Oral health status in Sichuan Province: findings from the oral health survey of Sichuan, 2015–2016

To investigate oral health status in the residents of Sichuan Province, southwest China, a cross-sectional study was performed using the latest Oral Health Survey Basic Methods recommended by the World Health Organization. A multistage stratified random cluster-sampling method was used to enroll participants from the following three groups： children aged 3-5 years, adolescents aged 12 years, and people aged 65-74 years. In these three groups, the mean numbers of teeth that were affected by caries were 3.28, 0.86 and 5.13, respectively, resulting in a prevalence of 63.47%, 37.20% and 83.20%, respectively. Relative to the high rate of decayed teeth, the prevalence of fillings was very low in all age groups （0.97%, 7.24% and 5.43%, respectively）, In the 12-year-old adolescent group, only 3.61% had good pit and fissure sealing. In addition, the rate of dental fluorosis was 24.80%, and the Community Fluorosis Index value was 0.39. In the elder group, the community periodontal index was 2.92. The prevalence in the elderly of having lost at least one tooth was 75.54%. Additionally, 4.44% of these participants were edentulous. The incidence of dental prosthesis was 51.75%, the proportion with a removable partial denture, a fixed denture, full dentures, dental implants and an informal fixed bridge was 21.59%, 11.45%, 4.64%, 0 and 16.67%, respectively. In this study, 8.2% of the elderly participants were affected by different types of oral mucosal lesions. Among such lesions, recurrent aphthous ulcers were most prevalent （2.69%） and oral lichen planuses were second （1.6%）. The conclusion presented in this survey is that oral diseases, especially dental caries and periodontal disease, are frequent and common in Sichuan province, China. Moreover, the treatment rate is very low, and primary prevention and treatment options are therefore urgently needed in this population.

Brugada syndrome associated with out-of-hospital cardiac arrest: A case report

BACKGROUND Brugada syndrome(BrS)is an inherited disease characterized by an electrocardiogram(ECG)with a coved-type ST-segment elevation in the right precordial leads(V1-V3),which predisposes to sudden cardiac death(SCD)due to polymorphic ventricular tachycardia or ventricular fibrillation in the absence of structural heart disease.We report the case of a 29-year-old man with out-ofhospital cardiac arrest.BrS is associated with a high incidence of SCD in adults,and increasing the awareness of BrS and prompt recognition of the Brugada ECG pattern can be lifesaving.CASE SUMMARY A 29-year-old man suffered from out-of-hospital cardiac arrest,and after defibrillation,his ECG demonstrated a coved-type elevated ST segment in V1 and V2.These findings were compatible with type 1 Brugada pattern,and ECG of his brother showed a type 2 Brugada pattern.The diagnosis was BrS,NYHF IV,multiple organ dysfunction syndrome,sepsis,and hypoxic ischemic encephalopathy.The patient had no arrhythmia episodes after discharge throughout a follow-up period of 36 mo.CONCLUSION Increasing awareness of BrS and prompt recognition of the Brugada ECG pattern can be lifesaving.

Identification and characterization of noncoding RNAs-associated competing endogenous RNA networks in major depressive disorder

