Medical expenditures for colorectal cancer diagnosis and treatment: A 10-year high-level-hospital-based multicenter retrospective survey in China, 2002-2011

Objective: Colorectal cancer(CRC) causes a substantial burden of disease in China and the evidence of economic burden triggered is fundamental for priority setting. The aim of this survey was to quantify medical expenditures and the time trends for CRC diagnosis and treatment in China.Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 13 provinces across China. For each eligible CRC patient diagnosed from 2002 to 2011, clinical information and expenditure data were extracted using a uniform questionnaire. All expenditure data were reported in Chinese Yuan(CNY)using 2011 values.Results: Of the 14,536 CRC patients included, the average age at diagnosis was 58.2 years and 15.8% were stageI cases. The average medical expenditure per patient was estimated at 37,902 CNY [95 % confidence interval(95%CI): 37,282-38,522], and the annual average increase rate was 9.2% from 2002 to 2011(P for trend <0.001), with a cumulative increase of 2.4 times(from 23,275 CNY to 56,010 CNY). The expenditure per patient in stages Ⅰ, Ⅱ, Ⅲ and Ⅳ were 31,698 CNY, 37,067 CNY, 38,918 CNY and 42,614 CNY, respectively(P<0.001). Expenditure significantly differed within various subgroups. Expenses for drugs contributed the largest proportion(52.6%).Conclusions: These conservative estimates illustrated that medical expenditures for CRC diagnosis and treatment in tertiary hospitals in China were substantial and increased rapidly over the 10 years, with drugs continually being the main expense by 2011. Relatively, medical expenditures are lower for CRC in the earlier stages. These findings will facilitate the economic evaluation of CRC prevention and control in China.

Research progress of integrated traditional Chinese and Western medicine in the treatment of advanced gastric cancer

Gastric cancer(GC)is a malignant tumor originating from the gastric epithelium,and its incidence and mortality rates rank third among all malignant tumors worldwide.It is also one of the most common cancers in China and is treated predominantly by Western medicine in clinical practice.However,with the advancements in medical technology and informatics,the values of traditional Chinese medicine(TCM)in preventing and treating GC and improving prognosis have increasingly been recognized.According to TCM,clinical manifestations of GC can be divided into Yege(dysphagia),regurgitation,stomach pain,and Zhengxia(abdominal mass).Due to the unbalanced distribution of health care resources in China,most GC patients already have progressive or advanced-stage disease at the first diagnosis.As a result,most GC patients have poor physical function,and surgery or chemotherapy alone will aggravate the impairment to the immune function and seriously affect the quality of life.In contrast,TCM therapies have shown promising efficacy in the management of these patients.Here we review the role of the integrated TCM and Western medicine in treating advanced GC.

Emerging role of autophagy in colorectal cancer:Progress and prospects for clinical intervention

Autophagy is a physiological mechanism in which cells degrade themselves and quickly recover the degraded cell components.Recent studies have shown that autophagy plays an important role in the occurrence,development,treatment,and prognosis of colorectal cancer.In the early stages of colorectal cancer,autophagy can inhibit the production and development of tumors through multiple mechanisms such as maintaining DNA stability,inducing tumor death,and enhancing immune surveillance.However,as colorectal cancer progresses,autophagy may mediate tumor resistance,enhance tumor metabolism,and other pathways to promote tumor development.Therefore,intervening in autophagy at the appropriate time has broad clinical application prospects.This article summarizes the recent research progress of autophagy and colorectal cancer and is expected to provide new theoretical basis and reference for clinical treatment of colorectal cancer.

Advances in the application of cryotherapy to the treatment of breast cancer

Cryotherapy is a minimally invasive treatment.With increasing rate of breast cancer detection,ablation therapy has become an alternative approach for the treatment of this pathology due to its advantages of minimally invasive,fewer complications,good efficacy,and repeatability.Preclinical and clinical studies of cryotherapy for breast cancer published through December 2022 were identified through a literature search using PubMed,ClinicalTrials.gov,and CNKI.This article reviews the progress of cryoablation in the treatment of breast cancer.

