Objective To explore the causal relationship between breast cancer and free fatty acid receptor 4(FFAR4)by using two-sample Mendelian randomization.Methods By using Genome-wide Association Studies and expression quantitative trait locus(eQTL)data,single nucleotide polymorphism sites closely related to breast cancer and FFAR4 were extracted.Causal effect values were calculated by using five methods:inverse variance weighting(IVW),MR-Egger,weighted median,simple mode and weighted mode.Cochran Q tests were used to detect heterogeneity,MR-Egger intercept tests and MR-PRESSO tests were used to assess level multiplicity,and the hold-out method was employed for sensitivity analysis to ensure robustness of the results.Additionally,Bayesian co-location analysis was used to evaluate whether FFAR4 expression shares the same causal genetic variant with breast cancer in given genomic region.Results A total of 12 eQTLs closely related to FFAR4 expression levels were included in this study.The results of IVW analysis showed that increased FFAR4 expression levels increased the risk of overall breast cancer,Luminal A,Luminal B/HER2-negative,and HER2-enhanced subtypes of breast cancer.The co-location analysis showed that the posterior probability of FFAR4 expression level and total breast cancer shared causal variation was 0.889.Conclusion There may be a causal relationship between FFAR4 expression and breast cancer.

Objective To explore the causal relationship between breast cancer and free fatty acid receptor 4(FFAR4)by using two-sample Mendelian randomization.Methods By using Genome-wide Association Studies and expression quantitative trait locus(eQTL)data,single nucleotide polymorphism sites closely related to breast cancer and FFAR4 were extracted.Causal effect values were calculated by using five methods:inverse variance weighting(IVW),MR-Egger,weighted median,simple mode and weighted mode.Cochran Q tests were used to detect heterogeneity,MR-Egger intercept tests and MR-PRESSO tests were used to assess level multiplicity,and the hold-out method was employed for sensitivity analysis to ensure robustness of the results.Additionally,Bayesian co-location analysis was used to evaluate whether FFAR4 expression shares the same causal genetic variant with breast cancer in given genomic region.Results A total of 12 eQTLs closely related to FFAR4 expression levels were included in this study.The results of IVW analysis showed that increased FFAR4 expression levels increased the risk of overall breast cancer,Luminal A,Luminal B/HER2-negative,and HER2-enhanced subtypes of breast cancer.The co-location analysis showed that the posterior probability of FFAR4 expression level and total breast cancer shared causal variation was 0.889.Conclusion There may be a causal relationship between FFAR4 expression and breast cancer.

Objective To investigate the involvement of phosphofurin acidic cluster sorting protein-2(PACS-2)in mitochondrial function and apoptosis in N2a/APP695swe cells and further explore the role and significance of PACS-2 in the development of Alzheimer's disease(AD).Methods The CCK8 method was used to analyze the cell survival rate of N2a/APP695swe cells treated with different concentrations of tetrahydroxy stilbene glycoside(TSG)for 48h and to select the appropriate concentration of TSG for subsequent experiments.N2a/WT cells and N2a/APP695swe cells were routinely cultured in vitro,and the experimental cells were divided into 3 groups:blank control group(WT group):N2a/WT cells;model group(APP group):N2a/APP695swe cells;treatment group(TSG group):N2a/APP695swe cells with appropriate concentrations of TSG intervention.TUNEL method to observe apoptosis by fluorescence microscopy;JC-1 method for flow detection of cellular mitochondrial membrane potential;WB to detect protein expression of PACS-2;RT-qPCR to detect PACS-2 mRNA expression.Results CCK8 method was used to analyze the cell survival rate of different concentrations of TSG acting on cells after 48h:the protective effect of 100 μmol/L TSG was the most significant and the difference was statistically significant(P<0.01).The TUNEL method of fluorescence microscopy observed the apoptosis:compared with the WT group,the apoptosis rate of APP group was increased,compared with the APP group,the apoptosis rate of TSG group was decreased,and the differences were statistically significant(P<0.05).The JC-1 method was used to detect the mitochondrial membrane potential of cells:compared with the WT group,the membrane potential of APP group was decreased,compared with the APP group,the membrane potential of TSG group was increased,and the differences were statistically significant(P<0.05);Western blot(WB)detection of PACS-2 protein expression:compared with the WT group,PACS-2 expression was significantly higher in the APP group,and compared with the APP group,PACS-2 expression was significantly lower in the TSG group,with statistically significant differences(P<0.05);The RT-qPCR detected the mRNA expression of PACS-2:the expression of PACS-2 was elevated in the APP group compared with the WT group and decreased in the TSG group compared with the APP group,with statistically significant differences(P<0.05).Conclusion PACS-2 has an important role in the development of AD,and its upregulation may promote the development of AD.The cerebroprotective drug TSG may exert cytoprotective effects by downregulating PACS-2 to inhibit apoptosis and improve mitochondrial function in AD model cells.

