The moderating effect of physical activity on the relationship between bullying and mental health among sexual and gender minority youth

Background:Sexual and gender minority youth frequently experience bullying,which often contributes to higher depressive symptoms and lower self-esteem.Given that physical activity(PA)can mitigate depressive symptoms and improve self-esteem,we examined the moderating effect of PA on the relationship between bullying and mental health among sexual and gender minority youth.Methods:Data from the Lesbian,Gay,Bisexual,Transgender,and Queer National Teen Survey(n=9890)were analyzed.Hierarchical regression analyses examined the influence of history and frequency of being bullied,PA,and the interaction of these variables on depressive symptoms and self-esteem.Simple slopes analyses were used to probe significant interactions.Results:Results indicated the importance of accounting for bullying history when examining effects of PA on mental health.PA was negatively related to depression(t=-4.18,p<0.001)and positively related to self-esteem(t=12.11,p<0.001).Bullying frequency was positively related to depression(t=19.35,p<0.001)and negatively related to self-esteem(t=-12.46,p<0.001).There was a significant interaction between bullying frequency and PA for depression(t=4.45,p<0.001)and self-esteem(t=-4.69,p<0.001).Post hoc analyses suggested that the positive effects of PA on mental health may be limited to those not bullied because it had a negligible effect on those who were bullied.Conclusion:Results suggest that sexual and gender minority youth exercise interventions aiming to improve mental health should first address bullying history;otherwise,their effectiveness may be limited to those who have been bullied.

Direct cost variance analysis of peroral endoscopic myotomy vs heller myotomy for management of achalasia:A tertiary referral center experience

BACKGROUND Laparoscopic Heller myotomy(LHM)has been the traditional surgical treatment for achalasia.Recently,peroral endoscopic myotomy(POEM)has demonstrated similar clinical outcomes with shorter procedure times.Studies comparing the direct cost-effectiveness of POEM vs LHM are limited.AIM To compare costs of POEM vs LHM.METHODS Haider SA et al.Comparing costs:POEM vs Heller myotomy WJGE https://www.wjgnet.com 594 October 16,2023 Volume 15 Issue 10 This retrospective chart review aimed to compare the outcomes and cost of clinical care between patients who underwent POEM and LHM procedures for achalasia.The study was conducted at a tertiary academic center from January 2019 to December 2020.Clinical outcomes,including post-operative Eckardt scores and adverse events,were assessed and compared between the two groups.Direct cost variance analysis was utilized to evaluate the cost of clinical care incurred by patients undergoing POEM in the year preceding the procedure,during the index admission,and one year post-procedure,in comparison to patients undergoing LHM.RESULTS Of 30 patients were included(15 POEM and 15 LHM)in the study.Patients in the POEM group had a mean Eckardt score of 0.5±0.5 post-procedure,which was no different from patients in the LHM group(0.7±0.6,P=0.17)indicating comparative efficacy.However,the total costs of the admission for the procedure in the LHM group were on average$1827 more expensive than in the POEM group(P<0.01).Total healthcare costs one year prior to index procedure were$7777 higher in the LHM group,but not statistically different(P=0.34).The patients in the LHM group one year after the index procedure had accrued$19730.24 larger total cost,although this was not statistically different from POEM group(P=0.68).CONCLUSION Despite similar clinical outcomes,the cost of the index procedure admission for POEM was significantly lower than for LHM.The difference was primarily related to shorter time increments utilized in the operating room during the index procedure,and shorter length of hospital stay following POEM.

Mechanisms and functions of DNA mismatch repair

脱氧核糖核酸失配修理(MMR ) 是在维持 genomic 稳定性起一个关键作用的一条高度保存的生物小径。MMR 的特性主要为在 DNA 和再结合期间产生的基础底的失配和插入 / 删除错误对。MMR 也压制 homeologous 再结合并且是最近显示损坏在真核细胞的房间发信号在脱氧核糖核酸起一个作用。分别地， Escherichia 关口 i 傻瓜和 MutL 和他们的真核细胞的相当或相同的事物， MutSalpha 和 MutLalpha 是在联系 MMR 的染色体维护的关键播放器。参予各种各样的脱氧核糖核酸的许多另外的蛋白质部件新陈代谢的小径例如 PCNA 和 RPA，为 MMR 也是必要的。在 MMR 的缺点与染色体宽的不稳定性被联系，倾向到包括世袭 non-polyposis 颜色的癌症的某些类型表面的癌症，到某些化学疗法的代理人的抵抗，和在成熟分裂的畸形和在哺乳动物的系统的绝育。

