Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor (PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha (HNF4α)‒glucose transporter 2 (GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4α expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4α expression, while silencing PXR upregulated HNF4α and GLUT2 expression. Silencing HNF4α decreased GLUT2 expression, while overexpressing HNF4α increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4α reversed the atorvastatin-induced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4α mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4α downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4α plasmid increased Slc2a2 promoter activity. Hnf4α silencing or pregnenolone-16α-carbonitrile (PCN) suppressed the Slc2a2 promoter activity by decreasing HNF4α recruitment to the Slc2a2 promoter. Liver-specific Hnf4α deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4α and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4α‒GLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes.

Objective:To understand the iodine nutritional status and the prevalence of goiter and thyroid nodules among children in Suqian City, and to provide a basis for prevention and treatment of iodine deficiency disorders.Methods:From May 2019 to July 2020, the counties (districts) in Suqian City were divided into 5 areas according to east, west, south, north, and middle, each area selected 1 township (street) every year, and 40 non-boarding students aged 8 - 10 years were selected (balanced age and gender) from 1 primary school from each township (street). Children's urine samples and household salt samples were collected to detect urinary iodine and salt iodine contents, and some children were subjected to thyroid examination and height and weight measurements.Results:A total of 1 999 urine samples were collected from children aged 8 to 10 years, and the median urinary iodine was 221.0 μg/L. There was a statistically significant difference among different counties (districts, H = 147.89, P < 0.05). A total of 1 999 edible salt samples were collected from children's homes, and the salt iodine content was (24.01 ± 4.55) mg/kg. Among them, iodized salts was 1 979, the coverage rate of iodized salt was 99.00%; the qualified iodized salts was 1 910, and the iodized salt qualified rate was 96.51%, and the consumption rate of qualified iodized salt was 95.55%. A total of 1 000 cases of children's thyroid were examined, and 22 cases of goiter, 51 cases of solid thyroid nodules, and 54 cases of thyroid cyst were detected, and the detection rates were 2.20%, 5.10%, and 5.40%, respectively. There were significant differences in the detection rates of solid nodules and cysts beteen different counties (districts, χ 2 = 16.41, 37.66 , P < 0.05), but there was no significant difference in the detection rates of goiter (χ 2 = 8.65 , P > 0.05). According to Spearman correlation analysis, children's thyroid volume was positively correlated with height and weight ( r = 0.403, 0.315, P < 0.05). Conclusions:The iodine nutrition of children in Suqian City is at an excessively suitable level of iodine, and the salt iodine monitoring indicators meet the national iodine deficiency disorders elimination standards (the coverage rate of iodized salt ≥ 95%, and the consumption rate of qualified iodized salt > 90%). The children's thyroid volume is affected by factors such as height and weight.

Objective:To establish and evaluate a rapid nucleic acid detection method for SARS-CoV-2 based on COYOTE ? Flash20 real-time fluorescent quantitative PCR instrument. Methods:A rapid reaction system was constructed by using specific primer and probe sets targeting ORF1ab and N gene of SARS-CoV-2, and the sensitivity and specificity of the system were verified. At the same time, 108 clinical samples of COVID-19 were used to evaluate the application of this method.Results:The detection method did not require nucleic acid extraction, and the manual operation time was only one minute. After the sample was sent to the system, the test could be completed in 30 minutes. The detection limit of this method was 4×10 2 copies/ml. It had no cross-reactivity with other human coronaviruses (including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, SARS-CoV and MERS-CoV) and other respiratory viruses. The evaluation of clinical sample application showed that the total coincidence rate with the conventional RT-qPCR which required nucleic acid extraction was 98.15%. Conclusions:Through the application evaluation of the rapid fluorescent quantitative PCR method of SARS-CoV-2, it was found that the method was simple, fast, specific and sensitive, and it was suitable for real-time and rapid detection needs in varieties of situations.

Objective:To study the effects of different pre-sequencing sample processing modes on the results of whole genome sequencing with high-throughput sequencing (HTS) by taking the largest RNA virus (human coronavirus, HCoV) as the representative.Methods:Cell-cultured human coronavirus HCoV-OC43 strains were used as the representative samples and divided into different groups based on pre-sequencing processing modes as follows: untreated group, DNase and RNase treatment before nucleic acid extraction group, DNase treatment after nucleic acid extraction group, and DNase and RNase treatment before nucleic acid extraction and DNase treatment after nucleic acid extraction group. Nucleic acid samples of each group were analyzed by direct RNA sequencing (without amplification) and DNA sequencing after sequence independent single primer amplification (SISPA), respectively.Results:No significant difference in viral genome coverage rates was observed between different groups. The highest genome coverage and sequencing accuracy were obtained in DNase treatment after nucleic acid extraction group by direct RNA sequencing, and the ratio of viral reads and the sequencing depth of each locus were effectively improved by SISPA amplification.Conclusions:This study provided an optimized technical strategy for whole genome sequencing of RNA viruses such as coronavirus.

