miR-30a-5p/PHTF2 axis regulates the tumorigenesis and metastasis of lung adenocarcinoma

Background:Lung adenocarcinoma is a very pervasive histological form of lung cancers,and inhibiting metastasis is crucial for effective treatment.In this investigation,we explored the functional interaction of miR-30a-5p and the putative transcription factor 2 of the homeodomain(PHTF2)in dictating the aggressiveness and metastasis of lung adenocarcinoma.Method:We collected clinical samples to evaluate the expression patterns of miR-30a-5p and PHTF2 in lung adenocarcinoma along with normal tissues.Cellular experiments including cell count kit(CCK)-8 growth assay,apoptosis analysis,migration and invasion examinations were performed to assess the aggressiveness of lung adenocarcinoma cells.Furthermore,we examined tumorigenesis and metastasis in a nude mouse model.Results:MiR-30a-5p exhibited downregulation pattern in lung adenocarcinoma samples.Transfection of miR-30a-5p mimic in lung adenocarcinoma cells resulted in the suppression of malignant characteristics.Notably,the administration of miR-30a-5p mimic also curbed tumorigenesis and metastasis of lung adenocarcinoma cells in animal model.Moreover,PHTF2 was found to be a molecular target of miR-30a-5p.Upregulating PHTF2 counteracted the tumor-suppressive effect of the miR-30a-5p mimic.Conclusion:miR-30a-5p functions as a tumor-suppressive molecule while PHTF2 acts as an oncogenic factor in the development and metastasis of lung adenocarcinoma.Therefore,targeting miR-30a-5p and PHTF2 could be developed into a promising therapeutic approach for inhibiting metastasis in lung adenocarcinoma.

Effects of autophagy inhibitor 3-methyladenine on a diabetic mice model

AIM:To investigate the role of autophagy inhibitor 3-methyladenine(3-MA)on a diabetic mice model(DM)and the potential mechanism.METHODS:Male C57BL/6J mice were randomly divided into a normal control group(NC group)and an DM group.DM were induced by multiple low-dose intraperitoneal injection of streptozotocin(STZ)60 mg/kgd for 5 consecutive days.DM mice were randomly subdivided into untreated group(DM group),3-MA(10 mg/kgd by gavage)treated group(DM+3-MA group)and chloroquine(CQ;50 mg/kg by intraperitoneal injection)treated group(DM+CQ group).The fasting blood glucose(FBG)levels were recorded every week.At the end of experiment,retinal samples were collected.The expression levels of pro-apoptotic proteins cleaved caspase-3,cleaved poly ADP-ribose polymerase 1(PARP1)and Bax,anti-apoptotic protein Bcl-2,fibrosisassociated proteins Fibronectin and type 1 collagenα1 chain(COL1A1),vascular endothelial growth factor(VEGF),inflammatory factors interleukin(IL)-1βand tumor necrosis factor(TNF)-α,as well as autophagy related proteins LC3,Beclin-1 and P62 were determined by Western blotting.The oxidative stress indicators 8-hydroxydeoxyguanosine(8-OHdG)and malondialdehyde(MDA)were detected by commercial kits.RESULTS:Both 3-MA and CQ had shor t-term hypoglycemic effect on FBG and reduced the expression of VEGF and inflammatory factors IL-1βand TNF-αin DM mice.3-MA also significantly alleviated oxidative stress indicators 8-OHdG and MDA,decreased the expression of fibrosisrelated proteins Fibronectin and COL1A1,pro-apoptotic proteins cleaved caspase-3,cleaved PARP1,as well as the ratio of Bax/Bcl-2.CQ had no significant impact on the oxidative stress indicators,fibrosis,and apoptosis related proteins.The results of Western blotting for autophagy related proteins showed that the ratio of LC3 II/LC3 I and the expression of Beclin-1 in the retina of DM mice were decreased by 3-MA treatment,and the expression of P62 was further increased by CQ treatment.CONCLUSION:3-MA has anti-apoptotic and anti-fibrotic effects on the retina of DM mice,and can attenuate retinal oxidative stress,VEGF expression and the production of inflammatory factors in the retina of DM mice.The underlying mechanism of the above effects of 3-MA may be related to its inhibition of early autophagy and hypoglycemic effect.

From Diabetes to Diabetic Complications:Role of Autophagy

Diabetes and its complications reduce quality of life and are life-limiting.At present,diabetes treatment consists of hypoglycemic agents to control blood glucose and the use of insulin-sensitizing drugs to overcome insulin resistance.In diabetes,autophagy is impaired and thus there is poor intracellular environment homeostasis.Pancreaticβ-cells and insulin target tissues are protected by enhancing autophagy.Autophagy decreasesβ-cell apoptosis,promotesβ-cell proliferation,and alleviates insulin resistance.Autophagy in diabetes is regulated by the mammalian target of rapamycin(mTOR)/adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK)pathway and others.Autophagy enhancers can likely be used as a treatment for diabetes and its complications.This review examines the evidence linking autophagy to diabetes.