Role of surgery and transplantation in the treatment of hepatic metastases from neuroendocrine tumor

Neuroendocrine tumors(NET) are a heterogeneous group of cancers, with indolent behavior. The most common primary origin is the gastro-intestinal tract but can also appear in the lungs, kidneys, adrenals, ovaries and other organs. In general, NET is usually discovered in the metastatic phase(40%-80%). The liver is the most common organ involved when metastases occur(40%-93%), followed by bone(12%-20%) and lung(8%-10%).A number of different therapeutic options are available for the treatment of hepatic metastases including surgical resection, transplantation, ablation, trans-arterial chemoembolization, chemotherapy and somatostatin analogues. Recently, molecular targeted therapies have been used, usually in combination with other treatment options, to improve outcomes in patients with metastases. This article emphasizes on the role of surgery in the treatment of liver metastases from NET.

Endometrial response to conceptus-derived estrogen and interleukin-1β at the time of implantation in pigs

The establishment of pregnancy is a complex process that requires a well-coordinated interaction between the implanting conceptus and the maternal uterus. In pigs, the conceptus undergoes dramatic morphological and functional changes at the time of implantation and introduces various factors, including estrogens and cytokines,interleukin-1β2(IL1 B2), interferon-γ(IFNG), and IFN-δ(IFND), into the uterine lumen. In response to ovarian steroid hormones and conceptus-derived factors, the uterine endometrium becomes receptive to the implanting conceptus by changing its expression of cell adhesion molecules, secretory activity, and immune response. Conceptus-derived estrogens act as a signal for maternal recognition of pregnancy by changing the direction of prostaglandin(PG) F2αfrom the uterine vasculature to the uterine lumen. Estrogens also induce the expression of many endometrial genes,including genes related to growth factors, the synthesis and transport of PGs, and immunity. IL1 B2, a pro-inflammatory cytokine, is produced by the elongating conceptus. The direct effect of IL1 B2 on endometrial function is not fully understood. IL1 B activates the expression of endometrial genes, including the genes involved in IL1 B signaling and PG synthesis and transport. In addition, estrogen or IL1 B stimulates endometrial expression of IFN signaling molecules,suggesting that estrogen and IL1 B act cooperatively in priming the endometrial function of conceptus-produced IFNG and IFND that, in turn, modulate endometrial immune response during early pregnancy. This review addresses information about maternal-conceptus interactions with respect to endometrial gene expression in response to conceptus-derived factors, focusing on the roles of estrogen and IL1 B during early pregnancy in pigs.

Therapeutic implications of advanced age at time of spinal cord injury

A recent demographic shift towards increased age at time of spinal cord injury (SCI), as well as decreased functional recovery following SCI in older populations, create the need to investigate how age effects SCI pathology and repair (Scivoletto et al., 2003). While decreased neuroplasticity or physical strength with age may contribute to functional deficits, work from our lab and others have identified exacerbated acute inflammatory events as contributors to age-dependent secondary injury. Specifically, our recent paper identified that increased production of reactive oxygen species (ROS) from macrophage nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) with age exacerbates secondary injury after SCI (Zhang et al., 2019).

Expression of nucleus accumbens-1 in colon cancer negatively modulates antitumor immunity