BACKGROUND Major depressive disorder(MDD)is a common and serious mental illness.Many novel genes in MDD have been characterized by high-throughput methods such as microarrays or sequencing.Recently,noncoding RNAs(ncRNAs)were suggested to be involved in the complicated environmental-genetic regulatory network of MDD occurrence;however,the interplay among RNA species,including protein-coding RNAs and ncRNAs,in MDD remains unclear.AIM To investigate the RNA expression datasets downloaded from a public database and construct a network based on differentially expressed long noncoding RNA(lncRNAs),microRNAs(miRNAs),and mRNAs between MDD and controls.METHODS Gene expression data were searched in NCBI Gene Expression Omnibus using the search term“major depressive disorder.”Six array datasets from humans were related to the search term:GSE19738,GSE32280,GSE38206,GSE52790,GSE76826,and GSE81152.These datasets were processed for initial assessment and subjected to quality control and differential expression analysis.Differentially expressed lncRNAs,miRNAs,and mRNAs were determined,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed,and protein-protein interaction network was generated.The results were analyzed for their association with MDD.RESULTS After analysis,3 miRNAs,12 lncRNAs,and 33 mRNAs were identified in the competing endogenous RNA network.Two of these miRNAs were earlier shown to be involved in psychiatric disorders,and differentially expressed mRNAs were found to be highly enriched in pathways related to neurogenesis and neuroplasticity as per Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The expression of hub gene fatty acid 2-hydroxylase was enriched,and the encoded protein was found to be involved in myelin formation,indicating that neurological development and signal transduction are involved in MDD pathogenesis.CONCLUSION The present study presents candidate nc RNAs involved in the neurogenesis and neuroplasticity pathways related to MDD.

Pilot study of genome-wide DNA methylation and gene expression for treatment response to escitalopram in panic disorder

BACKGROUND Antidepressants,particularly selective serotonin reuptake inhibitors,are currently considered the first-line treatment for panic disorder(PD).However,little is known about the relationship between the biomarkers that may predict better treatment.AIM To compare genome-wide methylation and gene expression patterns between responsive and non-responsive patients with PD after 4 wk of escitalopram treatment.METHODS Thirty patients with PD were enrolled in this study(responders=13;nonresponders=17).All patients were assessed using the PD Severity Scale-Chinese version before and after treatment.The Illumina Infinium MethylationEPIC(850k)BeadChip for genome-wide methylation screening and mRNA sequencing was used in all patients with PD.RESULTS A total of 701 differentially methylated positions(DMPs)were found between responders and non-responders(|Δβ|≥0.06,q<0.05),and the hyper-and hypomethylated CpG sites were 511(72.9%)and 190(27.1%),respectively.Relative to non-responders,there were 59 differential transcripts,of which 20 were downregulated and 39 were upregulated(q<0.05).However,no differen tially expressed genes were identified by mRNA sequencing after correcting for multiple testing(|log2(FC)|>1,q>0.05).CONCLUSION This preliminary study showed that DMPs might be associated with the treatment response to escitalopram in PD;however,these DMPs need to be verified in large samples.

Effects of aging on gene expression in blood of captive Tibetan macaques (Macaca thibetana) and comparisons with expression in humans

DEAR EDITOR,Changes in gene expression occur as animals,including primates,age.Macaques have long been used as a model species for primate evolution and biomedical studies.Here,to study gene expression in Tibetan macaques (Macaca thibetana,TMs) and its differences to humans,we applied RNA-Seq to obtain the blood transcriptomes of 24 TMs.

Glutamate decarboxylase 1 gene polymorphisms are associated with respiratory symptoms in panic disorder

BACKGROUND Genetic factors play an important role in the pathogenesis of panic disorder(PD).However,the effect of genetic variants on PD remains controversial.AIM To evaluate the associations between glutamate decarboxylase 1(GAD1)gene polymorphisms and PD risk and assess the effect of GAD1 gene polymorphisms on the severity of clinical symptoms in PD.METHODS We recruited 230 PD patients and 224 healthy controls in this study.All participants were assessed for anxiety and panic symptom severity using the Hamilton Anxiety Rating Scale(HAM-A)and Panic Disorder Severity Scale(PDSS).GAD1 gene polymorphisms(rs1978340 and rs3749034)were genotyped and assessed for allele frequencies.RESULTS There were no significant differences between cases and controls in the genotype distributions or allele frequencies of GAD1(rs1978340 and rs3749034).In addition,the effect of GAD1(rs1978340 and rs3749034)on PD severity was not significant.However,regarding respiratory symptoms,patients with the GAD1 rs1978340 A/A genotype had significantly higher scores than those with the A/G or G/G genotype.CONCLUSION Here,we showed that the A/A genotype of GAD1 rs1978340 was associated with increased severity of respiratory symptoms in patients with PD.

