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Honokiol Prevents Intestinal Barrier Dysfunction in Mice with Severe Acute Pancreatitis and Inhibits JAK/STAT1 Pathway and Acetylation of HMGB1

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Chinese Journal of Integrative Medicine 2024年第6期30卷 534-542页

作者： LI Jie CHEN Ya-feng GAO Lei LI Yi-jie FENG Dian-xu department of General surgery Putuo HospitalShanghai University of Traditional Chinese MedicineShanghai200062China

Objective To investigate the effect of honokiol(HON)and the role of high-mobility group protein B1(HMGB1)on the pathogenesis of severe acute pancreatitis(SAP).Methods Thirty mice were numbered according to weight,and randomly divided into 5 groups using a random number table,including control,SAP,SAP and normal saline(SAP+NS),SAP and ethyl pyruvate(SAP+EP),or SAP+HON groups,6 mice in each group.Samples of pancreas,intestine,and blood were collected 12 h after SAP model induction for examination of pathologic changes,immune function alterations by enzyme linked immunosorbent assay(ELISA),and Western blot.In vitro experiments,macrophages were divided into 5 groups,the control,lipopolysaccharide(LPS),LPS+DMSO(DMSO),LPS+anti-HMGB1 monoclonal antibody(mAb),and LPS+HON groups.The tight connection level was determined by transmission electron microscopy and fluorescein isothiocyanate-labeled.The location and acetylation of HMGB1 were measured by Western blot.Finally,pyridone 6 and silencing signal transducer and activator of the transcription 1(siSTAT1)combined with honokiol were added to determine whether the Janus kinase(JAK)/STAT1 participated in the regulation of honokiol on HMGB1.The protein expression levels of HMGB1,JAK,and STAT1 were detected using Western blot.Results Mice with SAP had inflammatory injury in the pancreas,bleeding of intestinal tissues,and cells with disrupted histology.Mice in the SAP+HON group had significantly fewer pathological changes.Mice with SAP also had significant increases in the serum levels of amylase,lipase,HMGB1,tumor necrosis factor-α,interleukin-6,diamine oxidase,endotoxin-1,and procalcitonin.Mice in the SAP+HON group did not show these abnormalities(P<0.01).Studies of Caco-2 cells indicated that LPS increased the levels of occludin and claudin-1 as well as tight junction permeability,decreased the levels of junctional adhesion molecule C,and elevated intercellular permeability(P<0.01).HON treatment blocked these effects.Studies of macrophages indicated that LPS led to low nucle

关键词： severe acute pancreatitis intestinal barrier dysfunction honokiol high-mobility group protein B1 Januskinase signal transducerand activatorof transcription1

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Promotion effect of FOXCUT as a microRNA sponge for miR-24-3p on progression in triple-negative breast cancer through the p38 MAPK signaling pathway

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Chinese Medical Journal 2024年第1期137卷 105-114页

作者： Xiafei Yu Fangze Qian Xiaoqiang Zhang Yanhui Zhu Gao He Junzhe Yang Xian Wu Yi Zhou Li Shen Xiaoyue Shi Hongfei Zhang Xiao’an Liu department of Breast surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China

Background:Triple-negative breast cancer(TNBC)is a type of highly invasive breast cancer with a poor prognosis.According to new research,long noncoding RNAs(lncRNAs)play a significant role in the progression of cancer.Although the role of lncRNAs in breast cancer has been well reported,few studies have focused on TNBC.This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript(FOXCUT)in triple-negative breast cancer.Methods:Based on a bioinformatic analysis of the cancer genome atlas(TCGA)database,we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues,which was further validated in an external cohort of tissues from the General surgery department of the First Affiliated Hospital of Nanjing Medical University.The functions of FOXCUT in proliferation,migration,and invasion were detected in vitro or in vivo.Luciferase assays and RNA immunoprecipitation(RIP)were performed to reveal that FOXCUT acted as a competitive endogenous RNA(ceRNA)for the microRNA miR-24-3p and consequently inhibited the degradation of p38.Results:lncRNA FOXCUT was markedly highly expressed in breast cancer,which was associated with poor prognosis in some cases.Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo.Mechanistically,FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38,which might act as an oncogene in breast cancer.Conclusion:Collectively,this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.