BACKGROUND Nucleus accumbens-1(NAC-1)is highly expressed in a variety of tumors,including colon cancer,and is closely associated with tumor recurrence,metastasis,and invasion.AIM To determine whether and how NAC-1 affects antitumor immunity in colon cancer.METHODS NAC-1-siRNA was transfected into RKO colon cancer cells to knock down NAC expression;tumor cells with or without knockdown of NAC-1 were treated with CD8+T cells to test their cytocidal effect.The level of the immune checkpoint programmed death receptor-1 ligand(PD-L1)in colon cancer cells with or without knockdown of NAC-1 was analyzed using Quantitative real-time polymerase chain reaction and Western blotting.A double luciferase reporter assay was used to examine the effects of NAC-1 on the transcription of PD-L1.Mice bearing MC-38-OVA colon cancer cells expressing NAC-shRNA or controlshRNA were treated with OT-I mouse CD8+T cells to determine the tumor response to immunotherapy.Immune cells in the tumor tissues were analyzed using flow cytometry.NAC-1,PD-L1 and CD8+T cells in colon cancer specimens from patients were examined using immunohistochemistry staining.RESULTS Knockdown of NAC-1 expression in colon cancer cells significantly enhanced the cytocidal effect of CD8+T cells in cell culture experiments.The sensitizing effect of NAC-1 knockdown on the antitumor action of cytotoxic CD8+T cells was recapitulated in a colon cancer xenograft animal model.Furthermore,knockdown of NAC-1 in colon cancer cells decreased the expression of PD-L1 at both the mRNA and protein levels,and this effect could be rescued by transfection of an RNAi-resistant NAC-1 expression plasmid.In a reporter gene assay,transient expression of NAC-1 in colon cancer cells increased the promoter activity of PD-L1,indicating that NAC-1 regulates PD-L1 expression at the transcriptional level.In addition,depletion of tumoral NAC-1 increased the number of CD8+T cells but decreased the number of suppressive myeloid-derived suppressor cells and regulatory T cells.CONCLUSION Tumor expression of NAC-1 is a negative determinant of immunotherapy.

In vivo anti-tumor activity of murine hematopoietic stem cells expressing a p185HER2-specific chimeric T-cell receptor gene

We have confirmed efficient anti-tumor activities of the peripheral lymphocytes transduced with a p185HER2-specific chimeric T-cell receptor gene both in murine and in human in our previous studies. To further test the feasibility of chimeric T-cell receptor in a bone marrow transplantation model, we first, made two murine tumor cell lines: MT901 and MCA-205, to express human p185HER2 by retroviral gene transduction. Murine bone marrow cells were retrovirally transduced to express the chimeric T-cell receptor and gene-modified bone marrow cells were transplanted into lethally irradiated mouse. Six months post transplantation, p185HER2-positive tumor cells:MT-901/HER2 or MCA-205/ HER2 was subcutaneously or intravenously injected to make mouse models simulating primary breast cancer or pulmonary metastasis. The in vivo anti-tumor effects were monitored by the size of the subcutaneous tumor or counting the tumor nodules in the lungs after India ink staining. The size of the subcutaneous tumor was significantly inhibited and the number of pulmonary nodules were significantly decreased in mouse recipients transplanted with chimeric T-cell receptor modified bone marrow cells compared with the control group. Our results suggest the efficient in vivo anti-tumor activities of chimeric T-cell receptor gene modified bone marrow cells.

Outcome of gastric antral vascular ectasia and related anemia after orthotopic liver transplantation

BACKGROUND Gastric antral vascular ectasia(GAVE)is a significant complication of cirrhosis.Numerous medical,surgical,and endoscopic treatment modalities have been proposed with varied satisfactory results.In a few small studies,GAVE and associated anemia have resolved after orthotopic liver transplantation(OLT).AIM To assess the impact of OLT on the resolution of GAVE and related anemia.METHODS We retrospectively reviewed clinical records of adult patients with GAVE who underwent OLT between September 2012 and September 2019.Demographics and other relevant clinical findings were collected,including hemoglobin levels and upper endoscopy findings before and after OLT.The primary outcome was the resolution of GAVE and its related anemia after OLT.RESULTS Sixteen patients were identified.Mean pre-OLT Hgb was 7.7 g/dL and mean 12 mo post-OLT Hgb was 11.9 g/dL,(P=0.001).Anemia improved(defined as Hgb increased by 2g)in 87.5%of patients within 6 to 12 mo after OLT and resolved completely in half of the patients.Post-OLT esophagogastroduodenoscopy was performed in 10 patients,and GAVE was found to have resolved entirely in 6 of those patients(60%).Although GAVE and associated anemia completely resolved in the majority of our patients after OLT,GAVE persisted in a few patients after transplant.Further studies in a large group of patients are necessary to understand the causality of disease and to better understand the factors associated with the persistence of GAVE post-transplant.

