Molecular Epidemiology and Clinical Characteristics of Hand, Foot and Mouth Disease in North Sichuan Region, China, 2018-2023: A Descriptive Study

Background: Hand, foot and mouth disease (HFMD) remains an important public health problem in China. Many studies on the epidemiological characteristics of HFMD have been reported, but studies in North Sichuan region have been neglected. Methods: HFMD-related enterovirus infected cases were clinically confirmed and underwent real-time RT-PCR (rRT-PCR) from May 2018 to October 2023 in Guangyuan Central Hospital. Results: During 2018-2023, other EV (437 cases, 81.08%) was the most predominant serotype followed by CV-A16 (94 cases, 17.44%), EV-A71 (8 cases, 1.48%) was the least predominant serotype. Peak infections occurred in July and October. There were no significant differences in gender, age and serotypes. HFMD was concentrated in children under 47 months of age, with the highest incidence in children aged 12 - 23 months and the highest proportion of other EV infections in the whole age group. COVID-19 did not cause significant changes in gender, age and serotype. Overall, there was a significant increase in the proportion of children aged 12 - 23 months infected with CV-A16, and an increase in the proportion of children aged over 36 months infected with other EVs. Conclusions: The incidence of HFMD caused by EV-A71 has decreased significantly, and other EVs have become the main pathogens of HFMD in North Sichuan region in recent years. In the prevention and control of CV-A16, more attention should be paid to children aged 12 - 23 months and the dominant serotype should be closely monitored. Our study highlights the importance of developing of new diagnostic reagents and vaccines for the prevention and control of enterovirus infection. This study for the first time provides insights into district interventions to local conditions.

Clinical Application of Sex Hormone in Different Physiological Periods in the Diagnosis of Infertility Patients

Background: Infertility is characterized by the inability to conceive after a year of regular unprotected intercourse. Aims: This study aimed to investigate the diagnostic value of sex hormone levels during different physiological periods in the diagnosis of infertility patients. Methods: From December 2019 to May 2021, a total of 93 infertility patients were admitted and selected as the observation group. Among them, 31 cases were in the follicular stage, 31 cases in the ovulation stage, and 31 cases in the luteal stage. Ninety-three healthy women for fertility evaluation due to male infertility were selected as the control group. The control group included 31 women in the follicular phase, 31 women in the ovulatory phase, and 31 women in the luteal phase. The levels of sex hormones (prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), testosterone (T), and progesterone (P)) during different physiological phases were compared between the observation and control groups. Results: The follicular phase showed no significant difference in LH levels between the observation group and the control group. The observation group showed higher levels of PRL and P compared to the control group, while the levels of FSH, E2, and T were lower in the observation group compared to the control group. The ovulation phase showed no significant difference in PRL levels between the two groups. The observation group showed lower levels of LH, FSH, E2, T, and P compared to the control group. The luteal phase showed no statistical difference in E2 levels between the two groups. The observation group showed higher levels of PRL, LH, and FSH compared to the control group, while the levels of T and P were lower in the observation group compared to the control group. Conclusion: Infertile women show variations in hormone levels compared to the normal levels during the follicular phase, ovulatory phase, and luteal phase.

Development and application of hepatocellular carcinoma risk prediction model based on clinical characteristics and liver related indexes