关键词： Triple negative breast neoplasms RNA,long noncoding FOXCUT miR-24-3p p38 MAPK signaling pathway Disease progression

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Safflower Yellow Inhibits Progression of Hepatocellular Carcinoma by Modulating Immunological Tolerance via FAK Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 339-347页

作者： JI Hua-feng YANG Zi-qiang HAN Jun-jun LI He-fang JIN Zhao-qing CHEN Wei-qing CHEN Fei-hua GONG Mou-chun department of General surgery First People's Hospital of Hangzhou Lin'an DistrictHangzhou(311300)China

Objective To explore the anti-tumor effect of safflower yellow(SY)against hepatocellular carcinoma(HCC)and the underlying potential mechanism.Methods An in vitro model was established by mixing Luc-Hepa1-6 cells and CD3^(+)CD8^(+)T cells,followed by adding programmed cell death protein 1(PD-1)antibody(Anti-mPD-1)with or without SY.The apoptosis was detected by flow cytometry and the level of inflammatory cytokines was determined by enzyme-linked immunosorbent assay.The protein levels of programmed cell death 1 ligand 1(PD-L1),chemokine ligand(CCL5),C-X-C motif chemokine ligand 10(CXCL10)were measured by Western blot.An in situ animal model was established in mice followed by treatment with anti-mPD-1 with or without SY.Bioluminescence imaging was monitored with an Aniview 100 imaging system.To establish the FAK-overexpressed Luc-Hepa1-6 cells,cells were transfected with adenovirus containing pcDNA3.1-FAK for 48 h.Results The fluorescence intensity,apoptotic rate,release of inflammatory cytokines,and CCL5/CXCL10 secretion were dramatically facilitated by anti-mPD-1(P<0.01),accompanied by an inactivation of PD-1/PD-L1 axis,which were extremely further enhanced by SY(P<0.05 or P<0.01).Increased fluorescence intensity,elevated percentage of CD3+CD8+T cells,facilitated release of inflammatory cytokines,inactivated PD-1/PD-L1 axis,and increased CCL5/CXCL10 secretion were observed in Anti-mPD-1 treated mice(P<0.01),which were markedly enhanced by SY(P<0.05 or P<0.01).Furthermore,the enhanced effects of SY on inhibiting tumor cell growth,facilitating apoptosis and inflammatory cytokine releasing,suppressing the PD-1/PD-L1 axis,and inducing the CCL5/CXCL10 secretion in Anti-mPD-1 treated mixture of Luc-Hepa1-6 cells and CD3+CD8+T cells were abolished by FAK overexpression(P<0.01).Conclusion SY inhibited the progression of HCC by mediating immunological tolerance through inhibiting FAK.

关键词： hepatocellular carcinoma safflower yellow Chinese medicine tumor microenvironment programmed cell death protein 1 focal adhesion kinase

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Utility of plasma D-dimer for diagnosis of venous thromboembolism after hepatectomy

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World Journal of Clinical Cases 2024年第2期12卷 276-284页

作者： Taiichiro Miyake Hiroaki Yanagimoto Daisuke Tsugawa Masayuki Akita Riki Asakura Keisuke Arai Toshihiko Yoshida Shinichi So Jun Ishida Takeshi Urade Yoshihide Nanno Kenji Fukushima Hidetoshi Gon Shohei Komatsu Sadaki Asari Hirochika Toyama Masahiro Kido Tetsuo Ajiki Takumi Fukumoto Division of Hepato-Biliary-Pancreatic surgery Department of SurgeryKobe University Graduate School of MedicineKobe 650-0017HyogoJapan

BACKGROUND Venous thromboembolism(VTE)is a potentially fatal complication of hepatectomy.The use of postoperative prophylactic anticoagulation in patients who have undergone hepatectomy is controversial because of the risk of postoperative bleeding.Therefore,we hypothesized that monitoring plasma D-dimer could be useful in the early diagnosis of VTE after hepatectomy.AIM To evaluate the utility of monitoring plasma D-dimer levels in the early diagnosis of VTE after hepatectomy.METHODS The medical records of patients who underwent hepatectomy at our institution between January 2017 and December 2020 were retrospectively analyzed.Patients were divided into two groups according to whether or not they developed VTE after hepatectomy,as diagnosed by contrast-enhanced computed tomography and/or ultrasonography of the lower extremities.Clinicopathological factors,including demographic data and perioperative D-dimer values,were compared between the two groups.Receiver operating characteristic curve analysis was performed to determine the D-dimer cutoff value.Univariate and multivariate analyses were performed using logistic regression analysis to identify significant predictors.RESULTS In total,234 patients who underwent hepatectomy were,of whom(5.6%)were diagnosed with VTE following hepatectomy.A comparison between the two groups showed significant differences in operative time(529 vs 403 min,P=0.0274)and blood loss(530 vs 138 mL,P=0.0067).The D-dimer levels on postoperative days(POD)1,3,5,7 were significantly higher in the VTE group than in the non-VTE group.In the multivariate analysis,intraoperative blood loss of>275 mL[odds ratio(OR)=5.32,95%confidence interval(CI):1.05-27.0,P=0.044]and plasma D-dimer levels on POD 5≥21μg/mL(OR=10.1,95%CI:2.04-50.1,P=0.0046)were independent risk factors for VTE after hepatectomy.CONCLUSION Monitoring of plasma D-dimer levels after hepatectomy is useful for early diagnosis of VTE and may avoid routine prophylactic anticoagulation in the postoperative period.

