Ultrasound features of congenital cytomegalovirus infection in the first trimester:A case report

BACKGROUND Congenital cytomegalovirus(CMV)infection represents a significant public health concern as the most prevalent viral infection in newborns,potentially leading to severe neurological and developmental complications.The majority of cases are asymptomatic and remain undetected during pregnancy due to the absence of effective screening methods.CASE SUMMARY A 27-year-old primigravida presented for early pregnancy ultrasound,which revealed an atypical finding:A normal anechoic thalamus appearing hyperechoic on the mid-sagittal view of the fetal head.Subsequent ultrasound examinations during mid and late gestation demonstrated classic intracranial features sug-gestive of congenital CMV infection.Chromosomal karyotyping and microarray analysis of the fetus yielded no significant abnormalities.Following compre-hensive prenatal counseling regarding potential adverse fetal outcomes,the patient elected to continue her pregnancy.She ultimately underwent cesarean delivery at 42 weeks gestation at another facility,resulting in the birth of a female neonate.At five months of age,the infant presented with epilepsy and significant growth and developmental delays.CONCLUSION Congenital CMV infection occurs during the first trimester may manifest as hyperechoic thalamus which can be revealed by ultrasound in the mid-saggital view of the fetal head.Future research should investigate the correlation between echogenic thalamus and developmental outcomes,as well as explore early sc-reening techniques for suspected congenital CMV infection cases.

Construction of a nomogram model to predict technical difficulty in performing laparoscopic sphincter-preserving radical resection for rectal cancer

BACKGROUND Colorectal surgeons are well aware that performing surgery for rectal cancer becomes more challenging in obese patients with narrow and deep pelvic cavities.Therefore,it is essential for colorectal surgeons to have a comprehensive understanding of pelvic structure prior to surgery and anticipate potential surgical difficulties.AIM To evaluate predictive parameters for technical challenges encountered during laparoscopic radical sphincter-preserving surgery for rectal cancer.METHODS We retrospectively gathered data from 162 consecutive patients who underwent laparoscopic radical sphincterpreserving surgery for rectal cancer.Three-dimensional reconstruction of pelvic bone and soft tissue parameters was conducted using computed tomography(CT)scans.Operative difficulty was categorized as either high or low,and multivariate logistic regression analysis was employed to identify predictors of operative difficulty,ultimately creating a nomogram.RESULTS Out of 162 patients,21(13.0%)were classified in the high surgical difficulty group,while 141(87.0%)were in the low surgical difficulty group.Multivariate logistic regression analysis showed that the surgical approach using laparoscopic intersphincteric dissection,intraoperative preventive ostomy,and the sacrococcygeal distance were independent risk factors for highly difficult laparoscopic radical sphincter-sparing surgery for rectal cancer(P<0.05).Conversely,the anterior-posterior diameter of pelvic inlet/sacrococcygeal distance was identified as a protective factor(P<0.05).A nomogram was subsequently constructed,demonstrating good predictive accuracy(C-index=0.834).CONCLUSION The surgical approach,intraoperative preventive ostomy,the sacrococcygeal distance,and the anterior-posterior diameter of pelvic inlet/sacrococcygeal distance could help to predict the difficulty of laparoscopic radical sphincter-preserving surgery.

Study on sex differences and potential clinical value of threedimensional computerized tomography pelvimetry in rectal cancer patients