Transcriptomic analysis elucidates the enhanced skeletal muscle mass, reduced fat accumulation, and metabolically benign liver in human follistatin-344 transgenic pigs

Follistatin(FST) is an important regulator of skeletal muscle growth and adipose deposition through its ability to bind to several members of the transforming growth factor-β(TGF-β) superfamily, and thus may be a good candidate for future animal breeding programs. However, the molecular mechanisms underlying the phenotypic changes have yet to be clarified in pig. We generated transgenic(TG) pigs that express human FST specifically in skeletal muscle tissues and characterized the phenotypic changes compared with the same tissues in wild-type pigs. The TG pigs showed increased skeletal muscle growth, decreased adipose deposition, and improved metabolism status(P<0.05). Transcriptome analysis detected important roles of the PIK3–AKT signaling pathway, calcium-mediated signaling pathway, and amino acid metabolism pathway in FST-induced skeletal muscle hypertrophy, and depot-specific oxidative metabolism changes in psoas major muscle. Furthermore, the lipid metabolism-related process was changed in adipose tissue in the TG pigs. Gene set enrichment analysis revealed that genes related to lipid synthesis, lipid catabolism, and lipid storage were down-regulated(P<0.01) in the TG pigs for subcutaneous fat, whereas genes related to lipid catabolism were significantly up-regulated(P<0.05) in the TG pigs for retroperitoneal fat compared with their expression levels in wild-type pigs. In liver, genes related to the TGF-β signaling pathway were over-represented in the TG pigs, which is consistent with the inhibitory role of FST in regulating TGF-β signaling. Together, these results provide new insights into the molecular mechanisms underlying the phenotypic changes in pig.

Multiple left ventricular myxomas combined with severe rheumatic valvular lesions: A case report

BACKGROUND Primary cardiac tumors are uncommon,of which cardiac myxoma accounts for 50%-80%.Left ventricular myxoma has been rarely reported,accounting for only 3%-4%of all cardiac myxomas.Multiple left ventricular myxomas are,relatively,even rarer.CASE SUMMARY In this report,we present a case of multiple left ventricular myxomas combined with severe rheumatic valve lesions.Symptomatically,the patient presented with fatigue,shortness of breath,and palpitation after activities.The patient underwent complete surgical resection of multiple left ventricular myxomas combined with mechanical replacement of the mitral and aortic valves,tricuspid valvuloplasty.The patient recovered well after the operation,with no obvious related complications.CONCLUSION Multiple left ventricular myxomas may coexist with severe rheumatic valve disease.Operation is an effective treatment.

Poly-dopamine, poly-levodopa, and poly-norepinephrine coatings: Comparison of physico-chemical and biological properties with focus on the application for blood-contacting devices

Thanks to its simplicity,versatility,and secondary reactivity,dopamine self-polymerized coatings(pDA)have been widely used in surface modification of biomaterials,but the limitation in secondary molecular grafting and the high roughness restrain their application in some special scenarios.Therefore,some other catecholamine coatings analog to pDA have attracted more and more attention,including the smoother poly-norepinephrine coating(pNE),and the poly-levodopa coating(pLD)containing additional carboxyl groups.However,the lack of a systematic comparison of the properties,especially the biological properties of the above three catecholamine coatings,makes it difficult to give a guiding opinion on the application scenarios of different coatings.Herein,we systematically studied the physical,chemical,and biological properties of the three catecholamine coatings,and explored the feasibility of their application for the modification of biomaterials,especially cardiovascular materials.Among them,the pDA coating was the roughest,with the largest amount of amino and phenolic hydroxyl groups for molecule grafting,and induced the strongest platelet adhesion and activation.The pLD coating was the thinnest and most hydrophilic but triggered the strongest inflammatory response.The pNE coating was the smoothest,with the best hemocompatibility and histocompatibility,and with the strongest cell selectivity of promoting the proliferation of endothelial cells while inhibiting the proliferation of smooth muscle cells.To sum up,the pNE coating may be a better choice for the surface modification of cardiovascular materials,especially those for vascular stents and grafts,but it is still not widely recognized.

