Molecular Epidemiology and Risk Factors of Herpes Simplex Virus Type 2 in Pregnant Women

Background:Herpes simplex virus type 2(HSV-2)infection is the main cause of genital and neonatal herpes infections.It has considerable public health importance among women as the virus may lead to adverse outcomes in pregnancy and neonatal infection.This study determines the molecular epidemiology and risk factors ofHSV-2 infection among pregnant women.Methods:In this cross-sectional study,all pregnant women admitted to three university hospitals for natural birth and Caesarean sections were enrolled.HSV detection and typing were carried out based on PCR and reverse dot blotting method,respectively.ANOVA and bivariate correlations were used to analyze the data.Results:In this study,the prevalence of genital herpes infection was 5.7%.A significant positive correlation was found between age group<25 years and HSV-2 shedding(P=0.026).Twelve participants(60%)with HSV-2 shedding were younger than 25.A significant correlation was found between the presence of genital lesion and HSV-2(P=0.02).Among participants with HSV-2 infection,the use of condom was low.Neonatal complications were not seen in newborns from mothers with HSV-2 shedding.Conclusion:PCR assay may help in promoting early diagnosis and more effective treatment for patients.Also,it shortens hospital stay and enhances patients?condition.HSV-2 transmission is rapid following the onset of sexual activity and likely to result in the significant prevalence of genital disease.

Positive correlation between latent Epstein-Barr virus infection and severity of illness in inflammatory bowel disease patients

BACKGROUND Emerging studies indicate the critical involvement of microorganisms,such as Epstein-Barr virus(EBV),in the pathogenesis of inflammatory bowel disease(IBD).Immunosuppressive therapies for IBD can reactivate latent EBV,complicating the clinical course of IBD.Moreover,the clinical significance of EBV expression in B lymphocytes derived from IBD patients’intestinal tissues has not been explored in detail.AIM To explore the clinical significance of latent EBV infection in IBD patients.METHODS Latent EBV infection was determined by double staining for EBV encoded RNA and CD20 in colon specimens of 43 IBD patients who underwent bowel resection.Based on the staining results,the patients were divided into two groups,according to their latent EBV infection states-negative(n=33)and positive(n=10).Illness severity of IBD were assigned according to Crohn’s disease activity index(ulcerative colitis)and Mayo staging system(Crohn’s disease).The clinicpathological data were analyzed between the two different latent EBV groups and also between the mild-to-moderate and severe disease groups.RESULTS Systolic pressure(P=0.005),variety of disease(P=0.005),the severity of illness(P=0.002),and pre-op corticosteroids(P=0.025)were significantly different between the EBV-negative and EBV-positive groups.Systolic pressure(P=0.001),variety of disease(P=0.000),pre-op corticosteroids(P=0.011)and EBV infection(P=0.003)were significantly different between the mild-to-moderate and severe disease groups.CONCLUSION IBD patients with latent EBV infection may manifest more severe illnesses.It is suggested that the role of EBV in IBD development should be further investigated,latent EBV infection in patients with serious IBD should be closely monitored,and therapeutic course should be optimized.

Epigenetic regulation of insulin-like growth factor axis in hepatocellular carcinoma

The insulin-like growth factor(IGF) signaling path-way is an important pathway in the process of hepa-tocarcinogenesis,and the IGF network is clearly dysregulated in many cancers and developmental abnormalities.In hepatocellular carcinoma(HCC),only a minority of patients are eligible for curative treatments,such as tumor resection or liver transplant.Unfortunately,there is a high recurrence of HCC after surgical tumor removal.Recent research efforts have focused on targeting IGF axis members in an attempt to find therapeutic options for many health problems.In this review,we shed lights on the regulation of members of the IGF axis,mainly by micro RNAs in HCC.Micro RNAs in HCC attempt to halt the aberrant expression of the IGF network,and a single micro RNA can have multiple downstream targets in one or more signaling pathways.Targeting micro RNAs is a relatively new approach for identifying an efficient radical cure for HCC.

