Impact of polygenic risk score for triglyceride trajectory and diabetic complications in subjects with type 2 diabetes based on large electronic medical record data from Taiwan: a case control study.

BACKGROUND: The prevalence of diabetic dyslipidemia has gradually increased worldwide and individuals with hypertriglyceridemia often have a high polygenic burden of triglyceride (TG)-increasing variants. However, the contribution of genetic variants to dyslipidemia in patients with type 2 diabetes (T2D) remains limited. Therefore, in this study, we aimed to investigate the genetic characteristics of longitudinal changes in TG levels among patients with T2D and summarize the genetic effects of polygenic risk score (PRS) on TG trajectory and risk of diabetic complications. METHODS: We conducted a case-control study. A total of 11,312 patients with T2D with longitudinal TG and genetic data were identified from a large hospital database in Taiwan. We then performed a genome-wide association study and calculated the relative PRS. RESULTS: In total, 21 single-nucleotide polymorphisms (SNPs) related to TG trajectory were identified and yielded an area under the receiver operating characteristic curve (ROC) of 0.712 for high TG trajectory risk among Taiwanese patients with T2D. A cumulative genetic effect was observed for high TG trajectory, even when considering the adherence of a lipid-lowering agent in stratified analysis. An increased PRS increases high TG trajectory risk in a logistic regression model (odds ratio = 1.55; 95% confidence interval [CI] = 1.31-1.83 in the validation cohort). The TG-specific PRS was associated with the risk of diabetic microvascular complications, including diabetic retinopathy and nephropathy (with hazard ratios of 1.11 [95% CI = 1.01-1.21, P = 0.027] and 1.05 [95% CI = 1.01-1.1, P = 0.018], respectively). CONCLUSIONS: This study may contribute to the identification of patients with T2D who are at risk of abnormal TG levels and diabetic microvascular complications using polygenic information.

Genetic influences of the effect of circulating inflammatory cytokines on osteoarthritis in humans.

OBJECTIVE: The causal relationship between inflammatory cytokines and Osteoarthritis (OA) has not been well investigated. This study investigated the causal role of inflammatory cytokines in the risk of OA and total joint arthroplasty using the Mendelian randomization (MR) method. METHOD: Single nucleotide polymorphisms (SNPs) robustly associated with inflammatory cytokines were used as instrumental variables. The inverse-variance weighted (IVW) method with false discovery rate (FDR) adjusted P-value (q-value) for multiple comparisons were used as the main MR method to estimate causal effects based on the summary-level data for OA (knee and hip OA, respectively) and total joint arthroplasty (TJA). Sensitivity analyses validated the robustness of the results and ensured the absence of heterogeneity and horizontal pleiotropy. RESULTS: After FDR adjustment, macrophage colony-stimulating factor (MCSF) and vascular endothelial growth factor (VEGF) were identified as causally associated with knee OA (MCSF, odds ratio [OR]: 1.16, 95% confidence interval [CI]: 1.09-1.23, q = 5.05 × 10-5; VEGF, OR: 1.09, 95% CI: 1.04-1.15, q = 0.011). We also observed that genetically predicted MCSF and VEGF were positively associated with the risk of TJA, and MCP3 was negatively associated with for the risk of TJA, although the effects seem fairly modest. Sensitivity analysis further excluded the influence of heterogeneity and horizontal pleiotropy. CONCLUSIONS: Inflammatory cytokines, namely MCSF and VEGF, were causally associated with knee OA, which could enhance our understanding of inflammation in OA pathology.

Utilising TMS-EEG to Assess the Response to Cerebellar-Brain Inhibition.

