This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.

Objective To analyze the predictive value of microRNA-34a-5p(miR-34a-5p)expression in pancreatic cancer tissue on postoperative poor prognosis.Methods The surgically resected pancreatic cancer tissues and normal tissues adjacent to cancer from 123 patients with pancreatic cancer were collected to detect the expression of miR-34a-5p.The expression of miR-34a-5p in pancreatic cancer tissues for patients with different clinicopathological characteristics were compared.The patients were divided into the poor prognosis group and the good prognosis group according to their prognosis,and the clinical data of patients between the two groups was compared.The risk factors of poor prognosis for patients with pancreatic cancer were analyzed by Cox regression model,and the predictive value of miR-34a-5p expression in pancreatic cancer tissues on poor prognosis of patients was analyzed by receiver operating characteristic(ROC)curve.Results The expression of miR-34a-5p in pancreatic cancer tissues was lower than that in normal tissues adjacent to cancer(P<0.05).There were statistically significant differences in the expression of miR-34a-5p in pancreatic cancer tissues of patients with different differentiation degrees,TNM stages,and lymph node metastasis(P<0.05).The proportions of low differentiation,TNM stage for stage Ⅲ,lymph node metastasis and incisal margin of R1,and levels of carbohydrate antigen 199(CA199),neutrophils/lymphocytes ratio(NLR)and platelet/lymphocyte ratio(PLR)for patients in the poor prognosis group were higher than those in the good prognosis group(P<0.05),while miR-34a-5p expression was lower than that in the good prognosis group(P<0.05).Cox regression analysis showed that low differentiation,TNM stage for stage Ⅲ,lymph node metastasis,incisal margin of R1,decreased expression of miR-34a-5p and increased levels of CA199,NLR and PLR were risk factors of poor prognosis for patients with pancreatic cancer(P<0.05).ROC curve analysis showed that the optimal cut-off value of miR-34a-5p expression in pancreatic cancer tissue for predicting poor prognosis of patients was 0.48,the sensitivity was 78.82%,the specificity was 89.47%and the area under the curve was 0.855,with good predictive value.Conclusion The expression of miR-34a-5p in pancreatic cancer tissue is lower than that in normal tissue adjacent to cancer,and its expression is related to the differentiation degree,TNM stage and lymph node metastasis,which is also a risk factor and predictor of poor prognosis for patients with pancreatic cancer.

This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.

Objective To analyze the predictive value of microRNA-34a-5p(miR-34a-5p)expression in pancreatic cancer tissue on postoperative poor prognosis.Methods The surgically resected pancreatic cancer tissues and normal tissues adjacent to cancer from 123 patients with pancreatic cancer were collected to detect the expression of miR-34a-5p.The expression of miR-34a-5p in pancreatic cancer tissues for patients with different clinicopathological characteristics were compared.The patients were divided into the poor prognosis group and the good prognosis group according to their prognosis,and the clinical data of patients between the two groups was compared.The risk factors of poor prognosis for patients with pancreatic cancer were analyzed by Cox regression model,and the predictive value of miR-34a-5p expression in pancreatic cancer tissues on poor prognosis of patients was analyzed by receiver operating characteristic(ROC)curve.Results The expression of miR-34a-5p in pancreatic cancer tissues was lower than that in normal tissues adjacent to cancer(P<0.05).There were statistically significant differences in the expression of miR-34a-5p in pancreatic cancer tissues of patients with different differentiation degrees,TNM stages,and lymph node metastasis(P<0.05).The proportions of low differentiation,TNM stage for stage Ⅲ,lymph node metastasis and incisal margin of R1,and levels of carbohydrate antigen 199(CA199),neutrophils/lymphocytes ratio(NLR)and platelet/lymphocyte ratio(PLR)for patients in the poor prognosis group were higher than those in the good prognosis group(P<0.05),while miR-34a-5p expression was lower than that in the good prognosis group(P<0.05).Cox regression analysis showed that low differentiation,TNM stage for stage Ⅲ,lymph node metastasis,incisal margin of R1,decreased expression of miR-34a-5p and increased levels of CA199,NLR and PLR were risk factors of poor prognosis for patients with pancreatic cancer(P<0.05).ROC curve analysis showed that the optimal cut-off value of miR-34a-5p expression in pancreatic cancer tissue for predicting poor prognosis of patients was 0.48,the sensitivity was 78.82%,the specificity was 89.47%and the area under the curve was 0.855,with good predictive value.Conclusion The expression of miR-34a-5p in pancreatic cancer tissue is lower than that in normal tissue adjacent to cancer,and its expression is related to the differentiation degree,TNM stage and lymph node metastasis,which is also a risk factor and predictor of poor prognosis for patients with pancreatic cancer.

