简介：AbstractThe low success rates in the treatment of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant TB (XDR-TB), which account for 55% and 34% respectively, led the WHO to conclude that MDR/XDR-TB is a serious public health crisis. However, the virulence of MDR/XDR-Mycobacterium Tuberculosis(Mtb) has not been analyzed in details, which could provide a specific guidance for the control and prevention. In this review, we discuss different aspects of MDR/XDR-Mtb virulence and its relationship to fitness cost by probing the following questions: (1) what mediates the virulence of MDR/XDR-Mtb? (What is the relationship between fitness and virulence of Mtb? (2) Is it possible that drug-resistant Mtb(DR Mtb) can show higher fitness? (3) What is the definite effect on fitness of each drug-resistant mutant? (4) What other important factors affecting fitness in the mutant strain? (5) How to study the virulence of a large number of DR Mtb?And what prevention and control measures will be taken in the future, especially for the high virulent DR Mtb? We therefore summarized the congruent relationship between drug resistance and fitness from the global response-related genes to antibiotic resistance-contributing mutation, provided methods to explore the virulence of DR Mtb. This review may offer some critical information and concise guide to creating strategies for the prevention and control of drug-resistant Mtb.

简介：AbstractObjective:This article aimed to compare the peripheral blood flow intensity (BFI) in the maternal right and left kidney in uncomplicated third trimester pregnancies and to study possible associations between parenchymal BFI in the kidneys and maternal, labor and new-born characteristics.Methods:We conducted a prospective cohort study in third trimester pregnancies at Trondheim University Hospital, Norway, from January to April 2018. The BFI in the maternal kidneys was examined with color Doppler ultrasound and the peripheral BFI was calculated using the Pixel Flux-method which is a method based on pixel wise calculation of color in an image. Velocity was coded by the color bar in the ultrasound device. The peripheral BFI was calculated as the product of velocity and area encoded by all colored pixels divided by all pixels within the cortical layer by a software examining the color in each pixel of a standardized region of interest of the renal parenchyma in video-clips through a complete heart cycle. BFI (cm/s) was thus calculated as follows:The primary outcome measure was peripheral BFI in the renal cortex. We also examined associations between BFI in the entire cortex with maternal age, body mass index, blood pressure, pH in the umbilical artery, Apgar score after 5 minutes and birthweight.Results:In all, 51 pregnant women were included in the study, but 17 were excluded, mainly due to movement artifacts from the pulsating aorta, leaving 34 women in the final study population. We found significantly lower BFI in the cortex of the left kidney compared with the right kidney, 0.37 cm/s versus 0.69 cm/s, respectively (P = 0.04). Dividing into regions, the BFI was significantly lower in the proximal 25% of the left renal cortex compared to the corresponding right side (P= 0.01), and in the proximal 50% cortex (P= 0.02), but the differences were not significantly different in the distal 25% (P= 0.06) or in the distal 50% (P= 0.20) of the renal cortex.We observed a significant negative correlation between peripheral BFI in the left kidney and both systolic blood pressure (r = -0.38; P= 0.03) and diastolic blood pressure (r= -0.36; P= 0.04), and no significant correlations between BFI with maternal age, body mass index, blood pressure, pH in the umbilical artery, Apgar score after 5 minutes and birthweight in the left kidney (P > 0.05). We did not observe any significant correlations between BFI in the right kidney and maternal or new-born characteristics (P > 0.05).Conclusion:The BFI in the left renal cortex was lower compared with the right renal cortex, and BFI in the left renal cortex was negatively correlated with blood pressure, but not significantly correlated with maternal age, body mass index or newborn characteristics. We did not observe any significant correlations between BFI in the right kidney and maternal or new-born characteristics.