Integrated and dual-responsive lipopeptide nanovector with parallel effect to tumor and micro-environment regulation by efficient gene and drug co-delivery

The integrated lipopeptide(RVA)/gene complexes are fabricated with bi-directional regulation on tumor cells and micro-environment.After self-assembling and target coating modification,the poly(γ-glutamic acid)(γ-PGA)/RVA nano-vectors can sequentially respond to pH&redox stimuli,and guarantee efficient therapeutic gene delivery and control release of all-trans retinoic acid.The design provides a facile but promising strategy to treat refractory cancers.

ROCK inhibitor:Focus on recent updates

Rho-associated coiled-coil-containing protein kinase(RoCK)belongs to the serine-threonine family,and RoCK is involved in a variety of biological processes including cell migration,adhesion,proliferation and differentiation through phosphorylation of different downstream substrates.The aberrant activation of ROCK is associated with the pathological conditions in different systems including various diseases,including cancer,neurological diseases,inflammation,cardiovascular diseases and glaucoma.Therefore,the ROCK inhibitors have potential applicability for treating the aforementioned diseases.Four small molecule ROCK inhibitors have been approved for clinical use:fasudil,ripasudil,netarsudil and belumosudil.In recent years,more small molecule ROCK inhibitors have been identified.This paper reviews the ROCK inhibitors reported in past seven years.We mainly focused on the summarization of the structure-activity relationships,inhibitory efficacy,pharmacological mechanisms and the relevant clinical studies of the reported ROCK inhibitors.Besides the small molecular inhibitors,the peptides and biological extracts which exhibit ROCK inhibitory effects are also included.We also provide suggestions for the future development of the potent ROCK inhibitors.

Association analysis of genetic variants in critical patients with COVID-19 and validation in a Chinese population

Dear Editor,Genome-wide association studies(GWASs)have reported a genetic association between certain populations and the severity of COVID-19.In severe patients,changes in the locus 3p21.31(including SLC6A20,LZTFL1,CCR9,FYCO1,CXCR6,and XCR1)are associated with COVID-19 hospitalization(Ellinghaus et al.,2020).Moreover,variations in 9p34.2 region(including genes related to the ABO blood grouping)can affect both susceptibility and severity of COVID-19;in particular,individuals with blood group A may have an increased risk of COVID-19 infection,while those with blood group O may have a protective effect(Ellinghaus et al.,2020;Shelton et al.,2021).

Probiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice

ProBiotic-4 is a probiotic preparation composed of Bifidobacterium lactis,Lactobacillus casei,Bifidobacterium bifidum,and Lactobacillus acidophilus.This study aims to investigate the effects of ProBiotic-4 on the microbiota-gut-brain axis and cognitive deficits,and to explore the underlying molecular mechanism using senescence-accelerated mouse prone 8(SAMP8)mice.ProBiotic-4 was orally administered to 9-month-old SAMP8 mice for 12 weeks.We observed that ProBiotic-4 significantly improved the memory deficits,cerebral neuronal and synaptic injuries,glial activation,and microbiota composition in the feces and brains of aged SAMP8 mice.ProBiotic-4 substantially attenuated aging-related disruption of the intestinal barrier and blood-brain barrier,decreased interleukin-6 and tumor necrosis factor-αat both mRNA and protein levels,reduced plasma and cerebral lipopolysaccharide(LPS)concentration,toll-like receptor 4(TLR4)expression,and nuclear factor-κB(NF-κB)nuclear translocation in the brain.In addition,not only did ProBiotic-4 significantly decreased the levels ofγ-H2 AX,8-hydroxydesoxyguanosine,and retinoic-acid-inducible gene-I(RIG-I),it also abrogated RIG-I multimerization in the brain.These findings suggest that targeting gut microbiota with probiotics may have a therapeutic potential for the deficits of the microbiota-gut-brain axis and cognitive function in aging,and that its mechanism is associated with inhibition of both TLR4-and RIG-I-mediated NF-κB signaling pathway and inflammatory responses.