Prognostic value of hypoxia-inducible factor-1 alpha and prolyl 4-hydroxylase beta polypeptide overexpression in gastric cancer

AIM To investigate the relationship between hypoxia-inducible factor-1α(HIF-1α), prolyl 4-hydroxylase beta(P4 HB) expression, and clinicopathologic parameters, as well as the prognostic value of these genes for patients with gastric cancer(Gc).METHODS Hypoxia is a critical factor that shapes the Gc microenvironment. In previous reports, we have demonstrated that P4 HB is a potential target of HIF-1α. In the present study, gene expression profiling interactive analysis(GEPIA) was used to analyze the relationship between P4 HB and hypoxia-associated genes. To this end, 428 Gc tissue samples were used to analyze the expression of HIF-1α and P4 HB via immunohistochemical staining. Patient samples were classified as having weak-expression or over-expression both in terms of HIF-1α and P4 HB. Correlations between biomarkers and clinicopathological factors were analyzed to predict survival. RESULTS P4 HB demonstrated a positive correlation with hypoxiaassociated genes(P < 0.05). HIF-1α and P4 HB overexpression have a significant correlation with TNM staging(χ2 = 23.32, P = 0.00; χ2 = 65.64, P = 0.00) and peritoneum cavity metastasis(χ2 = 12.67, P = 0.00; χ2 = 39.29, P = 0.00). In univariate analysis, patients with a high HIF-1α expression trend had a shorter disease-free survival(DFS: 44.80 mo vs 22.06 mo) and overall survival(OS: 49.58 mo vs 39.92 mo). P4 HB overexpression reflected similar results: patients with over-expression of P4 HB had a shorter survival time than those with weak-expression(DFS: 48.03 mo vs 29.64 mo, OS: 52.48 mo vs 36.87 mo). Furthermore, HIF-1α is also a clinicopathological predictor of dismal prognosis according to multivariate analysis(DFS, 95%c I: 0.52-0.88, P < 0.00; OS, 95%c I: 0.50-0.85, P < 0.00). However, P4 HB was meaningful in DFS(95%c I: 0.58-1.00, P < 0.05) but not in OS(95%c I: 0.72-1.23, P > 0.05).CONCLUSION Overexpression of HIF-1α and P4 HB is associated with poor prognosis in patients with Gc. Thus, these genes may be potential prognostic biomarker candidates in GC.

Prognostic factors and therapeutic effects of different treatment modalities for colorectal cancer liver metastases

BACKGROUND Colorectal cancer(CRC)is one of the most common malignant tumors in China,and the liver is the most common metastatic site in patients with advanced CRC.Hepatectomy is the gold standard treatment for colorectal liver metastases.For patients who cannot undergo radical resection of liver metastases for various reasons,ablation therapy,interventional therapy,and systemic chemotherapy can be used to improve their quality of life and prolong their survival time.AIM To explore the prognostic factors and treatments of liver metastases of CRC.METHODS A retrospective analysis was conducted on 87 patients with liver metastases from CRC treated at the Liaoning Cancer Hospital and Institute between January 2005 and March 2011.According to different treatments,the patients were divided into the following four groups:Surgical resection group(36 patients);ablation group(23 patients);intervention group(15 patients);and drug group(13 patients).The clinicopathological data and postoperative survival of the four groups were analyzed.The Kaplan-Meier method was used for survival analysis,and the Cox proportional hazards regression model was used for multivariate analysis.RESULTS The median survival time of the 87 patients was 38.747±3.062 mo,and the 1-and 3-year survival rates were 87.5%and 53.1%,respectively.The Cox proportional hazards model showed that the following factors were independent factors affecting prognosis:The degree of tumor differentiation,the number of metastases,the size of metastases,and whether the metastases are close to great vessels.The results of treatment factor analysis showed that the effect of surgical treatment was better than that of drugs,intervention,or ablation alone,and the median survival time was 48.83±4.36 mo.The drug group had the worst prognosis,with a median survival time of only 13.5±0.7 mo(P<0.05).For patients with liver metastases of CRC near the great vessels,the median survival time(27.3 mo)of patients undergoing surgical resection was better than that of patients using other treatments(20.6 mo)(P<0.05).CONCLUSION Patients with a low degree of primary tumor differentiation,multiple liver metastases(number of tumors>4),and maximum diameter of liver metastases>5 cm have a poor prognosis.Among drug therapy,intervention,ablation,and surgical treatment options,surgical treatment is the first choice for liver metastases.When liver metastases are close to great vessels,surgical treatment is significantly better than drug therapy,intervention,and ablation alone.