简介：AbstractImportance:Tics usually start around 4-6 years old and affect about 1% of school-age children. Premonitory urges (PUs) are sensory phenomena that precede tics and are often described as unpleasant feelings. Recent evidence supports a relationship between PUs and tic severity, but reports are conflicting. In addition, there is no report of PUs in the Chinese population.Objective:To investigate the correlation between PUs and tic symptoms in the Chinese population with tic disorders.Methods:We recruited 252 Chinese individuals with chronic tic disorders (age 5-16 years). The Yale Global Tic Severity Scale (YGTSS) was used to assess tic symptoms, and the Premonitory Urge for Tics Scale (PUTS) was used to assess PUs. We calculated Spearman correlations between PUTS and YGTSS scores, and constructed a linear regression model to predict the tic symptom severity by PUs.Results:There was a significant positive correlation between PU severity (PUTS scores) and motor tic severity, total tic severity, tic-caused impairment (YGTSS scores) (P < 0.05). PU severity was a significant positive predictor of tic symptom severity (standardized beta coefficient = 0.174, t = 2.786, P = 0.006).Interpretation:We provide evidence for a correlation between PUs and tic symptoms. PU severity predicts tic symptom severity. Further research on PUs is needed to clarify the shared brain mechanism with tics, and their role in tic expression. A suitable tool to assess PUs in younger children is also needed.

简介：AbstractBackground:The ongoing new coronavirus pneumonia (Corona Virus Disease 2019, COVID-19) outbreak is spreading in China, but it has not yet reached its peak. Five million people emigrated from Wuhan before lockdown, potentially representing a source of virus infection. Determining case distribution and its correlation with population emigration from Wuhan in the early stage of the epidemic is of great importance for early warning and for the prevention of future outbreaks.Methods:The official case report on the COVID-19 epidemic was collected as of January 30, 2020. Time and location information on COVID-19 cases was extracted and analyzed using ArcGIS and WinBUGS software. Data on population migration from Wuhan city and Hubei province were extracted from Baidu Qianxi, and their correlation with the number of cases was analyzed.Results:The COVID-19 confirmed and death cases in Hubei province accounted for 59.91% (5806/9692) and 95.77% (204/213) of the total cases in China, respectively. Hot spot provinces included Sichuan and Yunnan, which are adjacent to Hubei. The time risk of Hubei province on the following day was 1.960 times that on the previous day. The number of cases in some cities was relatively low, but the time risk appeared to be continuously rising. The correlation coefficient between the provincial number of cases and emigration from Wuhan was up to 0.943. The lockdown of 17 cities in Hubei province and the implementation of nationwide control measures efficiently prevented an exponential growth in the number of cases.Conclusions:The population that emigrated from Wuhan was the main infection source in other cities and provinces. Some cities with a low number of cases showed a rapid increase in case load. Owing to the upcoming Spring Festival return wave, understanding the risk trends in different regions is crucial to ensure preparedness at both the individual and organization levels and to prevent new outbreaks.

