Objective To investigate the correlation of plasma homocysteine(Hcy)level and the polymorphisms of its key metabolic enzymes methylenetetrahy-drofolate reductase(MTHFR)gene with ischemic stroke(IS).Methods A total of 310 patients with IS were enrolled as the case group and 330 healthy subjects during the same period were selected as the control group.Plasma Hcy concentration was detected by enzyme cycling method,and the real-time fluorescent quantitative PCR(RT-qPCR)was used to detecte the genotypes of MTHFR C677T.Results The frequencies of TT genotype(36.13%),CT genotype(10.00%)and T allele(28.06%)of MTHFR gene C677T locus in stroke patients were significantly higher than that in control group(P＜0.05).The frequency of the TT genotype was significantly higher in IS group compared to control group,indicating a recessive mode of inheritance(P＜0.05);In the dominant mode of inheritance,the frequency of CT+TT genotype in IS group was also significantly higher than that in control group(P＜0.05);The plasma Hay concentration of MTHFR C677T genotype TT,CT and CC patients was statistically different(P＜0.05),which were(20.91±6.78)μmol/L(17.20±5.39)μmol/L,(14.35±4.32)μmol/L,respectively;The area under the ROC curve(AUC)of plas-ma total Hcy level was 0.610(95%CI:0.566～0.653,P＜0.001).It indicated that it might play an impor-tant role in predicting the risk of suffering from IS.Multivariate Logistic regression analysis showed that plasma Hcy level and MTHFR C677T gene polymorphism were important risk factors of IS.Conclusions Elevated plasma Hcy level is associated with IS,and the synergistic effect of elevated Hcy level and MTHFR C677T gene mutation may increase the risk of IS.

Objective To investigate the relationship between methylenetetra-hydrofolatereductase(MTHFR)gene polymorphism and serum homocysteine(Hcy)level and subtypes of ischemic stroke(IS).Methods The study was conducted according to the matched principle of case-control design,310 patients with IS and 330 healthy people during the same period were selected as the case group and the control group.Recycling enzyme method and the real-time fluorescent quantitative PCR(RT-qPCR)method were used to detect the level of serum Hcy and the genotypes of MTHFR C677T,respectively.Results There was a significantly difference in MTHFR C677T genotype and allele frequency between the case and control groups(P＜0.05).The correlation analysis with different subtypes indicated that the frequencies of CT genotype(38.02%),TT genotype(10.74%),and T allele(29.75%)were significantly different in the LAA group(OR=1.662,95%CI:1.058-2.608,P＜0.05;OR=2.373,95%CI:1.110-5.073,P＜0.05;OR=1.663,95%CI:1.190-2.323,P＜0.05);The frequencies of TT genotype(10.53%)and T allele(27.30%)in SAO group were also significantly different(OR=2.130,95%CI:1.046-4.336,P＜0.05;OR=1.474,95%CI:1.075-2.021,P＜0.05).Further analysis of serum Hcy level showed that LAA group(19.55±5.61)μmol/L and SAO group(16.37±5.20)μmol/L were significantly higher than the control group(14.46±4.61)μmol/L(P＜0.001);Among the patients of both subtypes the serum Hcy levels in those with CT genotypes and TT genotypes were significantly higher than those in patients of CC genotypes(P＜0.001).Conclusions The gene polymorphism of MTHFR C677T has a significant effect on Hcy level in pa-tients with LAA and SAO stroke.

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Objective:To investigate the feasibility of predicting the risk of spontaneous preterm birth in singleton pregnancy women with low risk of preterm birth by transabdominal-transvaginal ultrasound cervical length sequential screening in the second trimester.Methods:This prospective longitudinal cohort study included singleton pregnant women at 11-13 +6 gestational weeks who were admitted to Nanjing Drum Tower Hospital from January 2023 to September 2023. Transabdominal and transvaginal cervical lengths were measured during the mid-trimester fetal ultrasound scan at 18-24 weeks, and pregnancy outcomes were obtained after delivery. A short cervix was defined as a transvaginal cervical length of ≤25 mm, and the outcomes were defined as spontaneous preterm birth occurs between 20 and 36 +6 weeks and extremely preterm birth before 32 weeks. The area under the receiver operating characteristic (ROC) curve was used to evaluate the effectiveness of predicting spontaneous preterm birth by transabdominal and transvaginal cervix length, as well as the effectiveness of predicting short cervix by transabdominal cervical length. The relationship between transabdominal and transvaginal cervical length was evaluated using a scatter plot. Results:A total of 562 cases were included in this study, comprising 33 cases of spontaneous preterm birth (7 cases occurring before 32 weeks) and 529 cases of term birth. (1) Compared to the term birth group, transabdominal cervical length (median: 37.6 vs 33.2 mm; Z=-3.838, P<0.001) and transvaginal cervical length (median: 34.0 vs 29.9 mm, Z=-3.030, P=0.002) in the spontaneous preterm birth group were significantly shorter. (2) The areas under the ROC curve for predicting spontaneous preterm birth by transabdominal and transvaginal cervical length were 0.699 (95% CI: 0.588-0.809) and 0.657 (95% CI: 0.540-0.774), respectively. The sensitivity, specificity and positive predictive value of transvaginal cervical length Conclusions:In singleton pregnancy women with low risk of preterm birth, transabdominal-transvaginal cervical length sequential screening can reduce unnecessary transvaginal ultrasounds by approximately 41% without missing the diagnosis of pregnant women with a short cervix. This method also enhances the effectiveness of transvaginal cervical length to spontaneous preterm birth.