Utility of cooling patches to prevent hand-foot syndrome caused by pegylated liposomal doxorubicin in breast cancer patients

BACKGROUND Pegylated liposomal doxorubicin(PLD)uses the hydrophilic layer of liposomes to reach the sweat on the skin surface or accumulate in the sweat glands,producing toxic free radicals and oxidative damage,resulting in hand-foot syndrome(HFS).Regional cooling can induce vasoconstriction to reduce the release of drugs in the limbs and reduce the accumulation of drugs in sweat glands;thus,decreasing the incidence and severity of HFS.AIM To study the efficacy of cooling patches to prevent HFS caused by PLD in the short-term.METHODS This is a retrospective cohort study.Female breast cancer patients(n=101)who were treated with PLD in two breast wards at our department from February 2020 to February 2021 were enrolled in the study and were randomly divided into the cooling group(51 patients)and the control group(50 patients).Patients in the control group only received routine care,while the patients in the cooling group applied cooling patches,based on routine care,to the palm and back of the hands 15 min before chemotherapy infusion for 10 h.All patients took a corresponding dose of dexamethasone orally one day before chemotherapy,on the day of chemotherapy,and one day after chemotherapy.SPSS23.0 version was used to analyze the data in this study.The occurrence and severity of HFS was analyzed by the Mann-Whitney U test,and scores were analyzed by the Student’s t test or Wilcoxon rank-sum test.A P value<0.05 was regarded as statistically significant.RESULTS In this study,neither group of patients developed Grade 3 HFS.In the control group,the incidence of Grade 1 HFS and Grade 2 HFS was 38%and 2%,respectively.However,in the cooling group,only one person developed Grade 1 HFS(2%),and none of the patients developed Grade 2 HFS.These findings showed that cooling patches can effectively reduce the frequency and severity of HFS(P<0.0001)in the short-term.Before the fourth chemotherapy cycle,although general self-efficacy scale scores in the cooling group were low,they were still significantly higher than those in the control group(17.22±5.16 vs 19.63±6.42,P=0.041).Compared with the control group,the mean Hand-Foot Skin Reaction and Quality of Life Questionnaire score in the cooling group was significantly lower(18.08±7.01 vs 14.20±7.39,P=0.008).CONCLUSION Cooling patches can effectively reduce the frequency and severity of HFS caused by PLD in the short-term.In addition,it may help delay the decline in patients’self-efficacy.

PGC-MG7 combination could be used as a follow-up panel for monitoring dynamical progression of gastric precancerous diseases

Objective: The aim of this study was to investigate the value of the combined expression of the gastric mucosal differentiation protein pepsinogen C(PGC) and gastric cancer(GC)-associated antigen MG7 for the diagnosis of GC and prediction of the development from precancerous conditions to GC.Methods: The gastric mucosal biopsies of 285 subjects enrolled from a region with a high incidence of GC were obtained and histopathologically examined. Subjects testing negative for GC(n=208) were followed up from 1998 to 2015. The levels of PGC and MG7 in the biopsies were determined by immunohistochemistry.Results: PGC was positive in 91.4% of the non-atrophic gastritis, 26.5% of the atrophic gastritis, and 0% of the GC. MG7 was positive in 15.0% of the non-atrophic gastritis, 82.4% of the atrophic gastritis, and 94.8% of the GC. The non-atrophic gastritis group was predominantly "PGC+MG7-". The atrophic gastritis and GC groups were predominantly "PGC-MG7+". The rate of GC in subjects with "PGC-MG7+" staining was 113.4-fold higher [95% confidence interval(95% CI): 15.3-869.4, P<0.001] than that in subjects with other staining patterns.The sensitivity and specificity of the "PGC-MG7+" pattern were 92.2% and 78.8% for the detection of GC and77.2% and 97.9% for GC and precancerous disease, respectively. In the follow-up cohort of non-GC subjects, the risk of developing GC was higher in those with the "PGC-MG7+" staining pattern.Conclusions: Our data suggest that the "PGC-MG7+" pattern can be employed as a useful follow-up panel for detecting individuals with a high risk of GC, and the dynamic assessment of the follow-up panel needs multi-centre large-scale validation in the future.

