Preclinical and clinical evidence of the association of colibactinproducing Escherichia coli with anxiety and depression in colon cancer

BACKGROUND The association between the intestinal microbiota and psychiatric disorders is becoming increasingly apparent.The gut microbiota contributes to colorectal carcinogenesis(CRC),as demonstrated with colibactin-producing Escherichia coli(CoPEC).AIM To evaluate the association between CoPEC prevalence and anxiety-and depressive-like behaviors with both preclinical and clinical approaches.METHODS Patients followed after a CRC surgery and for whom the prevalence of CoPEC has been investigated underwent a psychiatric interview.Results were compared according to the CoPEC colonization.In parallel C57BL6/J wild type mice and mice with a CRC susceptibility were chronically infected with a CoPEC strain.Their behavior was assessed using the Elevated Plus Maze test,the Forced Swimming Test and the Behavior recognition system PhenoTyper®.RESULTS In a limited cohort,all patients with CoPEC colonization presented with psychiatric disorders several years before cancer diagnosis,whereas only one patient(17%)without CoPEC did.This result was confirmed in C57BL6/J wildtype mice and in a CRC susceptibility mouse model(adenomatous polyposis colimultiple intestinal neoplasia/+).Mice exhibited a significant increase in anxiety-and depressive-like behaviors after chronic infection with a CoPEC strain.CONCLUSION This finding provides the first evidence that CoPEC infection can induce microbiota-gut-brain axis disturbances in addition to its procarcinogenic properties.

Comparative assessment of clinical profile and outcomes after primary percutaneous coronary intervention in young patients with single vs multivessel disease

BACKGROUND Even though percutaneous coronary intervention(PCI)improved the survival of patients with acute myocardial infarction,still multivessel coronary artery disease remains an important factor burdening prognosis and it is being associated with a worse prognosis compared to single-vessel disease(SVD).AIM To compare the clinical profile and outcomes after the primary PCI in young patients with SVD vs multivessel disease(MVD).METHODS The retrospective cohort of patients were divided into two groups:SVD and MVD group.The study population consisted of both male and female young(≤45 years)patients presented with ST-elevation myocardial infarction(STEMI)at the National Institute of Cardiovascular Disease,Karachi,Pakistan and undergone primary PCI from 1 st July 2017 to 31 st March 2018.Pre and postprocedure management of the patients was as per the guidelines and institutional protocols.RESULTS A total of 571 patients with STEMI,≤45 years were stratified into two groups by the number of vessels involved,342(59.9%)with SVD and 229(40.1%)with MVD.The average age of these patients was 39.04±4.86 years.A lower prevalence of hypertension and diabetes was observed in SVD as compare to MVD group(25.1%vs 38%,P<0.01;11.7%vs 27.5%,P<0.001)respectively.While,smoking was more prevalent among the SVD group as compare to MVD group(36.3%vs 28.4%,P=0.05).The high-C Lesion was observed in a significantly higher number of younger patients with MVD as compared to SVD group(48.8%vs 39.2%,P=0.021).Post-procedure thrombolysis in myocardial infarction flow grade was found to be not associated with the number of diseased vessels with a P value of 0.426 and thrombolysis in myocardial infarction flow grade III was observed in 98%vs 96.5%of the patients is SVD vs MVD group.CONCLUSION The MVD comprised of around 40%of the young patients presented with STEMI.Also,this study shows that diabetes and hypertension have a certain role in the pathogenesis of multivessel diseases,therefore,preventive measures for diabetes and hypertension can be effective strategies in reducing the burden of premature STEMI.

Poor performance of the modified early warning score for predicting mortality in critically ill patients presenting to an emergency department