Benign course of residual inflammation at end of treatment of liver transplant recipients after sofosbuvir based therapy

BACKGROUND Persistent inflammation on histology after successful hepatitis C(HCV)treatment has been reported.However,data regarding the long-term impact in liver transplant recipients is limited,particularly after using direct-acting antiviral(DAA)therapies.AIM To evaluate the impact of successful treatment with DAAs on histological changes and occult HCV and to describe the clinical course of residual inflammation in liver transplant recipients.METHODS We conducted a case series of 13 chronic HCV infected liver transplant recipients successfully treated with DAAs between December 2013 and May 2014.All patients were treated for 24 wk and had non-detectable serum HCV RNA by the time of biopsy.Only patients with at least one liver biopsy at or after treatment were included.We examined liver biopsies for evidence of residual inflammation and the presence of intrahepatic HCV RNA.RESULTS Persistent inflammation was seen in 12/13 patients on end of treatment biopsy.Inflammation was still seen in the available five follow-up biopsies(range 38-48 wk after the end of treatment).Intrahepatic HCV RNA was undetectable in all biopsies.All patients had preserved graft function for a mean follow-up of 2.5 years,except one that developed chronic rejection.CONCLUSION After successful HCV treatment with DAAs,liver transplant recipients may have persistent inflammation on biopsy without evidence of intracellular RNA.The clinical outcome remained favorable in most patients.Further studies with a larger number and longer follow-up are needed to establish the implication of this finding on long-term graft function.

Surgical intervention combined with weight-bearing walking training promotes recovery in patients with chronic spinal cord injury:a randomized controlled study

For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein thrombosis.Surgery is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury patients.Development of effective therapies fo r chronic spinal co rd injury patients is needed.We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive rehabilitation.This clinical trial was registered at ClinicalTrials.gov(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord compression.We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training alone.Overall,the surgical procedures and intensive rehabilitation were safe.American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries.Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.

Control of CD4^(+) T cells to restrain inflammatory diseases via eukaryotic elongation factor 2 kinase

CD4^(+)T cells,particularly IL-17-secreting helper CD4^(+)T cells,play a central role in the inflammatory processes underlying autoimmune disorders.Eukaryotic Elongation Factor 2 Kinase(eEF2K)is pivotal in CD8^(+)T cells and has important implications in vascular dysfunction and inflammation-related diseases such as hypertension.However,its specific immunological role in CD4^(+)T cell activities and related inflammatory diseases remains elusive.Our investigation has uncovered that the deficiency of eEF2K disrupts the survival and proliferation of CD4^(+)T cells,impairs their ability to secrete cytokines.Notably,this dysregulation leads to heightened production of pro-inflammatory cytokine IL-17,fosters a pro-inflammatory microenvironment in the absence of eEF2K in CD4^(+)T cells.Furthermore,the absence of eEF2K in CD4^(+)T cells is linked to increased metabolic activity and mitochondrial bioenergetics.We have shown that eEF2K regulates mitochondrial function and CD4^(+)T cell activity through the upregulation of the transcription factor,signal transducer and activator of transcription 3(STAT3).Crucially,the deficiency of eEF2K exacerbates the severity of inflammation-related diseases,including rheumatoid arthritis,multiple sclerosis,and ulcerative colitis.Strikingly,the use of C188-9,a small molecule targeting STAT3,mitigates colitis in a murine immunodeficiency model receiving eEF2K knockout(KO)CD4^(+)T cells.These findings emphasize the pivotal role of eEF2K in controlling the function and metabolism of CD4^(+)T cells and its indispensable involvement in inflammation-related diseases.Manipulating eEF2K represents a promising avenue for novel therapeutic approaches in the treatment of inflammation-related disorders.

Data and subject heterogeneity and data sharing:keys to translational success in spinal cord injury research?

Spinal cord injury(SCI)is a highly devastating and com plex inj u ry with many seconda ry consequences.Finding a treatment for SCI has been a rollercoaster ride through exciting peaks and sobering valleys.As a matter of fact,there are still no robust and reliable clinical treatments to minimize or repair spinal cord damage.