关键词： Hepatectomy Malignant tumor Postoperative complication D-dimer Early diagnosis Venous thromboembolism

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KLF4 Inhibits the Activation of Human Hepatic Stellate Cell In vitro

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Current Medical Science 2024年第3期44卷 512-518页

作者： Xing-yu YANG Zhe CHEN Jun TAN Yin-kai XUE Hai ZHENG department of Emergency surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China department of Thoracic surgery The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an710061China department of Thoracic surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China

Objective Hepatic stellate cells(HSCs)play a crucial role in liver fibrosis.Early-stage liver fibrosis is reversible and intimately associated with the state of HSCs.Kruppel-like factor 4(KLF4)plays a pivotal role in a wide array of physiological and pathological processes.This study aimed to investigate the effect of KLF4 on the proliferation,apoptosis and phenotype of quiescent HSCs Methods We designed a KLF4 lentiviral vector and a KLF4 siRNA lentiviral vector,to upregulate and silence KLF4 expression in human HSC LX-2 cells via transfection.Cell proliferation was assessed using the CCK-8 assay.Flow cytometry was used to detect the cell cycle distribution and apoptosis rate.Western blotting was used to determine the levels of some quiescence and activation markers of HSCs Results Overexpression of KLF4 significantly increased the levels of E-cadherin and ZO-1,which are quiescent HSC markers,while significantly decreased the levels of N-cadherin and a-SMA,known activated HSC markers.In contrast,cell proliferation and apoptosis rates were elevated in LX-2 cells in which KLF4 expression was silenced Conclusion KLF4 inhibits the proliferation and activation of human LX-2 HSCs.It might be a key regulatory protein in the maintenance of HSC quiescence and may serve as a target for the inhibition of hepatic fibrosis.

关键词： Kruppel-like factor 4 hepatic stellate cells LX-2 cells liver fibrosis

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Immunotherapy for esophageal cancer:Where are we now and where can we go

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World Journal of Gastroenterology 2024年第19期30卷 2496-2501页

作者： Yoshiaki Shoji Kazuo Koyanagi Kohei Kanamori Kohei Tajima Mika Ogimi Yamato Ninomiya Miho Yamamoto Akihito Kazuno Kazuhito Nabeshima Takayuki Nishi Masaki Mori department of Gastroenterological surgery Tokai University School of MedicineKanagawa 259-1193Japan

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.

关键词： Esophageal cancer Immunotherapy Immune checkpoint inhibitor Programmed cell death-1 Anti-cytotoxic T-lymphocyte-associated protein 4 Neoadjuvant therapy Adjuvant therapy Clinical trials Combination therapy

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Efficacy of ginseng-based Renshenguben oral solution for cancer-related fatigue among patients with advanced-stage hepatocellular carcinoma:A prospective multicenter cohort study

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 249-256页

作者： Ming-Da Wang Chen Yuan Ke-Chun Wang Nan-Ya Wang Ying-Jian Liang Hong Zhu Xiang-Min Tong Tian Yang department of Hepatobiliary and Pancreatic surgery General Surgery CenterFirst Hospital of Jilin UniversityChangchun 130021China department of Hepatobiliary surgery Eastern Hepatobiliary Surgery HospitalSecond Military Medical University(Naval Medical University)Shanghai 200438China department of Clinical Laboratory Laboratory Medicine CenterZhejiang Provincial People’s HospitalHangzhou Medical CollegeHangzhou 310000China department of Hepatobiliary surgery First Affiliated Hospital of Harbin Medical UniversityHarbin 150007China department of Medical Oncology First Affiliated Hospital of Soochow UniversitySuzhou 215006China fdepartment of Central Laboratory Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhou 310006China

Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor therapy.This study aimed to evaluate the efficacy and safety of Renshenguben(RSGB)oral solution,a ginseng-based traditional Chinese medicine,in alleviating CRF in patients with advanced hepatocellular carcinoma(HCC)receiving antitumor treatment.Methods:In this prospective,open-label,controlled,multicenter study,patients with advanced HCC at BCLC stage C and a brief fatigue inventory(BFI)score of≥4 were enrolled.Participants were assigned to the RSGB group(RSGB,10 mL twice daily)or the control group(with supportive care).Primary and secondary endpoints were the change in multidimensional fatigue inventory(MFI)score,and BFI and functional assessment of cancer therapy-hepatobiliary(FACT-Hep)scores at weeks 4 and 8 after enrollment.Adverse events(AEs)and toxicities were assessed.Results:A total of 409 participants were enrolled,with 206 assigned to the RSGB group.At week 4,there was a trend towards improvement,but the differences were not statistically significant.At week 8,the RSGB group exhibited a significantly lower MFI score(Pving various antitumor treatments showed similar results.Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI,BFI,and FACT-Hep scores at week 8.No serious drug-related AEs or toxicities were observed.Conclusions:RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period,with no discernible toxicities.These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.

