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PGRN exacerbates the progression of non-small cell lung cancer via PI3K/AKT/Bcl-2 antiapoptotic signaling

Genes & Diseases 2022年第6期9卷 1650-1661页

作者： Sicheng Chen Mengjun Bie Xiaowen Wang Mengtian Fan Bin Chen Qiong Shi Yingjiu Jiang department of cardiothoracic Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016PR China Ministry of Education Key Laboratory of Diagnostic medicine School of Laboratory MedicineChongqing Medical UniversityChongqing 400016PR China

Progranulin(PGRN)is a growth factor that is involved in the progression of multiple ***,the effects and molecular mechanisms by which PGRN induces lung cancer remain *** expression level of PGRN was analyzed by conducting immunohistochemistry of the histological sections of lung tissues from non-small-cell lung carcinoma(NSCLC)*** proliferation,apoptosis,migration,and invasion of NSCLC cells were assessed by the MTT assay,Western blot,degree of wound healing,and Transwell assays.A nude mouse xenograft model was used to validate the role of PGRN in *** expression level of PGRN was higher in male patients with lung adenocarcinoma than in those with lung squamous cell carcinoma;by contrast,no difference was observed in female *** overexpression of PGRN promoted the proliferation and anti-apoptosis of H520(derived from lung squamous cell carcinoma)cells,whereas knockdown of PGRN inhibited the proliferation and anti-apoptosis of A549(derived from lung adenocarcinoma)***(targeting PI3K)inhibited the increase in the expression of cell anti-apoptosis marker Bcl-2 induced by rhPGRN protein;the PI3K agonist 740 YeP partially reversed the decrease in Bcl-2 expression induced by PGRN deficiency in both A549 and H520 *** increased the expression of Ki-67,PCNA,and Bcl-2 in *** inhibited cell apoptosis depending on the PI3K/Akt/Bcl-2 signaling axis;PGRN positivity correlated with lung *** is a potential biomarker for the treatment and diagnosis of NSCLC,especially in lung adenocarcinoma.

关键词： Bcl-2 Cell apoptosis NSCLC PGRN PI3K/Akt

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One-year survival in recipients older than 50 bridged to heart transplant with Impella 5.5 via axillary approach

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Journal of Geriatric Cardiology 2023年第5期20卷 319-329页

作者： Smit Paghdar Smruti Desai Ji-Min Jang Jose Ruiz Sharan Malkani Parag Patel Daniel S Yip Juan C Leoni Jose Nativi Basar Sareyyupoglu Kevin Landolfo Si Pham Rohan M Goswami Division of Heart Failure and Transplant Mayo Clinic in FloridaUSA department of cardiothoracic Surgery Mayo Clinic in FloridaUSA

BACKGROUND Optimizing patients with advanced heart failure before orthotopic heart transplantation(OHT), especially in patients greater than 50 years old, is imperative to achieving successful post-transplant outcomes. Complications are well-described for patients bridged to transplant(BTT) with durable left ventricular assist device(LVAD) support. Given the lack of data available in older recipients after the recent increase in mechanical support use, we felt it crucial to report our center’s one-year outcomes in older recipients after heart transplantation with percutaneously placed Impella 5.5 as a *** Forty-nine OHT patients were supported with the Impella 5.5 intended as a bridge between December 2019 and October 2022 at Mayo Clinic in Florida. Data were extracted from the electronic health record at baseline and during their transplant episode of care after Institutional Review Boards approval as exempt for retrospective data *** Thirty-eight patients aged 50 or older were supported with Impella 5.5 as BTT. Ten patients underwent heart and kidney transplantation within this cohort. The median age at OHT was 63(58–68) years, with 32 male(84%) and six female patients(16%). Etiology was divided into ischemic(63%) and non-ischemic cardiomyopathy(37%). The baseline median ejection fraction was 19%(15–24). Most patients were in blood group O(60%), and 50% were diabetic. The average duration of support was 27 days(range 6–94). The median duration of follow-up is 488 days(185–693). For patients that have reached the 1-year follow-up timeframe(22 of 38, 58%), the 1-year post-transplant survival is 95%.CONCLUSION Our single-center data provides awareness for using the Impella 5.5 percutaneously placed axillary support device in older heart failure patients in cardiogenic shock as a bridge to transplantation. One-year survival outcomes after heart transplantation are excellent despite the older recipient’s age and prolonged pre-transplant support.