BACKGROUND Hepatocellular carcinoma(HCC)is difficult to diagnose with poor therapeutic effect,high recurrence rate and has a low survival rate.The survival of patients with HCC is closely related to the stage of diagnosis.At present,no specific serolo-gical indicator or method to predict HCC,early diagnosis of HCC remains a challenge,especially in China,where the situation is more severe.AIM To identify risk factors associated with HCC and establish a risk prediction model based on clinical characteristics and liver-related indicators.METHODS The clinical data of patients in the Affiliated Hospital of North Sichuan Medical College from 2016 to 2020 were collected,using a retrospective study method.The results of needle biopsy or surgical pathology were used as the grouping criteria for the experimental group and the control group in this study.Based on the time of admission,the cases were divided into training cohort(n=1739)and validation cohort(n=467).Using HCC as a dependent variable,the research indicators were incorporated into logistic univariate and multivariate analysis.An HCC risk prediction model,which was called NSMC-HCC model,was then established in training cohort and verified in validation cohort.RESULTS Logistic univariate analysis showed that,gender,age,alpha-fetoprotein,and protein induced by vitamin K absence or antagonist-II,gamma-glutamyl transferase,aspartate aminotransferase and hepatitis B surface antigen were risk factors for HCC,alanine aminotransferase,total bilirubin and total bile acid were protective factors for HCC.When the cut-off value of the NSMC-HCC model joint prediction was 0.22,the area under receiver operating characteristic curve(AUC)of NSMC-HCC model in HCC diagnosis was 0.960,with sensitivity 94.40%and specificity 95.35%in training cohort,and AUC was 0.966,with sensitivity 90.00%and specificity 94.20%in validation cohort.In early-stage HCC diagnosis,the AUC of NSMC-HCC model was 0.946,with sensitivity 85.93%and specificity 93.62%in training cohort,and AUC was 0.947,with sensitivity 89.10%and specificity 98.49%in validation cohort.CONCLUSION The newly NSMC-HCC model was an effective risk prediction model in HCC and early-stage HCC diagnosis.

Clinical significance of serum oxidative stress and serum uric acid levels before surgery for hepatitis B-related liver cancer

BACKGROUND The incidence and mortality of liver cancer are among the highest of all malignant tumors in China.The high recurrence rate after conventional hepatectomy is worrying.There is a lack of effective prognostic indicators for liver cancer.AIM To explore the clinical significance of preoperative serum oxidative stress and serum uric acid(UA)levels in hepatitis B-related liver cancer.METHODS The medical records of 110 hepatitis B-related liver cancer patients who under-went hepatectomy in Gansu Provincial Hospital were retrospectively analyzed.Recurrence in patients within 3 years after surgery was determined.The logistic regression model and Pearson or Spearman correlation were used to analyze the correlation between oxidative stress level and UA,and the recurrence of hepatitis B-related liver cancer.RESULTS Compared with the non-recurrence group,the levels of superoxide dismutase(SOD)and glutathione(GSH)in the recurrence group were lower and the levels of malondialdehyde(MDA)and UA were higher(all P<0.05).UA,SOD,MDA,and GSH were risk factors for postoperative recurrence in hepatitis B-related liver cancer patients(P<0.05).UA was positively correlated with MDA(r=0.395,P<0.001)and negatively correlated with GSH(r=-0.204,P=0.032).The area under the receiver operating characteristic curve(AUC)of SOD,MDA,GSH,and UA in predicting the prognosis was 0.276,0.910,0.199,and 0.784,respectively(all P<0.001).CONCLUSION The preoperative serum SOD,GSH,MDA,and UA levels had significant predictive effects on postoperative recurrence of hepatitis B-related liver cancer.

Clinical implications of forkhead box M1, cyclooxygenase-2, and glucose-regulated protein 78 in breast invasive ductal carcinoma

BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expression profiles and clinical implications of forkhead box M1(FOXM1),cyclooxygenase-2(COX-2),and glucose-regulated protein 78(GRP78)in BIDC.METHODS A total of 65 BIDC patients and 70 healthy controls who presented to our hospital between August 2019 and May 2021 were selected for analysis.The peripheral blood FOXM1,COX-2,and GRP78 levels in both groups were measured and the association between their expression profiles in BIDC was examined.Additionally,we investigated the diagnostic value of FOXM1,COX-2,and GRP78 in patients with BIDC and their correlations with clinicopathological features.Furthermore,BIDC patients were followed for 1 year to identify factors influencing patient prognosis.RESULTS The levels of FOXM1,COX-2,and GRP78 were significantly higher in BIDC patients compared to healthy controls(P<0.05),and a positive correlation was observed among them(P<0.05).Receiver operating characteristic analysis demonstrated that FOXM1,COX-2,and GRP78 had excellent diagnostic value in predicting the occurrence of BIDC(P<0.05).Subsequently,we found significant differences in FOXM1,COX-2,and GRP78 levels among patients with different histological grades and metastasis statuses(with vs without)(P<0.05).Cox analysis revealed that FOXM1,COX-2,GRP78,increased histological grade,and the presence of tumor metastasis were independent risk factors for prognostic death in BIDC(P<0.001).CONCLUSION FOXM1,COX-2,and GRP78 exhibit abnormally high expression in BIDC,promoting malignant tumor development and closely correlating with prognosis.These findings hold significant research implications for the future diagnosis and treatment of BIDC.