Cerebellar-brain inhibition (CBI) is a transcranial magnetic stimulation (TMS) paradigm indexing excitability of cerebellar projections to motor cortex (M1). Stimulation involved with CBI is often considered to be uncomfortable, and alternative ways to index connectivity between cerebellum and the cortex would be valuable. We therefore sought to assess the utility of electroencephalography in conjunction with TMS (combined TMS-EEG) to record the response to CBI. A total of 33 volunteers (25.7 ± 4.9 years, 20 females) participated across three experiments. These investigated EEG responses to CBI induced with a figure-of-eight (F8; experiment 1) or double cone (DC; experiment 2) conditioning coil over cerebellum, in addition to multisensory sham stimulation (experiment 3). Both F8 and DC coils suppressed early TMS-evoked EEG potentials (TEPs) produced by TMS to M1 (P < 0.05). Furthermore, the TEP produced by CBI stimulation was related to the motor inhibitory response to CBI recorded in a hand muscle (P < 0.05), but only when using the DC coil. Multisensory sham stimulation failed to modify the M1 TEP. Cerebellar conditioning produced changes in the M1 TEP that were not apparent following sham stimulation, and that were related to the motor inhibitory effects of CBI. Our findings therefore suggest that it is possible to index the response to CBI using TMS-EEG. In addition, while both F8 and DC coils appear to recruit cerebellar projections, the nature of these may be different.

[Expression and significance of INSM1 and SOX11 in pancreatic neuroendocrine tumor and solid pseudopapillary neoplasm].

OBJECTIVE: To investigate the expression and significance of insulinoma associated protein 1 (INSM1) and SRY-related high-mobility group box 11 (SOX11) in pancreatic neuroendocrine tumor (PNET) and solid pseudopapillary neoplasm (SPN). METHODS: To detect the expression of INSM1, SOX11, Syn, CgA, CD56, ß-catenin, and CD99 in 56 cases of PNET, 42 cases of SPN, 16 cases of ductal adenocarcinoma (DACC) and 8 cases of acinar cell carcinoma (ACC) by immunohistochemistry. The application value of combination of INSM1 and SOX11 was compared with conventional markers (Syn, CgA, CD56, ß-catenin, and CD99) in diagnosis and differential diagnosis of PNET and SPN. RESULTS: (1) In the 56 cases of PNET, the positive signals of INSM1 were located in the tumor and islet nucleus, the positive expression rate in the tumor tissues was 91.07% (51/56), whereas the signal was absent in 42 cases of SPN, 16 cases of DACC and 8 cases of ACC, and there were significant statistical difference between PNET with SPN, DACC, and ACC respectively (P < 0.001). (2) The positive signals of SOX11 were located in the tumor nucleus, with the positive expression rate was 92.86% (39/42) in SPN, however, the positive expression rate of SOX11 was 8.93% (5/56) in PNET, which included 3 cases of G1 and 2 cases of G3 types of PNET, the SOX11 positive signal was absent in 16 cases of DACC, 8 cases of ACC and peritumoral nomal pancreatic tissue, and the differences were statistically significant of positive rate between SPN with PNET, DACC and ACC, respectively (P < 0.001). (3) The sensitivity of INSM1(+)/SOX11(-) immunophenotype for PNET was 85.71%, vs. CD56 (57.14%), the difference was statistically significant (P=0.001); vs. Syn (80.36%) and CgA (71.43%), the difference was no statistically significant (P>0.05). The specificity of INSM1(+)/SOX11(-) for PNET was 100.00%, vs. Syn (42.86%) and CD56 (47.62%), the difference was statistically significant (P < 0.001); vs. CgA (92.86%), the difference was no statistically significant (P>0.05). The sensitivity of INSM1(-)/SOX11(+) immunophenotype for SPN was 92.86%, vs. ß-catenin (90.48%) and CD99 (85.71%), the difference was no statistically significant (P>0.05). The specificity of INSM1(-)/SOX11(+) for SPN was 96.43%, vs. CD99 (48.21%), the difference was statistically significant (P < 0.001); vs. ß-catenin (100.00%), the difference was no statistically significant (P>0.05). (4) The positive expression of INSM1 and SOX11 in PNET and SOX11 were not correlated with clinicopathological parameters (age, gender, tumor size, location, grade, and metastasis) (P>0.05). CONCLUSION: The positive expression patterns of INSM1 and SOX11 in PNET and SPN respectively are conductive to distinguish the both tumors. The combination of both take precedence over some corresponding conventional immunohistochemical markers in terms of sensitivity and specificity.