BACKGROUND:This study was undertaken to validate the use of the modified early warning score(MEWS) as a predictor of patient mortality and intensive care unit(ICU)/ high dependency(HD)admission in an Asian population.METHODS:The MEWS was applied to a retrospective cohort of 1 024 critically ill patients presenting to a large Asian tertiary emergency department(ED) between November 2006 and December2007.Individual MEWS was calculated based on vital signs parameters on arrival at ED.Outcomes of mortality and ICU/HD admission were obtained from hospital records.The ability of the composite MEWS and its individual components to predict mortality within 30 days from ED visit was assessed.Sensitivity,specificity,positive and negative predictive values were derived and compared with values from other cohorts.A MEWS of ≥4 was chosen as the cut-off value for poor prognosis based on previous studies.RESULTS:A total of 311(30.4%) critically ill patients were presented with a MEWS ≥4.Their mean age was 61.4 years(SD 18.1) with a male to female ratio of 1.10.Of the 311 patients,53(17%)died within 30 days,64(20.6%) were admitted to ICU and 86(27.7%) were admitted to HD.The area under the receiver operating characteristic curve was 0.71 with a sensitivity of 53.0%and a specificity of 72.1%in addition to a positive predictive value(PPV) of 17.0%and a negative predictive value(NPV)of 93.4%(MEWS cut-off of ≥4) for predicting mortality.CONCLUSION:The composite MEWS did not perform well in predicting poor patient outcomes for critically ill patients presenting to an ED.

Review of 10 years of research on breast cancer patients:Focus on indoleamine 2,3-dioxygenase

Therapeutic manipulation of the immune system in cancer has been an extensive area of research in the field of oncoimmunology.Immunosuppression regulates antitumour immune responses.An immunosuppressive enzyme,indoleamine 2,3-dioxygenase(IDO)mediates tumour immune escape in various malignancies including breast cancer.IDO upregulation in breast cancer cells may lead to the recruitment of regulatory T(T-regs)cells into the tumour microenvironment,thus inhibiting local immune responses and promoting metastasis.Immunosuppression induced by myeloid derived suppressor cells activated in an IDOdependent manner may enhance the possibility of immune evasion in breast cancer.IDO overexpression has independent prognostic significance in a subtype of breast cancer of emerging interest,basal-like breast carcinoma.IDO inhibitors as adjuvant therapeutic agents may have clinical implications in breast cancer.This review proposes future prospects of IDO not only as a therapeutic target but also as a valuable prognostic marker for breast cancer.

Equivalent efficacy study of QL1101 and bevacizumab on untreated advanced non-squamous non-small cell lung cancer patients: a phase 3 randomized, double-blind clinical trial

Objective:This phase 3 study aimed to test equivalence in efficacy and safety for QL1101,a bevacizumab analogue in Chinese patients with untreated locally advanced non-squamous non-small cell lung cancer(NSCLC).Methods:Eligible patients were randomly assigned 1:1 to receive carboplatin and paclitaxel in combination with either QL1101 or bevacizumab,15 mg/kg every 3-week for 6 cycles.This was followed by maintenance treatment with single agent QL1101 every 3-week.The primary end-point was objective response rate(ORR),with secondary end-points being progression-free survival(PFS),overall survival(OS),disease control rate(DCR),and adverse events(AEs).Results:Of 675 patients,535 eligible patients were randomized to the QL1101 group(n=269)and bevacizumab group(n=266).ORRs were 52.8%and 56.8%,respectively,for the QL1101 and bevacizumab groups,with an ORR hazard ratio 0.93(95%confidence interval:0.8-0131.1).The PFS,OS,DCR,and AEs were comparable between the 2 groups,which remained the same after stratification according to epidermal growth factor receptor mutation or smoking history.Conclusions:QL1101 showed similar efficacy and safety profiles as compared to bevacizumab among Chinese patients with untreated locally advanced non-squamous NSCLC.

Diagnostic values of questionnaires of Convergence Insufficiency Symptom Survey and College of Optometrists Vision Development Quality of Life in the screening of convergence insufficiency

AIM:To compare and analyse the diagnostic efficacy of the College of Optometrists Vision Development Quality of Life Questionnaire(COVD-QOL)and the Convergence Insufficiency Symptom Survey(CISS)in detecting convergence insufficiency and to compare their diagnostic value in clinical applications.METHODS:Using the diagnostic test method,62 adult patients with convergence insufficiency(age:24.74±3.75y)and 62 normal participants(age:23.61±3.13y)who visited the Optometry Clinic of West China Hospital of Sichuan University from April 2021 to January 2023 were included.All subjects completed the CISS and COVD-QOL.Statistical analysis of the sensitivity and specificity of the CISS and COVD-QOL and comparison and joint experimental analysis of their diagnostic efficacy were performed.RESULTS:The sensitivity of the CISS and COVD-QOL for convergence insufficiency was 64.5%and 71.0%,respectively,while the specificity was 96.8%and 67.7%,respectively.Compared to the CISS alone,the combination of the CISS and COVD-QOL demonstrated lower sensitivity and specificity.The areas under the receiver operating characteristic curve of CISS,COVD-QOL and CISS combined with COVD-QOL were 0.806,0.694 and 0.782,respectively.CONCLUSION:Considering the low sensitivity of the CISS and the low specificity of the COVD-QOL,it is recommended to supplement these questionnaires with other screening tests for the detection of convergence insufficiency.

