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Cancer cachexia:Focus on cachexia factors and inter-organ communication

Chinese medical Journal 2024年第1期137卷 44-62页

作者： Yongfei Wang Zikai Dong Ziyi An Weilin Jin the first clinical medical college of lanzhou university LanzhouGansu 730000China Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhouGansu 730000China

Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs,which is mediated by cancer cachexia factors.Cancer cachexia factors,being the general name of inflammatory factors,circulating proteins,metabolites,and microRNA secreted by tumor or host cells,play a role in secretory or other organs and mediate complex signal communication between organs during cancer cachexia.Cancer cachexia factors are also a potential target for the diagnosis and treatment.The pathogenesis of cachexia is unclear and no clear effective treatment is available.Thus,the treatment of cancer cachexia from the perspective of the tumor ecosystem rather than from the perspective of a single molecule and a single organ is urgently needed.From the point of signal communication between organs mediated by cancer cachexia factors,finding a deeper understanding of the pathogenesis,diagnosis,and treatment of cancer cachexia is of great significance to improve the level of diagnosis and treatment.This review begins with cancer cachexia factors released during the interaction between tumor and host cells,and provides a comprehensive summary of the pathogenesis,diagnosis,and treatment for cancer cachexia,along with a particular sight on multi-organ signal communication mediated by cancer cachexia factors.This summary aims to deepen medical community’s understanding of cancer cachexia and may conduce to the discovery of new diagnostic and therapeutic targets for cancer cachexia.

关键词： Cancer cachexia Cancer cachexia factors Inter-organ communication Tumor ecosystem Tumor microenvironment

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Ferritinophagy: A new idea for liver diseases regulated by ferroptosis

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 160-170页

作者： Zi-Bing Qian Jun-Feng Li Wan-Yuan Xiong Xiao-Rong Mao the first clinical medical college of lanzhou university Lanzhou 730000China Institute of Infectious Diseases The First Hospital of Lanzhou UniversityLanzhou 730000China Department of Infectious Disease The First Hospital of Lanzhou UniversityLanzhou 730000China

Background:The discovery of regulatory cell death has led to a breakthrough in the therapeutic field.Various forms of cell death,such as necrosis,apoptosis,pyroptosis,autophagy,and ferroptosis,play an important role in the development of liver diseases.In general,more than one form of cell death pathways is responsible for the disease state.Therefore,it is particularly important to study the regulation and interaction of various cell death forms in liver diseases.Data sources:We performed a PubMed search up to November 2022 with the following keywords:ferritinophagy,ferroptosis,and liver disease.We also used terms such as signal path,inducer,and inhibitor to supplement the query results.Results:This review summarized the basic characteristics of ferritinophagy and ferroptosis and the regulation of ferroptosis by ferritinophagy and reviewed the key targets and treatment strategies of ferroptosis in different liver diseases.Conclusions:Ferritinophagy is a potential therapeutic target in ferroptosis-related liver diseases.

关键词： Ferritinophagy Ferroptosis Liver disease

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Interaction between systemic iron parameters and left ventricular structure and function in the preserved ejection fraction population:a two-sample bidirectional Mendelian randomization study

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Journal of Geriatric Cardiology 2024年第1期21卷 64-80页

作者： Xiong-Bin MA Yong-Ming LIU Yan-Lin LV Lin QIAN the first clinical medical college of lanzhou university LanzhouGansuChina Geriatric Cardiovascular Department and Gansu clinical Research Center for Geriatric Diseases First Hospital of Lanzhou UniversityGansuChina