[Revision rate of periprosthetic joint infection post total hip or knee arthroplasty of 34 hospitals in China between 2015 and 2017: a multi-center survey].

Objective: To investigate the rate of periprosthetic joint infection (PJI) revision surgeries and clinical information of hip-/knee- PJI cases nationwide from 2015 to 2017 in China. Methods: An epidemiological investigation. A self-designed questionnaire and convenience sampling were used to survey 41 regional joint replacement centers nationwide from November 2018 to December 2019 in China. The PJI was diagnosed according to the Musculoskeletal Infection Association criteria. Data of PJI patients were obtained by searching the inpatient database of each hospital. Questionnaire entries were extracted from the clinical records by specialist. Then the differences in rate of PJI revision surgery between hip- and knee- PJI revision cases were calculated and compared. Results: Total of 36 hospitals (87.8%) nationwide reported data on 99 791 hip and knee arthroplasties performed from 2015 to 2017, with 946 revisions due to PJI (0.96%). The overall hip-PJI revision rate was 0.99% (481/48 574), and it was 0.97% (135/13 963), 0.97% (153/15 730) and 1.07% (193/17 881) in of 2015, 2016, 2017, respectively. The overall knee-PJI revision rate was 0.91% (465/51 271), and it was 0.90% (131/14 650), 0.88% (155/17 693) and 0.94% (179/18 982) in 2015, 2016, 2017, respectively. Heilongjiang (2.2%, 40/1 805), Fujian (2.2%, 45/2 017), Jiangsu (2.1%, 85/3 899), Gansu (2.1%, 29/1 377), Chongqing (1.8%, 64/3 523) reported relatively high revision rates. Conclusions: The overall PJI revision rate in 34 hospitals nationwide from 2015 to 2017 is 0.96%. The hip-PJI revision rate is slightly higher than that in the knee-PJI. There are differences in revision rates among hospitals in different regions.

B-Cell-Activating Factor Contributes to Elevation of the Content of Regulatory B Cells in Neonatal Sepsis.

We studied the role of B cell-activating factor (BAFF) in PI3K/AKT/mTOR signaling pathway in promoting proliferation and maintaining survival of regulatory B lymphocytes (Breg) in newborns with sepsis. The peripheral blood samples were collected from preterm neonates (n=40) diagnosed with sepsis on the day of diagnosis and on days 7, 14, and 21 after diagnosis, as well as from the matched preterm neonates without sepsis (n=40; control group). The peripheral blood mononuclear cells and B cells were isolated, cultured, and stimulated with LPS and immunostimulant CpG-oligodeoxynucleotide (CpG-ODN). Proliferation and differentiation of B-cells into CD19+CD24hiCD38hi Breg cells and the role of the PI3K/AKT/mTOR signaling pathway in these processes were studied by flow cytometry, real-time quantitative reverse transcription PCR (qRT-PCR), and Western blotting. BAFF levels in the peripheral blood of neonates with sepsis were significantly increased at one week after diagnosis in parallel with increasing trend of expression of BAFF receptor. When applied with LPS and CpG-ODN, BAFF promoted differentiation of B cells into CD19+CD24hiCD38hi Breg cells. Phosphorylation of 4E-BP1 factor and 70S6K kinase located downstream in PI3K/AKT/mTOR signaling pathway was significantly up-regulated when stimulated with BAFF in combination with LPS and CpG-ODN. Thus, increased level of BAFF activates PI3K/AKT/mTOR signaling pathway and induces in vitro differentiation of peripheral blood B cells into CD19+CD24hiCD38hi Breg cells.