Transcriptional reprogramming during human osteoclast differentiation identifies regulators of osteoclast activity

Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone formation.As novel antiosteoporotic therapeutics are needed,understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment targets.This study aimed to provide an overview of transcriptional reprogramming during human osteoclast differentiation.Osteoclasts were differentiated from CD14+monocytes from eight female donors.RNA sequencing during differentiation revealed 8980 differentially expressed genes grouped into eight temporal patterns conserved across donors.These patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density SNPs.Network analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional networks.The donor-specific expression patterns revealed genes at the monocyte stage,such as filamin B(FLNB)and oxidized low-density lipoprotein receptor 1(OLR1,encoding LOX-1),that are predictive of the resorptive activity of mature osteoclasts.The expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation,and these receptors are associated with bone mineral density SNPs,suggesting that they play a pivotal role in osteoclast differentiation and activity.The regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1(C5AR1),somatostatin receptor 2(SSTR2),and free fatty acid receptor 4(FFAR4/GPR120).Activating C5AR1 enhanced osteoclast formation,while activating SSTR2 decreased the resorptive activity of mature osteoclasts,and activating FFAR4 decreased both the number and resorptive activity of mature osteoclasts.In conclusion,we report the occurrence of transcriptional reprogramming during human osteoclast differentiation and identified SSTR2 and FFAR4 as antiresorptive G-protein coupled receptors and FLNB and LOX-1 as potential molecular markers of osteoclast activity.These data can help future investigations identify molecular regulators of osteoclast differentiation and activity and provide the basis for novel antiosteoporotic targets.

Status and Analysis of 832 Investigator-Initiated Coronavirus-Related Clinical Studies

Objective:To contribute to the development of clinical research on novel coronavirus by analyzing the clinical research data of COVID-19.Methods:Searches were performed on the database of“National Health Insurance Information Platform Medical Research Registration Information System”using the keywords“COVID-19”and“Novel coronavirus.”The search was performed till 31 December 2022.This paper presents a statistical analysis of the status quo of the registered projects in terms of the number of registered projects,the types of projects,the levels of the institutions,the types of research,the intervention measures,the research design,the main objectives of the research,and so on.Results:A total of 823 investigator-initiated clinical studies of COVID-19 were documented,and the number of studies registered peaked on December 31,2020,and December 31,2022.Among them,there were 819 items from general medical research(99.5%),812 items from medical institutions(98.7%),and 713 items from Medical Grade III,and Class A hospitals(86.6%).Among these items,534(64.9%)were observational studies.The most common intervention method used was administering existing drugs,with 140 studies utilizing them.This data analysis also included 128 case-control studies and 247 treatment-oriented studies.Conclusion:Researchers in local medical institutions have been actively carrying out clinical research related to COVID-19.However,they should refer to registered research to avoid duplicate research.

Pharmacokinetics and Bioequivalence Comparison of Two Fixed-Dose Combination of Rosuvastatin/Ezetimibe Formulations: A Randomized, Crossover, Open-Label Study in Healthy Volunteers

