1.Buzhong Yiqitang Induces Ferroptosis by Regulating PCBP1 to Attenuate Cisplatin Resistance in Non-small Cell Lung Cancer
Yuetong LIU ; He LI ; Qirui MU ; Jingyi HUANG ; Haoran CAI ; Chunying LIU ; Yuan GAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):90-97
ObjectiveTo explore the molecular mechanism of Buzhong Yiqitang in attenuating cisplatin resistance in non-small cell lung cancer (NSCLC) by inducing ferroptosis via poly(rC)-binding protein 1 (PCBP1). MethodsThe serum containing Buzhong Yiqitang was prepared and cisplatin-resistant human non-small cell lung cancer (NSCLC) cells (A549/DDP) were cultured and randomly grouped as follows: Blank (10% blank serum), model (10% blank serum+20 mg·L-1 cisplatin), Buzhong Yiqitang (10% serum containing Buzhong Yiqitang+20 mg·L-1 cisplatin), Fe-1 (10% blank serum+20 mg·L-1 cisplatin+5 μmol·L-1 Fe-1), and Buzhong Yiqitang+Fe-1 (10% serum containing Buzhong Yiqitang+20 mg·L-1 cisplatin+5 μmol·L-1 Fe-1). Firstly, PCR Array was used to screen ferroptosis-related genes regulated by Buzhong Yiqitang, and PCBP1 was identified as the target for studying the attenuation of cisplatin resistance by Buzhong Yiqitang. Subsequently, the median inhibitory concentration (IC50) of cisplatin in each group was determined by the cell counting kit-8 (CCK-8) method and the resistance index (RI) was calculated. The ultrastructure of A549/DDP cells in each group was observed by transmission electron microscopy. The protein levels of PCBP1 and glutathione peroxidase 4 (GPX4) were determined by Western blot. The lipid reactive oxygen species (ROS) content in each group was determined by the C11-BODIRY 581/591 fluorescence probe. The ferrous ion assay kit was used to measure the ferrous ion content in each group. The malondialdehyde (MDA) assay kit was used to determine the MDA content in each group. ResultsCompared with model group, the IC50 of cisplatin and the RI of A549/DDP cells decreased in the Buzhong Yiqitang group (P<0.05) but increased in the Fe-1 group (P<0.05). The IC50 of cisplatin and the RI of A549/DDP cells in the Buzhong Yiqitang+Fe-1 group were lower than those in the Fe-1 group (P<0.05). Compared with the model group, the Buzhong Yiqitang group showed obvious mitochondrial ferroptosis, while the mitochondrial damage became less obvious after Fe-1 treatment. Compared with that in the Fe-1 group, the mitochondrial ferroptosis was aggravated after the intervention with Buzhong Yiqitang. Compared with blank group, the model group showed down-regulated expression levels of PCBP1 and GPX4 (P<0.05) and increased content of lipid ROS, ferrous ions, and MDA (P<0.05) in A549/DDP cells. Compared with model group, the Buzhong Yiqitang group showed down-regulated expression levels of PCBP1 and GPX4 (P<0.05) and increased content of lipid ROS, ferrous ions, and MDA (P<0.05), while the Fe-1 group showed up-regulated expression levels of PCBP1 and GPX4 (P<0.05) and reduced content of lipid ROS, ferrous ions, and MDA (P<0.05). Compared with the Fe-1 group, the Buzhong Yiqitang+Fe-1 group showed down-regulated expression levels of PCBP1 and GPX4 and increased content of lipid ROS, ferrous ions, and MDA (P<0.05). ConclusionBuzhong Yiqitang attenuated cisplatin resistance in NSCLC by regulating PCBP1 to induce ferroptosis.
2.Safety analysis of Yttrium-90 resin microsphere selective internal radiation therapy on malignant liver tumors
Jia CAI ; Shiwei TANG ; Rongli LI ; Mingxin KONG ; Hongyan DING ; Xiaofeng YUAN ; Yuying HU ; Ruimei LIU ; Xiaoyan ZHU ; Wenjun LI ; Haibin ZHANG ; Guanwu WANG
Chinese Journal of Clinical Medicine 2025;32(1):24-29
Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (90Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent 90Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of 90Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (99mTc-MAA) perfusion test and received the 90Y-SIRT; one patient received 90Y-SIRT after the second 99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of 90Y-SIRT for treating malignant liver tumors are mild, indicating good safety.
