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Expert consensus on the monitoring and treatment of sepsis-induced immunosuppression

Military Medical Research 2023年第3期10卷 281-298页

作者： Fei Pei Ren‑Qi Yao Chao Ren Soheyl Bahrami Timothy RBilliar Irshad HChaudry De‑Chang Chen Xu‑Lin Chen Na Cui Xiang‑Ming Fang Yan Kang Wei‑Qin Li Wen‑Xiong Li Hua‑Ping Liang Hong‑Yuan Lin Ke‑Xuan Liu Ben Lu Zhong‑Qiu Lu Marc Maegele Tian‑Qing Peng You Shang Lei Su Bing‑Wei Sun Chang‑Song Wang Jian Wang Jiang‑Huai Wang Ping Wang Jian‑Feng Xie Li‑Xin Xie Li‑Na Zhang Basilia Zingarelli Xiang‑Dong Guan Jian‑Feng Wu Yong‑Ming Yao department of Critical Care Medicine the First Affiliated Hospital of Sun Yat-Sen University58 Zhongshan Er RoadYuexiu DistrictGuangzhou 510080GuangdongChina Translational Medicine Research Center Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital28 Fuxing RoadHaidian DistrictBeijing 100853China department of Burn surgery the First Affiliated Hospital of Naval Medical UniversityShanghai 200433China Ludwig-Boltzmann Institute for Experimental and Clinical Traumatology 1200 ViennaAustria department of surgery University of Pittsburgh Medical CenterPittsburghPA 15213USA Center for Surgical Research and department of surgery University of Alabama at BirminghamBirminghamAL 35294USA department of Critical Care Medicine Ruijin HospitalShanghai Jiaotong UniversityShanghai 200025China department of Burns the First Affiliated Hospital of Anhui Medical UniversityHefei 230022China department of Critical Care Medicine Peking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China department of Anesthesiology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 31003China department of Critical Care Medicine West China Hospital of Sichuan UniversityChengdu 610041China department of Critical Care Medicine General Hospital of Eastern Theater Command of Chinese PLANanjing 210002China department of Surgical Intensive Critical Unit Beijing Chao‑Yang HospitalCapital Medical UniversityBeijing 100020China State Key Laboratory of Trauma Burns and Combined InjuryResearch Institute of SurgeryDaping HospitalArmy Medical UniversityChongqing 400042China department of Critical Care Medicine Fourth Medical Center of the Chinese PLA General HospitalBeijing 100048China department of Anesthesiology Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China department of Critical Care Medicine and Hematology the Third Xiangya HospitalCentral South UniversityChangs

Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis.To provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed.Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed,Web of Science,and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire.Then,the Delphi method was used to form consensus opinions,and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions.This consensus achieved satisfactory results through two rounds of questionnaire survey,with 2 statements rated as perfect consistency,13 as very good consistency,and 9 as good consistency.After summarizing the results,a total of 14 strong recommended opinions,8 weak recommended opinions and 2 non-recommended opinions were produced.Finally,a face-to-face discussion of the consensus opinions was performed through an online meeting,and all judges unanimously agreed on the content of this consensus.In summary,this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.

关键词： Sepsis Immune function monitoring Immunomodulatory therapy Immunosuppression

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Xiaotan Sanjie recipe,a compound Chinese herbal medicine,inhibits gastric cancer metastasis by regulating GnT-V-mediated E-cadherin glycosylation

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Journal of Integrative Medicine 2023年第6期21卷 561-574页

作者： Nian Huang Hai-wei He Yu-yu He Wei Gu Ming-juan Xu Long Liu department of Integrative Medicine Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200433China department of Obstetrics and Gynecology Changhai HospitalNaval Medical UniversityShanghai 200433China School of Traditional Chinese Medicine Naval Medical UniversityShanghai 200433China department of Traditional Chinese Medicine Tianyou HospitalTongji UniversityShanghai 200333China