OBJECTIVE To explore the clinical effect of concurrent chemoradiotherapy combined with nituzumab in the treatment of locally advanced nasopharyngeal carcinoma in Guangxi,Yunnan and Guizhou.METHODS A total of 80 patients with locally advanced nasopharyngeal carcinoma who were pathologically confirmed and admitted to Affiliated Hospital of Youjiang Ethnomedicine from July 2021 to July 2022 from ethnic minority areas near the border of Guangxi,Yunnan and Guizhou were selected as the subjects of this study.They were randomly divided into control group(standard concurrent chemoradiotherapy)and observation group(combined treatment with nituzumab on the basis of control group),with 40 cases in each group.The levels of tumor markers,oxidative stress indicators,adverse reactions,complications,and recent clinical efficacy of the two groups were compared.RESULTS After treatment,the levels of superoxide dismutase(SOD),cytokeratin 19 fragment antigen21-1(CYFRA21-1),squamous cell carcinoma associated antigen(SCCAg)and serum ferritin(SF)were significantly decreased in both groups,while nitric oxide(NO)and malondialdehyde(MDA)were significantly increased.The levels of SCCAg,SF,CYFRA21-1,NO and MDA in observation group were lower than those in control group,and the level of SOD was higher than those in control group(P<0.05).Compared with the control group,the objective response rate(ORR)in the observation group was increased(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).There was no significant difference in the incidence of complications between the two groups(P>0.05).CONCLUSION Concurrent chemoradiotherapy combined with nituzumab can effectively improve the short-term survival rate and clinical efficacy of patients with locally advanced nasopharyngeal carcinoma,regulate tumor markers and oxidative stress levels,and alleviate the disease.

Objective To understand the current situation and influencing factors of kindergarten teach-ers'participation in training for preschool sex education in Luzhou city,and provide a basis for improving the sex education literacy of kindergarten teachers in the future.Methods A multi-stage stratified cluster sampling meth-od was adopted,and a questionnaire survey was conducted from December 2021 to January 2022 on the knowl-edge,attitude,and practice of preschool sex education among all the teachers in 24 kindergartens in Luzhou city.Results Among the 461 teachers,43.0％had participated in lectures/courses/training activities related to pre-school sex education;99.1％hoped to participate in lectures/courses/training activities related to preschool sex education;82.6％learned about child sexual knowledge through school education;75.5％expressed the hope to learn about child sexual knowledge through expert training.The results of multivariate Logistic regression showed that except private kindergartens as an inhibiting factor(OR=0.57,95％CI=0.37-0.87,P=0.008),high monthly income(OR=3.52,95％CI=1.13-9.30,P=0.011),more ways to know about sex education knowledge(OR=2.87,95％CI=1.76-4.70,P＜0.001),and social support(OR=1.58,95％CI=1.04-2.38,P=0.030)were promoting factors for teachers to participate in the training for preschool sex educa-tion.Conclusions The kindergarten teachers presented a participation rate but a high demand for the training for preschool sex education.They mainly obtain the sex education knowledge from school education.The nature of kindergarten,monthly income of teachers,social support situation,and ways of understanding sex education knowledge are the key factors influencing the teachers'participation in the training for preschool sex education.

Objective:To explore the effect of mini-clinical evaluation exercise (MiniCEX) and direct observation of procedural skills (DOPS) formative evaluation in standardized residency training of respiratory and critical care medicine.Methods:The residents who participated in standardized residency training of Zhongshan Hospital, Fudan Unviersity in 2019 were collected in study group, and the residents received the training in previous were collected in control group. The graduation examination scores, the effect of progressive rotations and the satisfaction of residents and examiners were compared between the two groups.Results:The scores of medical history writing, operation and clinical abilities were higher in the study group who were received MiniCEX-DOPS formative evaluation than those in the control group ( P<0.05). The scores of MiniCEX-DOPS evaluation in the third rotation were better than those in the first rotation ( P<0.05). The residents and examiners were generally satisfied with MiniCEX-DOPS evaluation. Conclusion:MiniCEX-DOPS evaluation is effective in residents training of respiratory and critical care medicine, and it is worth popularizing.

Objective : To investigate the behavior problems and influencing factors of school-age students from the third to the sixth grade in Zhongshan,and to provide evidence for early intervention of behavior problems in children. Methods : According to the proportion of population in urban area and township in Zhongshan,students of Grade Three to Six from eight primary schools（three in urban area and five in township）were recruited by stratified sampling method. The behavior problems in children were assessed by the Conners Parent Symptom Questionnaire（PSQ）. Sociodemographic information,family discipline and so on was investigated by a general questionnaire. The influencing factors for behavior problems were analyzed by a logistic regression model. Results : A total of 2 292 questionnaires were issued,and 2 236 valid questionnaires were recycled,with an effective rate of 97.56%. The positive rate of behavioral problems was 11.72%. The results of multivariate logistic regression analysis showed that the risk factors for behavior problems were females（OR=1.594,95%CI：1.170-2.171）,birth asphyxia（OR=2.372,95%CI：1.320-4.261）,main family discipline（laissez-faire：OR=3.326,95%CI：1.450-7.630;doting：OR=3.244,95%CI：1.867-5.638;autocratic：OR=2.609,95%CI：1.584-4.296,mixed：OR=2.313,95%CI：1.669- 3.207）,less than four hours per week for father-child communication（OR=1.551,95%CI：1.052-2.286）,negative life events（OR=2.188,95%CI：1.448-3.308）,living in township（OR=2.031,95%CI：1.330-3.102）,academic performance （average：OR=2.786,95%CI：1.868-4.156;poor：OR=6.665,95%CI：3.236-13.727;very poor：OR=25.068,95%CI：5.786-108.617）;the protective factors were occupation of mother as civil servants or professional personnel（OR=0.449,95%CI：0.238-0.844）and higher grades（Grade Five：OR=0.496,95%CI：0.339-0.727;Grade Six：OR=0.468,95%CI：0.309-0.710）. Conclusion Females,birth asphyxia,main family discipline,less communication between father and child,occupation of mother,negative life events,place of residence,academic performance and grade were the influencing factors for behavior problems.