3.Characteristics of mitochondrial translational initiation factor 2 gene methylation and its association with the development of hepatocellular carcinoma
Huajie XIE ; Kai CHANG ; Yanyan WANG ; Wanlin NA ; Huan CAI ; Xia LIU ; Zhongyong JIANG ; Zonghai HU ; Yuan LIU
Journal of Clinical Hepatology 2025;41(2):284-291
ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 (MTIF2) gene methylation and its association with the development and progression of hepatocellular carcinoma (HCC). MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples, including survival curve analysis, methylation signature analysis, the association of tumor signaling pathways, and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level, and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races, ethnicities, BMI levels, and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation (hazard ratio [HR]=0.492, P<0.001), while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels (P>0.05). The methylation profile of the MTIF2 gene based on different ages, sexes, BMI levels, races, ethnicities, and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age, and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population (P<0.05); the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ (P<0.05). Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population (P<0.05). ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.
4.Development and validation of a multidisciplinary risk assessment scale for immune checkpoint inhibitor-associated myocarditis
Yanan DAI ; Yuan LIU ; Yuchen XU ; Qingqing CAI ; Yan WANG ; Yuhong ZHOU ; Leilei CHENG ; Junbo GE
Chinese Journal of Clinical Medicine 2025;32(4):561-567
Objective To develop a risk assessment scale for immune checkpoint inhibitor (ICI)-associated myocarditis based on multidisciplinary collaboration, and to evaluate its diagnostic performance. Methods Based on multidisciplinary cooperation, integrating clinical experience from oncology and cardiology, literature data, and patient conditions, a risk assessment scale for ICI-associated myocarditis was developed. A total of 101 patients with malignancies who received immunotherapy at Zhongshan Hospital, Fudan University, from October 2020 to October 2024 were included as the validation cohort. Patients were stratified into low-risk (0-1 point), medium-risk (2-4 points), and high-risk (≥5 points) groups based on their scale scores. The association between pretictive risk stratifications and actual assessment results was assessed using the Cox proportional hazards regression model. The predictive value of the scale for ICI-associated myocarditis was evaluated using receiver operating characteristic (ROC) curve. Agreement between the scale scores and actual assessment results was assessed using Cohen’s Kappa coefficient. Results Based on the scale pretictive results, 28(27.7%), 8(7.9%), 65(64.4%) patients were at low risk, medium risk, and high risk for ICI-related myocarditis, respectively; however, 46(45.5%), 8(7.9%), 47(46.5%) were at low risk, medium risk, and high risk actually. Kaplan-Meier survival analysis showed that the cumulative incidence of ICI-related myocarditis in the high-risk group was significantly higher than that in the medium- and low-risk groups (P<0.05). In the multivariable-adjusted Cox proportional hazards model, the ICI-related myocarditis risk in high-risk group was about 4 times that in the low-risk group. ROC curve analysis demonstrated that the average area under the curve (AUC) for predicting ICI-related myocarditis was 0.81, with an accuracy of 0.74. The Cohen’s Kappa coefficient was 0.55, indicating moderate agreement. In the actual high-risk group, no patient was predicted to be at low risk; in the actual low-risk group, 16 patients were predicted to be at high risk. Conclusions This risk assessment scale for ICI-associated myocarditis shows high predictive performance. It provides oncologists with a simple yet effective multidisciplinary diagnostic reference tool, potentially enhancing early identification of ICI-associated myocarditis.
5.Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography: A single-blind, multicenter, randomized controlled trial
Wenbo MENG ; W. Joseph LEUNG ; Zhenyu WANG ; Qiyong LI ; Leida ZHANG ; Kai ZHANG ; Xuefeng WANG ; Meng WANG ; Qi WANG ; Yingmei SHAO ; Jijun ZHANG ; Ping YUE ; Lei ZHANG ; Kexiang ZHU ; Xiaoliang ZHU ; Hui ZHANG ; Senlin HOU ; Kailin CAI ; Hao SUN ; Ping XUE ; Wei LIU ; Haiping WANG ; Li ZHANG ; Songming DING ; Zhiqing YANG ; Ming ZHANG ; Hao WENG ; Qingyuan WU ; Bendong CHEN ; Tiemin JIANG ; Yingkai WANG ; Lichao ZHANG ; Ke WU ; Xue YANG ; Zilong WEN ; Chun LIU ; Long MIAO ; Zhengfeng WANG ; Jiajia LI ; Xiaowen YAN ; Fangzhao WANG ; Lingen ZHANG ; Mingzhen BAI ; Ningning MI ; Xianzhuo ZHANG ; Wence ZHOU ; Jinqiu YUAN ; Azumi SUZUKI ; Kiyohito TANAKA ; Jiankang LIU ; Ula NUR ; Elisabete WEIDERPASS ; Xun LI
Chinese Medical Journal 2024;137(12):1437-1446
Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.