关键词： Cancer-related fatigue Hepatocellular carcinoma Renshenguben oral solution Efficacy Safety Ginseng

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Hematochezia due to rectal invasion by an internal iliac artery aneurysm: A case report

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World Journal of Clinical Cases 2024年第11期12卷 1980-1989页

作者： Fang Li Bin Zhao Yong-Qiang Liu Guo-Qing Chen Rong-Feng Qu Chao Xu Zhui Long Jin-Song Wu Mao Xiong Wei-Hang Liu Li Zhu Xiao-Ling Feng Lei Zhang department of General surgery Chongqing General HospitalChongqing 401147China

BACKGROUND This case report presents the rare occurrence of hematochezia due to an internal iliac artery aneurysm leading to an arterioenteric fistula,expanding the differential diagnosis for gastrointestinal bleeding.It emphasizes the importance of considering vascular origins in cases of atypical hematochezia,particularly in the absence of common gastrointestinal causes,and highlights the role of imaging and multidisciplinary management in diagnosing and treating such unusual presentations.CASE SUMMARY A 75-year-old man with a history of hypertension presented with 12 d of hematochezia,experiencing bloody stools 7-8 times per day.Initial computed tomography(CT)scans revealed an aneurysmal rupture near the right internal iliac artery with suspected hematoma development.Hemoglobin levels progressively decreased to 7 g/dL.Emergency arterial angiography and iliac arterycovered stent placement were performed,followed by balloon angioplasty.Despite initial stabilization,minor rectal bleeding and abdominal pain persisted,leading to further diagnostic colonoscopy.This identified a neoplasm and potential perforation at the proximal rectum.An exploratory laparotomy confirmed the presence of a hematoma and an aneurysm invading the rectal wall,necessitating partial rectal resection,intestinal anastomosis,and ileostomy.Postoperative recovery was successful,with no further bleeding incidents and normal follow-up CT and colonoscopy results after six months.CONCLUSION In cases of unusual gastrointestinal bleeding,it is necessary to consider vascular causes for effective diagnosis and intervention.

关键词： Iliac artery aneurysm Hematoma Rectum Hematochezia Case report

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MicroRNA-329-3p inhibits the Wnt/β-catenin pathway and proliferation of osteosarcoma cells by targeting transcription factor 7-like 1

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Oncology Research 2024年第3期32卷 463-476页

作者： Hur SUN MASANORI KAWANO TATSUYA IWASAKI ICHRO ITONAGA YUTA KUBOTA HROSHI TSUMURA KAZUHRO TANAKA department of Orthopaedic surgery Faculty of MedicineOita UniversityOita879-5503Japan

An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(TCF/LEF)transcription factor family,interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding protein.This study sought to elucidate the impact of the interaction between miR 3293p and TCF7L1 on.the growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of approaches.MiR329-3p was significantly downregulated,while TCF7L1 was considerably up-regulated in all examined OS cell lines.Additionally,a clinical comparison study was performed using the TCGA database.Subsequently,the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo experiments.When miR 329-3p was transfected into the OS cell line,the expression of TCF7L1 decreased,the proliferation of OS cells was inhibited,the cytoskeleton disintegrated,and the nucleus condensed to fom apoptotic bodies.The expression of proteins that indicate apoptosis increased simultaneously.The cell cycle was arrested in the G0/G1 phase,and the G1/S transition was blocked.The introduction of miR 3293p also inhibited downstream Cyclin D1 of the Wnt pathway.Xenograf experiments indicated that the overexpression of miR-329-3p signi ficanly inhibited the growth of OS xenografts in nude mice,and the expression of TCF7L1 and C-Myc in tumor tssues decreased.MiR 329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in vivo.Osteosarcoma cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7LI by miR 3293p.Summarizing these results,it can be inferred that miR.3293p exerts anticancer efects in osteosarcoma by inhibiting TCF7L1.

关键词： MiR-329-3p TCF7L1 Wnt/β-catenin pathway Osteosarcoma Proliferation

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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 pancreas.These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010.In 2018,Japanese and Korean pathologists reached a consensus,classifying IPNBs into type l and type 2 IPNBs.IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis.From 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 IPNBs.The 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 mucin.Due 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 features.Surgical 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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