Development and validation of a three-long noncoding RNA signature for predicting prognosis of patients with gastric cancer

BACKGROUND Gastric cancer(GC)is one of the most frequently diagnosed gastrointestinal cancers throughout the world.Novel prognostic biomarkers are required to predict the prognosis of GC.AIM To identify a multi-long noncoding RNA(lncRNA)prognostic model for GC.METHODS Transcriptome data and clinical data were downloaded from The Cancer Genome Atlas.COX and least absolute shrinkage and selection operator regression analyses were performed to screen for prognosis associated lncRNAs.Receiver operating characteristic curve and Kaplan-Meier survival analyses were applied to evaluate the effectiveness of the model.RESULTS The prediction model was established based on the expression of AC007991.4,AC079385.3,and AL109615.2 Based on the model,GC patients were divided into“high risk”and“low risk”groups to compare the differences in survival.The model was re-evaluated with the clinical data of our center.CONCLUSION The 3-lncRNA combination model is an independent prognostic factor for GC.

Better prognostic determination of cT3 rectal cancer through measurement of distance to mesorectal fascia:A multicenter study

Objective:To forward the magnetic resonance imaging(MRI)based distance between the deepest tumor invasion and mesorectal fascia(DMRF),and to explore its prognosis differentiation value in cT3 stage rectal cancer with comparison of cT3 substage.Methods:This was a retrospective,multicenter cohort study including cT3 rectal cancer patients undergoing neoadjuvant chemoradiotherapy followed by radical surgery from January 2013 to September 2014.DMRF and cT3 substage were evaluated from baseline MRI.The cutoff of DMRF was determined by disease progression.Multivariate cox regression was used to test the prognostic values of baseline variables.Results:A total of 804 patients were included,of which 226(28.1%)developed progression.A DMRF cutoff of7 mm was chosen.DMRF category,the clock position of the deepest position of tumor invasion(CDTI)and extramural venous invasion(EMVI)were independent predictors for disease progression,and hazard ratios(HRs)were 0.26[95%confidence interval(95%CI),0.13-0.56],1.88(95%CI,1.33-2.65)and 1.57(95%CI,1.13-2.18),respectively.cT3 substage was not a predictor for disease progression.Conclusions:The measurement of DMRF value on baseline MRI can better distinguish cT3 rectal cancer prognosis rather than cT3 substage,and was recommended in clinical evaluation.

Prognostic value of modified Lauren classification in gastric cancer

BACKGROUND It remains controversial as to which pathological classification is most valuable in predicting the overall survival(OS)of patients with gastric cancer(GC).AIM To assess the prognostic performances of three pathological classifications in GC and develop a novel prognostic nomogram for individually predicting OS.METHODS Patients were identified from the Surveillance,Epidemiology,and End Results program.Univariate and multivariate analyses were performed to identify the independent prognostic factors.Model discrimination and model fitting were evaluated by receiver operating characteristic curves and Akaike information criteria.Decision curve analysis was performed to assess clinical usefulness.The independent prognostic factors identified by multivariate analysis were further applied to develop a novel prognostic nomogram.RESULTS A total of 2718 eligible GC patients were identified.The modified Lauren classification was identified as one of the independent prognostic factors for OS.It showed superior model discriminative ability and model-fitting performance over the other pathological classifications,and similar results were obtained in various patient settings.In addition,it showed superior net benefits over the Lauren classification and tumor differentiation grade in predicting 3-and 5-year OS.A novel prognostic nomogram incorporating the modified Lauren classification showed superior model discriminative ability,model-fitting performance,and net benefits over the American Joint Committee on Cancer 8th edition tumor-nodemetastasis classification.CONCLUSION The modified Lauren classification shows superior net benefits over the Lauren classification and tumor differentiation grade in predicting OS.A novel prognostic nomogram incorporating the modified Lauren classification shows good model discriminative ability,model-fitting performance,and net benefits.