Role of human papillomavirus in oropharyngeal squamous cell carcinoma: A review

Human papillomavirus(HPV) has been implicated in the pathogenesis of a subset of oropharyngeal squamous cell carcinoma. As a result, traditional paradigms in relation to the management of head and neck squamous cell carcinoma have been changing. Research into HPVrelated oropharyngeal squamous cell carcinoma is rapidly expanding, however many molecular pathological and clinical aspects of the role of HPV remain uncertain and are the subject of ongoing investigation. A detailed search of the literature pertaining to HPV-related oropharyngeal squamous cell carcinoma was performed and information on the topic was gathered. In this article, we present an extensive review of the current literature on the role of HPV in oropharyngeal squamous cell carcinoma, particularly in relation to epidemiology, risk factors, carcinogenesis, biomarkers and clinicalimplications. HPV has been established as a causative agent in oropharyngeal squamous cell carcinoma and biologically active HPV can act as a prognosticator with better overall survival than HPV-negative tumours. A distinct group of younger patients with limited tobacco and alcohol exposure have emerged as characteristic of this HPV-related subset of squamous cell carcinoma of the head and neck. However, the exact molecular mechanisms of carcinogenesis are not completely understood and further studies are needed to assist development of optimal prevention and treatment modalities.

Paraben Content in Adjacent Normal-malignant Breast Tissues from Women with Breast Cancer

Objective Accumulation of estrogenic compounds and other carcinogens in normal breast tissues contributes to unpredictable breast cancer incidence during adolescence and throughout life.To assess the role of parabens in this phenomenon,the paraben content of adjacent normal-malignant breast tissues is measured in women with breast cancer living in Isfahan Province,Iran.Methods Adjacent normal-malignant breast tissue samples were obtained from 53 subjects.The parabens including methyl-paraben(Me PB),ethyl-paraben(Et PB),propyl-paraben(Pr PB),and butylparaben(Bu PB)were extracted from the sample supernatant and then subjected to gas chromatography analysis.Results Some risk factors for breast cancer were stimulated by parabens in adjacent malignant-normal breast tissues among young and middle-aged women with breast cancer.We observed a significant association for dose-response pattern of Me PB[OR=98.34(11.43–185.2),P=0.027]for both ER+and PR+women and Me PB[OR=164.3(CI:112.3–216.3),P<0.001]for HER2+women than women with negative receptors.The risk of 95-fold increase in Me PB dose and 164-fold increase in∑PBs dose were significant for women with hereditary breast cancer in first-degree relatives.Conclusions These results may promote future epidemiology studies and strategies to improve women's lifestyle and consume paraben-free products.

Role of platelet parameters as a biomarker in diagnosis of acute appendicitis: A retrospective case-controlled study

Objective: To investigate the diagnostic value of platelet parameters in acute appendicitis. Methods: This retrospective case-controlled study was performed among 200 healthy people and 200 patients with a primary diagnosis of acute appendicitis between October 2017 and June 2018. The patients were classified into three groups: the acute complicated appendicitis (suppurative and gangrenous) group, acute non-complicated appendicitis group and the control group. Red blood cell, white blood cell, lymphocyte, monocyte and platelets count, red blood cell distribution width, hemoglobin, hematocrit, mean platelet volume, platelet distribution width, and C-reactive protein were compared between the groups. Results: Thirty-nine (19.5%) patients with acute appendicitis had no complication and 161 (80.5%) developed a complication. The white blood cell count, neutrophil count and C-reactive protein serum levels were significantly higher, whereas the mean age, lymphocyte count, monocyte count, red blood cell distribution width and platelet count were significantly lower in acute appendicitis patients with and without complications compared with the control group. Moreover, combined analysis of best diagnostic parameters (white blood cell, neutrophil and lymphocyte counts) showed that combined parallel sensitivity and specificity were 98.7% and 42.7%, respectively. Conclusions: White blood cell, lymphocyte counts and neutrophil count could be used for diagnosis of acute appendicitis. More over the utility of mean platelet volume for differential diagnosis might be overestimated.