BACKGROUND Laparoscopic rectal cancer radical surgery is a complex procedure affected by various factors.However,the existing literature lacks standardized parameters for the pelvic region and soft tissues,which hampers the establishment of consistent conclusions.AIM To comprehensively assess 16 pelvic and 7 soft tissue parameters through computerized tomography(CT)-based three-dimensional(3D)reconstruction,providing a strong theoretical basis to address challenges in laparoscopic rectal cancer radical surgery.METHODS We analyzed data from 218 patients who underwent radical laparoscopic surgery for rectal cancer,and utilized CT data for 3D pelvic reconstruction.Specific anatomical points were carefully marked and measured using advanced 3D modeling software.To analyze the pelvic and soft tissue parameters,we emp-loyed statistical methods including paired sample t-tests,Wilcoxon rank-sum tests,and correlation analysis.RESULTS The investigation highlighted significant sex disparities in 14 pelvic bone parameters and 3 soft tissue parameters.Males demonstrated larger measurements in pelvic depth and overall curvature,smaller measurements in pelvic width,a larger mesorectal fat area,and a larger anterior-posterior abdominal diameter.By contrast,females exhibited wider pelvises,shallower depth,smaller overall curvature,and an increased amount of subcutaneous fat tissue.However,there were no significant sex differences observed in certain parameters such as sacral curvature height,superior pubococcygeal diameter,rectal area,visceral fat area,waist circumference,and transverse abdominal diameter.CONCLUSION The reconstruction of 3D CT data enabled accurate pelvic measurements,revealing significant sex differences in both pelvic and soft tissue parameters.This study design offer potential in predicting surgical difficulties and creating personalized surgical plans for male rectal cancer patients with a potentially“difficult pelvis”,ultimately improving surgical outcomes.Further research and utilization of these parameters could lead to enhanced surgical methods and patient care in laparoscopic rectal cancer radical surgery.

Identification of differentially expressed mRNAs as novel predictive biomarkers for gastric cancer diagnosis and prognosis

BACKGROUND Gastric cancer(GC)has a high mortality rate worldwide.Despite significant progress in GC diagnosis and treatment,the prognosis for affected patients still remains unfavorable.AIM To identify important candidate genes related to the development of GC and iden-tify potential pathogenic mechanisms through comprehensive bioinformatics analysis.METHODS The Gene Expression Omnibus database was used to obtain the GSE183136 dataset,which includes a total of 135 GC samples.The limma package in R software was employed to identify differentially expressed genes(DEGs).Thereafter,enrichment analyses of Gene Ontology(GO)terms and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were performed for the gene modules using the clusterProfile package in R software.The protein-protein interaction(PPI)networks of target genes were constructed using STRING and visualized by Cytoscape software.The common hub genes that emerged in the cohort of DEGs that was retrieved from the GEPIA database were then screened using a Venn Diagram.The expression levels of these overlapping genes in stomach adenocarcinoma samples and non-tumor samples and their association with prognosis in GC patients were also obtained from the GEPIA database and Kaplan-Meier curves.Moreover,real-time quantitative polymerase chain reaction(RT-qPCR)and western blotting were performed to determine the mRNA and protein levels of glutamic-pyruvic transaminase(GPT)in GC and normal immortalized cell lines.In addition,cell viability,cell cycle distribution,migration and invasion were evaluated by cell counting kit-8,flow cytometry and transwell assays.Furthermore,we also conducted a retrospective analysis on 70 GC patients diagnosed and surgically treated in Wenzhou Central Hospital,Dingli Clinical College of Wenzhou Medical University,The Second Affiliated Hospital of Shanghai University between January 2017 to December 2020.The tumor and adjacent normal samples were collected from the patients to determine the potential association between the expression level of GPT and the clinical as well as pathological features of GC patients.RESULTS We selected 19214 genes from the GSE183136 dataset,among which there were 250 downregulated genes and 401 upregulated genes in the tumor samples of stage III-IV in comparison to those in tumor samples of stage I-II with a P-value<0.05.In addition,GO and KEGG results revealed that the various upregulated DEGs were mainly enriched in plasma membrane and neuroactive ligand-receptor interaction,whereas the downregulated DEGs were primarily enriched in cytosol and pancreatic secretion,vascular smooth muscle contraction and biosynthesis of the different cofactors.Furthermore,PPI networks were constructed based on the various upregulated and downregulated genes,and there were a total 15 upregulated and 10 downregulated hub genes.After a comprehensive analysis,several hub genes,including runt-related transcription factor 2(RUNX2),salmonella pathogenicity island 1(SPI1),lysyl oxidase(LOX),fibrillin 1(FBN1)and GPT,displayed prognostic values.Interestingly,it was observed that GPT was downregulated in GC cells and its upregulation could suppress the malignant phenotypes of GC cells.Furthermore,the expression level of GPT was found to be associated with age,lymph node metastasis,pathological staging and distant metastasis(P<0.05).CONCLUSION RUNX2,SPI1,LOX,FBN1 and GPT were identified key hub genes in GC by bioinformatics analysis.GPT was significantly associated with the prognosis of GC,and its upregulation can effectively inhibit the proliferative,migrative and invasive capabilities of GC cells.

