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HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway

Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 344-352页

作者： Qing-Zhi Hu Zhen-Rui Cao Wei-Xiong Zheng Min-Jie Zhao Jun-Hua Gong Cong Chen Zhong-Jun Wu Rui Tao department of Hepatobiliary surgery Bishan Hospital of Chongqing Medical UniversityChongqing 402760China department of Cardiothoracic surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China c department of Hepatobiliary surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Hepatobiliary surgery the Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune *** shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein ***:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using ***-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following *** blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular ***:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer *** HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.

关键词： Ischemia-reperfusion injury Liver transplantation Inflammation HSP110 Heat shock proteins NF-κB

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The role of intestinal flora on tumorigenesis,progression,and the efficacy of PD-1/PD-L1 antibodies in colorectal cancer

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Cancer Biology & Medicine 2024年第1期21卷 65-82页

作者： Sen Wang Benling Xu Yangyang Zhang Guangyu Chen Peng Zhao Quanli Gao Long Yuan department of Gastrointestinal surgery Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450003China department of Immunotherapy Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450003China

Intestinal flora affects the maturation of the host immune system,serves as a biomarker and efficacy predictor in the immunotherapy of several cancers,and has an important role in the development of colorectal cancer(CRC).Anti-PD-1/PD-L1 antibodies have shown satisfactory results in MSI-H/d MMR CRC but performed poorly in patients with MSS/p MMR *** recent years an increasing number of studies have shown that intestinal flora has an important impact on anti-PD-1/PD-L1 antibody efficacy in CRC *** and clinical evidence have suggested that anti-PD-1/PD-L1 antibody efficacy can be improved by altering the composition of the intestinal flora in ***,we summarize the studies related to the influence of intestinal flora on anti-PD-1/PD-L1 antibody efficacy in CRC and discuss the potential underlying mechanism(s).We have focused on the impact of the intestinal flora on the efficacy and safety of anti-PD-1/PD-L1 antibodies in CRC and how to better utilize the intestinal flora as an adjuvant to improve the efficacy of anti-PD-1/PD-L1 *** addition,we have provided a basis for the potential of the intestinal flora as a new treatment modality and indicator for determining patient prognosis.

关键词： Intestinal flora anti-PD-1/PD-L1 therapy colorectal cancer immune checkpoint inhibitor CD8~+T cell

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Multi-cohort comprehensive analysis unveiling the clinical value and therapeutic effect of GNAL in glioma

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Oncology Research 2024年第5期32卷 965-981页

作者： ZHEN LIU LIANGWANG YANG ZHENGXING XIE HUI YU TIANYI GU DAOMING SHI NING CAI SHENGHUA ZHUO department of Neurosurgery Affiliated Hospital of Jiangsu UniversityZhenjiang212000China department of Neurosurgery First Affiliated Hospital of Hainan Medical UniversityHaikou570100China department of Cardiothoracic surgery Affiliated Hospital of Jiangsu UniversityZhenjiang212000China department of General surgery Affiliated Hospital of Jiangsu UniversityZhenjiang212000China

Clinical data indicates that glioma patients have poor treatment outcomes and clinical *** role of olfactory signaling pathway-related genes(OSPRGs)in glioma has not been fully *** this study,we aimed to investigate the role and relationship between OSPRGs and *** and multivariate Cox regression analyses were performed to assess the relationship between OSPRGs and the overall survival of glioma based on public cohorts,and the target gene(G Protein Subunit Alpha L,GNAL)was *** association of GNAL expression with clinicopathological characteristics,gene mutation landscape,tumor immune microenvironment(TIME),deoxyribonucleic acid(DNA)methylation,and naris-occlusion controlled genes(NOCGs)was *** was used to evaluate GNAL level in *** analysis was conducted to evaluate the drug sensitivity,immunotherapy response,and functional enrichment of *** was an independent prognostic factor,and patients with low GNAL expression have a poor *** of GNAL was closely associated with clinicopathological characteristics,DNA methylation,and several immune-related *** infiltration analysis indicated that GNAL levels were negatively correlated with immune *** low-expression group showed efficacy with anti-PD-1 *** compounds with significantly different half-maximal inhibitory concentration(IC50)values between the GNAL high and low-expression groups were ***,its expression was associated with several immune cells,immune-related genes,and *** expression of GNAL is closely associated with clinicopathological characteristics,TIME,and the response to therapeutic interventions,highlighting its potential as a prognostic biomarker for glioma.