6.Role of BRAF gene mutation detection in thyroid nodules in guiding total thyroid cancer surgery
Jie LIU ; Wenqing CAI ; Dongxu YUAN ; Xiaoli LIU
International Journal of Surgery 2024;51(5):349-354
Thyroid carcinoma is a common malignant tumor of the endocrine system and its incidence has increased significantly in recent years. Surgery is the most important initial treatment for thyroid cancer, but total thyroidectomy increases the risk of postoperative hyponatremia and recurrent laryngeal nerve injury while prolonging the disease-free survival of patients, decreasing the risk of disease recurrence and reducing residual lesions. Therefore, how to make the best surgical decision based on preoperative findings is still controversial. V-raf murine sarcoma viral oncogene homolog B1 ( BRAF), as one of the common genetic mutations in thyroid malignant tumors, is closely related to the degree of malignancy and prognosis of the tumor. Preoperative BRAF gene testing can help determine the aggressive pathological features of thyroid tumors and provide scientific guidance for clinicians to decide the scope of surgical resection.This article reviews the guiding role of BRAF gene mutation detection results in total thyroid cancer resection.
7.Summary of the best evidence for early postoperative ambulation in patients with total knee arthroplasty
Libai CAI ; Yanjin LIU ; Muhua SHI ; Yuan XU ; Song ZHOU ; Huijing LI ; Miaoran CUI ; Mengfei YANG
Chinese Journal of Modern Nursing 2024;30(29):3951-3959
Objective:To comprehensively search, evaluate and summarize the relevant evidence of early ambulation in patients with total knee arthroplasty (TKA), so as to provide evidence-based basis for the nursing practice of early ambulation in patients with TKA.Methods:Clinical decisions, best practice manuals, guidelines, systematic reviews, expert consensus and evidence summaries for early postoperative ambulation of TKA patients were searched by computer on PubMed, Web of Science, BMJ Best Practice, Cochrane Library, UpToDate, OVID, CINAHL, Embase, Joanna Briggs Institute (JBI) Centre for Evidence-based Health Care, Physiotherapy Evidence Database, China National Knowledge Infrastructure, WanFang Data, VIP, China Biology Medicine disc, Guidelines International Network, National Guideline Clearinghouse, National Institute for Health and Care Excellence, Canadian Medical Association Clinical Practice Guideline, Scottish Intercollegiate Guidelines Network, American Academy of Orthopaedic Surgeons and American Association of Hip and Knee Surgeons. The retrieval time was from the establishment of the databases to March 31, 2023. Four nursing graduate students trained in evidence-based nursing systems independently evaluated the quality of the included literature and divided the evidence levels according to the JBI Evidence Pre Grading System (2014 edition) .Results:A total of 15 articles were included, including four clinical decision papers, three guidelines, six expert consensus papers, one evidence summary and one systematic review. According to the judgment of professionals, 23 pieces of best evidence were formed from seven aspects, including the director of ambulation, evaluation before ambulation, ambulation planning, ambulation timing, ambulation content, ambulation evaluation and health education.Conclusions:The best evidence of early postoperative ambulation of patients with TKA summarized in this study is scientific and practical, which can provide evidence-based basis for clinical nursing work.
8.Expert consensus on limb management of patients with transvenous temporary cardiac pacing
Radioactive Interventional Nursing Professional Committee of Chinese Nursing Association ; Huafen LIU ; Jiali ZHOU ; Zheng HUANG ; Zhixia ZHANG ; Jingyu LIANG ; Zhongxiang CAI ; Fuhong CHEN ; Yunying ZHOU ; Yunyan XIANYU ; Lin YAN ; Huidan YU ; Huizhen PENG ; Jian ZHU ; Yuan TIAN ; Yan ZHANG ; Hejun JIANG ; Su ZHANG
Chinese Journal of Nursing 2024;59(13):1581-1583
Objective To form the expert consensus on the limb management of patients with transvenous temporary cardiac pacing,standardize the limb management of patients with transvenous temporary cardiac pacing,and reduce complications related to the limb.Methods Using evidence-based methods,the evidence in this field was searched,evaluated and summarized,and relevant recommendations and research conclusions were extracted and classified by the level of evidence quality,and then the first draft of the consensus was formed.From December 2023 to January 2024,through 2 rounds of expert consultation and 4 rounds of expert meetings,the content was adjusted and the consensus was reached.Results Totally 16 experts participated in the consultation.The positive coefficient is 100%;the authoritative coefficient is 0.847 and 0.836;the average value of each index is more than>3.8;the coefficient of variation is less than 0.21.The Kendall's harmony coefficient of the 2 rounds of expert consultation is 0.372 and 0.314,respectively,which were statistically significant.The consensus covers the preoperative,intraoperative and postoperative on limb management of patients with transvenous temporary cardiac pacing.Totally 11 themes were involved,including the preoperative preparation,position and catheter fixation in operation,position and catheter fixation in postoperative,activity,turn and transfer,duty shift on limb,nursing care after withdrawal of the catheter,prevention of deep vein thrombosis of the operative limb and prevent infection.Conclusion The consensus is highly scientific,and it is helpful to standardize the limb management of patients with transvenous temporary cardiac pacing.