Establishment of a Multiplex Detection Method for Common Bacteria in Blood Based on Human Mannan-Binding Lectin Protein-Conjugated Magnetic Bead Enrichment Combined with Recombinase-Aided PCR Technology

Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannanbinding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with RAP.Methods Recombinant plasmids were used to evaluate the assay sensitivity.Common blood influenza bacteria were used for the specific detection.Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)assays.Kappa analysis was used to evaluate the consistency between the two assays.Results The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial species.The M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05).Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

As a highly invasive malignancy,esophageal cancer(EC)is a global health issue,and was the eighth most prevalent cancer and the sixth leading cause of cancerrelated death worldwide in 2020.Due to its highly immunogenic nature,emerging immunotherapy approaches,such as immune checkpoint blockade,have demonstrated promising efficacy in treating EC;however,certain limitations and challenges still exist.In addition,tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment(TIME);thus,understanding the TIME is urgent and crucial,especially given the importance of an immunosuppressive microenvironment in tumor progression.The aim of this review was to better elucidate the mechanisms of the suppressive TIME,including cell infiltration,immune cell subsets,cytokines and signaling pathways in the tumor microenvironment of EC patients,as well as the downregulated expression of major histocompatibility complex molecules in tumor cells,to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies.Therefore,personalized treatments could be developed to maximize the advantages of immunotherapy.

Effects of Bisphenol A and Its Substitute, Bisphenol F, on the Gut Microbiota in Mice

Objective The aim of this study was to assess the impact of bisphenol A(BPA)and its substitute,bisphenol F(BPF),on the colonic fecal community structure and function of mice.Methods We exposed 6–8-week-old male C57BL/6 mice to 5 mg/(kg∙day)and 50μg/(kg∙day)of BPA or BPF for 14 days.Fecal samples from the colon were analyzed using 16S rRNA sequencing.Results Gut microbiome community richness and diversity,species composition,and function were significantly altered in mice exposed to BPA or BPF.This change was characterized by elevated levels of Ruminococcaceae UCG-010 and Oscillibacter and decreased levels of Prevotella 9 and Streptococcus.Additionally,pathways related to carbohydrate and amino acid metabolism showed substantial enrichment.Conclusion Mice exposed to different BP analogs exhibited distinct gut bacterial community richness,composition,and related metabolic pathways.Considering the essential role of gut bacteria in maintaining intestinal homeostasis,our study highlights the intestinal toxicity of BPs in vertebrates.

Latest insights into the global epidemiological features,screening,early diagnosis and prognosis prediction of esophageal squamous cell carcinoma

As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major histological subtype of EC,and its incidence and mortality rates are decreasing globally.Due to the lack of specific early symptoms,ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis,and the incidence and mortality rates are still high in many countries,especially in China.Therefore,enormous challenges still exist in the management of ESCC,and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC.Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated,certain promising biomarkers are being investigated to facilitate clinical decision-making.With the advent and advancement of highthroughput technologies,such as genomics,proteomics and metabolomics,valuable biomarkers with high sensitivity,specificity and stability could be identified for ESCC.Herein,we aimed to determine the epidemiological features of ESCC in different regions of the world,especially in China,and focused on novel molecular biomarkers associated with ESCC screening,early diagnosis and prognosis prediction.