Influencing factors and risk prediction model for emergence agitation after general anesthesia for primary liver cancer

BACKGROUND General anesthesia is commonly used in the surgical management of gastrointestinal tumors;however,it can lead to emergence agitation(EA).EA is a common complication associated with general anesthesia,often characterized by behaviors,such as crying,struggling,and involuntary limb movements in patients.If treatment is delayed,there is a risk of incision cracking and bleeding,which can significantly affect surgical outcomes.Therefore,having a proper understanding of the factors influencing the occurrence of EA and implementing early preventive measures may reduce the incidence of agitation during the recovery phase from general anesthesia,which is beneficial for improving patient prognosis.AIM To analyze influencing factors and develop a risk prediction model for EA occurrence following general anesthesia for primary liver cancer.METHODS Retrospective analysis of clinical data from 200 patients who underwent hepatoma resection under general anesthesia at Wenzhou Central Hospital(January 2020 to December 2023)was conducted.Post-surgery,the Richmond Agitation-Sedation Scale was used to evaluate EA presence,noting EA incidence after general anesthesia.Patients were categorized by EA presence postoperatively,and the influencing factors were analyzed using logistic regression.A nomogram-based risk prediction model was constructed and evaluated for differentiation and fit using receiver operating characteristics and calibration curves.RESULTS EA occurred in 51(25.5%)patients.Multivariate analysis identified advanced age,American Society of Anesthesiologists(ASA)grade Ⅲ,indwelling catheter use,and postoperative pain as risk factors for EA(P<0.05).Conversely,postoperative analgesia was a protective factor against EA(P<0.05).The area under the curve of the nomogram was 0.972[95%confidence interval(CI):0.947-0.997]for the training set and 0.979(95%CI:0.951-1.000)for the test set.Hosmer-Lemeshow test showed a good fit(χ^(2)=5.483,P=0.705),and calibration curves showed agreement between predicted and actual EA incidence.CONCLUSION Age,ASA grade,catheter use,postoperative pain,and analgesia significantly influence EA occurrence.A nomogram constructed using these factors demonstrates strong predictive accuracy.

Inhibition of long non-coding RNA TUG1 on gastric cancer cell transference and invasion through regulating and controlling the expression of miR-144/c-Met axis

Objective: To discuss the expression of long noncoding RNA TUG1 (IneRNA-TUG1) in gastric carcinoma (GC) and its effects on the transferring and invading capacity of gastric carcinoma cells. Methods: Forty cases of carcinoma tissue and para-carcinoma tissue were selected from GC patients who underwent surgical removal in Zhejiang Provincial Hospital of Chinese Traditional Medicine and Wenzhou Central Hospital from January, 2013 to December, 2014; the expressing level of IncRNA-TUG I in GC and para-C tissues was detected by applying the qRT-PCR technique. The correlation between IncRNA-TUG1 expression and patients' clinical data was classified and analyzed. SGC-7901 cells were transfected using IncRNA-TUG1 specific siRNA. Changes of the transferring and invading capacity of siRNA-transfected SGC-7901 cells were scratch-tested and transwell-detected. qRT-PCR was applied to detect the expression level of microRNA-144 after IncRNA-TUG1 was silenced. Changes of c-Met mRNA and protein expressions was detected by qRT-PCR and western -blot test. Results: The expression level of lneRNA-TUG1 in GC tissue was significant higher than that in para-C tissue (P<0.05) and the high expression level of IncRNA-TUG1 in GC tissue was significantly correlated with tumor lymph nodes metastasis and advance TNM phasing (/'<0.05). The transferring and invading capacity of SGC-7901 cells was highly inhibited after being transfected by IncRNA-TUG1 specific siRNA (P<0.05). The results of qRT-PCR and western -blot proved that the expression of microRNA-144 was significantly boosted and the expression level of c-Met mRNA and protein was inhibited after IncRNA-TUG1 was silenced (P<0.05). Conclusions: IncRNA-TUG1 shows an up -regulated expression in GC tissue and that bears a correlation with clinicopathological features of malignant tumor. IncRNATUGI can promote the transferring and invading capacity of GC by inhibiting the pathway of microRNA-144/c-Met.