A small molecule inhibitor targeting SHP2 mutations for the lung carcinoma

The RAS/mitogen-activated protein kinase(MAPK)pathway disorder induced by the missense mutations in the tyrosine-protein phosphatase non-receptor type 11(PTPN11)gene which resulted in the nonreceptor protein tyrosine phosphatase SHP2 dysfunction has been reported in many lung cancer cases.Moreover,the Src homology region 2(SH2)-containing protein tyrosine phosphatase 2(SHP2)mutation or deletion triggers multiple signaling pathway dysfunctions including RAS/MAPK,RAS/extracellular-signal-regulated kinase(ERK),phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT),Janus kinase/signal transducers and activators of transcription(JAK/STAT)and Hippo/yes-associated protein(YAP)which affect the expression of growth factors,cytokines and hormones.In recent years,the developing of the small molecule SHP2 inhibitors received a lot of attention.In this review,we summarize the recent years'progresses of the SHP2 inhibitors development for the lung cancer treatment.

Exosomal miR-485-3p derived from pancreatic ductal epithelial cells inhibits pancreatic cancer metastasis through targeting PAK1

Background:Cell competition is an important feature in pancreatic cancer(PC)progression,but the underlying mechanism remains elusive.This study aims to explore the role of exosomes derived from normal pancreatic ductal epithelial cells involved in PC progression.Methods:PC cells and pancreatic stellate cells(PSCs)were treated with exosomes isolated from pancreatic ductal epithelial cells.Cell proliferation was assessed by CCK8 assays.Cell migration and invasion were assessed by Transwell assays.PC and matched adjacent non-tumor tissue specimens were obtained from 46 patients pathologically diagnosed with PC at Peking University First Hospital from 2013 to 2017.Tissue miR-485-3p and p21-activated kinase-1(PAK1)expression was examined by real-time polymerase chain reaction(RT-PCR),and the relationship of the two was analyzed using Pearman’s product-moment correlation.The clinical significance of miR-485-3p was analyzed using the Chi-square test,Wilcoxon rank-sum test,and Fisher exact probability,respectively.The binding of miR-485-3p to PAK15’-untranslated region(5’-UTR)was examined by luciferase assay.PC cells were xenografted into nude mice as a PC metastasis model.Results:Exosomes from pancreatic ductal epithelial cells suppressed PC cell migration and invasion as well as the secretion and migration of PSCs.MiR-485-3p was enriched in the exosomes of pancreatic ductal epithelial cells but deficient in those of PC cells and PSCs,in accordance with the lower level in PSCs and PC cells than that in pancreatic ductal cells.And the mature miR-485-3p could be delivered into these cells by the exosomes secreted by normal pancreatic duct cells,to inhibit PC cell migration and invasion.Clinical data analysis showed that miR-485-3p was significantly decreased in PC tissues(P<0.05)and was negatively associated with lymphovascular invasion(P=0.044).As a direct target of miR-485-3p,PAK1 was found to exert an inhibitory effect on PC cells,and there was a significantly negative correlation between the expression levels of miR-485-3p and PAK1(r=-0.6525,P<0.0001)in PC tissues.Moreover,miR-485-3p could suppress PC metastasisin vivo by targeting p21-activated kinase-1.Conclusions:Exosomal miR-485-3p delivered by normal pancreatic ductal epithelial cells into PC cells inhibits PC metastasis by directly targeting PAK1.The restoration of miR-485-3p by exosomes or some other vehicle might be a novel approach for PC treatment.