Objective:To explore the clinical significance of cervical length (CL) measured by transabdominal ultrasound during fetal structural anomalies screeing at 20-24 +6 weeks of gestation. Methods:This was a retrospective nested case-control study based on a prospective longitudinal cohort of "Prediction and Prevention of Early-onset Preeclampsia", which recruited 4 995 singleton pregnant women at the gestational age of 11-13 +6 weeks in Nanjing Drum Tower Hospital from April 2019 to August 2022. All the subjects underwent second-trimester ultrasound screening for fetal structural anomalies in our hospital with image records. This study excluded the women who were lost to follow-up, underwent cervical cerclage, terminated the pregnancy due to personal or social factors, or had miscarriage before 20 weeks of gestation, and those with iatrogenic preterm births, intrauterine fetal death or no second-trimester cervical sonography images. Propensity score matching was used to match pregnant women with spontaneous preterm birth ( n=101) and those with full-term delivery ( n=101) in a 1∶1 ratio, with factors of maternal age, body mass index, preterm birth history, cesarean section history, and pregnancy interval ≥5 years. CL was measured based on the retained ultrasound images. Nonparametric test or Chi-square test were used for statistical analysis. Receiver operating characteristic (ROC) curve was used to evaluate the correlation between CL measured by transabdominal ultrasound in the second trimester and spontaneous preterm birth. Results:The CL measured by transabdominal ultrasound at 20-24 +6 weeks of gestation was significantly shorter in the spontaneous preterm birth group than that in the full-term group [2.8 cm (2.5-3.3 cm) vs. 3.4 cm (3.0-3.9 cm), Z=－5.85, P<0.001]. If CL<3.4 cm was used as the cut-off value for predicting spontaneous preterm birth (20-36 +6 weeks), the specificity and the sensitivity were 0.50 and 0.77, respectively, and the sensitivity reached 0.92 for predicting preterm birth before 32 weeks and 1.00 for predicting preterm birth before 28 weeks. If CL<3.7 cm was used as the cut-off value, the specificity and the sensitivity were 0.36 and 0.87, respectively, and the sensitivity was 1.00 for predicting preterm birth before 32 weeks. The efficacy of preterm birth screening at 28-36 +6 weeks of gestation was comparable to that at 20-36 +6 weeks, if CL<3.4 cm and CL<3.7 cm were used as the cut-off value, the sensitivity were 0.76 and 0.86, respectively. Conclusion:Transabdominal ultrasound measurement of CL in the second trimester can be a preliminary screening to determine whether further transvaginal ultrasound measurement of CL is needed for women without a history of preterm birth or late spontaneous abortion.

ObjectiveTo predict the incidence trend of influenza-like illness proportion （ILI%） in Shanghai using the seasonal autoregressive integrated moving average model （SARIMA）， and to provide an important reference for timely prevention and control measures. MethodsTime series analysis was performed on ILI% surveillance data of Shanghai Municipal Center for Disease Control and Prevention from the 15^th week of 2015 to the 52^nd week of 2019， and a prediction model was established. Seasonal autoregressive integrated moving average （SARIMA） model was established using data from the foregoing 212 weeks， and prediction effect of the model was evaluated using data from the latter 36 weeks. ResultsFrom the 15^th week of 2015 to the 52^nd week of 2019， the average ILI% in Shanghai was 1.494%， showing an obvious epidemic peak. SARIMA（1，0，0） （2，0，0） ₅₂ was finally modeled. The residual of the model was white noise sequence， and the true values were all within the 95% confidence interval of the predicted values. ConclusionSARIMA（1，0，0） （2，0，0） ₅₂ can be used for the medium term prediction of ILI% in Shanghai， and can play an early warning role for the epidemic and outbreak of influenza in Shanghai.