Influence of SCENIC recommendations on terminology used for histopathologic diagnosis of inflammatory bowel disease-associated dysplasia

BACKGROUND Published in 2015,the International Consensus Recommendations on Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients(SCENIC)recommended abandoning the use of diagnostic term“dysplasia-associated lesion or mass(DALM)”for polypoid dysplastic lesions detected in patients with inflammatory bowel disease(IBD).The aim of this study was to investigate whether this recommendation had any influence on diagnostic terminologies used by pathologists in their practice.METHODS We retrospectively reviewed all pathology reports for surveillance colonoscopic biopsies from ulcerative colitis(UC)patients in our institution during 1/2012-12/2014(pre-SCENIC)and 1/2016-12/2018(post-SCENIC).These included 1203 biopsies from 901 UC patients during the pre-SCENIC period and 1273 biopsies from 977 UC patients during the post-SCENIC period.Their corresponding endoscopic findings and histopathologic diagnoses were recorded.Clinical indications for total colectomy for UC patients and corresponding histopathologic findings in colectomy specimens were also recorded and compared.RESULTS A total of 347 and 419 polyps/polypoid lesions were identified during the preSCENIC and post-SCENIC periods,among which 60 and 104 were dysplastic/adenomatous,respectively.More polypoid dysplastic lesions were simply diagnosed as“adenoma”during the post-SCENIC period in comparison with the pre-SCENIC period(97.1%vs 65.0%;P<0.001).The number of cases with a comment in pathology reports regarding the distinction between DALM and sporadic adenoma was also significantly decreased during the post-SCENIC period(5.8%vs 38.3%;P<0.001).In addition,the term“dysplasia”was more consistently used for random biopsies during the post-SCENIC period.Furthermore,the terms“sessile serrated adenoma/polyp”(SSA/P)and“serrated epithelial change”(SEC)were more consistently used for polypoid lesions and random biopsies,respectively,during the post-SCENIC period,although these were not specifically addressed in the SCENIC recommendations.The indications for colectomy remained unchanged,however,despite the standardization of diagnostic terminologies.CONCLUSION The SCENIC recommendations relieve pathologists from the burden of distinguishing DALM from sporadic adenoma in IBD patients,which helps the standardization of diagnostic terminologies used by pathologists.The consistent use of the diagnostic terminologies may help reduce potential confusions to clinicians and patients.

HIV encephalopathy is contributed by macrophages and microglia

Dear Editor,Acquired immunodeficiency syndrome(AIDS),characterized by a significant decrease in the number of CD4^(+)T cells,causes a defective T cell immune response,which subsequently leads to various conditional pathogenic infections and tumors(Calmy et al.,2018;Seligmann et al.,1987).Neurological disorders have been reported in 70%–80%of patients with AIDS(Saylor et al.,2016)。

Aldh2 deficiency plays a dual role in lung tumorigenesis and tumor progression

Alcohol consumption contributes to global mortality and cancer development.Acetaldehyde(ACE),the oxidized metabolite of alcohol,is highly reactive towards DNA,resulting in DNA adducts.ACE can be detoxified to acetate by acetaldehyde dehydrogenase type 2(ALDH2).ALDH2 deficiency can lead to ACE accumulation and DNA damage.