Objective:Xiaotan Sanjie recipe(XTSJ),a Chinese herbal compound medicine,exerts a significant inhibitory effect on gastric cancer(GC)metastasis.This work investigated the mechanism underlying the XTSJmediated inhibition of GC metastasis.Methods:The effect of XTSJ on GC metastasis and the associated mechanism were investigated in vitro,using GC cell lines,and in vivo,using a GC mouse model,by focusing on the expression of Glc-N-Actransferase V(GnT-V;encoded by MGAT5).Results:The migration and invasion ability of GC cells decreased significantly after XTSJ administration,which confirmed the efficacy of XTSJ in treating GC in vitro.XTSJ increased the accumulation of Ecadherin at junctions between GC cells,which was reversed by MGAT5 overexpression.XTSJ administration and MGAT5 knockdown alleviated the structural abnormality of the cell–cell junctions,while MGAT5 overexpression had the opposite effect.MGAT5 knockdown and XTSJ treatment also significantly increased the accumulation of proteins associated with the E-cadherin-mediated adherens junction complex.Furthermore,the expression of MGAT5 was significantly lower in the lungs of BGC-823-MGAT5+XTSJ mice than in those of BGC-823-MGAT5+solvent mice,indicating that the ability of gastric tumors to metastasize to the lung was decreased in vivo following XTSJ treatment.Conclusion:XTSJ prevented GC metastasis by inhibiting the GnT-V-mediated E-cadherin glycosylation and promoting the E-cadherin accumulation at cell–cell junctions.

关键词： Xiaotan Sanjie Recipe Gastric cancer Traditional Chinese medicine E-cadherin Metastasis Glc-N-Ac-transferase V

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Disseminated peritoneal leiomyomatosis with malignant transformation involving right ureter:A case report

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World Journal of Clinical Cases 2022年第5期10卷 1639-1644页

作者： Chen-Yueh Wen Herng-Sheng Lee Jen-Tai Lin Chia-Cheng Yu Division of Urology Department of SurgeryKaohsiung Veterans General HospitalKaohsiung 81346Taiwan Lee Department of Pathology and Laboratory MedicineKaohsiung Veterans General HospitalKaohsiung 81346Taiwan School of Medicine National Yang-Ming UniversityTaipei 814Taiwan department of Pharmacy Tajen UniversityPingtung 900Taiwan

BACKGROUND Disseminated peritoneal leiomyomatosis(DPL)with myxoid leiomyosarcoma is a rare variant of leiomysosarcoma,and hematuria as a presenting symptom has never been reported.Through this case report,we emphasize the investigation of the etiology,clinical presentation,diagnosis,treatment,and prognosis of DPL with malignant changes mimicking metastatic urinary tract cancer and to help develop further clinical management.CASE SUMMARY We describe a case of DPL with malignant transformation involving the right ureter after laparoscopic hysterectomy.An exploratory laparotomy was performed and all visible nodules were surgically removed.DPL with focal malignant transformation to myxoid leiomyosarcoma was confirmed based on pathology results.CONCLUSION Professionals who preoperatively diagnose DPL with malignant change to myxoid leiomyosarcoma involving the genitourinary tract should consider symptoms of abdominal pain,hematuria,and imaging of disseminated pelvic tumors in women,especially those with prior history of laparoscopic hysterectomy.Early complete removal of all tumors is the cornerstone to prevent DPL from malignant changes.

关键词： Disseminated peritoneal leiomyomatosis Leiomyosarcoma Laparoscopic hysterectomy Hematuria Ureteroneocystostomy Case report

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Emerging immunological strategies: recent advances and future directions

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Frontiers of Medicine 2021年第6期15卷 805-828页

作者： Hongyun Zhao Fan Luo Jinhui Xue Su Li Rui-Hua Xu department of Medical Oncology State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhou510060China department of Clinical Research State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhou510060China department of Experimental Research State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhou510060China

mmunotherapy plays a compelling role in cancer treatment and has already made remarkable progress.However,many patients receiving immune checkpoint inhibitors fail to achieve clinical benefits,and the response rates vary among tumor types.New approaches that promote anti-tumor immunity have recently been developed,such as small molecules,bispecific antibodies,chimeric antigen receptor T cell products,and cancer vaccines.Small molecule drugs include agonists and inhibitors that can reach the intracellular or extracellular targets of immune cells participating in innate or adaptive immune pathways.Bispecific antibodies,which bind two different antigens or one antigen with two different epitopes,are of great interest.Chimeric antigen receptor T cell products and cancer vaccines have also been investigated.This review explores the recent progress and challenges of different forms of immunotherapy agents and provides an insight into future immunotherapeutic strategies.