关键词： One approval transplant

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Risk factors and outcomes for patients with pancreatic cancer undergoing surgical exploration without resection due to metastatic disease:A national cohort study

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Hepatobiliary & Pancreatic Diseases International 2022年第3期21卷 279-284页

作者： Emil Sahlstrom Paulina Bereza-Carlson Johan Nilsson Bobby Tingstedt Bodil Andersson department of Clinical Sciences Lund SurgeryLund UniversitySweden department of Surgery Central Hospital KristianstadSweden department of Translational medicine Cardiothoracic surgery and bioinformaticsLund UniversitySweden department of Thoracic and vascular surgery Skane University hospitalLundSweden department of Surgery Skane University HospitalLundSweden

Background:Unresectable disease is sometimes diagnosed during surgery in patients with pancreatic ductal adenocarcinoma(PDAC).This study aimed to identify preoperative risk factors for metastatic disease diagnosed at surgical exploration and to investigate and compare survival in resected and nonresected ***:Patients were identified from the Swedish National Pancreatic and Periampullary Cancer Registry *** of metastatic disease were evaluated with a multivariable logistic regression model,and survival was evaluated with Kaplan-Meier estimates and log-rank ***:In total,1938 patients with PDAC were scheduled for *** unresectable situation was diagnosed intraoperatively in 399 patients(20.6%),including 234(12.1%)with metastasized *** risk factors for metastasis were involuntary weight loss(OR=1.72;95%CI:1.27-2.33)and elevated carbohydrate antigen 19-9(CA19-9)(35-599 U/m L,OR=1.79,95%CI:1.11-2.89;≥600 U/m L,OR=3.24,95%CI:2.04-5.17).Overall survival was lower among patients with metastasized disease than that among patients with a resectable tumor(P<0.001).Conclusions:Involuntary weight loss and an elevation of CA19-9 are preoperative risk factors for diagnosing metastasized disease during surgical exploration.

关键词： Pancreatic cancer Surgery Metastasized Exploration

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Tanshinone IIA Suppresses Non-Small Cell Lung Cancer Through Beclin-1-Mediated Autophagic Apoptosis

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Engineering 2022年第12期19卷 128-138页

作者： Shasha Bai Sainan Cui Wenhao Wen Elaine Lai-Han Leung Jing Bai Huiyuan Lin Yongfei Cui Lei Yang Zhongqiu Liu Yuan Zheng Rong Zhang School of Pharmaceutical Sciences Guangzhou University of Chinese MedicineGuangzhou 510006China State Key Laboratory of Quality Research in Chinese medicine/Macao Institute for Applied Research in medicine and Health Macao University of Science and TechnologyMacao 999078China cardiothoracic Surgery department The Second Clinical College of Guangzhou University of Chinese MedicineGuangdong Provincial Hospital of Chinese MedicineGuangzhou 510006China

It is necessary to develop a new strategy for treatment of lung cancer since it is the main cause of cancer *** IIA(Tan IIA),an active ingredient of a commonly used traditional Chinese herb Salvia miltiorrhiza,provides a new direction to develop a new strategy for the *** has been found that Tan IIA could inhibit lung cancer in vitro and in vivo by inducing autophagic *** IIA increased apoptotic cells and the expression of cleaved caspase 3 and cleaved caspase 9,decreased B-cell lymphoma-2(Bcl-2)/Bcl-2 associated X protein(Bax)ratio in human non-small cell lung cancer(NSCLC)cell lines,which was promoted by an autophagy activator Rapamycin,and weaken by autophagy inhibitor 3-methyladenine(3-MA).In addition,Tan IIA induced more autophagosomes,up-regulated light chain 3b(LC-3B)I and LC-3B II conversion and less sequestosome 1(SQSTM1/p62)expression,which cannot be weakened by the caspase 3 ***,overexpression of LC-3B gene(LC3B)and downregulation of autophagic gene 5(ATG5)further confirmed that Tan IIA induced autophagic apoptosis in NSCLC cell ***-1 gene(BECN1)overexpression and silence attenuated the effects of Tan IIA,suggesting autophagic apoptosis that Tan IIA induced was dependent on ***,our study demonstrated a new treatment mechanism of Tan IIA and suggested that Tan IIA is a potential new anti-cancer therapeutic option.