Definitions of remission in psoriasis: a systematic literature review from the National Psoriasis Foundation.

Psoriasis studies increasingly employ outcomes that indicate complete disease resolution, yet remission and cure are poorly defined for psoriasis. We conducted a systematic literature review to identify definitions of psoriasis remission and cure reported in the literature. Medline, EMBASE, and The Cochrane Central Register of Controlled Trials databases were searched on July 22, 2020, for full-text studies providing definitions for psoriasis remission/cure. Definitions were analysed descriptively for endpoint, time-frame, on/off treatment, patient-reported outcomes, and disease domains. We identified 106 studies that provided 41 unique remission definitions. Most definitions included endpoints based on Psoriasis Area and Severity Index (PASI), such as PASI75 (n = 16 studies), PASI90 (n = 10), PASI100 (n = 10), and PASI of 0 (n = 3), and descriptive endpoints related to 'skin clearance' (n = 18). Few definitions specified time-frame, on/off treatment or other psoriasis-related disease domains. One small consensus-initiative defined drug-free remission for plaque psoriasis by BSA of 0 without any therapy for at least 12 months. While there is no cure for psoriasis, seven studies defined psoriasis cure using similar endpoints to those used to define remission. We identified a variety of definitions of psoriasis remission. These results will inform the development of consensus-based definitions for psoriasis remission to support efforts to improve research and clinical outcomes.

[The purchase behavior of prepackaged food and its determinants among primary and middle school students in 6 provinces of China].

Objective: To examine the purchase behaviors of prepackaged food and its determinants among primary and middle school students in 6 provinces of China. Methods: A multi-stage sampling strategy was adopted to select 2 499 primary and middle school students and their parents from the eastern region of China(Beijing, Jiangsu Province, Guangdong Province), the northeast region(Heilongjiang Province), the central region(Henan Province) and the western region(Sichuan Province) from July 2020 to March 2021. Socio-demographic characteristics of students and their parents, eating-related behaviors and the purchase behaviors of prepackaged food of students, and parents' attitudes towards students' eating behavior were collected through questionnaire towards students and their parents. The χ² test was conducted to compare the purchase behaviors in different groups of students, and multivariate logistic stepwise regression analysis was used to analyze the determinants among primary and middle school students. Results: The age of 2 499 participants was(12.7±2.5) years. There were 1 272(50.9%) females and 1 279(51.2%) middle school students. About 1 404(56.2%) students bought prepackaged food. The top 6 prepackaged foods bought at least once a week were milk and dairy products(74.6%), baked food(58.7%), beverages(42.8%), puffed food(40.8%), chocolate and candy(39.8%), and nuts and dried fruits(37.5%). The multivariate logistic regression model analysis results showed that compared with primary school students, rural students, non-boarding students, students who did not like snacks and students whose parents paid attention to their children eating snacks, middle school students(OR=3.36, 95%CI:2.73-4.12), urban students(OR=1.33, 95%CI:1.11-1.61), boarding students(OR=2.15, 95%CI:1.66-2.79), students who liked snacks(OR=2.01, 95%CI:1.66-2.43), students whose parents did not pay attention to their children eating snacks(OR=1.27, 95%CI:1.05-1.54) were more likely to buy prepackaged food by themselves. Compared with students whose parents had education level of junior high school and below, students whose parents had education level of undergraduate and above(OR=0.70, 95%CI:0.53-0.92) were less likely to buy prepackaged food by themselves. Compared with students whose family monthly income was less than 5 000 yuan, students whose family monthly income was over 10 000 yuan(OR=0.67, 95%CI:0.52-0.87) were less likely to buy prepackaged food by themselves. Conclusion: Many primary and middle school students buy prepackaged food by themselves in 6 provinces of China. Individual characteristics such as grade, place of residence, boarding status, as well as family environment such as parents' education level, monthly income and concern about children eating snacks are the influencing factors of purchasing prepackaged food.

