New perspectives in prognostication of hepatocellular carcinoma:The role and clinical implications of transient receptor potential family genes

The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role of transient receptor potential(TRP)family genes in the disease’s progression and prognosis.Utilizing data from The Cancer Genome Atlas database,it establishes a new risk assessment model,emphasizing the interaction of TRP genes with tumor proliferation pathways,key metabolic reactions like retinol metabolism,and the tumor immune microenvironment.Notably,the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes,suggesting its potential as a prognostic biomarker and a target for personalized therapy,particularly in strategies combining immunotherapy and anti-TRP agents.

Pyroptosis-related genes play a significant role in the prognosis of gastric cancer

BACKGROUND Pyroptosis is an inflammatory form of programmed cell death,which has been shown to be related to the prognosis of many tumors.However,its role in gastric cancer(GC)is not fully understood.AIM To evaluate the expression of pyroptosis-related genes in GC and its correlation with prognosis.METHODS We constructed prognostic multigene markers of differentially expressed genes associated with pyroptosis by least absolute contraction and selection operator Cox regression.The risk model was analyzed by Kaplan-Meier curve,two-sided log-rank test and functional enrichment analysis.RESULTS Sixty-three pyroptosis-related genes were differentially expressed in tumor tissues and adjacent nontumor tissues.Based on these differentially expressed genes,5 gene signature were constructed and all GC patients were classified into two risk groups.Kaplan-Meier survival curve showed that the overall survival(OS)of patients in the high-risk group was significantly lower than that of the low-risk group.Multivariate Cox regression analyses showed that the risk score was an independent risk factor for OS.Receiver operating characteristic curve analysis confirmed the predictive ability of the model.External validation indicated increased OS in the low-risk group.The immune function and immune cell scores of the high-risk group were generally higher than those of the low-risk group.CONCLUSION Pyroptosis-related genes play a significant role in tumor immune microenvironment.This novel model,which contains 5 pyroptosis-related genes,is an independent predicting factor for OS in GC patients,and may help to evaluate the prognosis of GC.

Development of an innovative nomogram of risk factors to predict postoperative recurrence of gastrointestinal stromal tumors

BACKGROUND There are many staging systems for gastrointestinal stromal tumors(GISTs),and the risk indicators selected are also different;thus,it is not possible to quantify the risk of recurrence among individual patients.AIM To develop and internally validate a model to identify the risk factors for GIST recurrence after surgery.METHODS The least absolute shrinkage and selection operator(LASSO)regression model was performed to identify the optimum clinical features for the GIST recurrence risk model.Multivariable logistic regression analysis was used to develop a prediction model that incorporated the possible factors selected by the LASSO regression model.The index of concordance(C-index),calibration curve,receiver operating characteristic curve(ROC),and decision curve analysis were used to assess the discrimination,calibration,and clinical usefulness of the predictive model.Internal validation of the clinical predictive capability was also evaluated by bootstrapping validation.RESULTS The nomogram included tumor site,lesion size,mitotic rate/50 high power fields,Ki-67 index,intracranial necrosis,and age as predictors.The model presented perfect discrimination with a reliable C-index of 0.836(95%CI:0.712-0.960),and a high C-index value of 0.714 was also confirmed by interval validation.The area under the curve value of this prediction nomogram was 0.704,and the ROC result indicated good predictive value.Decision curve analysis showed that the predicting recurrence nomogram was clinically feasible when the recurrence rate exceeded 5%after surgery.CONCLUSION This recurrence nomogram combines tumor site,lesion size,mitotic rate,Ki-67 index,intracranial necrosis,and age and can easily predict patient prognosis.

Optimal cut-off and assessment of survival days are needed in risk factors for COVID-19 mortality

We recently read the study published on The Lancet by Dr.Zhou and colleagues,entitled“Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan,China:a retrospective cohort study”,with great interest[1].First,we do not think this study was a cohort study but should be a case-control study.

Breast-conserving surgery and combined therapy for women breast cancer: a report of 216 cases

Objective: To explore the therapeutic effect and associated techniques of breast-conserving therapy on patients with clinical stage I and stage II breast cancer. Methods: 216 female patients with breast cancer underwent breast-conserv- ing therapy from December 1993 to October 2004. Their data were analyzed retrospectively. The breast-conserving therapy consisted of lumpectomy or quadrant removal of the breast, postoperative radiotherapy, chemotherapy and endocrine ther- apy. Of them, 209 patients underwent axillary lymph node dissection. Results: There were no operative complications. 216 patients were followed-up 3 to 147 months, the medial follow-up time was 78 months. The local recurrence rate was 1.85%. Two patients died and one of them was not related with breast cancer. Presence or absence of fibrosis, shape of breast, asymmetry, pigmentation and handle were taken into consideration for cosmetic evaluation by the patients and experienced breast surgeon. Breasts were scored cosmetically as excellent and good in 199 patients, the rate of satisfactory was 92.13%. Conclusion: Breast-conserving therapy for early breast cancer is a safe and effective therapy. It has less trauma and less complications and can also raise the quality of life in the patients. But we must obey the strict indications and reasonable techniques.