Objective: To evaluate the bioequivalence (BE) of two fixed-dose combination (FDC) formulations of Rosuvastatin and Ezetimibe: Cresadex® EZE 20/10 mg (Abbott Laboratories) as the reference formulation (R), and Racor® Duo 20/10 mg (Laboratorios Leti, S.A.V.) as the test formulation (T). Method: A randomized, single-dose, two-period, two-sequence, open-label, crossover design was employed. Subjects received a single oral dose of either the Test or Reference formulation under fasting conditions, with a 12-day washout period between treatments. Male subjects aged 18 - 45 years with normal health and laboratory values were included. Exclusion criteria encompassed any medical conditions, recent surgery, drug or alcohol use, and hypersensitivity to the study drugs. Blood samples were collected at pre-dose and multiple post-dose time points and analyzed using a validated LC-MS/MS method to quantify Rosuvastatin and Ezetimibe concentrations in plasma. Descriptive statistics were used to summarize pharmacokinetic (PK) parameters. ANOVA was conducted to compare the ln-transformed values of Cmax, AUC0−t, and AUC0−∞. Schuirmann’s two one-sided t-tests were applied to assess bioequivalence (BE). Results: The 90% Confidence Intervals for the ln-transformed ratios of Cmax, AUC0−t, and AUC0−∞ fell within the acceptance range of 80% to 125%, demonstrating bioequivalence between the Test and Reference formulations. Both formulations were well-tolerated, with no serious adverse events reported. Conclusions: The results of this study confirm the bioequivalence of the two tested FDC Rosuvastatin/Ezetimibe formulations: Cresadex® EZE (Abbott Laboratories) and Racor® Duo (Laboratorios Leti, S.A.V.). These findings endorse the therapeutic interchangeability of these products, providing clinicians with greater flexibility in the treatment of hyperlipidemia.

Effect of vinegar supplementation on patients with esophageal lesions lightly stained with Lugol’s iodine solution:Prospective single-centre trial

BACKGROUND Esophageal chromoendoscopy with iodine solution is important for detecting early esophageal cancer.The effect of routine treatment for lesions lightly stained with Lugol’s iodine solution is limited,and the addition of natural substances to a regular diet is becoming increasingly common.Vinegar has antitumor effects as reported in previous studies.AIM To evaluate whether vinegar supplementation could improve the prognosis of patients with lightly stained esophageal lesions.METHODSThis prospective single-centre trial included consecutive patients with lightly stained lesions between June 2020 and April 2022.Patients in the experimental group received increased amounts of vinegar for 6 months.The primary outcome of the study was the clinical therapeutic effect.Complications related to vinegar ingestion and adverse events were also recorded in detail.RESULTS A total of 166 patients were included in the final analysis.There was no significant difference in the baseline data between the two groups.Intention-to-treat(ITT)analysis demonstrated that the rates at which endoscopic characteristics improved were 33.72%in the experimental group and 20.00%in the conventional group(P=0.007);and the rates at which biopsy pathology improved were 19.77%and 8.75%,respectively(P=0.011).Additional vinegar consumption had a statistically protective effect on the rate at which endoscopic characteristics improved[hazard ratio(HR)_(ITT)=2.183,95%CI:1.183-4.028;HR_(per-protocol(PP))=2.307,95%CI:1.202-4.426]and biopsy pathology improved(HR_(ITT)=2.931,95%CI:1.212-7.089;HR_(PP)=3.320,95%CI:1.295-8.507).No statistically significant effect of increased vinegar consumption on preventing high-grade intraepithelial neoplasia or early cancer was observed(HR_(ITT)=0.382,95%CI:0.079-1.846;HRPP=0.382,95%CI:0.079-1.846).The subgroup analyses indicated that the overall therapeutic improvement of endoscopic characteristics and biopsy pathology seemed more obvious in older(age>60)male patients with small lesions(lesion size≤0.5 cm).Three patients in the experimental group reported acid regurgitation and heartburn.No adverse event during gastroscopy were recorded during follow-up.CONCLUSION A moderately increased ingestion of vinegar could not directly reduce the risk of esophageal cancer in the mucosa dysplasia population,but it improved the endoscopic characteristics and ameliorated the biopsy pathology to a certain extent.Further research is needed to verify the effect of nutritional intervention on precancerous esophageal lesions.

Pharmacokinetics and Bioequivalence Evaluation of Two Rosuvastatin Calcium 20 mg Tablets: A Single Oral Dose, Randomized-Sequence, Open-Label, Two-Period Crossover Study in Healthy Volunteers under Fasting Conditions