Towards an Artificial Intelligence Framework for Data-Driven Prediction of Coronavirus Clinical Severity

The virus SARS-CoV2,which causes the Coronavirus disease COVID-19 has become a pandemic and has spread to every inhabited continent.Given the increasing caseload,there is an urgent need to augment clinical skills in order to identify from among the many mild cases the few that will progress to critical illness.We present a first step towards building an artificial intelligence(AI)framework,with predictive analytics(PA)capabilities applied to real patient data,to provide rapid clinical decision-making support.COVID-19 has presented a pressing need as a)clinicians are still developing clinical acumen given the disease’s novelty,and b)resource limitations in a rapidly expanding pandemic require difficult decisions relating to resource allocation.The objectives of this research are:(1)to algorithmically identify the combinations of clinical characteristics of COVID-19 that predict outcomes,and(2)to develop a tool with AI capabilities that will predict patients at risk for more severe illness on initial presentation.The predictive models learn from historical data to help predict specifically who will develop acute respiratory distress syndrome(ARDS),a severe outcome in COVID-19.Our experimental results based on two hospitals in Wenzhou,Zhejang,China identify features most predictive of ARDS in COVID-19 initial presentation which would not have stood out to clinicians.A mild increase in elevated alanine aminotransferase(ALT)(a liver enzyme)),a presence of myalgias(body aches),and an increase in hemoglobin,in this order,are the clinical features,on presentation,that are the most predictive.Those two centers’COVID-19 case series symptoms on initial presentation can help predict severe outcomes.Predictive models that learned from historical data of patients from two Chinese hospitals achieved 70%to 80%accuracy in predicting severe cases.

Dynamic alterations in the gut microbiota and metabolome during the development of methionine-choline-deficient diet-induced nonalcoholic steatohepatitis

AIM To investigate changes in gut microbiota and metabolism during nonalcoholic steatohepatitis(NASH) development in mice fed a methionine-choline-deficient(MCD) diet. METHODS Twenty-four male C57 BL/6 J mice were equally divided into four groups and fed a methionine-choline-sufficient diet for 2 wk(Control 2 w group,n = 6) or 4 wk(Control 4 w group,n = 6) or the MCD diet for 2 wk(MCD 2 w group,n = 6) or 4 wk(MCD 4 w group,n = 6). Liver injury,fibrosis,and intestinal barrier function were evaluated after 2 and 4 wk of feeding. The fecal microbiome and metabolome were studied using 16 s r RNA deep sequencing and gas chromatography-mass spectrometry. RESULTS The mice fed the MCD diet presented with simple hepatic steatosis and slight intestinal barrier deterioration after 2 wk. After 4 wk of feeding with the MCD diet,however,the mice developed prominent NASH with liver fibrosis,and the intestinal barrier was more impaired. Compared with the control diet,the MCD diet induced gradual gut microbiota dysbiosis,as evidenced by a marked decrease in the abundance of Alistipes and the(Eubacterium) coprostanoligenes group(P < 0.001 and P < 0.05,respectively) and a significant increase in Ruminococcaceae UCG 014 abundance(P < 0.05) after 2 wk. At 4 wk,the MCD diet significantly reduced the promising probiotic Bifidobacterium levels and markedly promoted Bacteroides abundance(P < 0.05,and P < 0.01,respectively). The fecal metabolomic profile was also substantially altered by the MCD diet: At 2 wk,arachidic acid,hexadecane,palmitic acid,and tetracosane were selected as potential biomarkers that were significantly different in the corresponding control group,and at 4 wk,cholic acid,cholesterol,arachidic acid,tetracosane,and stearic acid were selected. CONCLUSION The MCD diet induced persistent alterations in the gut microbiota and metabolome.