Objective To evaluate the diagnostic value and safety of domestic electromagnetic navigation bronchoscopy (ENB) guided transbronchial lung biopsy (TBLB) for peripheral pulmonary lesions.Methods Sixty-four patients with peripheral pulmonary lesions shown by thoracic CT in Zhongshan Hospital,Fudan University between Jul.and Dec.,2014 were collected.The patients were randomly assigned to test group (underwent ENB in combination with X-ray guided TBLB) and control group (underwent X-ray guided TBLB).The final diagnosis was confirmed by pathologic examination of surgically removed lesions or by 24 months clinical follow-up.The operative time as well as the intraoperative and postoperative complications were also recorded.Results Sixty-four patients had 70 peripheral pulmonary lesions.There was no difference in age,sex,the lesion size or location between the two groups.Pathology results showed that the diagnostic yield of test group and control group were 88.6％ and 62.9％,respectively,with statistical significance (P =0.012).Subgroup analysis showed that if the lesion's diameter was ≤2 cm,the diagnosis yield of test group was higher than control group (66.7％ vs.20.0％,P =0.266);if the lesion was ＞2 and ≤3 cm,the diagnosis yield of test group and control group were 100 ％ and 81.8 ％,respectively (P =0.485).But if the lesion was＞3 cm,the diagnostic yield of the 2 group was significantly different (94.4 ％ in test group,63.1％ in control group,P =0.042).Mean operation duration of the 2 group was (966 ± 372)s and (1 040 ± 470) s,respectively,with no statistical difference (P =0.600).However,there was statistical difference between the 2 groups on the X-ray time needed to find the pulmonary lessions [(7.0 ± 4.8)s vs.(37.0 ± 37.5) s,P =0.008).There was no pneumothoraxes and excessive bleeding in patients undergoing ENB.Conclusions Compared with X-ray guide TBLB,ENB guided TBLB for peripheral pulmonary lesions has a certain degree of security,and has superiority in reducing the X-ray time required to find the lesion and improving diagnostic yield especially when the lesion's diameter was ＞3 cm.

Objective To identify Anaplasma species circulating among livestock and rodents from Xitianmu Mountain area in Zhejiang province , Southeastern China and to analyze variations regarding to their 16S rRNA gene.Methods Samples of spleen, liver and blood were collected to extract DNAs .The 16S rRNA gene fragments of Anaplasma species were amplified by using a nested PCR and then sequenced .Ho-mology analysis was conducted by using BLAST program .The multiple sequence alignment and phylogenetic analyses comparing with the sequences of other Anaplasma species in GenBank were conducted by using MEGA 5.0 software.Results The 16S rRNA gene fragments of Anaplasma were detected in 1 cattle, 8 goats, 5 Rattus confucianus, 1 Apodemus agrarius, 1 Berylmys bowersi and 1 squirrel out of 129 animals. The natural infection rate of Anaplasma was 13.2% in animals from Xitianmu Mountain area in Zhejiang . The alignment and phylogenetic analyses indicated that there were at least four Anaplasma species prevalent in livestock and rodents from Xitianmu Mountain area , including Anaplasma phagocytophilum, Anaplasma marginale, Anaplasma centrale and Anaplasma bovis.Moreover, there was a variant that obviously differed from Anaplasmma bovis and other Anaplasma sp.in GenBank.Conclusion The Anaplasma infection was detected among livestock and rodents from Xitianmu Mountain area in Zhejiang province .A newly discovered variant in rodents was likely to be a novel species .More close attention should be paid to Anaplasma infec-tion among human in Xitianmu Mountain area .

Objective To explore the influence of scaffolding instruction on improvement of professional self-concept for undergraduate nursing students in clinical practice.Methods 90 nursing students from 176 undergraduate nursing students were randomly sampled,and were randomly divided into the experimental group and the control group with 45 students in each group.The experimental group took routine clinical practice and scaffolding instruction,students of the control group took routine clinical practice.After 1 week and 6 months,professional self-concept of the students of the two groups was measured by questionnaire.Results There were significant improvement in leadership ability,professional skills,flexibility,satisfaction,communication in the experimental group after 6 months,but this improvement was not found in the control group and after 1 week in both groups.Conclusions Scaffolding instruction can effectively improve professional self-concept for undergraduate nursing students in praxis.