关键词： Glioma Olfaction GNAL Tumor immune microenvironment Immunotherapy/chemotherapy response

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Efficacy and safety of low-dose cyclophosphamide combined with lenvatinib, pembrolizumab and TACE for unresectable hepatocellular carcinoma:A single-center, prospective,single-arm clinical trial

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Chinese Journal of Cancer Research 2024年第2期36卷 114-123页

作者： Yupeng Ren Yuxuan Li Mingbo Cao Yongchang Tang Feng Yuan Gaoyuan Yang Zhiwei He Zheng Shi Xiaorui Su Zhicheng Yao Meihai Deng department of Hepatobiliary surgery the Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China department of General surgery Qilu HospitalShandong UniversityJinan 250012China department of Hepatobiliary surgery the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China department of Hepatobiliary and Pancreatic surgery the Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China

Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of ***: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) *** OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher ***: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.

关键词： Hepatocellular carcinoma lenvatinib low-dose cyclophosphamide pembrolizumab transarterial chemoembolization

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ABHD17C represses apoptosis and pyroptosis in hepatocellular carcinoma cells

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BIOCELL 2024年第9期48卷 1299-1310页

作者： LINPEI WANG JIAWEI WANG CHUNFENG SHI WEI WANG JIAN WU Division of Hepatobiliary and Pancreatic surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou310030China department of Hepatobiliary and Pancreatic surgery The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou362000China

Background:Alpha/beta hydrolase domain-containing protein 17C(ABHD17C)is a depalmitoylation enzyme that removes the S-palmitoylation of targeted *** hepatocellular carcinoma(HCC)cells SNU449 and Hep3B use ABHD17C as an oncogene;however,the exact mechanism of this action is yet ***:The expression of ABHD17C in liver cancer tissues was analyzed by bioinformatics,and the expression of ABHD17C in clinical liver cancer tissues and adjacent normal tissues was ***,the proliferative viability of HCC cells after overexpression or knockdown of ABHD17C was examined,and pyroptosis and apoptosis proteins were ***:ABHD17C was overexpressed in human HCC tissues as well as numerous HCC cell *** of ABHD17C caused reduced viability,cell cycle arrest,and defective invasion and migration in HCC cells,while overexpression of ABHD17C exhibited the opposite ***,we discovered that the knockdown of ABHD17C resulted in enhanced apoptotic and pyroptotic phenotypes of HCC cells,whereas overexpression of ABHD17C attenuated such ***:It suggests that ABHD17C contributes to HCC carcinogenesis,making it a promising target for medication treatment.

关键词： ABHD17C Hepatocellular carcinoma Apoptosis Pyroptosis

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Pylorus-preserving gastrectomy for early gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 653-658页

作者： Ke-Kang Sun Yong-You Wu department of Gastrointestinal surgery The Affiliated Kunshan Hospital to Jiangsu UniversitySuzhou 215300Jiangsu ProvinceChina department of Gastrointestinal surgery The Second Affiliated Hospital of Soochow UniversitySuzhou 215008Jiangsu ProvinceChina

Pylorus-preserving gastrectomy(PPG)has been widely accepted as a function-preserving gastrectomy for middle-third early gastric cancer(EGC)with a distal tumor border at least 4 cm proximal to the *** procedure essentially preserves the function of the pyloric sphincter,which requires to preserve the upper third of the stomach and a pyloric cuff at least 2.5 *** suprapyloric and infrapyloric vessels are usually preserved,as are the hepatic and pyloric branches of the vagus *** with distal gastrectomy,PPG has significant advantages in preventing dumping syndrome,body weight loss and bile reflux *** postoperative complications after PPG have reached an acceptable *** can be considered a safe,effective,and superior choice in EGC,and is expected to be extensively performed in the future.

关键词： Gastric cancer Pylorus-preserving gastrectomy Oncological safety Gastric stasis

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Anti-vascular endothelial growth factor drugs combined with laser photocoagulation maintain retinal ganglion cell integrity in patients with diabetic macular edema: study protocol for a prospective, non-randomized, controlled clinical trial

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Neural Regeneration Research 2024年第4期19卷 923-928页

作者： Xiangjun Li Chunyan Li Hai Huang Dan Bai Jingyi Wang Anqi Chen Yu Gong Ying Leng department of Ophthalmology Affiliated Hospital of Beihua University department of Endocrinology Affiliated Hospital of Beihua University