Objectives: To compare the rate and extent of absorption of Racor® 20 mg (Rosuvastatin calcium 20 mg) tablet of Laboratorios Leti, S.A.V., with Crestor® 20 mg (Rosuvastatin calcium 20 mg) tablet of AstraZeneca, UK Limited in healthy adult human subjects under fasting conditions. Method: This was an open label, analyst blind, balanced, randomized, two-treatment, two-period, two-sequence, single oral dose, crossover, bioequivalence study in healthy, adult, human subjects under fasting condition. Twenty-four (24) subjects were planned as per the protocol and all subjects completed both periods of the study. The concentrations of Rosuvastatin in plasma were quantitated using a validated LC-MS/MS method of analysis and plasma levels were submitted for statistical analysis. Cmax, AUC0-t, AUC0-∞, Tmax, t1/2, Kel (hrs-1), percent AUC extrapolated [100 * (AUC0-∞ - AUC0-t)/AUC0-∞] (AUC_%Extrapobs) were calculated for rosuvastatin in plasma using SAS® version 9.1.3, SAS Institute. Inc. USA.CARY. ANOVA, 90% confidence interval using Schuirmann’s two one-sided test for bioequivalence, power and ratio analysis, for lntransformed pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞ were computed and reported for Rosuvastatin in plasma for BE. Results: Data showed that 90% confidence intervals for the test/reference geometric mean ratios (GMR) of Cmax (95.01 - 112.66), AUC0-t (93.38 - 111.67) and AUC0-∞ (93.65 - 111.29) were within the BE (80% - 125%) acceptance range. Conclusions: Two products formulation, reference (R) Crestor® (rosuvastatin calcium) of AstraZeneca and test (T), Racor® (rosuvastatin calcium) of Laboratorios Leti S.A.V., with a single dose of 20 mg, under fasting conditions were bioequivalent. No severe, serious or unexpected adverse events (AEs) were reported in this study.

A Bioequivalence Study of Empagliflozin/Metformin Fixed-Dose Combination in Healthy Subjects under Fasting Conditions

Background: This study evaluated the bioequivalence of empagliflozin 12.5 mg/metformin 1000 mg tablets compared to Synjardy® (Empagliflozin 12.5 mg/metformin 1000 mg) tablets in healthy male subjects under fasting conditions. Methods: This was a phase I, randomized, single-dose, two-period, two-sequence, crossover study to evaluate the bioequivalence (BE) profiles of two fixed-dose combinations (FDCs) of empagliflozin/metformin. Cmax, AUC0-t and AUC0-∞ from test and reference formulations were evaluated to access BE. The plasma concentrations were measured using a validated liquid chromatography-mass spectrometry (LC-MS/MS) method. Of the 24 subjects enrolled, 23 completed both periods of the study. The two formulations test and reference were considered bioequivalent if 90% confidence interval (CI) fell within 80.00% - 125.00% for Cmax, AUC0-t and AUC0-∞. Tolerability and safety were assessed throughout the study. Results: The pharmacokinetic (PK) parameters were similar between the test product (T) and reference product (R) Synjardy®. The 90% CI of the test/reference ratios of log-transformed PK parameters point estimates was Cmax: 89.87% (85.68% - 94.27%), AUC0-t: 87.91% (83.65% - 92.39%) and AUC0-∞: 87.16% (82.80% - 91.75%) to empagliflozin and Cmax: 92.19% (87.95% - 96.65%), AUC0-t: 91.38% (84.42% - 98.91%) and AUC0-∞: 93.78% (83.82% - 104.93%) to metformin respectively (90% CI for all PK parameters fell within 80.00% - 125.00%). Conclusion: Our results demonstrated BE between the test and reference formulations of oral tablets of empagliflozin 12.5 mg/metformin 1000 mg (FDC) in healthy male subjects under fasting conditions.

Microglia lactylation in relation to central nervous system diseases

The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

Data mining in clinical big data:the frequently used databases,steps,and methodological models

Many high quality studies have emerged from public databases,such as Surveillance,Epidemiology,and End Results(SEER),National Health and Nutrition Examination Survey(NHANES),The Cancer Genome Atlas(TCGA),and Medical Information Mart for Intensive Care(MIMIC);however,these data are often characterized by a high degree of dimensional heterogeneity,timeliness,scarcity,irregularity,and other characteristics,resulting in the value of these data not being fully utilized.Data-mining technology has been a frontier field in medical research,as it demonstrates excellent performance in evaluating patient risks and assisting clinical decision-making in building disease-prediction models.Therefore,data mining has unique advantages in clinical big-data research,especially in large-scale medical public databases.This article introduced the main medical public database and described the steps,tasks,and models of data mining in simple language.Additionally,we described data-mining methods along with their practical applications.The goal of this work was to aid clinical researchers in gaining a clear and intuitive understanding of the application of data-mining technology on clinical big-data in order to promote the production of research results that are beneficial to doctors and patients.

