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.

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.

How to use the Surveillance,Epidemiology,and End Results(SEER)data:research design and methodology

In the United States(US),the Surveillance,Epidemiology,and End Results(SEER)program is the only comprehensive source of population-based information that includes stage of cancer at the time of diagnosis and patient survival data.This program aims to provide a database about cancer incidence and survival for studies of surveillance and the development of analytical and methodological tools in the cancer field.Currently,the SEER program covers approximately half of the total cancer patients in the US.A growing number of clinical studies have applied the SEER database in various aspects.However,the intrinsic features of the SEER database,such as the huge data volume and complexity of data types,have hindered its application.In this review,we provided a systematic overview of the commonly used methodologies and study designs for retrospective epidemiological research in order to illustrate the application of the SEER database.Therefore,the goal of this review is to assist researchers in the selection of appropriate methods and study designs for enhancing the robustness and reliability of clinical studies by mining the SEER database.

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.

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.

Effect of lifestyle modification on hepatocellular carcinoma incidence and mortality among patients with chronic hepatitis B

BACKGROUND Research exploring the influence of healthier lifestyle modification(LSM)on the risk of hepatocellular carcinoma(HCC)in patients with chronic hepatitis B(CHB)is limited.AIM To emulate a target trial to determine the effect of LSM on HCC incidence and mortality among patients with CHB by large-scale population-based observational data.METHODS Among the patients with CHB enrolled in the Korean National Health Insurance Service between January 1,2009,and December 31,2017,those aged≥20 years who drank alcohol,smoked cigarettes,and were sedentary were analyzed.Exposure included at least one LSM,including alcohol abstinence,smoking cessation,and regular exercise.The primary outcome was HCC development,and the secondary outcome was liver-related mortality.We used 2:1 propensity score matching to account for covariates.RESULTS With 48766 patients in the LSM group and 103560 in the control group,the adjusted hazard ratio(HR)for incident HCC and liver-related mortality was 0.92[95%confidence interval(CI):0.87-0.96]and 0.92(95%CI:0.86-0.99)in the LSM group,respectively,compared with the control group.Among the LSM group,the adjusted HR(95%CI)for incident HCC was 0.84(0.76-0.94),0.87(0.81-0.94),and 1.08(1.00-1.16)for alcohol abstinence,smoking cessation,and regular exercise,respectively.The adjusted HR(95%CI)for liver-related mortality was 0.92(0.80-1.06),0.81(0.72-0.91),and 1.15(1.04-1.27)for alcohol abstinence,smoking cessation,and regular exercise,respectively.CONCLUSION LSM lowered the risk of HCC and mortality in patients with CHB.Thus,active LSM,particularly alcohol abstinence and smoking cessation,should be encouraged in patients with CHB.

Bioequivalence Study of Diclofenac 150 mg XR: A Single-Dose, Randomized, Open Label, 2-Period Crossover Study in Healthy Adult Volunteers

Objectives: Evaluate the bioequivalence (BE) of two oral tablets formulations of diclofenac 150 mg in healthy male subjects under fasting condition. This was a phase I, randomized, open label, balanced, two period, two sequences, single oral dose, crossover, analyst blind study. Methods: Twenty four (24) healthy subjects were randomly assigned to one of two sequences protocol: 150 mg XR of reference formulation (R), diclofenac sodium in the first period or the test formulation (T), diclofenac potassium in the second or vice versa. The plasma concentrations were determined using a validated LC-MS/MS method. Pharmacokinetic (PK) parameters included: maximum plasma concentration (Cmax), area under the plasma concentration—time curve from time 0 to the last measurable concentration (AUC0-t), and area under the plasma concentration—time from time 0 to infinity (AUC0-∞), were evaluated for BE. Results: The results showed that 90% confidence intervals for the test/reference geometric mean ratios (GMR) of Cmax (90.43 - 107.17), AUC0-t (93.08 - 116.46) and AUC0-∞ (92.52 - 117.39) were within the BE (80% - 125%) acceptance range. Conclusions: Two formulations, reference product (R) Voltaren® (diclofenac sodium) of Novartis and test product (T), Diklason Bi (diclofenac potassium) of Laboratorios Leti S.A.V., with a single dose of 150 mg XR, under fasting conditions were bioequivalent. No severe, serious or unexpected adverse events (AEs) were reported in this study.