关键词： Tan IIA Autophagy Apoptosis Beclin-1

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Sequential multidisciplinary minimally invasive therapeutic strategy for heart failure caused by four diseases: A case report

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World Journal of Clinical Cases 2022年第23期10卷 8255-8261页

作者： Chen-Ze Zhao Yan Yan Yong Cui Ni Zhu Xue-Yan Ding department of Cardiology Zhejiang Provincial People's HospitalHangzhou 310014Zhejiang ProvinceChina department of cardiothoracic Surgery No.903 Hospital of Chinese People's Liberation ArmyHangzhou 310043Zhejiang ProvinceChina department of cardiothoracic Surgery Zhejiang Provincial People's HospitalHangzhou 310014Zhejiang ProvinceChina department of Hematology The First Affiliated Hospital of Zhejiang Chinese Medicine UniversityHangzhou 310003Zhejiang ProvinceChina

BACKGROUND The coexistence with patent ductus arteriosus(PDA),mitral valve prolapse(MVP),atrial fibrillation(AF)and hyperthyroidism is extremely rare and *** optimal therapeutic strategy is difficult to *** SUMMARY A 27-year-old female with PDA,MVP,AF and hyperthyroidism presented with severe *** that a one-stage operation for PDA,MVP and AF is high risk,we preferred a sequential multidisciplinary minimally invasive therapeutic ***,PDA transcatheter closure was *** and heart failure were simultaneously controlled via medical ***-assisted thoracoscopic mitral valve repair and left atrial appendage occlusion were performed when heart failure was *** this therapeutic strategy,the patient’s sinus rhythm was restored and *** years after the treatment,the symptoms of heart failure were relieved,and the enlarged heart was *** Sequential multidisciplinary therapeutic strategies,which take advantage of both internal medicine and surgical approaches,might be reasonable for this type of disease.

关键词： Patent ductus arteriosus Mitral valve prolapse Atrial fibrillation Heart failure Sequential multidisciplinary therapeutic strategy Case report

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COVID-19 and the heart

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World Journal of Clinical Cases 2022年第28期10卷 9970-9984页

作者： Andrew Xanthopoulos Angeliki Bourazana Grigorios Giamouzis Evangelia Skoularigki Apostolos Dimos Alexandros Zagouras Michail Papamichalis Ioannis Leventis Dimitrios E Magouliotis Filippos Triposkiadis John Skoularigis department of Cardiology University Hospital of LarissaLarissa 41110Greece department of cardiothoracic Surgery University of ThessalyLarissa BiopolisLarissa 41110Greece

An outbreak of coronavirus disease 2019(COVID-19) occurred in December 2019 due to severe acute respiratory syndrome coronavirus 2(SARS-Co V-2),which is a strain of SARS-Co *** infected with the virus present a wide spectrum of manifestations ranging from mild flu-like symptoms,cough,fever and fatigue to severe lung injury,appearing as bilateral interstitial pneumonia or acute respiratory *** SARS-Co V-2 infection predominantly offends the respiratory system,it has been associated with several cardiovascular complications as *** example,patients with COVID-19 may either develop type 2 myocardial infarction due to myocardial oxygen demand and supply imbalance or acute coronary syndrome resulting from excessive inflammatory response to the primary *** incidence of COVID-19 related myocarditis is estimated to be accountable for an average of 7% of all COVID-19 related fatal cases,whereas heart failure(HF) may develop due to infiltration of the heart by inflammatory cells,destructive action of pro-inflammatory cytokines,micro-thrombosis and new onset or aggravated endothelial and respiratory ***,SARSCo V-2 can engender arrhythmias through direct myocardial damage causing acute myocarditis or through HF decompensation or secondary,through respiratory failure or severe res-piratory distress *** this comprehensive review we summarize the COVID-19 related cardiovascular complications(acute coronary syndromes,myocarditis,HF,arrhythmias) and discuss the main underlying pathophysiological mechanisms.

关键词： COVID-19 Virus Complications Cardiac Acute coronary syndromes Heart failure Myocarditis Arrhythmias

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Melatonin Alleviates Liver Fibrosis by Inhibiting Autophagy

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Current Medical Science 2022年第3期42卷 498-504页

作者： Lei JIE Ru-tao HONG Yu-jie ZHANG Lu-lin SHA Wei CHEN Xiao-fei REN department of Gastroenterology First Affiliated Hospital of Anhui Medical UniversityKey Laboratory of Digestive Disease of Anhui ProvinceHefei 230022China department of Critical Care medicine of cardiothoracic Surgery First Affiliated Hospital of Anhui Medical UniversityHefei 230022China