凝血因子Ⅲ在非小细胞肺癌高凝状态患者外周血中的表达及其临床意义

目的:研究凝血因子Ⅲ在非小细胞肺癌(non-small cell lung cancer,NSCLC)高凝状态患者外周血中的表达水平,并探讨其表达水平与临床病理特征和生存期的关系。方法:选取2013年1月至2014年10月云南省肿瘤医院病理和生化检测证实为NSCLC高凝状态患者74例,NSCLC无高凝状态患者42例作为研究对象,酶联免疫法检测血清凝血因子Ⅲ的表达水平,分析其与NSCLC临床病理特征和预后的关系。结果:化疗前NSCLC高凝状态患者血清凝血因子Ⅲ为(560.32~200.34)ng/L,显著高于无高凝状态患者(463.29~159.22)ng/L的表达水平(P=0.008),且显著高于化疗后凝血因子Ⅲ(471.39±160.31)ng/L的血清表达水平(P<0.001);凝血因子Ⅲ在NSCLC高凝状态患者血清中的表达水平与淋巴结转移(P=0.026)、远端转移(P=0.025)和TNM分期(P=0.007)有关,且与凝血酶原时间(PT)(r=-0.638,P=0.032)、活化部分凝血酶时间(APTT)(r=-0.702,P=0.028)呈负相关,与纤维蛋白原(FIB)(r=0.715,P=0.008)、血小板(PLT)(r=0.597,P=0.007)呈正相关;凝血因子Ⅲ高表达水平的NSCLC高凝状态患者1~3年总生存期显著低于低表达患者(P<0.05)。结论:NSCLC高凝状态患者血清凝血因子Ⅲ表达水平与淋巴结转移和TNM分期有关,对患者生存期具有预测的指导意义。

Curcumin protects against acetaminophen-induced apoptosis in hepatic injury

AIM:To explore the effects of curcumin(CMN)on hepatic injury induced by acetaminophen(APAP)in vivo.METHODS:Male mice were randomly divided into three groups:groupⅠ(control)mice received the equivalent volumes of phosphate-buffered saline(PBS)intraperitoneally(ip);GroupⅡ[APAP+carboxymethylcellulose(CMC)]mice received 1%CMC(vehicle)2h before APAP injection;GroupⅢ(APAP+CMN)mice received curcumin(10 or 20 mg/kg,ip)2 h before before or after APAP challenge.In GroupsⅡandⅢ,APAP was dissolved in pyrogen-free PBS and injected at a single dose of 300 mg/kg.CMN was dissolved in 1%CMC.Mice were sacrificed 16 h after the APAP injection to determine alanine aminotransferase(ALT)levels in serum and malondialdehyde(MDA)accumulation,superoxide dismutase(SOD)activity and hepatocyte apoptosis in liver tissues.RESULTS:Both pre-and post-treatment with curcumin resulted in a significant decrease in serum ALT compared with APAP treatment group(10 mg/kg:801.46±661.34 U/L;20 mg/kg:99.68±86.48 U/L vs 5406.80±1785.75 U/L,P<0.001,respectively).The incidence of liver necrosis was significantly lowered in CMN treated animals.MDA contents were significantly reduced in 20 mg/kg CMN pretreatment group,but increased in APAP treated group(10.96±0.87 nmol/mg protein vs 16.03±2.58 nmol/mg protein,P<0.05).The decrease of SOD activity in APAP treatment group and the increase of SOD in 20 mg/kg CMN pretreatment group were also detected(24.54±4.95 U/mg protein vs 50.21±1.93 U/mg protein,P<0.05).Furthermore,CMN treatment efficiently protected against APAPinduced apoptosis via increasing Bcl-2/Bax ratio.CONCLUSION:CMN has significant therapeutic potential in both APAP-induced hepatotoxicity and other types of liver diseases.