Silencing miRNA-324-3p protects against cerebral ischemic injury via regulation of the GATA2/A1R axis

Previous studies have suggested that miR-324-3p is related to the pathophysiology of cerebral ischemia,but the mechanism underlying this relationship is unclea r.In this study,we found that miR-324-3p expression was decreased in patients with acute ischemic stroke and in in vitro and in vivo models of ischemic stro ke.miR-324-3p agomir potentiated ischemic brain damage in rats subjected to middle cerebral artery occlusion,as indicated by increased infarct volumes and cell apoptosis rates and greater neurological deficits.In a PC12 cell oxygen-glucose deprivation/reoxygenation model,a miR-324-3 p mimic decreased cell viability and expression of the anti-apoptotic protein BCL2 and increased expression of the pro-apoptotic protein BAX and rates of cell apoptosis,whereas treatment with a miR-324-3p inhibitor had the opposite effects.Silencing miR-324-3p increased adenosine A1 receptor(A1R)expression thro ugh regulation of GATA binding protein 2(GATA2).These findings suggest that silencing miR-324-3p reduces ischemic brain damage via the GATA2/A1R axis.

Human cytomegalovirus-encoded US28 may act as a tumor promoter in colorectal cancer

AIM: To assess human cytomegalovirus-encoded US28 gene function in colorectal cancer(CRC) pathogenesis.METHODS: Immunohistochemical analysis was performed to determine US28 expression in 103 CRC patient samples and 98 corresponding adjacent noncancerous samples. Patient data were compared by age, sex, tumor location, histological grade, Dukes' stage, and overall mean survival time. In addition, the US28 gene was transiently transfected into the CRC LOVO cell line, and cell proliferation was assessed using a cell counting kit-8 assay. Cell cycle analysis by flow cytometry and a cell invasion transwell assay were also carried out.RESULTS: US28 levels were clearly higher in CRC tissues(38.8%) than in adjacent noncancerous samples(7.1%)(P = 0.000). Interestingly, elevated US28 amounts in CRC tissues were significantly associated with histological grade, metastasis, Dukes' stage, and overall survival(all P < 0.05); meanwhile, US28 expression was not significantly correlated with age, sex or tumor location. In addition, multivariate Coxregression data revealed US28 level as an independent CRC prognostic marker(P = 0.000). LOVO cells successfully transfected with the US28 gene exhibited higher viability, greater chemotherapy resistance, accelerated cell cycle progression, and increased invasion ability.CONCLUSION: US28 expression is predictive of poor prognosis and may promote CRC.

Immuno-oncology-microbiome axis of gastrointestinal malignancy

Research on the relationship between the microbiome and cancer has been controversial for centuries.Recent works have discovered that the intratumor microbiome is an important component of the tumor microenvironment(TME).Intratumor bacteria,the most studied intratumor microbiome,are mainly localized in tumor cells and immune cells.As the largest bacterial reservoir in human body,the gut microbiome may be one of the sources of the intratumor microbiome in gastrointestinal malignancies.An increasing number of studies have shown that the gut and intratumor microbiome play an important role in regulating the immune tone of tumors.Moreover,it has been recently proposed that the gut and intratumor microbiome can influence tumor progression by modulating host metabolism and the immune and immune tone of the TME,which is defined as the immuno-oncology-microbiome(IOM)axis.The proposal of the IOM axis provides a new target for the tumor microbiome and tumor immunity.This review aims to reveal the mechanism and progress of the gut and intratumor microbiome in gastrointestinal malignancies such as esophageal cancer,gastric cancer,liver cancer,colorectal cancer and pancreatic cancer by exploring the IOM axis.Providing new insights into the research related to gastrointestinal malignancies.