Objective: To explore the association between the cognition of Nutrition Facts Panel and prepackaged food purchase behavior among residents in six provinces in China. Methods: Using a multi-stage sampling method, 3 002 adults aged 18-70 were selected from the western region (Sichuan), eastern region (Guangdong, Jiangsu, Beijing), central region (Henan), and northeastern region (Heilongjiang) of China from July 2020 to March 2021. Socio-demographic characteristics of participants and their cognition of Nutrition Facts Panel and prepackaged food purchase behavior were collected through questionnaire. A multivariate binary logistic regression model was used to analyze the association between cognition of Nutrition Facts Panel and prepackaged food purchase behavior. Results: The age of 3 002 subjects was (42.3±13.4) years, among which 63.8% (1 914) were female, 66.7% knew the Nutrition Facts Panel, 49.8% would read it when purchasing, 30.7% could understand it, and 56.6% (1 699) bought prepackaged food more than once a week. The results of multivariate analysis showed that after adjusting for relevant confounding factors, compared with the participants knowing but not reading the Nutrition Facts Panel, the group knowing and reading was more likely to buy 11 types of prepackaged food at least once a week (all P<0.05). Compared with the participants reading but not understanding the Nutrition Facts Panel, the group reading and understanding was less likely to buy 11 types of prepackaged food at least once a week (all P<0.05). Conclusion: There was a correlation between cognition of Nutrition Facts Panel and prepackaged food purchase behavior among residents.
Adult ; Female ; Humans ; Male ; Food Labeling/methods* ; Food ; Nutritional Status ; Surveys and Questionnaires ; China ; Health Knowledge, Attitudes, Practice

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

Objective:The study aims to explore the abnormal characteristics in cerebral cortex among children with different subtypes of attention deficit hyperactivity disorder (ADHD).Methods:Four hundred and twelve samples were obtained from the Healthy Brain Network project of American Child Mind Institute. There were 288 children with ADHD (all subjects: age,M=10.03,SD=3.11; 151 of ADHD-C, 20 of ADHD-H, and 117 of ADHD-I) and 124 healthy controls (age,M=9.98,SD=2.98). Using FreeSurfer software, we processed the brain structure images and obtained the cortical volume, cortical thickness and surface area for each subject. Analysis of Variance (ANOVA) and post hoc comparison analyses were conducted.Results:ANOVA analysis showed significant differences of the cortical volume located in the left superior parietal gyrus ( Z=5.94) and superior temporal gyrus ( Z=5.49) among the 3 subtypes of ADHD children and the healthy controls (Monte Carlo, P<0.05). Compared with the healthy controls, ADHD-H group exhibited an increased cortical volume in the left superior parietal gyrus ( Z=6.79), while the ADHD-I group had a decreased volume in the left superior temporal gyrus ( Z=-5.12) and lateral occipital cortex ( Z=-6.40). ADHD-C group also had a decreased volume in the left lateral occipital cortex ( Z=-3.37). Among 3 subtypes of ADHD patients, both ADHD-I and ADHD-C groups had a smaller volume in the left superior parietal gyrus than that of the ADHD-H group (ADHD-I: Z=-7.33,MNI coordinate:x=-26.8,y=-60.6,z=45.4; ADHD-C: Z=-7.14,MNI coordinate:x=-26.6,y=-60.2,z=45.4). Additionally, there was no statistical difference in cortical volume between the ADHD-I and ADHD-C group (Monte Carlo, P>0.05). Subsequent supplementary analyses showed that the sample size and age had no significant effect on the above results. Moreover, analysis of cortical thickness and the surface area showed that the abnormality of the cortical volume in different ADHD subtypes was mainly determined by the surface area of the cerebral cortex. Conclusion:Cortical measures in the superior parietal gyrus might be the crucial features that distinguishes the different subtypes of ADHD. These results enable us to further explore the neurodevelopmental mechanism of ADHD and guide the precise and specific clinical treatment.