Chondroitinase ABC treatment of injured spinal cord in rats Evaluation of long-term outcomes

Chondroitin sulfate proteoglycans （CSPGs） which are produced by mature oligodendrocytes and reactive astrocytes can be upregulated after spinal cord injury and contribute to regenerative failure. Chondroitinase ABC （ChABC） digests glycosaminoglycan chains on CSPGs and can thereby overcome CSPG-mediated inhibition. However, many current studies have used an incomplete spinal cord injury model, and examined results after 8-12 weeks of ChABC treatment. In this study, a complete rat spinal cord transection injury model was used to study the long-term effects of ChABC treatment by subarachnoid catheter. Pathology of spinal cord regeneration was compared with control 24 weeks following ChABC treatment using immunohistochemistry and axon tracing techniques. At 24 weeks after injury, neurofilament 200 expression was significantly greater in the ChABC treatment group compared with the transection group. In the ChABC treatment group, axonal growth was demonstrated by a large number of biotinylated dextran amine positive axons caudal to, or past, the epicenter of injury. Biotinylated dextran amine-labeled fibers were found in the proximal end of the spinal cord in the transection alone group. These results confirm that ChABC can promote axon growth, neural regeneration, and repair after spinal cord injury in rats long after the initial injury.

为何美丽总是愁人的——《边城》“淡淡的忧伤”的寂寞源头

近年来，学术界已经公认沈从文的（边城》有牧歌般的田园诗风格，在诗意性的话语和简约的叙述中，作品笼罩着一股淡淡的忧伤，用沈从文的话说，就是“美丽总是愁人的”，而这种“淡淡的忧伤”是和沈从文的“寂寞”分不开的，这种寂寞来自“另一种情感的堆积”，还来自作家在文坛的孤独寂寞，也来自深刻的民族文化心理的孤独感。

Chylothorax following posterior low lumbar fusion surgery:A case report

BACKGROUND Postoperative chylothorax is usually regarded as a complication associated with cardiothoracic surgery;however,it is one of the rare complications in orthopedic surgery.This case report describes a female patient who developed chylothorax after a successful L4-S1 transforaminal lumbar interbody fusion surgery.The etiology,diagnosis,and treatment were analyzed and discussed.CASE SUMMARY A 50-year-old woman was admitted with repeated back and leg pain.She was diagnosed with L4 degenerative spondylolisthesis,L4/L5 and L5/S1 intervertebral disc herniation and L5 instability,and underwent successful posterior L4-S1 instrumentation and fusion surgery.Unfortunately,thoracic effusion was identified 2 d after operation.The thoracic effusion was finally confirmed to be chylous based on twice positive chyle qualitative tests.The patient was discharged after 12-d persisting drainage,3-d total parenteral nutrition and fasting,and other supportive treatments.No recurring symptoms were observed within 12 mo follow-up.CONCLUSION Differential diagnosis is crucial for unusual thoracic effusion.Comprehensive diagnosis and treatment of chylothorax are necessary.Thorough intraoperative protection to relieve high thoracic pressure caused by the prone position is important.

Erratum to:Discovery of Chrysoeriol,a PI3K-AKT-mTOR Pathway Inhibitor with Potent Antitumor Activity against Human Multiple Myeloma Cells In Vitro

The authors examined the original data of their work and noticed a misuse of the image of the bands of AKT and actin in fig.2A(as shown below on the upper panel).The error occurred during the preparation of the manuscript,mainly due to the wrongly labeling of image items or folders inadvertently.The correct one is shown in fig.2 on the lower panel.The authors sincerely apologize for the mistake and confirm that the change does not affect the scientific conclusion of the published work.

Effects of total dissolved gas supersaturated water on lethality and catalase activity of Chinese sucker(Myxocyprinus asiaticus Bleeker)

Total dissolved gas(TDG) supersaturation caused by dam sluicing can result in gas bubble trauma(GBT) in fish and threaten their survival.In the present study,Chinese suckers(Myxocyprinus asiaticus Bleeker) were exposed to TDG supersaturated water at levels ranging from 120% to 145% for 48 h.The median lethal concentration(LC 50) and the median lethal time(LT 50) were determined to evaluate acute lethal effects on Chinese suckers.The results showed that the LC 50 values of 4,6,8,and 10 h were 142%,137%,135%,and 130%,respectively.The LT 50 values were 3.2,4.7,7.8,9.2,and 43.4 h,respectively,when TDG supersaturated levels were 145%,140%,135%,130%,and 125%.Furthermore,the biological responses in Chinese suckers were studied by assaying the catalase(CAT) activities in gills and muscles at the supersaturation level of 140% within LT 50.The CAT activities in the gills and muscle tissues exhibited a regularity of a decrease after an increase.CAT activities in the muscles were increased significantly at 3/5LT 50(P<0.05) and then came back to the normal level.However,there were no significant differences between the treatment group(TDG level of 140%) and the control group(TDG level of 100%) on CAT activities in the gills before 3/5LT 50(P>0.05),but the activities were significantly lower than the normal level at 4/5LT 50 and LT 50(P<0.05).