Characterization of the CpsQ Regulon Reveals Its Role in the Transcription of Type Ⅵ Secretion System 2 Genes in Vibrio parahaemolyticus

Vibrio parahaemolyticus,a gram-negative halophilic bacterium that naturally inhabits coastal waters,causes gastroenteritis,skin infections,and septicemia in human beings[1].This bacterium produces multiple virulence factors,including thermostable direct hemolysin(TDH),TDH-related hemolysin(TRH),type Ⅲ secretion system 1(T3SS1),T3SS2,type Ⅵ secretion system 1(T6SS1),and T6SS2[1].Furthermore,Ⅴ.parahaemolyticus forms biofilms on the surface,which help it in adapting to unfavorable conditions[2].Mature biofilm formation requires special structures,including lateral and polar flagella,exopolysaccharide(EPS),and type Ⅳ pili[2].

Investigation of the feasibility of NRAV as a biomarker for hepatocellular carcinoma

The long non-coding RNA,Negative Regulator of Antiviral Response(NRAV)has been identified as a participant in both respiratory virus replication and immune checkpoints,however,its involvement in pan-cancer immune regulation and prognosis,particularly those of hepatocellular carcinoma(HCC),remains unclear.To address this knowledge gap,we analyzed expression profiles obtained from The Cancer Genome Atlas(TCGA)database,comparing normal and malignant tumor tissues.We found that NRAV expression is significantly upregulated in tumor tissues compared to adjacent nontumor tissues.Kaplan-Meier(K-M)analysis revealed the prognostic power of NRAV,wherein overexpression was significantly linked to reduced overall survival in a diverse range of tumor patients.Furthermore,noteworthy associations were observed between NRAV,immune checkpoints,immune cell infiltration,genes related to autophagy,epithelial-mesenchymal transition(EMT),pyroptosis,tumor mutational burden(TMB),and microsatellite instability(MSI)across different cancer types,including HCC.Moreover,NRAV upregulation expression was associated with multiple pathological stages by clinical observations.Furthermore,our investigation revealed a substantial elevation in the expression of NRAV in both HCC tumor tissues and cells compared to normal tissues and cells.The inhibition of NRAV resulted in the inhibition of cell proliferation,migration,and invasion in HCC cells,while also influencing the expression of CD274(PD-L1)and CD44,along with various biomarkers associated with EMT,autophagy,and pyroptosis.The aforementioned results propose NRAV as a promising prognostic biomarker for HCC.

Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer

Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.

Four centrosome-related genes to predict the prognosis and drug sensitivity of patients with colon cancer

BACKGROUND As the primary microtubule organizing center in animal cells,centrosome abnormalities are involved in human colon cancer.AIM To explore the role of centrosome-related genes(CRGs)in colon cancer.METHODS CRGs were collected from public databases.Consensus clustering analysis was performed to separate the Cancer Genome Atlas cohort.Univariate Cox and least absolute shrinkage selection operator regression analyses were performed to identify candidate prognostic CRGs and construct a centrosome-related signature(CRS)to score colon cancer patients.A nomogram was developed to evaluate the CRS risk in colon cancer patients.An integrated bioinformatics analysis was conducted to explore the correlation between the CRS and tumor immune microenvironment and response to immunotherapy,chemotherapy,and targeted therapy.Single-cell transcriptome analysis was conducted to examine the immune cell landscape of core prognostic genes.RESULTS A total of 726 CRGs were collected from public databases.A CRS was constructed,which consisted of the following four genes:TSC1,AXIN2,COPS7A,and MTUS1.Colon cancer patients with a high-risk signature had poor survival.Patients with a high-risk signature exhibited decreased levels of plasma cells and activated memory CD4+T cells.Regarding treatment response,patients with a high-risk signature were resistant to immunotherapy,chemotherapy,and targeted therapy.COPS7A expression was relatively high in endothelial cells and fibroblasts.MTUS1 expression was high in endothelial cells,fibroblasts,and malignant cells.CONCLUSION We constructed a centrosome-related prognostic signature that can accurately predict the prognosis of colon cancer patients,contributing to the development of individualized treatment for colon cancer.