Tu-Xian Decoction ameliorates diabetic cognitive impairment by inhibiting DAPK-1

Tu-Xian decoction(TXD),a traditional Chinese medicine(TCM)formula,has been frequently administered to manage diabetic cognitive impairment(DCI).Despite its widespread use,the mechanisms underlying TXD’s protective effects on DCI have yet to be fully elucidated.As a significant regulator in neurodegenerative conditions,death-associated protein kinase-1(DAPK-1)serves as a focus for understanding the action of TXD.This study was designed to whether TXD mediates its beneficial outcomes by inhibiting DAPK-1.To this end,a diabetic model was established using Sprague-Dawley(SD)rats through a high-fat,high-sugar(HFHS)diet regimen,followed by streptozotocin(STZ)injection.The experimental cohort was stratified into six groups:Control,Diabetic,TC-DAPK6,high-dose TXD,medium-dose TXD,and low-dose TXD groups.Following a 12-week treatment period,various assessments—including blood glucose levels,body weight measurements,Morris water maze(MWM)testing for cognitive function,brain magnetic resonance imaging(MRI),and histological analyses using hematoxylin-eosin(H&E),and Nissl staining—were conducted.Protein expression in the hippocampus was quantified through Western blotting analysis.The results revealed that TXD significantly improved spatial learning and memory abilities,and preserved hippocampal structure in diabetic rats.Importantly,TXD administration led to a down-regulation of proteins indicative of neurological damage and suppressed DAPK-1 activity within the hippocampal region.These results underscore TXD's potential in mitigating DCI via DAPK-1 inhibition,positioning it as a viable therapeutic candidate for addressing this condition.Further investigation into TXD's molecular mechanisms may elucidate new pathways for the treatment of DCI.

Circulating tumor DNA in lung cancer: real-time monitoring of disease evolution and treatment response

Lung cancer is one of the leading causes of all cancer-related deaths. Circulating tumor DNA (ctDNA) is released from apoptotic and necrotic tumor cells. Several sensitive techniques have been invented and adapted to quantify ctDNA genomic alterations. Applications of ctDNA in lung cancer include early diagnosis and detection, prognosis prediction, detecting mutations and structural alterations, minimal residual disease, tumor mutational burden, and tumor evolution tracking. Compared to surgical biopsy and radiographic imaging, the advantages of ctDNA are that it is a non-invasive procedure, allows real-time monitoring, and has relatively high sensitivity and specificity. Given the massive research on non-small cell lung cancer, attention should be paid to small cell lung cancer.

酸性pH培养条件短时阻止胚胎干细胞分化并减弱microRNA的功能

干细胞和癌细胞不同于大多终末分化细胞,更偏好利用糖酵解代谢提供能量.然而,糖酵解代谢在基因表达调控和细胞命运决定中的作用尚不清楚.本文确认了糖酵解代谢和乳酸的产生随着小鼠胚胎干细胞的分化而降低.更重要的是,作者发现乳酸积累导致的酸性环境能够在短时间内阻止小鼠和人的胚胎干细胞退出多能性状态,并且会下调miRNA调控通路中的关键蛋白AGO1的表达,从而削弱miR-290/302家族对其靶基因的抑制作用.研究同时发现,酸性pH也会下调多个癌细胞株中AGO1的表达,并减弱癌细胞中miRNA的抑制作用.该研究为酸性微环境调控胚胎干细胞的命运决定和基因表达提供了新证据和机理解释.

Differential transcriptomic landscapes of multiple organs from SARS-CoV-2 early infected rhesus macaques

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries,how-ever,the underlying mechanism,in particular immune responses in different organs,remains elusive.In this study,comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed.Compared to normal controls,SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs,with drastic transcriptomic changes in cerebral cortex and right ventricle.Intriguingly,cerebral cortex exhibited a hyperinflammatory state evidenced by sig-nificant upregulation of inflammation response-related genes.Meanwhile,expressions of coagulation,angio-genesis and fibrosis factors were also up-regulated in cerebral cortex.Based on our findings,neuropilin 1(NRP1),a receptor of SARS-CoV-2,was significantly elevated in cerebral cortex post infection,accompanied by active immune response releasing inflammatory factors and signal transmission among tissues,which enhanced infection of the central nervous system(CNS)in a positive feedback way,leading to viral encephalitis.Overall,our study depicts a multi-tissue/organ tran-scriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2,and provides important insights into the mechanistic basis for COVID-19-asso-ciated clinical complications.