A Deep Learning System to Screen Novel Coronavirus Disease 2019 Pneumonia

实时逆转录聚合酶链反应(RT-PCR)检测早期新冠病毒肺炎(COVID-19)患者的痰液或鼻咽拭子中的病毒RNA阳性率较低。同时,COVID-19的计算机断层扫描(CT)影像学的临床表现有其自身的特点,不同于甲型流感病毒性肺炎(IAVP)等其他类型的病毒性肺炎。本研究旨在应用深度学习技术,建立COVID-19、IAVP及健康人群肺部CT的早期筛查模型。本研究共采集618份CT样本,其中219份样本来自110例COVID-19患者(平均年龄50岁,其中男性63例,占57.3%),224份样本来自224例IAVP患者(平均年龄61岁,其中男性156例,占69.6%),175份样本来自健康人群(平均年龄39岁,其中男性97例,占55.4%)。所有CT样本均来自浙江省三家COVID-19定点收治医院。我们首先利用胸部CT图像集的三维(3D)深度学习模型分割出候选感染区域,然后利用位置敏感机制深度学习网络将这些分离的图像归类为COVID-19、IAVP以及与感染无关(ITI)的图像,并且输出相应置信度得分。最后,用Noisy-OR贝叶斯函数计算每份CT病例的感染类型及总置信度。测试数据集的实验结果表明,从整体CT病例来看,本研究利用深度学习系统建立的COVID-19患者的早期筛查模型的总体准确率为86.7%。该模型有望成为一线临床医生诊断COVID-19的一种有效的辅助方法。

Intratumour microbiome of pancreatic cancer

Pancreatic cancer is a high mortality malignancy with almost equal mortality and morbidity rates.Both normal and tumour tissues of the pancreas were previously considered sterile.In recent years,with the development of technologies for highthroughput sequencing,a variety of studies have revealed that pancreatic cancer tissues contain small amounts of bacteria and fungi.The intratumour microbiome is being revealed as an influential contributor to carcinogenesis.The intratumour microbiome has been identified as a crucial factor for pancreatic cancer progression,diagnosis,and treatment,chemotherapy resistance,and immune response.A better understanding of the biology of the intratumour microbiome of pancreatic cancer contributes to the establishment of better early cancer screening and treatment strategies.This review focuses on the possible origins of the intratumour microbiome in pancreatic cancer,the intratumour localization,the interaction with the tumour microenvironment,and strategies for improving the outcome of pancreatic cancer treatment.Thus,this review offers new perspectives for improving the prognosis of pancreatic cancer.

Different Concentrations of Notoginsenoside Rg1 Attenuate Hypoxic and Hypercapnia Pulmonary Hypertension by Reducing the Expression of ERK in Rat PASMCs

Pulmonary arterial hypertension (PAH) is a serious disease which is characterized by increased vascular resistance and pressure. We have previously hypothesized that panax notoginseng saponins (PNS) might attenuate pulmonary vasoconstriction under hypoxia and hypercapnia condition. This study aims to investigate the effect of notoginsenoside Rg1, a main ingredient of PNS, with various concentrations (8, 40, 100 mg/L, respectively) on extracellular signal regulated kinase (ERK1/2) signaling pathway in pulmonary arterial smooth muscle cells (PASMCs). In addition, PASMCs were randomly divided into six groups: SD rat under normoxic condition as control group (N group), hypoxia hypercapnia group (H group), DMSO control group (HD group), Rg1-treatment groups (RgLRgM and RgH group). Western-blot and RT-PCR were used to test the expression of p-ERK protein and the expression of ERK1 mRNA and ERK2 mRNA. This study provided the evidence that the expression of p-ERK protein and the expression of ERK1 mRNA and ERK2 mRNA in HD group and H group were obviously higher than that in N group (P < 0.01), Whereas the level of ERK1/2 mRNA in Rg1-treatment groups was significantly lower than that in HD group and H group (P < 0.01), and the proper concentration of Rg1 is 40 mg/L. These results suggested that notoginsenoside Rg1 can attenuate pulmonary vasoconstriction which may lead to HHPV through reducing the expression of ERK1/2.