BACKGROUND Left ventricular(LV)remodeling and diastolic function in people with heart failure(HF)are correlated with iron status;however,the causality is uncertain.This Mendelian randomization(MR)study investigated the bidirectional causal relationship between systemic iron parameters and LV structure and function in a preserved ejection fraction population.METHODS Transferrin saturation(TSAT),total iron binding capacity(TIBC),and serum iron and ferritin levels were extracted as instrumental variables for iron parameters from meta-analyses of public genome-wide association studies.Individuals without myocardial infarction history,HF,or LV ejection fraction(LVEF)<50%(n=16,923)in the UK Biobank Cardiovascular Magnetic Resonance Imaging Study constituted the outcome dataset.The dataset included LV end-diastolic volume,LV endsystolic volume,LV mass(LVM),and LVM-to-end-diastolic volume ratio(LVMVR).We used a two-sample bidirectional MR study with inverse variance weighting(IVW)as the primary analysis method and estimation methods using different algorithms to improve the robustness of the results.RESULTS In the IVW analysis,one standard deviation(SD)increased in TSAT significantly correlated with decreased LVMVR(β=-0.1365;95%confidence interval[CI]:-0.2092 to-0.0638;P=0.0002)after Bonferroni adjustment.Conversely,no significant relationships were observed between other iron and LV parameters.After Bonferroni correction,reverse MR analysis showed that one SD increase in LVEF significantly correlated with decreased TSAT(β=-0.0699;95%CI:-0.1087 to-0.0311;P=0.0004).No heterogeneity or pleiotropic effects evidence was observed in the analysis.CONCLUSIONS We demonstrated a causal relationship between TSAT and LV remodeling and function in a preserved ejection fraction population.

关键词： fraction function parameters

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Azacitidine maintenance therapy for blastic plasmacytoid dendritic cell neoplasm allograft: A case report

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World Journal of clinical Cases 2024年第1期12卷 136-141页

作者： Li-Li Tao Hui-Ting Wen Zi-Yi Wang Juan Cheng Li Zhao Department of Hematology The First Clinical Medical CollegeLanzhou UniversityLanzhou 730000Gansu ProvinceChina Department of Hematology The First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’*** was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.

关键词： Blastic plasmacytoid dendritic cell neoplasm Azacitidine Allogeneic hematopoietic stem cell transplantation Maintenance therapy Case report

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The Epstein-Barr virus-miRNA-BART6-5p regulates TGF-β/SMAD4 pathway to induce glycolysis and enhance proliferation and metastasis of gastric cancer cells

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Oncology Research 2024年第5期32卷 999-1009页

作者： XUHUI ZHAO XIAOMIN HUANG CHUNYAN DANG XIA WANG YUJIAO QI HONGLING LI The first clinical medical college Gansu University of Traditional Chinese MedicineLanzhou730000China Department of Oncology Gansu People’s HospitalLanzhou730000China The clinical medical college Ningxia Medical UniversityNingxia750004China

Background:EBV-miR-BARTs exhibit significant relevance in epithelial tumors,particularly in EBVassociated gastric and nasopharyngeal cancers.However,their specific mechanisms in the initiation and progression of gastric cancer remain insufficiently explored.Material and Methods:Initially,EBV-miRNA-BART6-5p and its target gene SMAD4 expression were assessed in EBV-associated gastric cancer tissues and cell lines.Subsequent transfection induced overexpression of EBV-miRNA-BART6-5p in AGS and MKN-45,and downregulation in EBVpositive cells(SUN-719).The subsequent evaluation aimed to observe their impact on gastric cancer cell proliferation,migration,and glycolytic processes,with the TGF-β/SMAD4 signaling pathway value clarified using a TGF-βinhibitor.Results:EBV-miRNA-BART6-5p exhibits pronounced upregulation in EBV-associated gastric cancer tissues and EBV-positive cells,while its target gene SMAD4 demonstrates downregulated expression.Upregulation of it can promote the proliferation and migration of gastric cancer cells.Additionally,We found EBV-miRNA-BART6-5p promotes glycolysis of gastric cancer cells.Inhibition of the TGF-β/SMAD4 signaling pathway resulted in suppressed proliferation and migration of gastric cancer cells,concomitant with a diminished glycolytic capacity.Conclusion:In this study,we found that EBV-miRNA-BART6-5p can target SMAD4,effectively increasing glycolysis in gastric cancer cells by regulating the TGF-β/SMAD4 signaling pathway,thereby enhancing the proliferation and metastasis of gastric cancer cells.Our findings may offer new insights into the metabolic aspects of gastric cancer.