Mechanism and therapeutic strategy of hepatic TM6SF2-deficient non-alcoholic fatty liver diseases via in vivo and in vitro experiments

BACKGROUND The lack of effective pharmacotherapies for nonalcoholic fatty liver disease(NAFLD)is mainly attributed to insufficient research on its pathogenesis.The pathogenesis of TM6SF2-efficient NAFLD remains unclear,resulting in a lack of therapeutic strategies for TM6SF2-deficient patients.AIM To investigate the role of TM6SF2 in fatty acid metabolism in the context of fatty liver and propose possible therapeutic strategies for NAFLD caused by TM6SF2 deficiency.METHODS Liver samples collected from both NAFLD mouse models and human participants(80 cases)were used to evaluate the expression of TM6SF2 by using western blotting,immunohistochemistry,and quantitative polymerase chain reaction.RNA-seq data retrieved from the Gene Expression Omnibus database were used to confirm the over-expression of TM6SF2.Knockdown and overexpression of TM6SF2 were performed to clarify the mechanistic basis of hepatic lipid accumulation in NAFLD.MK-4074 administration was used as a therapeutic intervention to evaluate its effect on NAFLD caused by TM6SF2 deficiency.RESULTS Hepatic TM6SF2 levels were elevated in patients with NAFLD and NAFLD mouse models.TM6SF2 overexpression can reduce hepatic lipid accumulation,suggesting a protective role for TM6SF2 in a high-fat diet(HFD).Downregulation of TM6SF2,simulating the TM6SF2 E167K mutation condition,increases intracellular lipid deposition due to dysregulated fatty acid metabolism and is characterized by enhanced fatty acid uptake and synthesis,accompanied by impaired fatty acid oxidation.Owing to the potential effect of TM6SF2 deficiency on lipid metabolism,the application of an acetyl-CoA carboxylase inhibitor(MK-4074)could reverse the NAFLD phenotypes caused by TM6SF2 deficiency.CONCLUSION TM6SF2 plays a protective role in the HFD condition;its deficiency enhanced hepatic lipid accumulation through dysregulated fatty acid metabolism,and MK-4074 treatment could alleviate the NAFLD phenotypes caused by TM6SF2 deficiency.

25-Hydroxyvitamin D Is Associated with Islet Homeostasis in Type-2 Diabetic Patients with Abdominal Obesity

Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T2D)patients.Methods A total of 4670 T2D patients from seven communities in Shanghai,China were enrolled.The anthropometric indices,biochemical parameters,serum 25(OH)D,and islet function[including C-peptide(C-p)and glucagon]were measured.Results The fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),glucagon,and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels increased.Next,the population was divided into two groups:abdominal obesity and non-abdominal obesity groups.After adjustment,the 25(OH)D level was found to be associated with HbA1c,glucagon,and homeostasis model assessment ofβ(HOMA-β)in the non-abdominal obesity group.There was a significant relationship between 25(OH)D and HbA1c,glucagon,HOMA-IR,baseline insulin or C-p in the abdominal obesity group.In the abdominal obesity group,the ordinary least squares(OLS)regression and quantile regression revealed that 25(OH)D was obviously associated with glucagon and fasting C-p levels.In the abdominal obesity group,the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p(P=0.0124).Furthermore,the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation(SD)below the mean(P=0.0002),and lower at the mean of the course of diabetes(P=0.0007).Conclusion 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal obesity.The 25(OH)D influenced C-p in part by influencing glucagon.The effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity,in terms of islet homeostasis,is influenced by the course of diabetes.

带气囊导管构建脊髓缺血模拟再灌注与缺血分离模型

背景:采用带有气囊的导管急性压迫脊髓缺血模拟人类损伤可以造成再灌注与缺血分离的动物模型。目的:应用免疫组化和生物化学分析方法观察不同缺血时间窗处理对损伤脊髓的影响。方法:SD大鼠36只,随机分为假手术组,带气囊导管造成大鼠脊髓缺血10,30,45,60,90min组。结果与结论:再灌注48h后,随着缺血时间的延长,脊髓前角神经元坏死和凋亡逐渐加重,丙二醛水平逐渐增加,超氧化物歧化酶活性逐渐下降,大鼠的神经行为学病症加重。提示用带气囊的导管建立缺血再灌注大鼠模型成功,再灌注后大鼠脊髓的损伤随缺血时间的延长而加重。

Meditation-based Interventions Might be Helpful for Coping with the Corona Virus Disease 2019(COVID-19)