关键词： cancer immunotherapy bispecific antibodies small molecules chimeric antigen receptor T therapy cancer vaccines

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Suppression of esophageal cancer cell growth using curcumin,(-)-epigallocatechin-3-gallate and lovastatin

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World Journal of Gastroenterology 2012年第2期18卷 126-135页

作者： Fei Ye Gui-Hong Zhang Bao-Xiang Guan Xiao-Chun Xu department of Clinical cancer Prevention The Universityof Texas MD Anderson Cancer Center Houston TX 77030United States department of Pathology Anhui Medical University Hefei 230032 Anhui ProvinceChina

AIM:To determine the effects of curcumin,(-)-epigallocatechin-3-gallate (EGCG),lovastatin,and their combinations on inhibition of esophageal cancer.METHODS:Esophageal cancer TE-8 and SKGT-4 cell lines were subjected to cell viability methyl thiazolyl tetrazolium and tumor cell invasion assays in vitro and tumor formation and growth in nude mouse xenografts with or without curcumin,EGCG and lovastatin treatment.Gene expression was detected using immunohistochemistry and Western blotting in tumor cell lines,tumor xenografts and human esophageal cancer tissues,respectively.RESULTS:These drugs individually or in combinations significantly reduced the viability and invasion capacity of esophageal cancer cells in vitro.Molecularly,these three agents reduced the expression of phosphorylated extracellular-signal-regulated kinases (Erk1/2),c-Jun and cyclooxygenase-2 (COX-2),but activated caspase 3 in esophageal cancer cells.The nude mouse xenograft assay showed that EGCG and the combinations of curcumin,EGCG and lovastatin suppressed esophageal cancer cell growth and reduced the expression of Ki67,phosphorylated Erk1/2 and COX-2.The expression of phosphorylated Erk1/2 and COX-2 in esophageal cancer tissue specimens was also analyzed using immunohistochemistry.The data demonstrated that 77 of 156 (49.4%) tumors expressed phosphorylated Erk1/2 and that 121 of 156 (77.6%) esophageal cancers expressed COX-2 protein.In particular,phosphorylated Erk1/2 was expressed in 23 of 50 (46%) cases of esophageal squamous cell carcinoma (SCC) and in 54 of 106 (50.9%) cases of adenocarcinoma,while COX-2 was expressed in 39 of 50 (78%) esophageal SCC and in 82 of 106 (77.4%) esophageal adenocarcinoma.CONCLUSION:The combinations of curcumin,EGCG and lovastatin were able to suppress esophageal cancer cell growth in vitro and in nude mouse xenografts,these drugs also inhibited phosphorylated Erk1/2,c-Jun and COX-2 expression.

关键词：食管癌细胞没食子酸酯洛伐他汀细胞生长姜黄素儿茶素 Western印迹细胞外信号调节激酶

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Downregulation of miR-193a-5p correlates with lymph node metastasis and poor prognosis in colorectal cancer

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World Journal of Gastroenterology 2014年第34期20卷 12241-12248页

作者： Peng Zhang Deng-Bo Ji Hai-Bo Han Yun-Fei Shi Chang-Zheng Du Jin Gu Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Colorectal SurgeryPeking University Cancer Hospital and Institute Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Cell BiologyPeking University Cancer Hospital and Institute Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of PathologyPeking University Cancer Hospital and Institute

AIM:To investigate the correlation of miR-193a-5p with lymph node metastasis and postoperative survival of colorectal cancer(CRC)patients.METHODS:A total of 304 formalin-fixed,paraffinembedded specimens(69 paired cancer and normal tissues,55 primary tumors of stageⅢCRC and matched lymph nodes,and 56 primary tumors of stageⅡCRC)were included in this study.The relative expression lev-els of miR-193a-5p in the normal mucosa,primary cancer,and metastatic lymph node lesions were measured by quantitative real-time reverse transcriptase polymerase chain reaction.We evaluated the association of its expression with colorectal cancer lymph node metastasis,clinicopathological factors,and patient survival.RESULTS:The relative expression level of miR-193a-5p was significantly lower in CRC tissues than in the normal mucosa(P=0.0060).The expression levels of miR-193a-5p were lower in primary CRC tissues with lymph node metastases than in those without metastases(P=0.0006),and decreased expression of miR-193a-5p correlated with advanced lymph node metastatic stage(P=0.0007).Kaplan-Meier analysis showed that patients with low miR-193a-5p expression had decreased disease-free survival(DFS)(P=0.0026)and poor overall survival(OS)(P=0.0003).Interestingly,for the group of patients with lymph node metastases,miR-193a-5p expression was also related to survival.Patients with low miR-193a-5p expression had decreased DFS(P=0.0262)and poor OS(P=0.0230).Moreover,multivariate analysis indicated that downregulation of miR-193a-5p was an independent predictor of poor OS.CONCLUSION:Downregulation of miR-193a-5p correlates with lymph node metastasis and poor survival of CRC.miR-193a-5p may be a useful biomarker for CRC diagnosis,metastasis and prognosis prediction.