Quantitative characterization of cell physiological state based on dynamical cell mechanics for drug efficacy indication

Cell mechanics is essential to cell development and function,and its dynamics evolution reflects the physiological state of cells.Here,we investigate the dynamical mechanical properties of single cells under various drug conditions,and present two mathematical approaches to quantitatively characterizing the cell physiological state.It is demonstrated that the cellular mechanical properties upon the drug action increase over time and tend to saturate,and can be mathematically characterized by a linear timeinvariant dynamical model.It is shown that the transition matrices of dynamical cell systems significantly improve the classification accuracies of the cells under different drug actions.Furthermore,it is revealed that there exists a positive linear correlation between the cytoskeleton density and the cellular mechanical properties,and the physiological state of a cell in terms of its cytoskeleton density can be predicted from its mechanical properties by a linear regression model.This study builds a relationship between the cellular mechanical properties and the cellular physiological state,adding information for evaluating drug efficacy.

The choice of a neoadjuvant chemotherapy cycle for breast cancer has significance in clinical practice: results from a population-based, real world study

Objective:Neoadjuvant chemotherapy(NAC)is currently used in both early stage and locally advanced breast cancers.The survival benefits of standard vs.non-standard NAC cycles are still unclear.This study aimed to investigate the relationship between NAC cycles and survival based on real world data.Methods:We identified patients diagnosed with invasive primary breast cancers who underwent NAC followed by surgery.Patients who received at least 4 NAC cycles were defined as having received standard cycles,while patients who received less than 4 NAC cycles were defined as having received non-standard cycles.Kaplan-Meier curves and Cox proportional hazard models were used to estimate the disease-free survival(DFS)and overall survival(OS).Results:Of the 1,024 included patients,700 patients received standard NAC cycles and 324 patients received non-standard NAC cycles.The DFS estimates were 87.1%and 81.0%(P=0.007)and the OS estimates were 90.0%and 82.6%(P=0.001)in the standard and non-standard groups,respectively.Using multivariate analyses,patients treated with standard NAC cycles showed significant survival benefits in both DFS[hazard ratio(HR):0.62,95%confidence interval(CI):0.44–0.88]and OS(HR:0.54,95%CI:0.37–0.79).Using stratified analyses,standard NAC cycles were associated with improved DFS(HR:0.59,95%CI:0.36–0.96)and OS(HR:0.49,95%CI:0.28–0.86)in the HER2 positive group.Similar DFS(HR:0.50,95%CI:0.25–0.98)and OS(HR:0.45,95%CI:0.22–0.91)benefits were shown for the triple negative group.Conclusions:Standard NAC cycles were associated with a significant survival benefit,especially in patients with HER2 positive or triple negative breast cancer.

How to select gastric cancer patients suitable for immunotherapy?

Stomach cancer is the fourth leading cause of cancer-related deaths worldwide[1].There are approximately one million new cases of gastric cancer worldwide each year,with about 45%occurring in China[1].In China,the number of deaths from gastric cancer ranks second among all tumors each year[2],the majority of patients are diagnosed at an advanced or late stage,making them ineligible for surgical treatment.Some of these patients can regain the opportunity for surgery through conversion therapy,while more patients can only receive comprehensive treatment with cytotoxic drugs,anti-metabolite drugs,DNA-targeting drugs,and targeted drugs[3].