Objective Melatonin has been reported to suppress inflammation and alleviate liver fibrosis,but its effect on autophagy in liver fibrosis has not been *** study investigated the effect of melatonin on autophagy in an animal model of liver fibrosis and the hepatic stellate cell(HSC)-T6 cell *** The model was established in rats through carbon tetrachloride treatment,and melatonin was administered at three doses(2.5,5.0,and 10.0 mg/kg).Haematoxylin and eosin staining and Van Gieson’s staining were performed to examine the pathological changes of *** expression of alpha-smooth muscle actin(α-SMA)and Beclin1 in liver tissues was detected by immunohistochemical *** protein levels ofα-SMA,Beclin1 and LC3 in the animal model were detected by Western blot analysis,and gene levels of Beclin1 and LC3 were detected by quantitative real-time PCR(qRT-PCR)in the animal ***-T6 cells were activated by platelet-derived growth factor-BB(PDGF-BB).The expression ofα-SMA,Beclin1 and collagen I was detected by Western blot analysis,and the gene expression of Beclin1 and LC3 was detected by *** Melatonin reduced the expression ofα-SMA,Beclin1 and LC3 in liver *** addition,melatonin inhibited the activation of HSC-T6 cells and the expression ofα-SMA,Beclin1 and LC3 in these *** results revealed that melatonin could inhibit autophagy and HSC *** Melatonin might ameliorate liver fibrosis by regulating autophagy,suggesting that melatonin is a potential therapeutic agent for liver fibrosis.

关键词： autophagy liver fibrosis hepatic stellate cells melatonin

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The clinical impact of tricuspid regurgitation in patients with a biatrial orthotopic heart transplant

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Frontiers of medicine 2023年第3期17卷 527-533页

作者： Kevin M.Veen Grigorios Papageorgiou Casper F.Zijderhand Mostafa M.Mokhles Jasper J.Brugts Olivier C.Manintveld Alina A.Constantinescu Jos A.Bekkers Johanna J.Makkenberg Ad J.J.CBogers Kadir Caliskan department of cardiothoracic Surgery Erasmus MC3000 CA RotterdamThe Netherlands department of Biostatistics Erasmus MC3000 CA RotterdamThe Netherlands department of Cardiology Erasmus MC3000 CA RotterdamThe Netherlands

In this study,we aim to elucidate the clinical impact and long-term course of tricuspid regurgitation(TR),taking into account its dynamic nature,after biatrial orthotopic heart transplant(OHT).All consecutive adult patients undergoing biatrial OHT(1984−2017)with an available follow-up echocardiogram were ***-models were used to model the evolution of *** mixed-model was inserted into a Cox model in order to address the association of the dynamic TR with *** total,572 patients were included(median age:50 years,males:74.9%).Approximately 32% of patients had moderate-to-severe TR immediately after ***,this declined to 11%on 5 years and 9% on 10 years after surgery,adjusted for survival *** mechanical support was associated with less TR during follow-up,whereas concurrent LV dysfunction was significantly associated with more TR during *** at 1,5,10,20 years was 97%±1%,88%±1%,66%±2% and 23%±2%,*** presence of moderate-to-severe TR during follow-up was associated with higher mortality(HR:1.07,95%CI(1.02–1.12),p=0.006).The course of TR was positively correlated with the course of creatinine(R=0.45).TR during follow-up is significantly associated with higher mortality and worse renal ***,probability of TR is the highest immediately after OHT and decreases ***,it may be reasonable to refrain from surgical intervention for TR during earlier phase after OHT.

关键词： orthotopic heart transplant tricuspid regurgitation clinical impact biatrial heart transplantation

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From hardware store to hospital:a COVID-19-inspired,cost-effective,open-source,in vivo-validated ventilator for use in resource-scarce regions

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Bio-Design and Manufacturing 2022年第1期5卷 133-140页

作者： Matthew H.Park Yuanjia Zhu Hanjay Wang Nicholas ATran Jinsuh Jung Michael JPaulsen Annabel M.Imbrie‑Moore Samuel Baker Robert Wilkerson Mateo Marin‑Cuartas Danielle M.Mullis Y.Joseph Woo department of cardiothoracic Surgery Stanford UniversityFalk Cardiovascular Research Building CV-235300 Pasteur DriveStanfordCA 94305-5407USA department of Mechanical Engineering Stanford UniversityStanfordCAUSA department of Bioengineering Stanford UniversityStanfordCAUSA department of Comparative medicine Stanford UniversityStanfordCAUSA University department of Cardiac Surgery Leipzig Heart CenterLeipzigGermany