Environmental siblings of black agents of human chromoblastomycosis

Agents of human chromoblastomycosis,a skin disease almost exclusively caused by members of the order Chaetothyriales,are assumed to be traumatically inoculated into the skin with sharp environmental materials such as plant thorns or wooden splinters carrying the respective opportunist.In the supposition that such fungi should have their main habitat in the environment,we investigated the occurrence of black fungi in living areas of patients with chromoblastomycosis.In South America Fonsecaea agents are prevalent as agents of the disease,while also related Cladophialophora species,known from other types of skin infections,are known from the continent.Ninety environmental isolates were preliminarily selected as possible agents of chromoblastomycosis,based on morphology.Judging from ITS sequence data isolates were attributed to the genera Cladophialophora,Cyphellophora,Exophiala,Fonsecaea,Phialophora,and Veronaea.A total of 45 fungi morphologically identified as Fonsecaea or Cladophialophora isolated from debris and thorns of living prickly plants in Brazil were processed for taxonomic studies.Phylogenetic analysis revealed that the isolates indeed belonged to the Chaetothyriales,but only rarely an agent of chromoblastomycosis was concerned;only two strains of F.pedrosoi and one F.monophora were isolated from debris plants.The remaining isolates belonged to hitherto unknown molecular siblings of Fonsecaea.Two novel taxa are introduced.

Genome-wide 5-Hydroxymethylcytosine Profiling Analysis Identifies MAP7D1 as A Novel Regulator of Lymph Node Metastasis in Breast Cancer

Although DNA 5-hydroxymethylcytosine(5 hmC)is recognized as an important epigenetic mark in cancer,its precise role in lymph node metastasis remains elusive.In this study,we investigated how 5 hmC associates with lymph node metastasis in breast cancer.Accompanying with high expression of TET1 and TET2 proteins,large numbers of genes in the metastasis-positive primary tumors exhibit higher 5 hmC levels than those in the metastasis-negative primary tumors.In contrast,the TET protein expression and DNA 5 hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors.Through genomewide analysis of 8 sets of primary tumors,we identified 100 high-confidence metastasis-associated5 hmC signatures,and it is found that increased levels of DNA 5 hmC and gene expression of MAP7 D1 associate with high risk of lymph node metastasis.Furthermore,we demonstrate that MAP7 D1,regulated by TET1,promotes tumor growth and metastasis.In conclusion,the dynamic5 hmC profiles during lymph node metastasis suggest a link between DNA 5 hmC and lymph node metastasis.Meanwhile,the role of MAP7 D1 in breast cancer progression suggests that the metastasis-associated 5 hmC signatures are potential biomarkers to predict the risk for lymph node metastasis,which may serve as diagnostic and therapeutic targets for metastatic breast cancer.

A hydrogel spinal dural patch with potential anti-inflammatory,pain relieving and antibacterial effects

CSFL caused by spinal dural defect is a common complication of spinal surgery,which need repair such as suture or sealants.However,low intracranial pressure symptoms,wound infection and prolonged hospital associated with pin-hole leakage or loose seal effect were often occurred after surgical suture or sealants repair.Stable,pressure resistance and high viscosity spinal dural repair patch in wet environment without suture or sealants was highly needed.Herein,a bioactive patch composed of alginate and polyacrylamide hydrogel matrix cross-linked by calcium ions,and chitosan adhesive was proposed.This fabricated patch exhibits the capabilities of promoting defect closure and good tight seal ability with the bursting pressure is more than 790 mm H2O in wet environment.In addition,the chitosan adhesive layer of the patch could inhibit the growth of bacterial in vitro,which is meaningful for the postoperative infection.Furthermore,the patch also significantly reduced the expression of GFAP,IBA-1,MBP,TNF-α,and COX-2 in early postoperative period in vivo study,exerting the effects of anti-inflammatory,analgesic and adhesion prevention.Thus,the bioactive patch expected to be applied in spinal dural repair with the good properties of withstanding high pressure,promoting defect closure and inhibiting postoperative infection.