Long noncoding RNA NALT1-induced gastric cancer invasion and metastasis via NOTCH signaling pathway

BACKGROUNDLong noncoding RNAs (lncRNAs) are aberrant and play critical roles in gastriccancer (GC) progression and metastasis. Searching for coexpressed lncRNAclusters or representative biomarkers related to malignant phenotypes of GC mayhelp to elucidate the mechanism of tumor development and predict the prognosisof GC.AIMTo investigate the prognostic value of NOTCH1 associated with lncRNA in T cellacute lymphoblastic leukemia 1 (NALT1) in GC and the mechanism of itsinvolvement in GC invasion and metastasis.METHODSRNA sequencing and corresponding clinical data were downloaded from TheCancer Genome Atlas database. The significance module was studied byweighted gene coexpression network analysis. A total of 336 clinical sampleswere included in the study. Gene silencing, reverse transcription polymerasechain reaction, western blotting, scrape motility assay, and Transwell migrationassay were used to assess the function of hub-lncRNAs.RESULTSAt the transcriptome level, 3339 differentially expressed lncRNAs were obtained.weighted gene coexpression network analysis was used to obtain 15 lncRNAclusters and observe their coexpression. Pearson’s correlation showed that blue module was correlated with tumor grade and survival. NALT1 was the hublncRNAof blue module and was an independent risk factor for GC prognosis.NALT1 was overexpressed in GC and its expression was closely related toinvasion and metastasis. The mechanism may involve NALT1 regulation ofNOTCH1, which is associated with lncRNA in T cell acute lymphoblasticleukemia, through cis regulation, thereby affecting the expression of the NOTCHsignaling pathway.CONCLUSIONNALT1 is overexpressed and promotes invasion and metastasis of GC. Themechanism may be related to regulation of NOTCH1 by NALT1 and its effect onNOTCH signaling pathway expression.

Clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization combined with radiotherapy in hilar cholangiocarcinoma

BACKGROUND Radical surgical resection is regarded as the best treatment for hepatic hilar cholangiocarcinoma. However, 60%-70% of patients have lost the chance of surgery at the time of diagnosis. Simple biliary stent or drainage tube placement may fail in a short time due to tumor invasion or overgrowth, bile accumulation, or biofilm formation. Effective palliative treatments to extend the effective drainage time are of great significance for improving the quality of life of patients and changing the prognosis of patients. AIM To investigate the clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization (TACE) combined with radiotherapy in hilar cholangiocarcinoma.METHODS A retrospective analysis was conducted on patients clinically diagnosed with hilar cholangiocarcinoma from June 2014 to January 2017 at the Liaoning Provincial Cancer Hospital. Patients were evaluated by specialists, and those who were not suitable for surgery or unwilling to undergo surgery and met the inclusion criteria were included in the study. There were a total of 72 patients (34 males and 38 females) with an average age of 59.9 years (range, 40-72 years). According to percutaneous transhepatic biliary angiography and the patients’ wishes, stent implantation or biliary drainage tube implantation was used to relieve biliary obstruction. The patients were divided into either a control group or a combined treatment group according to their follow-up treatment. The control group consisted of a total of 35 patients who received simple biliary drainage tube placement and biliary stent implantation (7 patients with bilateral stents and 6 with a unilateral stent) and 22 patients receiving biliary drainage tube placement alone. The combined treatment group received TACE and extracorporeal radiotherapy after biliary drainage or biliary stent implantation and consisted of a total of 37 patients, including 21 patients receiving combined treatment after biliary stent placement (14 patients with bilateral stents and 7 with a unilateral stent) and 16 undergoing combined therapy after implanting the biliary drainage tube. In the combination treatment group, the TACE chemotherapy regimen employed gemcitabine and cisplatin, and the embolic agent was iodized oil. A particular dose was determined according to the patient's body surface area and the tumor staining indicated by DSA. In vitro radiotherapy was performed with intensity-modulated radiotherapy or threedimensional conformal radiotherapy at an average dose of 48.3 Gy. Both groups were followed from stent implantation or drainage tube implantation until the patient quitted or died. The median length of follow-up observation was 13 mo. The differences in overall survival time and the effect of different jaundice reducing methods (single stent, double stent, or biliary drainage) on the patency time and survival time of biliary stents were compared between the two groups;the related factors affecting overall survival time were analyzed. RESULTS The median survival time of the control group was 10.5 mo;the median survival time of patients with biliary stent implantation and those with percutaneous biliary drainage was 9.6 mo and 11.4 mo, respectively, and there was no statistically significant difference between them. The median survival time of the combined treatment group was 20.0 mo, which was significantly higher than that of the control group (P < 0.05). Among patients in the combined treatment group, the median survival time of patients who underwent biliary stent implantation and those who accepted percutaneous biliary drainage before the combination therapy was 19.5 mo and 20.1 mo, respectively, and there was no significant difference between them. In the combination treatment group, the mean time of median stent patency was 15.6 mo, which was significantly higher than that of the control group (7.0 mo;P < 0.05). The independent factors affecting survival time included age, whether to receive combination therapy, percutaneous biliary drainage tube implantation, and Bismuth-Corlette classification as type IV. CONCLUSION Gemcitabine and cisplatin-based TACE combined with radiotherapy can prolong the survival of patients with hilar cholangiocarcinoma. Independent predictors of survival include selection of combination therapy, Bismuth-Corlette classification as type IV, selection of percutaneous biliary drainage tube implantation, and age.