关键词： EBV TGF-β/SMAD4 Glycolysis Gastric cancer

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Predictive model for non-malignant portal vein thrombosis associated with cirrhosis based on inflammatory biomarkers

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1213-1226页

作者： Guo-Le Nie Jun Yan Ying Li Hong-Long Zhang Dan-Na Xie Xing-Wang Zhu Xun Li The first School of clinical Medicine Lanzhou UniversityLanzhou 730000Gansu ProvinceChina Department of General Surgery The First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina

BACKGROUND Portal vein thrombosis(PVT),a complication of liver cirrhosis,is a major public health concern.PVT prediction is the most effective method for PVT diagnosis and treatment.AIM To develop and validate a nomogram and network calculator based on clinical indicators to predict PVT in patients with cirrhosis.METHODS Patients with cirrhosis hospitalized between January 2016 and December 2021 at the first Hospital of lanzhou university were screened and 643 patients with cirrhosis who met the eligibility criteria were retrieved.Following a 1:1 propensity score matching 572 patients with cirrhosis were screened,and relevant clinical data were collected.PVT risk factors were identified using the least absolute shrinkage and selection operator(LASSO)and multivariate logistic regression analysis.Variance inflation factors and correlation matrix plots were used to analyze multicollinearity among the variables.A nomogram was constructed to predict the probability of PVT based on independent risk factors for PVT,and its predictive performance was verified using a receiver operating characteristic curve(ROC),calibration curves,and decision curve analysis(DCA).Finally,a network calculator was constructed based on the nomograms.RESULTS This study enrolled 286 cirrhosis patients with PVT and 286 without PVT.LASSO analysis revealed 13 variables as strongly associated with PVT occurrence.Multivariate logistic regression analysis revealed nine indicators as independent PVT risk factors,including etiology,ascites,gastroesophageal varices,platelet count,D-dimer,portal vein diameter,portal vein velocity,aspartate transaminase to neutrophil ratio index,and platelet-to-lymphocyte ratio.LASSO and correlation matrix plot results revealed no significant multicollinearity or correlation among the variables.A nomogram was constructed based on the screened independent risk factors.The nomogram had excellent predictive performance,with an area under the ROC curve of 0.821 and 0.829 in the training and testing groups,respectively.Calibr

关键词： Portal vein thrombosis Liver cirrhosis Nomogram Inflammatory markers Aspartate aminotransferase to neutrophil ratio index Platelet-to-lymphocyte ratio

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Efficacy of electroacupuncture on myocardial protection and postoperative rehabilitation in patients undergoing cardiac surgery with cardiopulmonary bypass:a systematic review and Meta-analysis

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Journal of Traditional Chinese Medicine 2024年第1期44卷 1-15页

作者： QIN Xiaoyu WANG Chunai XUE Jianjun ZHANG Jie LU Xiaoting DING Shengshuang GE Long WANG Minzhen the first clinical medical college Gansu University of Chinese MedicineLanzhou 730030China Department of Anesthesiology Gansu Provincial Hospital of Traditional Chinese MedicineLanzhou 730050China Evidence-based Medicine Center Lanzhou UniversityLanzhou 730030China Institute of Epidemiology and Statistics School of Public HealthLanzhou UniversityLanzhou 730030China

OBJECTIVE:To evaluate the efficacy of electroacupuncture(EA)intervention on myocardial protection and postoperative rehabilitation in patients undergoing cardiac surgery with cardiopulmonary bypass(CPB).METHODS:Eight databases,including Pub Med,Embase,the Cochrane Library,Web of Science,Chinese Bio medical Literature Database,China National Knowledge Infrastructure Database,Wanfang Data,China Science and Technology Journal Database,and two clinical trial registries,were searched.All randomized controlled trials(RCTs)related to EA intervention in cardiac surgery with CPB were collected.Based on the inclusion and exclusion criteria,two researchers independently screened articles and extracted data.After the quality evaluation,RevMan 5.3 software was used for analysis.RESULTS:Fourteen RCTs involving 836 patients were included.Compared with the control treatment,EA significantly increased the incidence of cardiac automatic rebeat after aortic unclamping[relative risk(RR)=1.15,95%confidence interval(CI)(1.01,1.31),P<0.05;moderate].Twenty-four hours after aortic unclamping,EA significantly increased the superoxide dismutase[standardized mean difference(SMD)=0.96,95%CI(0.32,1.61),P<0.05;low],and interleukin(IL)-2[SMD=1.33,95%CI(0.19,2.47),P<0.05;very low]expression levels and decreased the malondialdehyde[SMD=-1.62,95%CI(-2.15,-1.09),P<0.05;moderate],tumour necrosis factor-α[SMD=-1.28,95%CI(-2.37,-0.19),P<0.05;moderate],and cardiac troponin I[SMD=-1.09,95%CI(-1.85,-0.32),P<0.05;low]expression levels as well as the inotrope scores[SMD=-0.77,95%CI(-1.22,-0.31),P<0.05;high].There was no difference in IL-6 and IL-10 expression levels.The amount of intraoperative sedative[SMD=-0.31,95%CI(-0.54,-0.09),P<0.05;moderate]and opioid analgesic[SMD=-0.96,95%CI(-1.53,-0.38),P<0.05;low]medication was significantly lower in the EA group than in the control group.Moreover,the postoperative tracheal intubation time[SMD=-0.92,95%CI(-1.40,-0.45),P<0.05;low]and intensive care unit stay[SMD=-1.71,95%CI(-3.06,-0.36),P<0.05;low]were significan