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简介：AbstractBackground:Due to development of magnetic resonance-based functional imaging, it is easier to detect micro-structural alterations of tumor tissues. The aim of this study was to conduct a preliminary evaluation of the correlation of non-Gaussian diffusion kurtosis imaging (DKI) parameters with expression of molecular markers (epidermal growth factor receptor [EGFR]; anaplastic lymphoma kinase [ALK]; Ki-67 protein) in patients with advanced lung adenocarcinoma, using routine diffusion-weighted imaging as the reference standard.Methods:Data from patients with primary lung adenocarcinoma diagnosed at Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS) from 2016 to 2019 were collected for retrospective analysis. The pathologic and magnetic resonance imaging data of 96 patients who met the inclusion criteria were included in this study. Specifically, the Kapp and Dapp parameters measured from the DKI model; apparent diffusion coefficient (ADC) value from the diffusion-weighted imaging model; and the EGFR, ALK, and Ki-67 biomarkers detected by immunohistochemistry and/or molecular biology techniques after biopsy or surgery were evaluated. The relations between quantitative parameters (ADC, Kapp, Dapp) and pathologic outcomes (EGFR, ALK, and Ki-67 expression) were analyzed by Spearman correlation test.Results:Of the 96 lung adenocarcinoma lesions (from 96 patients), the number of EGFR- and ALK-positive and high Ki-67 expressing lesions were 53, 12, and 83, respectively. The Kapp values were significantly higher among patients with EGFR-positive mutations (0.81 ± 0.12 vs. 0.66 ± 0.10, t = 6.41, P < 0.001), ALK rearrangement-negative (0.76 ± 0.12 vs. 0.60 ± 0.15, t = 4.09, P < 0.001), and high Ki-67 proliferative index (PI) (0.76 ± 0.12 vs. 0.58 ± 0.13, t = 4.88, P < 0.001). The Dapp values were significantly lower among patients with high Ki-67 PI (3.19 ± 0.69 μm2/ms vs. 4.20 ± 0.83 μm2/ms, t = 4.80, P < 0.001) and EGFR-positive mutations (3.11 ± 0.73 μm2/ms vs. 3.59 ± 0.77 μm2/ms, t = 3.12, P = 0.002). The differences in mean Dapp (3.73 ± 1.26 μm2/ms vs. 3.26 ± 0.68 μm2/ms, t = 1.96, P = 0.053) or ADC values ([1.34 ± 0.81] × 10-3 mm2/s vs. [1.33 ± 0.41] × 10-3 mm2/s, t = 0.07, P = 0.941) between the groups with or without ALK rearrangements were not statistically significant. The ADC values were significantly lower among patients with EGFR-positive mutation ([1.19 ± 0.37] × 10-3 mm2/s vs. [1.50 ± 0.53] × 10-3 mm2/s, t = 3.38, P = 0.001) and high Ki-67 PI ([1.28 ± 0.39] × 10-3 mm2/s vs. [1.67 ± 0.77] × 10-3 mm2/s, t = 2.88, P = 0.005). Kapp was strongly positively correlated with EGFR mutations (r = 0.844, P = 0.008), strongly positively correlated with Ki-67 PI (r = 0.882, P = 0.001), and strongly negatively correlated with ALK rearrangements (r = -0.772, P = 0.001). Dapp was moderately correlated with EGFR mutations (r = -0.650, P = 0.024) or Ki-67 PI (r = -0.734, P = 0.012). ADC was moderately correlated with Ki-67 PI (r = -0.679, P = 0.033).Conclusions:The Kapp value of DKI parameters was strongly correlated with different expression of EGFR, ALK, and Ki-67 in advanced lung adenocarcinoma. The results potentially indicate a surrogate measure of the status of different molecular markers assessed by non-invasive imaging tools.

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简介：AbstractBackground:The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, which is critically involved in the pathogenesis of a variety of skin diseases. The aim of this study was to detect AhR and its downstream regulators including cytochrome P450 (CYP1A1), AhR nuclear translocation (ARNT), and aryl hydrocarbon receptor repressor (AhRR) in serum, peripheral blood mononuclear cells (PBMCs), and skin lesions in patients with atopic dermatitis (AD).Methods:Twenty-nine AD patients defined according to the criteria of Hanifin and Rajka and Chinese criteria of AD were included. Subjects without allergic and chronic diseases were recruited as controls. Patients and controls were selected from the dermatology outpatient clinic of Peking University People’s Hospital from August 1 to December 31 in 2018. Enzyme-linked immunosorbent assay was performed to detect serum AhR level. The mRNA of AhR, AhRR, ARNT, and CYP1A1 in PBMCs were measured by realtime quantitative polymerase chain reaction. AhR expression in skin lesions was measured by immunohistochemistry.Results:AhR was significantly higher expressed in serum (41.26 ± 4.52 vs. 33.73 ± 2.49 pmol/L, t = 6.507, P < 0.001) and skin lesions (0.191 ± 0.041 vs. 0.087 ± 0.017, t = 10.036, P < 0.001) of AD patients compared with those of controls. The mRNA levels of AhR (1.572 ± 0.392 vs. 1.000 ± 0.173, t= 6.819, P < 0.001), AhRR (2.402 ± 1.716 vs. 1.000 ± 0.788, t= 3.722, P < 0.001), CYP1A1 (2.258 ± 1.598 vs. 1.000 ± 0.796, t= 3.400, P = 0.002) in PBMCs of AD patients were higher compared with those of controls. The difference in mRNA levels of ARNT was not statistically significant between the patients and controls (1.383 ± 0.842 vs. 1.000 ± 0.586, t= 1.653, P = 0.105). AhR mRNA levels in PBMCs positively correlated with eczema area and severity index score and serum interleukin-6 levels.Conclusion:AhR and its downstream regulators were highly expressed in serum, PBMCs, and skin of AD patients, which might contribute to the pathogenesis of AD.