The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting *** major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser ***,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many *** might result from the incomplete recovery of retinal ganglion cell ***,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision *** this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their *** patients will be followed up for 12 *** primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after *** secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after *** measure is the incidence of adverse events at 1,3,6,9,and 12 months after *** study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up *** trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal

关键词： choroidal thickness diabetic macular edema laser photocoagulation retinal ganglion cell-inner plexiform layer thickness retinal ganglion cells retinal nerve fiber layer thickness thickness of the macular area vascular endothelial growth factor visual acuity

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NIR-triggered on-site NO/ROS/RNS nanoreactor:Cascade-amplified photodynamic/photothermal therapy with local and systemic immune responses activation

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Opto-Electronic Advances 2024年第6期7卷 58-73页

作者： Ziqing Xu Yakun Kang Jie Zhang Jiajia Tang Hanyao Sun Yang Li Doudou He Xuan Sha Yuxia Tang Ziyi Fu Feiyun Wu Shouju Wang Laboratory of Molecular Imaging Department of RadiologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China department of Breast surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China department of Women&Children Research Center The First Affiliated HospitalNanjing Medical UniversityNanjing 210029China

Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune *** these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS *** not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor *** in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/*** such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.

关键词： photothermal therapy photodynamic therapy nitric oxide reactive nitrogen species triple-negative breast cancer immune response nanoreactor

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A prognosis model for predicting immunotherapy response of esophageal cancer based on oxidative stress-related signatures

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Oncology Research 2024年第1期32卷 199-212页

作者： JING GUO CHANGYONG TONG JIANGUANG SHI XINJIAN LI XUEQIN CHEN department of Thoracic surgery The First Affiliated Hospital of Ningbo UniversityNingboChina department of Chinese Traditional Medicine The First Affiliated Hospital of Ningbo UniversityNingboChina

Oxidative stress(OS)is intimately associated with tumorigenesis and has been considered a potential therapeutic ***,the OS-associated therapeutic target for esophageal squamous cell carcinoma(ESCC)remains *** our study,gene expression data of ESCC and clinical information from public databases were *** LASSO-Cox regression analysis,a risk score(RS)signature map of prognosis was constructed and performed external verification with the GSE53625 *** ESTIMATE,xCell,CIBERSORT,TIMER,and ImmuCellAI algorithms were employed to analyze infiltrating immune cells and generate an immune microenvironment(IM).Afterward,functional enrichment analysis clarified the underlying mechanism of the *** was utilized for forecasting the survival rate of individual ESCC *** a result,we successfully constructed an OS-related genes(OSRGs)model and found that the survival rate of high-risk groups was lower than that of low-risk *** AUC of the ROC verified the strong prediction performance of the signal in these two cohorts *** to independent prognostic analysis,the RS was identified as an independent risk factor for *** nomogram and follow-up data revealed that the RS possesses favorable predictive value for the prognosis of ESCC ***-PCR detection demonstrated increased expression of MPC1,COX6C,CYB5R3,CASP7,and CYCS in esophageal cancer *** conclusion,we have constructed an OSRGs model for ESCC to predict patients’prognosis,offering a novel insight into the potential application of the OSRGs model in ESCC.

关键词： Esophageal carcinoma OS Prognosis Risk markers Immune cell infiltration

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A Review of Type 1 and Type 2 Intraductal Papillary Neoplasms of the Bile Duct

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Current Medical Science 2024年第3期44卷 485-493页

作者： Xia-hui HUANG Tian-xiang CHEN Hong-liang LIU Ming-wen HUANG department of General surgery The Second Affiliated Hospital of Nanchang UniversityNanchang330006China

Intraductal papillary neoplasm of the bile duct(IPNB)is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the *** lesions have been recognized as one of the three major precancerous lesions in the biliary tract since *** 2018,Japanese and Korean pathologists reached a consensus,classifying IPNBs into type l and type 2 *** are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and *** a molecular genetic perspective,IPNBs exhibit early genetic variations,and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 *** histological subtypes of IPNBs include gastric,intestinal,pancreaticobiliary,or oncocytic subtypes,but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant *** to the rarity of these lesions and the absence of specific clinical and laboratory features,imaging is crucial for the preoperative diagnosis of IPNB,with local bile duct dilation and growth along the bile ducts being the main imaging *** resection remains the optimal treatment for IPNBs,but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

关键词： intraductal papillary neoplasm of the bile duct subclassification neoplasms precancerous tissue prognosis

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