Clinical Value of Hepatitis B Virus RNA Detection in Patients with Chronic Hepatitis B Infection

Objective:To study the clinical value of hepatitis B virus pregenomic RNA(HBV-pgRNA)detection in the treatment of hepatitis B.Methods:60 patients with hepatitis B were included in the study.Serum HBV-pgRNA and HBV DNA levels in different phases of infection and during treatment were detected,and serum hepatitis B surface antigen(HbsAg)titer was detected by chemiluminescent immunoassay.DNA was extracted from liver biopsy tissue,and covalently closed circular DNA was detected to predict the therapeutic value in patients.Results:At the initial stage of treatment,the level of HBV-pgRNA in phase I,II,III,and IV showed a gradual decrease.Comparing the levels of HBV-pgRNA before and after treatment,we found that the level of HBV-pgRNA was significantly lower after treatment(P<0.05).Among the indicators for predicting HBsAg seroconversion,the accuracy of HBV-pgRNA level was 85.0%(51/60).Conclusion:The clinical value of HBV-pgRNA detection in the treatment of hepatitis B is high.

A Comprehensive Study of the Association between LEPR Gene rs1137101 Variant and Risk of Digestive System Cancers

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case–control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk.Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reactionrestriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis.Results After Bonferroni correction,the case–control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population.Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

Application of Fusobacterium nucleatum as a biomarker in gastrointestinal malignancies

The morbidity and mortality of gastrointestinal(GI)malignancies are among the highest in the world,posing a serious threat to human health.Because of the insidious onset of the cancer,it is difficult for patients to be diagnosed at an early stage,and it rapidly progresses to an advanced stage,resulting in poor treatment and prognosis.Fusobacterium nucleatum(F.nucleatum)is a gram-negative,sporefree anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal,esophageal,gastric,and pancreatic cancers via various intricate mechanisms.Recent development in novel research suggests that F.nucleatum may function as a biomarker in GI malignancies.Detecting the abundance of F.nucleatum in stool,saliva,and serum samples of patients may aid in the diagnosis,risk assessment,and prognosis monitoring of GI malignancies.This editorial systematically describes the biological roles and mechanisms of F.nucleatum in GI malignancies focusing on the application of F.nucleatum as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of F.nucleatum and GI tumors-related research.

Enhancing predictive accuracy in hypertriglyceridemia-induced acute pancreatitis:Role of red cell distribution width and prospective studies

This letter addresses the study titled“Red cell distribution width:A predictor of the severity of hypertriglyceridemia-induced acute pancreatitis”by Lv et al published in the World Journal of Experimental Medicine.The study offers a valuable analysis of red cell distribution width(RDW)as a predictive marker for persistent organ failure in patients with hypertriglyceridemia-induced acute pancreatitis.The study results suggest that RDW,combined with the Bedside Index for Severity in Acute Pancreatitis score,could enhance the predictive accuracy for severe outcomes.Further investigation into the role of RDW in different severities of acute pancreatitis is recommended.Additionally,the need for large-scale and multicenter prospective studies to validate these findings is emphasized.

Evaluation of the value of combined detection of tumor markers CA724,carcinoembryonic antigen,CA242,and CA19-9 in gastric cancer

BACKGROUND Gastric cancer is a global health concern that poses a significant threat to human well-being.AIM To detecting serum changes in carcinoembryonic antigen(CEA),carbohydrate antigens(CA)724,CA242,and CA19-9 expression among patients with gastric cancer.METHODS Eighty patients diagnosed with gastric cancer between January 2020 and January 2023 were included in the observation group,while 80 patients with benign gastric diseases were included in the control group.Both groups were tested for tumor markers(CA724,CEA,CA242,and CA19-9].Tumor marker indicators(CA724,CEA,CA242,and CA19-9)were compared between the two groups,assessing positive rates of tumor markers across various stages in the observation group.Additionally,single and combined detection of various tumor markers were examined.RESULTS The sensitivity,specificity,accuracy,positive predictive value,and negative predictive value observed for the combined detection of CA724,CEA,CA242,and CA19-9 were higher than those of CA724,CEA,CA242,and CA19-9 individually.Therefore,the combined detection of CA724,CEA,CA242,and CA19-9 has a high diagnostic accuracy and could reduce the occurrence of missed or misdiagnosed cases,facilitating the early diagnosis and treatment of patients.CONCLUSION CA724,CEA,CA242,and CA19-9 serum levels in gastric cancer patients significantly surpassed those in non-gastric cancer patients(P<0.05).Their combined detection can improve the diagnostic accuracy for gastric cancer,warranting clinical promotion.