miR-211 regulates the antioxidant function of lens epithelial cells affected by age-related cataracts

AIM： To investigate the effects and mechanism of miR-211 in mediating the antioxidant function of lens epithelial cells affected by age-related cataracts. METHODS： Real-time quantitative polymerase chain reaction （RT-qPCR） was used to detect miR-211 expression in the anterior lens capsules of healthy people, the anterior lens capsules of patients with age-related cataracts, and human epithelial cell line （SRA01/04） cells exposed to oxidative stress. A 2＇, 7＇-dichloro-fluorescein diacetate （DCFH-DA） probe was used to measure the levels of endogenous reactive oxygen species （ROS） in human lens epithelial cells （hLECs） exposed to 400 pmol/L H2O2 for lh. SRA01/04 cells were transfected with either miR-211 mimics, mimic controls, miR-211 inhibitors or inhibitor controls. After 72h, these cells were exposed to 400 IJmollL H2O2 for lh, then p53 and Bax mRNA expression were measured using RT-qPCR. p53 and Bax protein expression were also measured by Western blotting analysis. Finally, cell viability was assessed using an MTS assay. RESULTS： Compared to the control group, expression of miR-211 in the anterior lens capsules of age-related cataract patients and in SRA01/04 cells exposed to oxidative stress was significantly increased （P〈0.001）. Levels of endogenous ROS were significantly elevated in hLECs exposed to oxidative stress （P〈0.001）. Compared to the mimic control group, the hLECs in the miR-211 mimic group expressed significantly higher levels of p53 and Bax mRNA and protein while cell viability was significantly reduced （P〈0.001）. Conversely, p53 and Bax mRNA and protein expression were significantly reduced in the miR-211 inhibitor group as compared to the control group, while the cells in this group had much higher levels of call viability （P〈0.001）. CONCLUSION： miR-211 is upregulatsd in the anterior lens capsules of age-related cataract patients, miR-211 decreased the antioxidative stress capacity of lens epithelial cells by upregulating p53 and Bax, while inhibiting cell proliferation and repair. This finding suggests that miR-211 may play a key role in the development of age-related cataracts.

Sp1 contributes to overexpression of stanniocalcin 2 through regulation of promoter activity in colon adenocarcinoma

BACKGROUND Aberrant expression of stanniocalcin 2 (STC2) is implicated in colon adenocarcinoma (COAD). A previous study identified that STC2 functions as a tumor promoter to drive development of some cancers, but the role of its overexpression in the development of COAD remains unclear. AIM To evaluate the regulation mechanism of STC2 overexpression in COAD. METHODS The expression of STC2 in COAD was assessed by TCGA COAD database and GEO (GSE50760). Methylation level of the STC2 promoter was evaluated with beta value in UALCAN platform, and the correlation between STC2 expression and survival rate was investigated with TCGA COAD. Transcription binding site prediction was conducted by TRANSFAC and LASAGNA, and a luciferase reporter system was used to identify STC2 promoter activity in several cell lines, including HEK293T, NCM460, HT29, SW480, and HCT116. Western blotting was performed to evaluate the role of Sp1 on the expression of STC2. RESULTS The central finding of this work is that STC2 is overexpressed in COAD tissues and positively correlated with poor prognosis. Importantly, the binding site of the transcription factor Sp1 is widely located in the promoter region of STC2. A luciferase reporter system was successfully constructed to analyze the transcription activity of STC2, and knocking down the expression of Sp1 significantly inhibited the transcription activity of STC2. Furthermore, inhibition of Sp1 remarkably decreased protein levels of STC2. CONCLUSION Our data provide evidence that the transcription factor Sp1 is essential for the overexpression of STC2 in COAD through activation of promoter activity. Taken together, our finding provides new insights into the mechanism of oncogenic function of COAD by STC2.

