Oral squamous cell carcinoma(OSCC)is the predominant type of oral cancer,while some patients may develop oral multiple primary cancers(MPCs)with unclear etiology.This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs.Clinicopathological data from patients with oral single primary carcinoma(SPC,n=202)and oral MPCs(n=34)were collected and compared.Copy number alteration(CNA)analysis was conducted to identify chromosomal-instability differences among oral MPCs,recurrent OSCC cases,and OSCC patients with lymph node metastasis.Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients.Additionally,CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients.Our findings revealed that,in contrast to oral SPC,females predominated the oral MPCs(70.59%),while smoking and alcohol use were not frequent in MPCs.Moreover,long-term survival outcomes were poorer in oral MPCs.From a CNA perspective,no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis.In addition to commonly mutated genes such as CASP8,TP53 and MUC16,in oral MPCs we also detected relatively rare mutations,such as HS3ST6 and RFPL4A.Furthermore,this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals,and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

Objective This study aims to analyze the relationship between reproductive tract microecological changes,metabolic differences,and pregnancy outcomes at different time points in the frozen-thawed embryo transfer cycle while patients are undergoing hormone replacement therapy,which will be a breakthrough point for improving outcomes.Methods A total of 20 women undergoing frozen-thawed single blastocyst transfer for the first time at the Reproductive Medicine Center of Fujian Maternal and Child Health Hospital between July 2022 and January 2023 were recruited for this study.Their vaginal and cervical secretions were collected for 16S rRNA sequencing and non-targeted metabolomics analysis on days 2-5 of menstruation,day 7 after estrogen replacement therapy started,the day when progesterone was added,and the day of transplantation.The subjects were divided into different groups according to their clinical pregnancy status and the sequencing results were analyzed using bioinformatics methods.Results 1)The alpha-diversity index of the vaginal and cervical microbiota was higher on days 2-5 of menstruation(P<0.01),but did not differ significantly on day 7 after oral estrogen replacement therapy started,the day of progesterone administration,and the day of transplantation(P≥0.1).2)Both the pregnant group and the non-pregnant group showed a variety of microorganisms and metabolites with significant differences in the lower reproductive tract at different time points.3)Microbial analysis at different time points showed that there were significant differences in vaginal flora,including Peptoniphilus,Enterocloster,Finegoldia,Klebsiella,Anaerobutyricum,Agathobaculum,Sporanaerobacter,Bilophila,Prevotella,and Anaerococcus in the pregnant group(P<0.05).4)Metabolite analysis at different time points showed that there were significant differences in 3-hydroxybenzoic acid,linatine,(R)-amphetamine,hydroxychloroquine,and L-altarate in the vaginal secretions of the pregnant group(P<0.05),and that there were significant differences in isocitric acid,quassin,citrinin,and 12(R)-HETE in the cervical secretions(P<0.05).5)Metabolite analysis at different time points showed that,in the non-pregnant group,there were significant differences in linatine,decanoyl-L-carnitine,aspartame,sphingosine,and hydroxychloroquine in the vaginal secretions(P<0.05),and the isocitric acid,quassin,ctrinin,and 12(R)-HETE in the cervical secretions(P<0.05).6)Combined microbiome and metabolomics analysis showed that certain metabolites were significantly associated with microbial communities,especially Klebsiella.Conclusions Significant differences in the microbiota genera and metabolites at different time points were found during the frozen-embryo transfer cycle of hormone replacement therapy,which may be used as potential biomarkers to predict pregnancy outcomes of embryo transfer.

BACKGROUND: It has been explained in many big sample experiments that community comprehensive prevention from the risks of cardiocerebrovascular disease can reduce its morbidity and mortality. But, it is required more samples to verify the evaluations of the process and effect of intervention.OBJECTIVE: To understand the effect of community comprehensive prevention on cardiocerebrovascular disease and hygienic costs demanded and summarizes the suitable patterns of comprehensive prevention on cardiocerebrovascular disease in countryside.DESIGN: Healthy people in community were taken as the objects and community intervention was designed.SETTING: Department of Community Hygienic Service of People's Hospital in Guzheng Town, Zhongshan City, Guangdong Province and Neurological Institute of Guangzhou Medical College.PARTICIPANTS: Totally 32 000 inhabitants were collected from 8 villages in Guzheng Town, Zhongshan City, Guangdong Province from March 1992 to March 2002, aged varied from 20 to 74 years, of which, 14 600inhabitants were male and 17 400 inhabitants were female.METHODS: The intervention of community-based prevention was applied on cardiocerebrovascular disease, including managementof hypertension,smoking control, rational nutrient, nationwide body building and diabetic management.MAIN OUTCOME MEASURES: [1] Awareness, attitude and behavior related to cardiocerebrovascular disease. [2] Management rate and control rate of hypertension. [3] Morbidity and mortality of cerebral apoplexy.RESULTS: [1] By 10-year intervention, awareness rate of hypertension in whole group was 70.29%. [2] Management rate and control rate of hypertension were increased yearly, in which, the management rate was increased from 25.66% in 1997 to 80.50% in 2002, the total control rate was increased from 4.43% in 1997 to 45.80% in 2002, the control rate of blood pressure ＜160/95 mm HG (1 mm Hg=0.133 kPa) was 58.80%and that ＜140/90 mm Hg was 32.80%. [3] The systolic and diastolic pressures in intervention community were decreased averagely, in which the D-values are 7.23 mm Hg and 3.92 mm Hg respectively. [4] The awareness, attitude and behavior related to cardiocerebrovascular disease were enhanced remarkably. [5] Morbidity and mortality of cerebral apoplexy were in tendency of decreasing yearly, from 146.90/100 000 and 108.63/100 000 in 1997 to 105.83/100 000 and 69.90/100 000 in 2002 respectively, by 41.07/100 000 and 38.73/100 000 respectively in 6 years and the age of incidence was postponed. [6] It was indicated in economic analysis that the average ratio of profit to cost between 1997 and 2001 was 2.32.CONCLUSION: Community-based comprehensive prevention on cardiocerebrovascular disease improves the awareness, attitude and behavior in community group and reduces morbidity and mortality of cerebral apoplexy.