is difficult to detect in its early stages and current treatment methods are associated with significant side effects and a high risk of developing drug resistance.This study aims to investigate the effect of phycocyanin(PC)on the apoptosis of human HCC HepG2 cells and its potential mechanism.HepG2 cells were treated with PC at concentrations of 0.1,0.25,0.5,1,2.5,5,and 10 μg/mL for 12 h,and with 10 μg/mL PC and 2.5 μmol/L Wip1 inhibitor(Wip1i)alone or in combination for 12 and 24 h,respectively.Cell proliferation levels were assessed using the CCK-8 cell proliferation-toxicity assay kit.Apoptosis levels were measured by Annexin V-FITC/Propidium Iodide double staining combined with flow cytometry.TMT(Tandem Mass Tag)proteomics quantitative technol-ogy was applied to analyze differential protein expression.Western blotting was used to detect the expres-sion levels of Wip1,p53,and phosphorylated-p53(Ser15)proteins.The CCK-8 assay revealed that PC effectively inhibited HepG2 cell proliferation in a concentration-dependent manner,with a half-maximal inhibitory concentration(IC50)of 19.37 μg/mL.Flow cytometry results showed that PC significantly in-duced apoptosis,with an apoptosis rate of 30.40％.Quantitative proteomics analysis indicated that PC induced activation of the p53 pathway.The CCK-8 assay showed that Wip1i enhanced the cytotoxic effect of PC on HepG2 cells.Western blotting confirmed that PC inhibited Wip1 expression,induced p53 pro-tein phosphorylation,and promoted the expression of total p53 protein.Additionally,Wip1i further en-hanced PC-mediated activation of the p53 pathway,increasing the expression of p53 and pP53(S15).In conclusion,PC may induce apoptosis by inhibiting the activity of the p53 negative regulator Wip1,thereby promoting apoptosis through the Wip1/p53 pathway.