Objective:The study aims to explore the abnormal characteristics in cerebral cortex among children with different subtypes of attention deficit hyperactivity disorder (ADHD).Methods:Four hundred and twelve samples were obtained from the Healthy Brain Network project of American Child Mind Institute. There were 288 children with ADHD (all subjects: age,M=10.03,SD=3.11; 151 of ADHD-C, 20 of ADHD-H, and 117 of ADHD-I) and 124 healthy controls (age,M=9.98,SD=2.98). Using FreeSurfer software, we processed the brain structure images and obtained the cortical volume, cortical thickness and surface area for each subject. Analysis of Variance (ANOVA) and post hoc comparison analyses were conducted.Results:ANOVA analysis showed significant differences of the cortical volume located in the left superior parietal gyrus ( Z=5.94) and superior temporal gyrus ( Z=5.49) among the 3 subtypes of ADHD children and the healthy controls (Monte Carlo, P<0.05). Compared with the healthy controls, ADHD-H group exhibited an increased cortical volume in the left superior parietal gyrus ( Z=6.79), while the ADHD-I group had a decreased volume in the left superior temporal gyrus ( Z=-5.12) and lateral occipital cortex ( Z=-6.40). ADHD-C group also had a decreased volume in the left lateral occipital cortex ( Z=-3.37). Among 3 subtypes of ADHD patients, both ADHD-I and ADHD-C groups had a smaller volume in the left superior parietal gyrus than that of the ADHD-H group (ADHD-I: Z=-7.33,MNI coordinate:x=-26.8,y=-60.6,z=45.4; ADHD-C: Z=-7.14,MNI coordinate:x=-26.6,y=-60.2,z=45.4). Additionally, there was no statistical difference in cortical volume between the ADHD-I and ADHD-C group (Monte Carlo, P>0.05). Subsequent supplementary analyses showed that the sample size and age had no significant effect on the above results. Moreover, analysis of cortical thickness and the surface area showed that the abnormality of the cortical volume in different ADHD subtypes was mainly determined by the surface area of the cerebral cortex. Conclusion:Cortical measures in the superior parietal gyrus might be the crucial features that distinguishes the different subtypes of ADHD. These results enable us to further explore the neurodevelopmental mechanism of ADHD and guide the precise and specific clinical treatment.

OBJECTIVE:To study the correlation of UGT1A1 gene polymorphisms with the incidence and severity of irinote-can-associated ADR in the patients with irinotecan-based chemotherapy. METHODS:56 patients with advanced gastroenteric tumor and small cell lung carcinoma were selected from our hospital and treated with irinotecan-based chemotherapy. The occurrence of ADR was observed during chemotherapy. Gene DNA were collected from peripheral blood sample,and UGT1A1 gene polymor-phisms was determined. The relationship of genotypes with ADR was analyzed. RESULTS:TA sequence of UGT1A1*28 genetic lo-cus was as follows:wild-type genotype TA6/6(42 cases,75.0%),heterozygous mutation-type TA6/7(13 cases,23.2%)and ho-mozygous mutation-type TA7/7(1 cases,1.8%);that of UGT1A1*6 genetic locus was as follows:wild-type genotype(44 cases, 78.6%),heterozygous mutation-type(10 cases,17.9%)and homozygous mutation-type(2 cases,3.6%). In UGT1A1*28 genetic locus,6 wild-type genotype patients and 3 mutation-type patients suffered from Ⅲ degree or above hypoleukemia and/or neutrope-nia (14.3% vs. 21.4%,P>0.01),among which only one homozygous mutation-type patient suffered from hypoleukemia and/or neutropenia(100%);6 wild-type genotype patients and 2 mutation-type patients suffered from Ⅲ degree or above diarrhea(14.3%vs. 14.3%,P>0.01),among which only one homozygous mutation-type patient suffered from Ⅲ degree or above diarrhea (100%). In UGT1A1*6 genetic locus,3 wild-type genotype patients and 8 mutation-type patients suffered from Ⅲ degree or above neutropenia (6.8% vs. 66.6%,P<0.01),and 2 wild-type genotype patients and 7 mutation-type patients suffered from Ⅲ degree or above diarrhea(4.5% vs. 58.3%,P<0.01). CONCLUSIONS:Among patients with advanced gastroenteric tumor and small cell lung carcinoma,UGT1A1 gene wild-type gene promoter is most common,followed by heterozygous mutation-type,and homozy-gous mutant rare. For TA7/7 homozygous mutation-type patients,irinotecan-based chemotherapy increase the risk of Ⅲ degree or above hypoleukemia and/or neutropenia and diarrhea. For TA6/7 heterozygotes patients and TA6/6 wild-type patients, irinote-can-based chemotherapy doesn't affect the incidence of Ⅲ degree or above neutropenia and diarrhea. For UGT1A1*6 genetic locus mutation-type patients,irinotecan-based chemotherapy significantly increase the risk of Ⅲ degree or above neutropenia and diar-rhea.