Increased levels of lactate dehydrogenase and hypertension are associated with severe illness of COVID-19

BACKGROUND Coronavirus disease 2019(COVID-19)is amid an ongoing pandemic.It has been shown that patients with cardiovascular comorbidities are at higher risk of severe illness of COVID-19.AIM To find out the relationship between cardiovascular comorbidities and severe illness of COVID-19.METHODS The clinical data of 140 COVID-19 patients treated from January 22,2020 to March 3,2020 at our hospital were retrospectively collected.The clinical characteristics were compared between patients with mild illness and those with severe illness.RESULTS There were 75 male patients and 65 female patients(53.6%vs 46.4%).The mean age was 45.4±14.6 years(range,2-85 years).Most of the patients had mild illness(n=114,81.4%)and 26 patients had severe illness(18.6%).The most common symptom was fever(n=110,78.6%),followed by cough(n=82,58.6%)and expectoration(n=51,36.4%).Eight patients were asymptomatic but were positive for severe acute respiratory syndrome coronavirus 2 RNA.Patients with severe illness were significantly more likely to be hypertensive than those with mild illness[(10/26,38.4%)vs(22/114,19.3%),P=0.036].The levels of lactate dehydrogenase were significantly higher in the severe illness group than in the mild illness group(299.35±68.82 vs 202.94±63.87,P<0.001).No patient died in either the severe illness or the mild illness group.CONCLUSION Hypertension and elevated levels of lactate dehydrogenase may be associated with severe illness of COVID-19.

Vitamin D attenuates TGF-β1-induced lung fibroblast proliferation and migration through repression of RasGRP3

Background:Transforming growth factor-β1(TGF-β1)is a pleiotropic cytokine that plays a central role in the pathogenesis of idiopathic pulmonary fibrosis(IPF).While previous studies have revealed a cross-talk between vitamin D and TGF-β1 signaling,it is still unclear how they interact with each other to regulate the progression of IPF.Methods:In this work,we searched for a novel mediator of TGF-β1 activity in lung fibroblasts and examined its regulation by vitamin D.In addition,we investigated the mechanism underlying the interaction between vitamin D and TGF-β1 signaling in lung fibroblast activation.Bioinformatic analysis was performed to identify TGF-β1 downstream target genes.Knockdown and overexpression expression experiments were conducted to determine gene function in the regulation of lung fibroblast proliferation and migration.Results:Analysis of publicly available datasets revealed that RAS guanyl releasing protein 3(RasGRP3)was upregulated in TGF-β1-treated lung fibroblasts and lung tissues from IPF patients relative to healthy controls.Our data confirmed the upregulation of RasGRP3 by TGF-β1 in human MRC5 lung fibroblasts.Overexpression of RasGRP3 enhanced MRC5 cell proliferation and migration.Knockdown of RasGRP3 blocked TGF-β1-induced MRC5 proliferation and migration.Vitamin D abolished TGF-β1-induced RasGRP3 upregulation,which was reversed by inhibition of the vitamin D receptor(VDR).Mechanistically,vitamin D promoted VDR enrichment and prevented mothers against decapentaplegic homolog(SMAD)2 and 3 occupancy at the promoter of RasGRP3.Additionally,overexpression of RasGRP3 reversed the suppressive effect of vitamin D on MRC5 cell proliferation and migration.Conclusion:In conclusion,vitamin D antagonizes TGF-β1-induced lung fibroblast activation by repressing RasGRP3 transcription.

Expression of SOX4 in Endometrial Cancer and its Relationship with Clinical-pathological Characteristics in Endometrial Cancer Patients

Objective:To investigate the expression of SOX4 in endometrial carcinoma tissues and its relationship with clinicopathological features.Methods:The clinical and pathological data of 51 patients with pathologically diagnosed endometrial carcinoma who underwent panhysterectomy in the Wenzhou Central Hospitai from March 2017 to March 2019 were retrospectively analyzed.There were 22 cases of typeⅠendometrial carcinoma and 29cases of type Ⅱ endometrial carcinoma.The immunohistochemical expression of SOX4 was detected,and its relationship with clinicopathological parameters was analyzed.Results:Compared with the contro1 group,SOX4 in endometrial cancer group increased significantly(P-0.05);High SOX4 expression were closely related to differentiation,c1inica1 stage and 1ymph node metastasis of endometrial cancer(Pi0.05).Conclusion:Sox4 is related to the occurrence and development of EC.SOX4 may be a clinical evaluation index of EC and a reference index for clinical pathological diagnosis,it is helpful for clinicians to better analyze the high risk factors of EC patients and provide new ideas for early diagnosis,prognosis evaluation and targeted treatment of EC.