Objective To investigate the clinical characteristics and predictors of mortality in patients with candidemia in intensive care unit (ICU). Methods The patients with candidemia admitted to ICU of Peking University People's Hospital from January 2010 to December 2017 were enrolled. The general clinical data, indicators related to Candidia infection and prognosis were collected, and the clinical characteristics, infection characteristics and prognosis of patients with candidiasis were analyzed. Patients were divided into death group and survival group according to hospital survival status. The differences of each index were compared between two groups. The independent risk factors of mortality in patients with candidemia were analyzed by multivariate Logistic regression analysis. Results A total of 95 patients (55 males) with candidemia were included, with an average age of (69.3±16.5) years, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) was 24.7±3.6, sequential organ failure assessment (SOFA) was 6.6±2.7. Candida albicans accounted for the largest proportion of Candida infections (n = 56, 58.9%). Thirty-two (33.7%) patients received inadequate antifungal therapy and 38 (40.0%) patients received inadequate source control. Fifty-five (57.9%) patients were died in hospital. Compared with the survival group, patients in the death group was older (years: 72.5±14.6 vs. 64.9±18.0, P < 0.05), had higher APACHEⅡ and SOFA scores (26.6±2.2 vs. 22.1±3.6, 7.9±2.0 vs. 4.7±2.4, both P ﹤ 0.01), higher rate of glucocorticoid treatment (18.2% vs. 10.0%, P < 0.05), and higher proportion of Candida albicans and Candida glabrata (69.1% vs. 45.0%, 10.9% vs. 7.5%, both P < 0.05), the rate of multi-site Candida infection also significantly increased (47.3% vs. 17.5%, P < 0.05). Intra-abdominal infection was the primary infection site and more common in death group (49.1% vs. 35.0%, P < 0.05). The rates of sepsis (87.3% vs. 62.5%), inadequate antifungal therapy (49.1% vs. 10.0%), inadequate source control (60.0% vs. 12.5%) in death group were all higher than those in survival group (all P < 0.01). It was shown by multivariate Logistic regression analysis that APACHE Ⅱ[odds ratio (OR) = 1.605, P = 0.002, β = 0.473], SOFA (OR = 1.501, P = 0.029, β = 0.406), inadequate antifungal therapy (OR = 12.084, P = 0.006, β = 2.492) and inadequate source control (OR = 7.332, P = 0.024, β = 1.992) were independent risk factors for mortality in ICU patients with candidemia. Conclusions Candidemia patients were severe and had poor prognosis. APACHE Ⅱ, SOFA, inadequate antifungal therapy and inadequate source control were independent risk factors of mortality.

Objectives: The purpose of this study is to understand the relationships among plasma glucose, blood pressure level and Traditional Chinese Medicine (TCM) syndromes in Shanghai community residents, and provide a theoretical basis for the prevention of community chronic disease based on TCM syndrome differentiation.Methods: Residents above35 years old will attend the Type 2 Diabetes Mellitus (T2 DM) risk assessment at Community Health Center. By distributing questionnaires and performing glucose testing, we screened the residents at high risk of T2 DM, and conducted a physical examination of them. Further, a body constitution questionnaire was required to be completed by the residents. Results: In total, 933 residents were screened. The plasma glucose and blood pressure levels related to age, waist circumference, hip circumference, body mass index (BMI) and waist-to-height ratio (WHtR) . Residents with increasing blood pressure have an increased risk of T2 DM (P ＜ 0.01) . Total 529 questionnaires were completed, and 129 subjects (24.4％) have single TCM syndromes, 75 subjects (14.2％) have at least two TCM syndromes and 325 subjects (61.4％) have no TCM syndromes. Conclusion: Plasma glucose and blood pressure are associated and interacted with several physical indexes. TCM syndromes distribution was found no significant change among subjects with different plasma glucose and blood pressure.

Objective:To compare the applicability and consistency of NRS2002,SGA and MNA in general surgery hospitalized patients and analyze the effect in clinical outcomes of NRS resuits with respect to each tool.Method:The 150 patients hospitalized in our hospital were chosen as object of study,to screen and evaluate nutritional risk of patients by NRS 2002,SGA and MNA,respectively,on the second hospital day,then to compare the consistency of NRS results with respect to the four tools on clinical outcomes.Results:The applicabilities of hospital NRS2002,SGA and MNA were alternatively 97.25,97.25％ and 98.35％.The evaluation of patients' NRS corresponding to different four tools was consistent.The effects of screening results of MNA,NRS2002 and SGA on clinical outcomes were most closely related.Conclusion:The three nutritional evaluation tools can be applied to the screening of malnutrition in General Surgery.The effects of screening results of NRS2002 and SGA on clinical outcomes were most closely related.