A Prospective, Multicentric, Post Marketing Surveillance to Evaluate Efficacy & Safety of Ranitidine HCl (150 & 300 mg IR/CR) in Indian Patients with Gastroesophageal Reflux Disease (PROGRADE)

Purpose: Ranitidine hydrochloride (HCl) remains an important medication for treating acid-peptic ailments such as Gastroesophageal reflux disease (GERD). The main objective of this Post Marketing Surveillance (PMS) clinical study was to test the efficacy and safety of Ranitidine HCl in Indian patients suffering from GERD. Patients and Methods: Data of 2446 patients (1307 males;1121 females) from 21 centers across India were analyzed. Patients received either of the three treatments: Ranitidine HCl 150 mg twice a day (BID) (ARM-A), Ranitidine HCl 300 mg once daily (OD) or BID (ARM-B), and Ranitidine HCl 300 mg OD (ARM-C). Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS) score and Heartburn Severity score were used to assess the drug’s efficacy. The adverse events reported by patients or investigators were analyzed to assess the safety profile of Ranitidine. Results: Of the 2446 subjects screened, 2428 were enrolled. There was a significant reduction in GSAS scores from baseline to the end of the study visit in all three ARMs. The GSAS scores reduced from 2.02 to 0.23 in ARM-A, 2.01 to 0.24 in ARM-B, and 2.07 to 0.26 in ARM-C patients. In ARM A, 72.82% had 24 hours heartburn-free days, and 66.89% had 7 consecutive heartburn-free days, which was more significant than the other two ARMs. 128 (5.27%) patients reported ADRs due to Ranitidine HCl at different doses. The most frequently reported ADR was constipation (17.18%), followed by oliguria (14.06%), cold (13.28%), and dysuria (12.5%). Of 128 ADRs, 113 (88.28%) were mild, and only 11 (8.59%) ADRs were related to the study drug. No severe ADRs were reported during the study. Conclusion: Ranitidine HCl 150/300 mg tablet was found to be an effective and safe H2-receptor antagonist for treating GERD in Indian Patients.

New frontiers in ectopic pancreatic tissue management

The pancreatic development variations are relatively frequent but are often overlooked in clinical practice.This is due to the fact that they do not present with a distinct clinical picture and are usually asymptomatic.It also refers to the ectopic pancreatic tissue in the stomach.This anomaly can be diagnosed in any part of the digestive system,but it is mostly seen in the upper gastrointestinal tract,especially in the stomach,duodenum and jejunum.The management of this condition has evolved due to the development of minimally invasive procedures.

Are case reports valuable?Exploring their role in evidence based medicine and patient care

Case reports,often overlooked in evidence-based medicine(EBM),play a pivotal role in healthcare research.They provide unique insights into rare conditions,novel treatments,and adverse effects,serving as valuable educational tools and generating new hypothesis.Despite their limitations in generalizability,case reports contribute significantly to evidence-based practice by offering detailed clinical information and fostering critical thinking among healthcare professionals.By acknowledging their limitations and adhering to reporting guidelines,case reports can contribute significantly to medical knowledge and patient care within the evolving landscape of EBM.This editorial explores the intrinsic value of case reports in EBM and patient care.

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.

Clinical features and treatment outcomes of major depressive disorder with genital symptoms

To the Editor:Major depressive disorder(MDD)is a mood disorder characterized by complex patterns of emotional,cognitive,and behavioral symptomology and deficits in daily functioning.Genital symptoms,including a reduction in libido and menstrual disturbances,have been considered to be a classic symptom of MDD for many decades.Previous evidence has reached a broad consensus that the incidence of genital symptoms is higher in patients with MDD than in the general population.A systematic review and meta-analysis found a bidirectional association between MDD and genital symptoms,with patients with MDD showing a 50–70%increased risk of developing genital symptoms,while individuals with genital symptoms had a 130–210%increased risk of developing MDD.^([1])As previously reported,50–70%of people with MDD experience sexual dysfunction.^([2])To date,few studies have focused on the comparison of clinical features between patients with MDD with and without genital symptoms,and the longitudinal prognosis.