Is germinal center selection required for influenza vaccination?

It has long been believed that the generation of high-affinity neutralizing antibodies is critical for antiviral humoral immunity.The production of high-affinity antibodies depends on the formation of germinal centers(GC)in lymph nodes and a subset of T cells called follicular helper T(T_(FH))cells in GCs.

Cyphellophora and its relatives in Phialophora: biodiversity and possible role in human infection

Cyphellophora is a genus of black yeast-like fungi characterised by having simple phialides with multiseptate,curved conidia.Judging from SSU and LSU data,Cyphellophora was found to be located in a well-supported clade within the Chaetothyriales comprising a number of species occurring on human skin and nail.Cyphellophora is phylogenetically close to Phialophora europaea,P.reptans and P.oxyspora,though morphologically these species produce singlecelled phialoconidia rather than multiseptate ones.Pseudomicrodochium suttonii and P.fusarioides have dark colonies and phylogenetically fit in with Cyphellophora;the type species of Pseudomicrodochium,P.aciculare,has similar,septate conidia but has a hyaline thallus.In the present study,multilocus phylogenetic analyses were combined with morphology and physiology.Sequences of the internal transcribed spacer region,the DNA dependent RNA polymerase II largest subunit and the partial beta tubulin gene were analysed for a set of 30 strains.Two novel species,Cyphellophora pauciseptata and Phialophora ambigua were discovered.Cyphellophora eucalypti was reduced to synonymy of C.guyanensis.The role of the studied fungi between colonization and infection of human skin was discussed.Putative virulence factors for these black yeast-like fungi were hypothesized to be the ability to assimilate monoaromatic hydrocarbons,to produce melanin pigments,and to tolerate the temperature of epidermal human skin.

SARS-CoV-2 leads to myocardial injury in rhesus macaque

Dear Editor,Coronavirus disease 2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,which induces multiple cardiovascular complications including acute myocardial injury resulting from acute coronary syndrome,myocarditis,stress-cardiomyopathy,arrhythmias,cardiogenic shock,and cardiac arrest.The incidence of myocardial injury in COVID-19 patients was up to 20%or higher in the subpopulation with existing cardiovascular diseases,accounting for 69.4%of mortality.1 Although the presence of angiotensin-converting enzyme 2(ACE2)in cardiomyocytes could result in viral myocarditis in COVID-19 patients,the cardiopathology involved in COVID-19 is still unclear.

Chip-based multimodal super-resolution microscopy for histological investigations of cryopreserved tissue sections

Histology involves the observation of structural features in tissues using a microscope.While diffraction-limited optical microscopes are commonly used in histological investigations,their resolving capabilities are insufficient to visualize details at subcellular level.Although a novel set of super-resolution optical microscopy techniques can fulfill the resolution demands in such cases,the system complexity,high operating cost,lack of multi-modality,and low-throughput imaging of these methods limit their wide adoption for histological analysis.In this study,we introduce the photonic chip as a feasible high-throughput microscopy platform for super-resolution imaging of histological samples.Using cryopreserved ultrathin tissue sections of human placenta,mouse kidney,pig heart,and zebrafish eye retina prepared by the Tokuyasu method,we demonstrate diverse imaging capabilities of the photonic chip including total internal reflection fluorescence microscopy,intensity fluctuation-based optical nanoscopy,single-molecule localization microscopy,and correlative light-electron microscopy.Our results validate the photonic chip as a feasible imaging platform for tissue sections and pave the way for the adoption of super-resolution high-throughput multimodal analysis of cryopreserved tissue samples both in research and clinical settings.