Objective:To evaluate narrow band imaging-magnifying endoscopy (NBI-ME) for the further assessment of lesions of low-grade intraepithelial neoplasia (LGIN) in the gastric biopsy.Methods:Data of 180 patients who underwent NBI-ME before endoscopic submucosal dissection (ESD) for biopsy of gastric LGIN at the First Affiliated Hospital of Soochow University from January 2017 to October 2020 were analyzed retrospectively. Taking the pathological results after ESD as the gold standard, the sensitivity, the specificity, the positive predictive value, the negative predictive value, and the accuracy of NBI-ME in predicting the pathological upgrading of gastric LGIN lesions after ESD were calculated, and the receiver operator characteristic (ROC) curve was drawn.Results:Among 180 gastric LGIN lesions, 115 (63.89%) were pathological upgraded and 65 (36.11%) were not after ESD. There were 10 missed diagnoses, 19 misdiagnoses, and 151 correct diagnoses in NBI-ME examination before ESD. The sensitivity, the specificity, the positive predictive value, the negative predictive value, and the accuracy of NBI-ME in predicting the pathological upgrading of gastric LGIN lesions after ESD were 91.3% (105/115), 70.8% (46/65), 84.7% (105/124), 82.1%(46/56) and 83.9% (151/180), respectively. The area under the ROC curve was 0.810 (95% CI: 0.737-0.883). Conclusion:Further NBI-ME examination of gastric LGIN lesions diagnosed by biopsy pathology can accurately predict whether the lesions have pathological upgrading after ESD, which is of important guiding significance for the patients to choose the treatment strategy of further follow-up or endoscopic resection.

Objective:To explore the reference interval of urinary iodine concentration(UIC)/urinary creatinine(UCr) ratio evaluating the iodine nutritional status in early pregnancy women.Methods:A reference interval of UIC/UCr ratio was determined among 5 609 early pregnant women with normal thyroid function, negative thyroid autoantibodies, and no history of diseases or taking drug that may affect thyroid function. Then we verified the reliability of this reference interval in a group of 7 514 women in early pregnancy.Results:We determined the UIC/UCr ratio of 75-149 μg/g as the reference interval. In the reference interval, thyroglobulin antibody(TgAb), thyroid peroxidase antibody(TPOAb), and thyroglobulin(Tg) were all at lower levels, and the overall distributions were approximately U-shaped. The prevalence of thyroid dysfunction, the positive rates of antibodies and the proportion of Tg>40 μg/L were the lowest within the reference interval, while higher on both sides of the interval.Conclusion:The reasonable reference interval of the UIC/UCr ratio in iodine-sufficient regions is 75-149 μg/g in early pregnerty women.

Objective To learn about the current situation and trends of novel coronavirus diseases 2019 (COVID-2019) in foreign countries. Methods The data on confirmed COVID-2019 cases were collected between January 20, 2020 and February 18, 2020 and by age, sex, nationality, contact history, region, and country were performed stratified analysis and onset time analysis. Results From January 20th to February 18th, the cumulative number of confirmed cases of COVI D-2019 abroad was 804. Excluding the 454 cases on the 'Diamond Princess' cruise ship in Japan, the daily number of new cases fluctuated, showed a trend of rising first and then maintaining a steady trend. The peak date for new cases was on February 1, with the number of cases reaching 26. The confirmed cases were mainly concentrated in Asian countries, but also distributed in Europe, North America, Oceania and Africa. As of February 15, there was no more increase reported in the number of countries where confirmed cases occurred after reaching 25. Among these countries, Singapore, Japan, and Thailand were with the highest number of cases, with 77, 65, and 35 cases, respectively. In accordamce to available information on confirmed cases, the cases with history of exposure to confirmed cases were more than those with history of living or traveling in Hubei. And more cases were non-Chinese nationalities, 40 years old and above, and males . Conclusion The novel coronavirus has transmitted abroad, and produced second-generation cases. Although the incidence is low abroad , its trend fluctuates greatly, so sufficient attention must be paid to the possibility of further transmission.

The safety of prophylactic vaccine is one of the key points both in clinical trials and evaluation. Based on the review practice of vaccine registration clinical trials in recent years, we puts forward a series of thoughts and suggestions on the common problems of safety study on vaccine, including the hypothesis of safety study, the consideration of inclusion/exclusion criteria and suspension/termination criteria for study; the routine requirements of safety study and some special issue such as medical laboratory test index, vaccine virus shedding and safety of adjuvant, and further clarifies the requirements of safety observation on sequential enrollment; also emphasized the scientific judgment of causality and the quality of safety monitoring. It can be used for reference by vaccine researchers and to explore appropriate solutions to promote vaccine research & development and risk control in China.