Radiomics model for distinguishing tuberculosis and lung cancer on computed tomography scans

BACKGROUND Pulmonary tuberculosis(TB)and lung cancer(LC)are common diseases with a high incidence and similar symptoms,which may be misdiagnosed by radiologists,thus delaying the best treatment opportunity for patients.AIM To develop and validate radiomics methods for distinguishing pulmonary TB from LC based on computed tomography(CT)images.METHODS We enrolled 478 patients(January 2012 to October 2018),who underwent preoperative CT screening.Radiomics features were extracted and selected from the CT data to establish a logistic regression model.A radiomics nomogram model was constructed,with the receiver operating characteristic,decision and calibration curves plotted to evaluate the discriminative performance.RESULTS Radiomics features extracted from lesions with 4 mm radial dilation distances outside the lesion showed the best discriminative performance.The radiomics nomogram model exhibited good discrimination,with an area under the curve of 0.914(sensitivity=0.890,specificity=0.796)in the training cohort,and 0.900(sensitivity=0.788,specificity=0.907)in the validation cohort.The decision curve analysis revealed that the constructed nomogram had clinical usefulness.CONCLUSION These proposed radiomic methods can be used as a noninvasive tool for differentiation of TB and LC based on preoperative CT data.

Reduced microRNA-451 expression in eutopic endometrium contributes to the pathogenesis of endometriosis

BACKGROUND Endometriosis (EMs) is a chronic and recurrent,but benign,disease in women of reproductive age,and EMs patients have a high risk of developing gynecological tumors and autoimmune disorders.The etiology of EMs is not clear.Certain genetic markers in the eutopic endometrium are key in the pathogenesis of EMs.MicroRNAs (miRNAs) are implicated in several biological processes,such as cell proliferation,differentiation,and apoptosis.MiR-451 is interesting,as it acts as a tumor suppressor and is relevant to the poor prognosis of cancers.AIM To evaluate the expression levels and role of miR-451 in the eutopic endometrium and predict possible targets of miR-451 and related signaling pathways.METHODS Quantitative real-time polymerase chain reaction was used to evaluate miR-451 expression in cultured cell lines as well as in pathologic tissues from 40 patients with EMs and 20 donors with no history of the disease (controls).Cell Counting Kit-8 and flow cytometric assays were performed to determine cell proliferation and survival rates after transfection with miR-451 mimics and siRNAs.MiR-451 targets were predicted using miRDB and miRcode target-predicting databases.RESULTS We observed lower miR-451 levels in eutopic endometrial tissues from patients with EMs than in control tissues,and this difference was not related to the American Society for Reproductive Medicine stage.Ectopic overexpression of miR-451 in eutopic cells induced apoptosis and inhibited cell proliferation.SiRNA-mediated miR-451 knockdown reversed these effects.Using miRDB and miRcode,we identified 12 potential miR-451 target genes.We hypothesize that the expression of YWHAZ,OSR1,TTN,and CDKN2D may be regulated by miR- 451 and be involved in disease pathogenesis.CONCLUSION Reduced miR-451 expression in the eutopic endometrium contributes to the pathogenesis of EMs by promoting cell proliferation and reducing apoptosis.Thus,miR-451 is a novel biomarker for EMs.YWHAZ,OSR1,TTN,and CDKN2D are potential target genes of miR-451 and may have key roles in this disease.