The Coronavirus Disease 2019(COVID-19)has been characterized as the first pandemic caused by a novel coronavirus and drawn intense attention in China and globally.With the incidence and mortality rates of COVID-19 rapidly growing worldwide,people have been experiencing tremendous psychological distress during the pandemic.Elevated psychological stress could compromise the human capacity to fight against COVID-19.However,effective interventions and timely mental health care to increase resilience and improve psychological wel being is still lacking,which would be the focus of this article.In this article,we briefly summarize why meditation practice may have the potential to help minimize stress-related psychological symptoms associated with the coronavirus outbreak and how we can respond efficiently and effectively to this outbreak via taking advantage of meditation.We also provide a brief introduction of a meditation program that we developed and advocate to popularize meditation practice as a viable approach to improve wellbeing while combatting COVID-19 worldwide.

Targeted deep sequencing reveals the genetic heterogeneity in well-differentiated pancreatic neuroendocrine tumors with liver metastasis

Background:Pancreatic neuroendocrine tumor is a rare and heterogeneous entity,and approximately half of the patients harbored liver metastasis when initially diagnosed,whose prognosis is dismal.High-throughput sequencing has largely uncovered the genomic features of pancreatic neuroendocrine tumor,but the genetic alterations in the metastatic cases remain relatively unclear,which we aimed to study.Methods:Pathologically confirmed well-differentiated pancreatic neuroendocrine tumor samples resected in our hospital from 2000 to 2019 were collected.We performed deep sequencing on the exome of 341 tumor-related genes,and compared the differences of genetic alterations between the metastatic and the non-metastatic cases,as well as between the primary and the paired liver metastatic tumors.Results:Sequencing data of 79 samples from 29 pancreatic neuroendocrine tumor patients were included into analysis.A total of 2,471 somatic variants were identified,75.5%of which were considered as low-abundance.NOTCH1 was the most frequently mutated gene,altered in 26(53.1%)pancreatic neuroendocrine tumor samples from 18(62.1%)patients.Compared with the non-metastatic pancreatic neuroendocrine tumors,the metastatic cases were discovered with more single nucleotide variants and copy number variations,indicating the increased genomic instability.In addition,among the paired metastatic cases,the primary and the metastatic lesions shared limited mutated genes.Conclusions:Through the targeted deep sequencing,we identified the intratumor,intraindividual,and interindividual heterogeneity in the pancreatic neuroendocrine tumor patients,particularly in the metastatic cases,bringing potential challenges for the current biopsy strategies in guiding clinical treatments.

COVID-19-associated gastrointestinal and liver injury:clinical features and potential mechanisms

Coronavirus disease-2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The infection is spreading globally and poses a huge threat to human health.Besides common respiratory symptoms,some patients with COVID-19 experience gastrointestinal symptoms,such as diarrhea,nausea,vomiting,and loss of appetite.SARS-CoV-2 might infect the gastrointestinal tract through its viral receptor angiotensin-converting enzyme 2(ACE2)and there is increasing evidence of a possible fecal–oral transmission route.In addition,there exist multiple abnormalities in liver enzymes.COVID-19-related liver injury may be due to drug-induced liver injury,systemic inflammatory reaction,and hypoxia–ischemia reperfusion injury.The direct toxic attack of SARS-CoV-2 on the liver is still questionable.This review highlights the manifestations and potential mechanisms of gastrointestinal and hepatic injuries in COVID-19 to raise awareness of digestive system injury in COVID-19.

西格列他钠与西格列汀单药治疗2型糖尿病患者的随机、双盲、Ⅲ期临床试验(CMAS)

西格列他钠(Chiglitazar,CGZ)是新型过氧化物酶体增殖物激活受体(PPAR)全激动剂,在针对2型糖尿病(T2DM)患者的前期探索性临床研究中已初步显示良好的疗效与安全性特征.本Ⅲ期临床试验比较CGZ与西格列汀(SGT)在经生活方式控制血糖不佳的T2DM患者中的有效性和安全性.患者随机(1:1:1)接受CGZ 32 mg(n=245)、CGZ 48 mg(n=246)或SGT 100 mg(n=248)治疗24周.CGZ 32 mg组、48 mg组与SGT 100 mg组在主要疗效终点指标——24周糖化血红蛋白(HbA_(1c))较基线变化值上分别为-1.40%、-1.47%和-1.39%,CGZ两组与SGT组为非劣效.CGZ具有更强降低空腹和餐后2 h血糖及空腹胰岛素的趋势.三组总体不良事件发生率相似,CGZ 48 mg组轻度水肿略增加,CGZ两组均有轻度体重增加.试验结果表明,西格列他钠对生活方式控制血糖不佳的T2DM患者具有总体良好的疗效和安全性,为这一PAR全激动剂治疗T2DM提供了确证性临床试验证据.