Therapeutic utility of human umbilical cord-derived mesenchymal stem cells-based approaches in pulmonary diseases:Recent advancements and prospects

Pulmonary diseases across all ages threaten millions of people and have emerged as one of the major public health issues worldwide.For diverse disease con-ditions,the currently available approaches are focused on alleviating clinical symptoms and delaying disease progression but have not shown significant therapeutic effects in patients with lung diseases.Human umbilical cord-derived mesenchymal stem cells(UC-MSCs)isolated from the human UC have the capacity for self-renewal and multilineage differentiation.Moreover,in recent years,these cells have been demonstrated to have unique advantages in the treatment of lung diseases.We searched the Public Clinical Trial Database and found 55 clinical trials involving UC-MSC therapy for pulmonary diseases,including coronavirus disease 2019,acute respiratory distress syndrome,bron-chopulmonary dysplasia,chronic obstructive pulmonary disease,and pulmonary fibrosis.In this review,we summarize the characteristics of these registered clinical trials and relevant published results and explore in depth the challenges and opportunitiesfaced in clinical application.Moreover,the underlying mole-cular mechanisms involved in UC-MSC-based therapy for pulmonary diseases are also analyzed in depth.In brief,this comprehensive review and detailed analysis of these clinical trials can be expected to provide a scientific reference for future large-scale clinical application.

Developing and validating a predictive model of delivering large-forgestational-age infants among women with gestational diabetes mellitus

BACKGROUND The birth of large-for-gestational-age(LGA)infants is associated with many shortterm adverse pregnancy outcomes.It has been observed that the proportion of LGA infants born to pregnant women with gestational diabetes mellitus(GDM)is significantly higher than that born to healthy pregnant women.However,traditional methods for the diagnosis of LGA have limitations.Therefore,this study aims to establish a predictive model that can effectively identify women with GDM who are at risk of delivering LGA infants.AIM To develop and validate a nomogram prediction model of delivering LGA infants among pregnant women with GDM,and provide strategies for the effective prevention and timely intervention of LGA.METHODS The multivariable prediction model was developed by carrying out the following steps.First,the variables that were associated with LGA risk in pregnant women with GDM were screened by univariate analyses,for which the P value was<0.10.Subsequently,Least Absolute Shrinkage and Selection Operator regression was fit using ten cross-validations,and the optimal combination factors were se-lected by choosing lambda 1se as the criterion.The final predictors were deter-mined by multiple backward stepwise logistic regression analysis,in which only the independent variables were associated with LGA risk,with a P value<0.05.Finally,a risk prediction model was established and subsequently evaluated by using area under the receiver operating characteristic curve,calibration curve and decision curve analyses.RESULTS After using a multistep screening method,we establish a predictive model.Several risk factors for delivering an LGA infant were identified(P<0.01),including weight gain during pregnancy,parity,triglyceride-glucose index,free tetraiodothyronine level,abdominal circumference,alanine transaminase-aspartate aminotransferase ratio and weight at 24 gestational weeks.The nomogram’s prediction ability was supported by the area under the curve(0.703,0.709,and 0.699 for the training cohort,validation cohort,and test cohort,respectively).The calibration curves of the three cohorts displayed good agreement.The decision curve showed that the use of the 10%-60%threshold for identifying pregnant women with GDM who are at risk of delivering an LGA infant would result in a positive net benefit.CONCLUSION Our nomogram incorporated easily accessible risk factors,facilitating individualized prediction of pregnant women with GDM who are likely to deliver an LGA infant.