关键词： miR-193a-5p colorectal cancer Lymph node metastasi

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A Single-institution Experience with Open Irreversible Electroporation for Locally Advanced Pancreatic Carcinoma

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Chinese Medical Journal 2016年第24期129卷 2920-2925页

作者： Li Yan Yong-Liang Chen Ming Su Tian Liu Kai Xu Feng Liang Wan-Qing Gu Shi-Chun Lu department of Hepatobiliary surgery Chinese PLA General Hospital Beijing 100853 China department of General surgery People's Hospital of Rizhao Rizhao Shandong 276800 China

Background： Locally advanced pancreatic carcinoma （LAPC） is characterized by poor prognosis despite recommended concurrent chemoradiotherapy. Irreversible electroporation （IRE） has emerged as a potential option for the management of unresectable pancreatic cancer. This study was conducted to evaluate the safety and short-term efficacy of open IRE for the treatment of LAPC. Methods： Retrospective data of 25 consecutive patients receiving IRE for T3 lesions from July 2015 to June 2016 at a single center were analyzed. The perioperative and long-term IRE-related complications were reviewed to evaluate the safety of the procedure. The tumor reduction and biological response were analyzed through computed tomography/magnetic resonance imaging; the serum level of CA19-9 was measured as a secondary endpoint to evaluate the short-term efficacy of IRE. Results： All patients were successfully treated; the median tumor size was 4.2 cm and the median IRE time was 36 min. Four intraoperative procedure-related complications were observed （16%）： two transient hypertensive episodes, one hypotension case, and one transient supraventricular tachycardia case. Nine postoperative complications were described, including three Grade A pancreatic fistulas, three delayed gastric emptying, one acute pancreatitis, one upper gastrointestinal hemorrhage, and one portal vein thrombosis. The overall rate of stable disease was 28%, 36% achieved partial response, and lower serum CA19-9 levels were recorded in all patients at discharge. Conclusions： IRE is feasible for the treatment of LAPC and is a reasonable intervention strategy owing to its combined attributes of safety and efficacy.

关键词： CA 19-9 Irreversible Electroporation Locally Advanced Pancreatic Carcinoma

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Serum and cerebrospinal fluid tau protein level as biomarkers for evaluating acute spinal cord injury severity and motor function outcome

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Neural Regeneration Research 2019年第5期14卷 896-902页

作者： Ying Tang Hong-Liang Liu Ling-Xia Min Hao-Shi Yuan Lei Guo Peng-Bo Han Yu-Xin Lu Jian-Feng Zhong Dong-Lin Wang Key Laboratory of Biorheological Science and Technology Ministry of Education (Chongqing University) Chongqing University Cancer Hospital department of Rehabilitation Southwest Hospital Third Military Medical University department of Spine surgery Second Affiliated Hospital of Xi'an Medical University department of Orthopedics Chinese PLA Beijing Army General Hospital