关键词： electroacupuncture cardiopulmonary bypass thoracic surgery myocardial ischaemia-reperfusion injury myocardial protection postoperative rehabilitation Meta-analysis randomized controlled trial

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Drug repurposing for cancer therapy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1981-2013页

作者： Ying Xia Ming Sun Hai Huang Wei-Lin Jin Center for clinical Laboratories The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004PR China The first Affiliated Hospital of Guizhou university of Traditional Chinese Medicine Guiyang 550001PR China School of clinical Laboratory Science Guizhou Medical UniversityGuiyang 550004PR China Division of Gastroenterology and Hepatology Department of Medicine andDepartment of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMD 21287USA Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhou 730000PR China

Cancer,a complex and multifactorial disease,presents a significant challenge to global health.Despite significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic strategy.However,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer therapeutics.One promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved drugs.Drug repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety profiles.In light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat cancer.We describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor microenvironment.In addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug delivery.We also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy regimen.To conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.

关键词： drugs integrating spite

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Multidisciplinary comprehensive treatment of massive hepatocellular carcinoma with hemorrhage:A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2225-2232页

作者： Xian-Shuai Kou Fan-Fan Li Yun Meng Jian-Ming Zhao Sheng-Fen Liu Lan Zhang The first clinical medical college Gansu University of Chinese MedicineLanzhou 730000Gansu ProvinceChina Department of Thoracic Surgery The First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina Department of Surgery Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Department of Orthopedics Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC),a major contributor to cancer-related deaths,is particularly prevalent in Asia,largely due to hepatitis B virus infection.Its prognosis is generally poor.This case report contributes to the medical literature by detailing a unique approach in treating a large HCC through multidisciplinary collaboration,particularly in patients with massive HCC complicated by ruptured bleeding,a scenario not extensively documented previously.CASE SUMMARY The patient presented with large HCC complicated by intratumoral bleeding.Treatment involved a multidisciplinary approach,providing individualized care.The strategy included drug-eluting bead transarterial chemoembolization,sorafenib-targeted therapy,laparoscopic partial hepatectomy,and standardized sintilimab monoclonal antibody therapy.Six months after treatment,the patient achieved complete radiological remission,with significant symptom relief.Imaging studies showed no lesions or recurrence,and clinical assessments confirmed complete remission.This report is notable as possibly the first docu-mented case of successfully treating such complex HCC conditions through integrated multidisciplinary efforts,offering new insights and a reference for future similar cases.CONCLUSION This study demonstrated effective multidisciplinary treatment for massive HCC with intratumoral bleeding,providing insights for future similar cases.

关键词： Hepatocellular carcinoma Transarterial chemoembolization Sintilimab Sorafenib Translational therapy Multidisciplinary team Case report

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The pathogenic mechanism of TAR DNA-binding protein 43(TDP-43)in amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第4期19卷 800-806页

作者： Xinxin Wang Yushu Hu Renshi Xu medical college of Nanchang university Department of Neurology Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeThe Clinical College of Nanchang Medical College

The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory regions.However,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the disease.The disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries.The TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral sclerosis.This review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).

关键词： amyotrophic lateral sclerosis axonal transport liquid-liquid phase separation noncellular autonomous functions oxidative stress pathogenesis post-translational modification protein quality control system stress granules TAR DNA-binding protein 43(TDP-43)

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