年龄相关的情绪偏向效应的时间进程（英文）

来自记忆、注意和决策等领域的大量研究发现，在加工情绪刺激时老年人具有正性情绪偏向或负性情绪规避的特点．本研究采用oddball变式，将情绪面孔图片作为分心刺激呈现．实验过程中记录被试脑电，考察不同情绪效价对脑电波的影响，同时考察老年人在非任务相关条件下情绪加工和情绪调节的时间进程．研究发现，在相对早期时间窗口（270--460ms），年轻组脑电不受情绪效价影响，而老年组中悲伤情绪面孔较之快乐和中性情绪面孔引发了一个更大的正成分（P3a）．在晚期时间窗口（500--850ms），年轻组中悲伤情绪面孔吸引了被试更多注意并引发了一个更大的正性慢波．相反，老年组在晚期加工阶段，情绪效价效应消失．研究揭示了老年人和年轻人在加工非任务相关的情绪刺激时存在的时间进程差异，年龄相关的正性情绪效应发生在晚期时间窗口，表现为年轻组的负性情绪偏向和老年组的无情绪偏向．研究结果为社会情绪选择理论提供了来自脑电数据的支持．

转染嵌合性T细胞受体基因小鼠T淋巴细胞的体外抗肿瘤作用

目的:研究小鼠T淋巴细胞在转染嵌合性T细胞受体基因后的体外抗肿瘤作用。方法:应用重组DNA技术,将HER2特异性嵌合性T-细胞受体构建入逆转录病毒载体;转入包装细胞后,收集病毒上清,转染小鼠T淋巴细胞,转基因后的小鼠T淋巴细胞分别与HER2阳性(SK-OV-3)或阴性(MCF-7)的肿瘤细胞系共培养,检测其细胞因子γ干扰素释放,51Cr释放法检测CTL评价其抗肿瘤效应。结果:所构建载体经酶切鉴定符合要求,乒乓法转染包装细胞系GP+E86,检测病毒滴度为1.2×106,Retronectin结合离心法转染经抗CD3/CD28单抗活化的小鼠T淋巴细胞,转染效率可达50%以上;转染嵌合性T细胞受体基因的T淋巴细胞与HER2阳性或阴性的肿瘤细胞系共培养后可检测到HER2特异性的细胞因子γ干扰素释放,51Cr释放法测CTL可见转染嵌合性T细胞受体基因T淋巴细胞对HER2阳性的肿瘤细胞具显著杀伤效应。结论:转染嵌合性T细胞受体基因的小鼠T淋巴细胞在体外可通过细胞因子释放和CTL效应发挥显著的抗肿瘤作用。

老年大鼠黑质中铁蓄积诱导的氧化应激效应(英文)

背景:脑内一些区域内胶质细胞中铁的过多沉积和由铁介导的氧化应激反应可能与帕金森病等一些神经退行性疾病的发病有关,但目前对老年F344大鼠中脑黑质内铁沉积的亚细胞结构研究客观评价标准并不多见。目的:观察老年F344大鼠黑质部位铁的沉积,为进一步了解PD的发病机制提供理论依据。设计:随机对照实验研究。单位:首都医科大学北京神经科学研究所和DepartmentofAnatomy&Neurobiology,UniversityofKentucky,CollegeofMedicine,LexintonU.S.A。材料:选择24个月(6只),3个月(4只)Fischer(F344)雄性大鼠。干预:将灌注固定后的脑组织取出中脑部分置于振动切片机上,将其切成40μm脑薄片。分别采用免疫组织化学方法:激光共聚焦显微镜;透射电子显微镜及电子探针元素能量微分析等技术,对中脑黑质部位铁的沉积做一系统组织化学及形态学观察。主要观察指标:在光镜、激光共聚焦显微镜、透射电子显微镜下观察及电子探针元素能量微分析中脑黑质部位铁的沉积。结果:在光镜下,作为铁的主要储存形式-铁结合蛋白在黑质的网状部有明显增加并伴随着小胶质的增加,激光共聚焦显微镜下观察到它们很少存在于多巴胺神经元及星形质细胞内,而主要存在于小胶质中,利用电子探针检测结果显示的游离铁元素,主要位于星形胶质细胞的胞浆内,?