Tau protein, a microtubule-associated protein, has a high specific expression in neurons and axons. Because traumatic spinal cord injury mainly affects neurons and axons, we speculated that tau protein may be a promising biomarker to reflect the degree of spinal cord injury and prognosis of motor function. In this study, 160 female Sprague-Dawley rats were randomly divided into a sham group, and mild, moderate, and severe spinal cord injury groups. A laminectomy was performed at the T8 level to expose the spinal cord in all groups. A contusion lesion was made with the NYU-MASCIS impactor by dropping a 10 g rod from heights of 12.5 mm(mild), 25 mm(moderate) and 50 mm(severe) upon the exposed dorsal surface of the spinal cord. Tau protein levels were measured in serum and cerebrospinal fluid samples at 1, 6, 12, 24 hours, 3, 7, 14 and 28 days after operation. Locomotor function of all rats was assessed using the Basso, Beattie and Bresnahan locomotor rating scale. Tau protein concentration in the three spinal cord injury groups(both in serum and cerebrospinal fluid) rapidly increased and peaked at 12 hours after spinal cord injury. Statistically significant positive linear correlations were found between tau protein level and spinal cord injury severity in the three spinal cord injury groups, and between the tau protein level and Basso, Beattie, and Bresnahan locomotor rating scale scores. The tau protein level at 12 hours in the three spinal cord injury groups was negatively correlated with Basso, Beattie, and Bresnahan locomotor rating scale scores at 28 days(serum: r =-0.94; cerebrospinal fluid: r =-0.95). Our data suggest that tau protein levels in serum and cerebrospinal fluid might be a promising biomarker for predicting the severity and functional outcome of traumatic spinal cord injury.

关键词： nerve regeneration spinal cord injury tau injury severity outcome cerebrospinal fluid serum biomarker Basso,Beattie,and Bresnahan locomotor rating scale neural regeneration

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Effect of demethyltransferase FTO on tumor progression

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BIOCELL 2022年第11期46卷 2387-2397页

作者： LING SHENG YUEHONG SHEN HONGYU YANG School of Stomatology Weifang Medical UniversityWeifang261035China department of Oral and Maxillofacial surgery Shenzhen HospitalPeking UniversityShenzhen518036China

N6-methyladenosine(m6A)modification is the most widespread and conserved internal mRNA modification in mammalian cells.It greatly affects genetic regulation by enhancing the involvement of diverse cellular enzymes and thus,plays a significant role in basic life processes.Numerous studies on m6A modification identified FTO as a crucial demethylase that participates in various biological processes.Not only does FTO play a pivotal role in obesity-related conditions,but it also influences the occurrence,development,and prognosis of several cancers,such as acute myeloid leukemia,breast cancer,liver cancer,and lung cancer.Moreover,FTO also shows a close association with immunity and viral infections.This article summarized the molecular mechanism of FTO in tumorigenesis and tumor progression.

关键词： m6A modification Fat mass and obesity-associated protein Molecular functional mechanism

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Relationship between anal cancer recurrence and cigarette smoking

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World Journal of Clinical Oncology 2023年第7期14卷 259-264页

作者： Kevin R McMahon Nicholas Gemma McKenzie Clapp Patricia Sanchez-Montejo Joseph Dibello Erica Laipply department of General surgery Summa Health SystemAkronOH 44304United States

BACKGROUND The incidence of anal cancer has been increasing in the United States.Smoking is a well-established risk factor;however,the impact of smoking on disease recurrence and outcome has not been well studied.The aim of this study was to assess the association between anal cancer recurrence and cigarette smoking.AIM To investigate the relationship between cigarette smoking status and anal cancer treatment outcome.METHODS The cancer registry from a single,community hospital was screened for patients with anal cancer between 2010 and 2021.The following characteristics were gathered from the database:Age;sex;cigarette smoking history;American Joint Committee on cancer Clinical Stage Group;response to therapy;recurrence;time to recurrence;mortality;time to death;and length of follow-up.Patients were divided into the following groups:Current smokers;former smokers;and never smokers.SPSSv25.0 software(IBM Corp.,Armonk,NY,United States)was used for statistical analysis.RESULTS A total of 95 patients from the database met the screening criteria.There were 37 never smokers,22 former smokers,and 36 current smokers.There was no difference between groups in regards to race or sex.There was no difference in the American Joint Committee on cancer Clinical Stage Group between groups.The former smokers were significantly older when compared to never smokers and current smokers(66.5±13.17 vs 57.4±7.82 vs 63.7±13.80,P=0.011).Former smokers and current smokers had a higher recurrence rate compared to never smokers(30.8%and 20.8%compared to zero,P=0.009).There was not a significant difference in recurrence between former smokers and current smokers.There was no difference in the mortality,non-response rate,or time to death between the groups.CONCLUSION Our data contributes evidence that cigarette smoking status is associated with increased recurrence for patients with anal cancer.

关键词： Anal cancer Smoking Recurrence Nigro protocol Chemoradiation Retrospective review

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