Resource-scarce regions with serious COVID-19 outbreaks do not have enough ventilators to support critically ill patients,and these shortages are especially devastating in developing *** help alleviate this strain,we have designed and tested the accessible low-barrier in vivo-validated economical ventilator(ALIVE Vent),a COVID-19-inspired,cost-effective,open-source,in vivo-validated solution made from commercially available *** ALIVE Vent operates using compressed oxygen and air to drive inspiration,while two solenoid valves ensure one-way flow and precise cycle *** device was functionally tested and profiled using a variable resistance and compliance artificial lung and validated in anesthetized large *** functional test results revealed its effective operation under a wide variety of ventilation conditions defined by the American Association of Respiratory Care guidelines for ventilator *** large animal test showed that our ventilator performed similarly if not better than a standard ventilator in maintaining optimal ventilation *** FiO2,respiratory rate,inspiratory to expiratory time ratio,positive-end expiratory pressure,and peak inspiratory pressure were successfully maintained within normal,clinically validated ranges,and the animals were recovered without any *** regions with limited access to ventilators,the ALIVE Vent can help alleviate shortages,and we have ensured that all used materials are publicly *** this pandemic has elucidated enormous global inequalities in healthcare,innovative,cost-effective solutions aimed at reducing socio-economic barriers,such as the ALIVE Vent,can help enable access to prompt healthcare and life saving technology on a global scale and beyond COVID-19.

关键词： COVID-19 Ventilator Open-source

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Overexpression of mitogen-activated protein kinase phosphatase-1 in endothelial cells reduces blood-brain barrier injury in a mouse model of ischemic stroke

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Neural Regeneration Research 2023年第8期18卷 1743-1749页

作者： Xiu-De Qin Tai-Qin Yang Jing-Hui Zeng Hao-Bin Cai Shao-Hua Qi Jian-Jun Jiang Ying Cheng Long-Sheng Xu Fan Bu department of Neurology&Psychology Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Chinese MedicineShenzhenGuangdong ProvinceChina department of cardiothoracic Surgery Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Chinese MedicineShenzhenGuangdong ProvinceChina department of Neurology The University of Texas Health Science Center at HoustonHoustonTXUSA department of Nephrology Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Chinese MedicineShenzhenGuangdong ProvinceChina department of Anesthesiology and Pain medicine The Affiliated Hospital of Jiaxing UniversityJiaxingZhejiang ProvinceChina

Ischemic stroke can cause blood-brain barrier(BBB)injury,which worsens brain damage induced by *** expression of tight junction proteins in endothelial cells(ECs)can increase intracellular space and BBB *** inhibition of mitogen-activated protein kinase,the negative regulatory substrate of mitogen-activated protein kinase phosphatase(MKP)-1,improves tight junction protein function in ECs,and genetic deletion of MKP-1 aggravates ischemic brain ***,whether the latter affects BBB integrity,and the cell type-specific mechanism underlying this process,remain *** this study,we established an adult male mouse model of ischemic stroke by occluding the middle cerebral artery for 60 minutes and overexpressed MKP-1 in ECs on the injured side via lentiviral transfection before *** found that overexpression of MKP-1 in ECs reduced infarct volume,reduced the level of inflammatory factors interleukin-1β,interleukin-6,and chemokine C-C motif ligand-2,inhibited vascular injury,and promoted the recovery of sensorimotor and memory/cognitive *** of MKP-1 in ECs also inhibited the activation of cerebral ischemia-induced extracellular signal-regulated kinase(ERK)1/2 and the downregulation of occludin ***,to investigate the mechanism by which MKP-1 exerted these functions in ECs,we established an ischemic stroke model in vitro by depriving the primary endothelial cell of oxygen and glucose,and pharmacologically inhibited the activity of MKP-1 and ERK1/*** findings suggest that MKP-1 inhibition aggravates oxygen and glucose deprivation-induced cell death,cell monolayer leakage,and downregulation of occludin expression,and that inhibiting ERK1/2 can reverse these *** addition,co-inhibition of MKP-1 and ERK1/2 exhibited similar effects to inhibition of ERK1/*** findings suggest that overexpression of MKP-1 in ECs can prevent ischemia-induced occludin downregulation and cell death via deactivatin

关键词： blood-brain barrier brain injury cerebral ischemia endothelial cells extracellular signal-regulated kinase 1/2 functional recovery mitogenactivated protein kinase phosphatase 1 occludin oxygen and glucose deprivation transient middle cerebral artery occlusion

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