9.Action mechanism of Huotu Jiji Pellets in the treatment of erectile dysfunction:An exploration based on network pharmacology and molecular docking
Xue-Qin CHEN ; Xuan ZHOU ; Hong-Ping SHEN ; Jia-Yi SONG ; Yun-Jie CHEN ; Yuan-Bin ZHANG ; Yi-Li CAI ; Yi YU ; Ya-Hua LIU
National Journal of Andrology 2024;30(3):241-248
Objective:To explore the potential action mechanism of Huotu Jiji Pellets(HJP)in the treatment of erectile dys-function(ED)based on network pharmacology and molecular docking.Methods:We identified the main effective compounds and active molecular targets of HJP from the database of Traditional Chinese Medicine Systems Pharmacology(TCMSP)and Integrative Pharmacology-Based Research Platform of Traditional Chinese Medicine(TCMIP)and the therapeutic target genes of ED from the data-bases of Genecards.Then we obtained the common targets of HJP and ED using the Venny software,constructed a protein-protein in-teraction(PPI)network of HJP acting on ED,and screened out the core targets with the Cytoscape software.Lastly we performed GO functional enrichment and KEGG pathway enrichment analyses of the core targets followed by molecular docking of HJP and the core targets using Chem3D and AutoDock Tools and QuickVina-W software.Results:A total of 64 effective compounds,822 drug-related targets,1 783 disease-related targets and 320 common targets were obtained in this study.PPI network analysis showed that the core targets of HJP for ED included ESR1,HSP90AA1,SRC,and STAT3.GO functional enrichment analysis indicated the involvement of the core targets in such biological processes as response to xenobiotic stimulus,positive regulation of kinase activity,and positive regu-lation of MAPK cascade.KEGG pathway enrichment analysis suggested that PI3K-Akt,apoptosis,MAPK,HIF-1,VEGF,autophagy and other signaling pathways may be related to the mechanism of HJP acting on ED.Molecular docking prediction exhibited a good doc-king activity of the key active molecules of HJP with the core targets.Conclusion:This study showed that HJP acted on ED through multi-components,multi-targets and multi-pathways,which has provided some evidence and reference for the clinical treatment and subsequent studies of the disease.
10.Safety of endoscopic ultrasound-guided fine-needle aspiration for pancreatic lesions
Ke CHEN ; Jidong CAI ; Yuan LIU ; Ziting JIANG ; Xiujiang YANG ; Jianqiang LIU
Chinese Journal of Digestive Endoscopy 2024;41(6):459-464
Objective:To investigate the safety and risk factors of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic lesions.Methods:Five thousand one hundred and sixty patients who underwent EUS-FNA in the Department of Endoscopy, Fudan University Shanghai Cancer Center from January 2012 to December 2022 were retrospectively reviewed. The incidence of adverse events was calculated, and independent risk factors were analyzed by univariate and logistic regression.Results:The incidences of postoperative pancreatitis, intraoperative bleeding and postoperative bleeding were 1.38% (68/4 930), 0.82% (42/5 143) and 0.78% (40/5 143) respectively. No perforation or death occurred. Age >60 years ( OR=0.581, 95% CI: 0.356-0.946, P=0.029), tumor located in the neck, body and tail ( OR=0.355, 95% CI: 0.194-0.652, P=0.001), lesion diameter of >20-40 mm ( OR=0.450, 95% CI: 0.227-0.893, P=0.023), and lesion diameter >40 mm ( OR=0.382, 95% CI: 0.168-0.869, P=0.022) were independent protective factors for postoperative pancreatitis. Transduodenal puncture ( OR=2.435, 95% CI: 1.319-4.496, P=0.005) was an independent risk factor for postoperative pancreatitis. Puncture for 3-4 pass ( OR=0.439,95% CI: 0.235-0.821, P=0.010), lesion diameter of >20-40 mm ( OR=0.154, 95% CI: 0.069-0.341, P<0.001), and lesion diameter >40 mm ( OR=0.326, 95% CI: 0.143-0.743, P=0.008) were independent protective factors for intraoperative bleeding. Fine-needle biopsy (FNB) needle ( OR=2.314, 95% CI: 1.189-4.502, P=0.014) was an independent risk factor for postoperative bleeding. Conclusion:EUS-FNA is a safe procedure with low incidence of adverse events. The occurrence of postoperative pancreatitis and intraoperative bleeding is mainly related to clinical characteristics of the lesion, while postoperative bleeding is related to the type of puncture needle.

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