Objective To investigate the possibility of using well-differentiated human airway epithelial cells (HAE) to isolate and identify human influenza A virus from a stale respiratory tract specimen.Methods The stale specimen used in this study was a nasopharyngeal swab specimen collected from a patient with unexplained pneumonia in Qinghai in 2010.It was positive for influenza A virus (H3N2) RNA, but negative for hemagglutination.Equal amount of the specimen was inoculated on HAE and on Madin-Darby canine kidney (MDCK) cells for virus isolation and passage.Cytopathic effects were observed daily after inoculation.Hemagglutination inhibition test was performed at every passage.Electron microscope was used to observe viral morphology.Viral genome was sequenced, followed by molecular evolutionary analysis.Results No progeny virus was isolated in MDCK cells, while a influenza A virus subtype H3N2 strain [A/Qinghai/178/2010(H3N2)] was isolated in HAE with a typical morphology and cytopathic effect of influenza A infection.The hemagglutination inhibition activity was 1∶16.Results of the molecular evolutionary analysis of viral genome showed that the influenza A virus (H3N2) strain was highly homologous to the A/Nanjing/1655/2010(H3N2) strain, which was isolated during the 2010 influenza pandemic in Nanjing.Conclusion HAE can be used for isolation and identification of virus from stale respiratory tract specimens.It is more sensitive than MDCK cells with regard to human influenza virus isolation.

Objective: We aimed, in our prospective study, to assess the predictive value of serum non-invasive and biochemical markers for clinical diagnosis of significant fibrosis (including early stages). Methods: We measured sH2a levels in serum, comparing with routine liver function markers. We compared blindly pretreatment serum samples from a cohort of hepatitis B patients without non-alcoholic fatty liver disease(NAFLD), which had histological grades of liver fibrosis, with NAFLD individuals and CHB with NAFLD patients. Statistical analysis was by Student′s t test, and receiver-operating characteristic (ROC) curves were drawn. Results: ROC curves showed that serum sH2a had greater diagnostic performance than routine liver function markers compared with histological grades of liver fibrosis(S0, S1-2, S3-4). ROC curves showed that using a sH2a cut-off point of 0.79 was with highest sensitivity as 63% and highest specificity as 80%. And sensitivity as 96.7% and specificity as 75.5% when using a sH2a cut-off point of 0.77. Conclusions sH2a has the potential to be a uniquely sensitive and specific novel marker for liver fibrosis and function.

Objective To observe normal range based on normal adult echocardiography with data mining retrospectively.Methods Analyzed the echocardiography data of 15 553 patients who came to Peking university People's Hospital from Nov 2012 to Nov 2014 without obvious abnormalities of cardiac structure and function.The reference range of 15 parameters were calculated and analyzed in correlation with gender,age and other factors for each group.Results The reference ranges of basic measurement parameters in two-dimensional echocardiography:main pulmonary artery diameter(MPA) (2.14 ± 0.22)cm,diameter of ascending aorta (asc Aorta) (2.87 ± 0.35) cm;The reference ranges of basic measurement parameters in M-mode echocardiography:aortic root diameter (Ao root diam) (2.82 ± 0.35) cm,left atrial dimension (LA dimension) (3.14 ± 0.37) cm,interventricular septal end-diastole thickness (Ⅳsd) (0.86 ±0.12)cm,left ventricular internal diameter at end-diastole (LVIDd)(4.67 ± 0.41)cm,left ventricular internal diameter at end-systole (LVIDs) (2.83 ± 0.34) cm,left ventricular posterior wall end-diastolic thickness(LVPWd) (0.85 ± 0.12) cm,end diastolic volume (EDV) (101.21 ± 19.83) ml,end-systole volume (ESV) (31.09 ± 9.07) ml,ejection fraction (EF) (69.55 ± 5.70) ％;The reference ranges of basic measurement parameters in pulsed doppler echocardiography:mitral A wave velocity (MVA) (73.14 ±16.42) cm/s,mitral E wave velocity(MVE) (84.18 ± 16.17) cm/s,E/A (1.21 ± 0.35),aortic peak velocity (Ao V2 max) (124.95 ± 19.87) cm/s.The measured parameters of males were higher than those of females and value of measured was increased with age for example measured parameters in LVIDd (r =0.225,P =0.00),IVSd(r =0.216,P =0.00),LA dimension (r =0.231,P =0.00) and E/A(r =0.212,P =0.00),with age were positive correlated.The range of 15 parameters in this study and the ASE 2015 guide are similar but have slightly different,such as this research shows that men's left ventricular end-diastolic diameter (4.77 ±0.41) cm,the ASE recommend (5.02 ±0.41) cm which is smaller than the result of this study.And this study for women (4.60 ± 0.40) cm is higher than the ASE recommended (4.50 + 0.36)cm.Conclusions Based on preliminary analysis of large data from normal adult echocardiography,the rang of measured values could be used as a normal reference value of echocardiographyfor routine practice in China.