Epithelial-mesenchymal transition in breast cancer progression and metastasis

Breast cancer is the most common cancer in women,and approximately 90% of breast cancer deaths are caused by local invasion and distant metastasis of tumor cells.Epithelial-mesenchymal transition(EMT) is a vital process for large-scale cell movement during morphogenesis at the time of embryonic development.Tumor cells usurp this developmental program to execute the multi-step process of tumorigenesis and metastasis.Several transcription factors and signals are involved in these events.In this review,we summarize recent advances in breast cancer researches that have provided new insights in the molecular mechanisms underlying EMT regulation during breast cancer progression and metastasis.We especially focus on the molecular pathways that control EMT.

An event-related potential study of working memory in children

To examine the neural mechanisms o working memory in children, event-related potentials (ERPs) were recorded from the 12―13 year-old while they performed a delayed match-to-sample task. The ERP results revealed that new and studied objects both evoked a late positive ERP componen peaking around 350 ms during the working memory process. New objects evoke a more positive ERP waveform than the studied objects. The scalp distri bution showed that the frontal-central electrode sites were associated with object working memory proc esses. When tracking new or studied targets among visual distracters, ERPs of targets and distracters revealed differential responses as early as 150 ms The visual targets evoked larger and more positive ERP responses than the distracters. The typica old-new effect was observed between ERPs of stud ied and new distracters. However, ERPs of new and studied targets differed at about 250 ms, in which new targets evoked more positive-going and slightly earlier ERP responses. In addition, a P3a componen was found for new targets only, and was absent in ERPs of studied targets at frontal and central sites The present study results reveal the spatial and temporal characteristics of neural mechanisms un derlying working memory in children, some of which are distinct from those in adults.

Prostate tumor neuroendocrine differentiation via EMT: The road less traveled

The long-standing challenge in the treatment of prostate cancer is to overcome therapeutic resistance during progression to lethal disease.Aberrant transforming-growth factor-b(TGF-b)signaling accelerates prostate tumor progression in a transgenic mouse model via effects on epithelial-mesenchymal transition(EMT),and neuroendocrine differentiation driving tumor progression to castration-resistant prostate cancer(CRPC).Neuroendocrine prostate cancer(NEPC)is highly aggressive exhibiting reactivation of developmental programs associated with EMT induction and stem cell-like characteristics.The androgen receptor(AR)is a critical driver of tumor progression as well as therapeutic response in patients with metastatic CRPC.The signaling interactions between the TGF-β mechanistic network and AR axis impact the EMT phenotypic conversions,and perturbation of epithelial homeostasis via EMT renders a critical venue for epithelial derived tumors to become invasive,acquire the neuroendocrine phenotype,and rapidly metastasize.Combinations of microtubule targeting taxane chemotherapy and androgen/AR targeting therapies have survival benefits in CRPC patients,but therapeutic resistance invariability develops,leading to mortality.Compelling evidence from our group recently demonstrated that chemotherapy(cabazitaxel,second line taxane chemotherapy),or TGF-β receptor signaling targeted therapy,caused reversion of EMT to mesenchymal-epithelial transition and tumor re-differentiation,in in vitro and in vivo prostate cancer models.In this review,we discuss the functional contribution of EMT dynamic changes to the development of the neuroendocrine phenotypedthe newly characterized pathological feature of prostate tumors in the context of the tumor microenvironment-navigated cell lineage changes and the role of this neuroendocrine phenotype in metastatic progression and therapeutic resistance.

A critical role of the thioredoxin domain containing protein 5(TXNDC5) in redox homeostasis and cancer development

Correct folding of nascent peptides occurs in the endoplasmic reticulum(ER).It is a complicate process primarily accomplished by the coordination of multiple redox proteins including members of the protein disulfide isomerase(PDI)family.As a critical member of the PDI family,thioredoxin domain containing protein 5(TXNDC5)assists the folding of newly synthesized peptides to their mature form through series of disulfide bond exchange reactions.Interestingly,TXNDC5 is frequently found overexpressed in specimens of many human diseases including various types of cancer.In this review,we summarized the biochemical function of TXNDC5 in mammalian cells and the recent progress on the understanding of its role and molecular mechanisms in cancer development.Findings of TXNDC5 in the activation of intracellular signaling pathways,stimulation of cell growth&proliferation,facilitation of cell survival and modulation of extracellular matrix to affect cancer cell invasion and metastasis are reviewed.These published studies suggest that strategies of targeting TXNDC5 can be developed as potentially valuable methods for the treatment of certain types of cancer in patients.