Green tea and the risk of gastric cancer: Epidemiological evidence

Gastric cancer (GC) is one of the leading causes of cancer death in the world. Numerous efforts are being made to find chemoprotective agents able to reduce its risk. Amongst these, green tea has been reported to have a protective effect against stomach cancer. This article aims to critically evaluate all epidemiological studies reporting an association between green tea consumption and GC risk. MEDLINE, EBSCOHOST and Google Scholar were used to search for clinical trials of green tea and its correlation to stomach cancer. Studies include cohort and case-control studies. Outcome of interests are inverse association, no association, and positive association. Seventeen epidemiologic studies were reviewed. Eleven studies were conducted in Japan, five in China, and one with Japanese descendent in Hawaii. Ten case-control studies and seven cohortstudies were included. The relative risks or odds ratio of GC for the highest level of green tea consumption was compared. Seven studies suggested no association, eight an inverse association, and one a positive association. One study had shown a significantly lowered GC risk when tea was served warm to cold. Another study also showed a significantly risk with lukewarm tea. All studies that analyzed men and women separately have suggested a reduced risk in women than in men, albeit no significant difference. This review demonstrates that there is insufficient information to support green tea consumption reduces the risk of GC. More studies on the subject matter are warranted.

Medical management of metabolic and cardiovascular complications after liver transplantation

Liver transplantation represents the only curative option for patients with endstage liver disease,fulminant hepatitis and advanced hepatocellular carcinoma.Even though major advances in transplantation in the last decades have achieved excellent survival rates in the early post-transplantation period,long-term survival is hampered by the lack of improvement in survival in the late post transplantation period(over 5 years after transplantation).The main etiologies for late mortality are malignancies and cardiovascular complications.The latter are increasingly prevalent in liver transplant recipients due to the development or worsening of metabolic syndrome and all its components(arterial hypertension,dyslipidemia,obesity,renal injury,etc.).These comorbidities result from a combination of pre-liver transplant features,immunosuppressive agent side-effects,changes in metabolism and hemodynamics after liver transplantation and the adoption of a sedentary lifestyle.In this review we describe the most prevalent metabolic and cardiovascular complications present after liver transplantation,as well as proposing management strategies.

Hypoxia increases adipogenesis and affects adipocytokine production in orbital fibroblasts-a possible explanation of the link between smoking and Graves' ophthalmopathy

AIM:To assess the effects of hypoxia on human orbital fibroblasts(OF)on adipogenesis and adipocytokine production.METHODS:Human OF were derived from tissues obtained from patients with Graves’ophthalmopathy(GO)and from patients without known thyroid diseases undergoing blepharoplasty.The OF were cultured separately under normoxic and hypoxic conditions.Comparisons of adipocytokine concentrations using multiplex ELISA and lipid accumulation in the cells using Oil Red O staining were subsequently performed.RESULTS:There was increased adipogenesis in OF from GO subject when exposed to hypoxic culture conditions.This was not observed in OF from normal controls.Hypoxia led to an increase in leptin and a decrease in MCP-1 secretion in OF cultures.CONCLUSION:Hypoxia induces adipogenesis in OF and may represent a mechanism by which smoking contributes to deterioration of GO.We also found novel changes to leptin and MCP-1 production in OF cultures exposed to hypoxia suggesting important roles of these cytokines in the disease process.

Maintaining clarity:Review of maintenance therapy in nonsmall cell lung cancer

The purpose of this article is to review the role of maintenance therapy in the treatment of advanced nonsmall cell lung cancer(NSCLC). A brief overview about induction chemotherapy and its primary function in NSCLC is provided to address the basis of maintenance therapies foundation. The development of how maintenance therapy is utilized in this population is discussed and current guidelines for maintenance therapy are reviewed. Benefits and potential pitfalls of maintenance therapy are addressed, allowing a comprehensive review of the achieved clinical benefit that maintenance therapy may or may not have on NSCLC patient population. A review of current literature was conducted and a table is provided comparing the results of various maintenance therapy clinical trials. The table includes geographical location of each study, the number of patients enrolled, progression free survival and overall survival statistics, post-treatment regimens and if molecular testing was conducted. The role of molecular testing in relation to therapeutic treatment options foradvanced NSCLC patients is discussed. A treatment algorithm clearly depicts first line and second line treatment for management of NSCLC and includes molecular testing, maintenance therapy and the role clinical trials have in treatment of NSCLC. This treatment algorithm has been specifically tailored and developed to assist clinicians in the management of advanced NSCLC.