Cervical Disc Arthroplasty Combined with Interbody Fusion for the Treatment of Cervical Myelopathy with Diffuse Idiopathic Skeletal Hyperostosis： A Case Report

Diftuse idiopathic skeletal hyperostosis （DISHL also known as Forestier＇s disease, was originally reported by Forestier and Rotes-Querol in 1950. It is a common but underdiagnosed skeletal disease characterized by massive ossification of the anterior longitudinal ligament of several vertebral bodies. The most common symptom of cervical DISH is dysphagia due to mechanical compression of the esophagus. Reports of cervical myelopathy associated with DISH are rare. Here, we present a case describing a DISH patient with cervical myelopathy who was effectively treated by a carefully designed surgical procedure.

Indoleamine 2,3-dioxygenase and regulatory dendritic cells contribute to the allograft protection induced by infusion of donor-specific splenic stromal cells

It has been reported that splenic stromal cells(SSCs)are capable of directly supporting the development of CD11c ^(lo)CD45RB^(+) IL-10-producing dendritic cells(DCs)from lineage-negative c-kit^(+) progenitor cells in the absence of exogenous cytokines.In vitro,DCs that differentiate on stromal cells suppress mixed leukocyte reaction responses and induce primary alloreactive CD4^(+) T cells to differentiate into IL-10-producing Tr1 cells.However,the precise mechanisms by which these SSCs exert their regulatory functions in vivo remain undefined.Furthermore,their possible contribution to the development of allograft transplantation tolerance has yet to be examined.Here,we have used both murine skin and cardiac allograft transplantation models to explore whether in vivo alloresponses can be regulated by infusion with donor-derived SSCs and to investigate the possible mechanisms by which SSCs exert regulatory effects to prevent allograft rejection.We show that intravenous SSC infusion prolonged murine skin allograft survival.The prolonged graft survival is associated with augmentation of the generation of regulatory DC subsets and CD4^(+) CD25^(+) Foxp3^(+) regulatory T cells(Tregs),as well as upregulation of the production of suppressive cytokines IL-10 and transforming growth factor(TGF)-b.Moreover,we found that indoleamine 2,3-dioxygenase and SSC-derived regulatory DCs contribute to allograft protection by infusion of donor-specific SSCs.Our data suggest that donor-derived SSCs could be used as a therapeutic target to promote transplantation tolerance.

SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism

The SARS-CoV-2 infection causes severe immune disruption.However,it is unclear if disrupted immune regulation still exists and pertains in recovered COVID-19 patients.In our study,we have characterized the immunephe no type of B cells from 15 recovered COVID-19 patients,and found that healthy controls and recovered patients had similar B-cell populations before and after BCR stimulation,but the frequencies of PBC in patients were significantly increased when compared to healthy controls before stimulation.However,the percentage of unswitched memory B cells was decreased in recovered patients but not changed in healthy controls upon BCR stimulation.Interestingly,we found that CD19 expression was significantly reduced in almost all the B-cell subsets in recovered patients.Moreover,the BCR signaling and early B-cell response were disrupted upon BCR stimulation.Mechanistically,we found that the reduced CD19 expression was caused by the dysregulation of cell metabolism.In conclusion,we found that SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhandng B-cell metabolism,which may provide a new intervention target to cure COVID-19.

The regulators of BCR signaling during B cell activation

B lymphocytes produce antibodies under the stimulation of specific antigens,thereby exerting an immune effect.B cells identify antigens by their surface B cell receptor(BCR),which upon stimulation,directs the cell to activate and differentiate into antibody generating plasma cells.Activation of B cells via their BCRs involves signaling pathways that are tightly controlled by various regulators.In this review,we will discuss three major BCR mediated signaling pathways(the PLC-g2 pathway,PI3K pathway and MAPK pathway)and related regulators,which were roughly divided into positive,negative and mutual-balanced regulators,and the specific regulators of the specific signaling pathway based on regulatory effects.

主动脉球囊阻塞术在控制骶尾部手术出血中的应用

进行骶尾部肿瘤根治手术时常常会出现危及生命的大出血。当前，有效、安全地控制这类出血仍是一个难题。在此我们报道在骶尾部肿瘤切除手术中应用球囊间歇阻塞腹主动脉远端来控制出血的一种方法。球囊管由股动脉插入，并进入腹主动脉。操作中，通过比较双侧脚趾的氧饱和度信号和超声定位来引导和确保球囊进入腹主动脉中肾动脉远端的位置。腹主动．脉内血流每阻断60分钟就开放10分钟。在进行骶尾部肿瘤切除手术的5例患者使用球囊阻塞后，失血量均小于300ml，手术时间短于2小时。手术后患者的肾脏、盆腔脏器以及下肢功能未出现明显改变。故经皮主动脉球囊阻塞术可对骶尾部肿瘤切除手术中出血进行有效而安全的控制。