Application of fluorescence in situ hybridization in the detection of bladder transitional-cell carcinoma: A multi-center clinical study based on Chinese population

Objective:To evaluate the diagnostic value of fluorescence in situ hybridization(FISH)in bladder cancer.Methods:We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and conducted FISH tests and cytology examinations from August 2007 to December 2008.Receiver operating characteristic(ROC)curve analysis was performed and the area under curve(AUC)values were calculated for both the FISH and urine cytology tests.Results:A cohort of 988 healthy volunteers was enrolled to establish a reference range for the normal population.A total of 4807 patients with hematuria were prospectively,randomly enrolled for the simultaneous analysis of urine cytology,FISH testing,and a final diagnosis as determined by the pathologic findings of a biopsy or a surgically-excised specimen.Overall,the sensitivity of FISH in detecting transitional-cell carcinoma was 82.7%,while that of cytology was 33.4%(p<0.001).The sensitivity values of FISH for non-muscle invasive and muscle invasive bladder transitional-cell carcinoma were 81.7%and 89.6%,respectively(p=0.004).The sensitivity values of FISH for low and high grade bladder cancer were 82.6%and 90.1%,respectively(p=0.002).Conclusion:FISH is significantly more sensitive than voided urine cytology for detecting bladder cancer in patients evaluated for gross hematuria at all cancer grades and stages.Higher sensitivity using FISH was obtained in high grade and muscle invasive tumors.

Selective serotonin reuptake inhibitors in the treatment of major depressive disorder after brain trauma:Systematic review and metaanalysis

BACKGROUND Traumatic brain injury(TBI)poses a considerable risk to human health.After TBI,individuals are susceptible to a range of psychiatric disorders,with depression being a primary complication.Selective serotonin reuptake inhibitors(SSRIs)are frequently used in the treatment of depression;however,their efficacy in addressing major depressive disorder(MDD)in adults following TBI remains uncertain.AIM To investigate the efficacy of SSRIs in the treatment of MDD after TBI.METHODS A comprehensive search across multiple databases was conducted following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement,encompassing studies published until May 2024.This review focused on studies that examined the efficacy of SSRIs in the treatment of MDD following TBI.Studies were assessed based sample size,treatment duration,treatment methodologies,severity of brain injury,assessment techniques,and drug response.A random-effects model was used to derive the summary effect size.RESULTS Eight studies compared the reduction in depression scores in patients with MDD after TBI and SSRI treatment.The eight studies did not exhibit heterogeneity(I^(2)=38%).The depression score for MDD after TBI in the SSRI group decreased more than that in the control group[odds ratio(OR)1.68,95%CI:1.09-2.58,P=0.02].The adverse reactions after treatment included diarrhea,dizziness,dry mouth,nausea,or vomiting.There was no difference in the incidence of adverse reactions after treatment between the two groups(OR 1.16,95%CI:0.78-1.73,P=0.46).These studies did not show significant heterogeneity(I^(2)=44%).CONCLUSION SSRIs may be effective in treating patients with MDD after TBI.Adequately powered,randomized,controlled trials are required to confirm these findings.

Building and sharing medical cohorts for research

Cohort studies are costly and time consuming.They require not only laboratory equipment and assays but also collaboration from participants and health agencies.Due to cost constraints,they are often confined to a specific population.Nevertheless,they play a crucial role in providing fundamental insights for medical advancements,shedding light on the origins of diseases,and acting in socioeconomic influence in policy making.