Global research trends in the microbiome related to irritable bowel syndrome: A bibliometric and visualized study

BACKGROUND Irritable bowel syndrome(IBS) is a common functional gastrointestinal disorder. Dysregulation of the gut–brain axis plays a central role in the pathophysiology of IBS. It is increasingly clear that the microbiome plays a key role in the development and normal functioning of the gut–brain axis.AIM To facilitate the identification of specific areas of focus that may be of relevance to future research. This study represents a bibliometric analysis of the literature pertaining to the microbiome in IBS to understand the development of this field.METHODS The data used in our bibliometric analysis were retrieved from the Scopus database. The terms related to IBS and microbiome were searched in titles or abstracts within the period of 2000–2019. VOSviewer software was used for data visualization.RESULTS A total of 13055 documents related to IBS were retrieved at the global level. There were 1872 scientific publications focused on the microbiome in IBS. There was a strong positive correlation between publication productivity related to IBS in all fields and productivity related to the microbiome in IBS(r = 0.951, P < 0.001). The United States was the most prolific country with 449(24%) publications, followed by the United Kingdom(n = 176, 9.4%), China(n = 154, 8.2%), and Italy(n = 151, 8.1%). The h-index for all retrieved publications related to the microbiome in IBS was 138. The hot topics were stratified into four clusters:(1) The gut–brain axis related to IBS;(2) Clinical trials related to IBS and the microbiome;(3) Drugmediated manipulation of the gut microbiome;and(4) The role of the altered composition of intestinal microbiota in IBS prevention.CONCLUSION This is the first study to evaluate and quantify global research productivity pertaining to the microbiome in IBS. The number of publications regarding the gut microbiota in IBS has continuously grown since 2013. This finding suggests that the future outlook for interventions targeting the gut microbiota in IBS remains promising.

Typing of pancreatic cancer-associated fibroblasts identifies different subpopulations

AIM To determine whether it is possible to identify different immune phenotypic subpopulations of cancer-associated fibroblasts (CAFs) in pancreatic cancer (PC). METHODS We defined four different stromal compartments in surgical specimens with PC: The juxtatumoural, peripheral, lobular and septal stroma. Tissue microarrays were produced containing all pre-defined PC compartments, and the expression of 37 fibroblast (FB) and 8 extracellular matrix (ECM) markers was evaluated by immunohistochemistry, immunofluorescence (IF), double-IF, and/or in situ hybridization. The compartment-specific mean labelling score was determined for each marker using a four-tiered scoring system. DOG1 gene expression was examined byquantitative reverse transcription PCR (qPCR). RESULTS CD10, CD271, cytoglobin, DOG1, miR-21, nestin, and tenascin C exhibited significant differences in expression profiles between the juxtatumoural and peripheral compartments. The expression of CD10, cytoglobin, DOG1, nestin, and miR-21 was moderate/strong in juxtatumoural CAFs (j-CAFs) and barely perceptible/weak in peripheral CAFs (p-CAFs). The upregulation of DOG1 gene expression in PC compared to normal pancreas was verified by qPCR. Tenascin C expression was strong in the juxtatumoural ECM and barely perceptible/weak in the peripheral ECM. CD271 expression was barely perceptible in j-CAFs but moderate in the other compartments. Galectin-1 was stronger expressed in j-CAFs vs septal fibroblasts, PDGFRβ, tissue transglutaminase 2, and hyaluronic acid were stronger expressed in lobular fibroblasts vs p-CAFs, and plectin-1 was stronger expressed in j-CAFs vs l-FBs. The expression of the remaining 33 markers did not differ significantly when related to the quantity of CAFs/FBs or the amount of ECM in the respective compartments.CONCLUSION Different immune phenotypic CAF subpopulations can be identified in PC, using markers such as cytoglobin, CD271, and miR-21. Future studies should determine whether CAF subpopulations have different functional properties.