[Clinical significance of ultrasound combined with serological indexes for predicting nonalcoholic fatty liver disease in patients with chronic hepatitis B with normal or slightly elevated alanine aminotransferase].

Objective: To investigate and establish the related factors of non-invasive score model for prediction of non-alcoholic fatty liver disease in chronic hepatitis B patients with normal or mildly elevated alanine aminotransferase (ALT). Methods: A total of 128 cases with chronic hepatitis B who had undergone liver biopsy were included. According to the presence or absence of hepatocyte steatosis on the pathological results of liver biopsy, they were divided into a fatty infiltration and a non-fatty infiltration group. Patients' demographic characteristics, laboratory test indexes, and pathological test results were collected. Univariate and multivariate logistic regression analysis combined with clinical screening variables were used to establish a predictive model. The prediction efficiency of the new model was evaluated by the receiver operating curve, and the difference between the accuracy of the new model and ultrasound in the diagnosis of fatty liver was compared by Delong's-test. Result: Multivariate regression analysis showed that serum triglyceride, serum uric acid and platelets were highly correlated with intrahepatic steatosis (P<0.05). The regression equation triglyceride-uric acid-platelet (TUP)-1=-8.195+0.011×uric acid+1.439×triglyceride+0.012×platelet count was established by combining the above variables. Tthe equation TUP-2=-7.527+0.010×uric acid+1.309×triglyceride+0.012×platelet count+1.397×fatty liver (ultrasound) was established (yes=1; no=0) after incorporating the results of abdominal ultrasound. The diagnostic value of TUP-1 and TUP-2 models for fatty liver was better than that of ultrasound alone and there was no statistically significant difference in diagnostic value between TUP-1 and TUP-2 models (Z=1.453, P=0.146). Conclusion: Compared with abdominal ultrasonography alone, the new model is more effective in diagnosing fatty liver and has good application value.

Optical design and performance of the biological small-angle X-ray scattering beamline at the Taiwan Photon Source.

The optical design and performance of the recently opened 13A biological small-angle X-ray scattering (SAXS) beamline at the 3.0 GeV Taiwan Photon Source of the National Synchrotron Radiation Research Center are reported. The beamline is designed for studies of biological structures and kinetics in a wide range of length and time scales, from angstrom to micrometre and from microsecond to minutes. A 4 m IU24 undulator of the beamline provides high-flux X-rays in the energy range 4.0-23.0 keV. MoB4C double-multilayer and Si(111) double-crystal monochromators (DMM/DCM) are combined on the same rotating platform for a smooth rotation transition from a high-flux beam of ∼4 × 1014 photons s-1 to a high-energy-resolution beam of ΔE/E ≃ 1.5 × 10-4; both modes share a constant beam exit. With a set of Kirkpatrick-Baez (KB) mirrors, the X-ray beam is focused to the farthest SAXS detector position, 52 m from the source. A downstream four-bounce crystal collimator, comprising two sets of Si(311) double crystals arranged in a dispersive configuration, optionally collimate the DCM (vertically diffracted) beam in the horizontal direction for ultra-SAXS with a minimum scattering vector q down to 0.0004 Å-1, which allows resolving ordered d-spacing up to 1 µm. A microbeam, of 10-50 µm beam size, is tailored by a combined set of high-heat-load slits followed by micrometre-precision slits situated at the front-end 15.5 m position. The second set of KB mirrors then focus the beam to the 40 m sample position, with a demagnification ratio of ∼1.5. A detecting system comprising two in-vacuum X-ray pixel detectors is installed to perform synchronized small- and wide-angle X-ray scattering data collections. The observed beamline performance proves the feasibility of having compound features of high flux, microbeam and ultra-SAXS in one beamline.

High-resolution MRI of the vessel wall helps to distinguish moyamoya disease from atherosclerotic moyamoya syndrome.

AIM: To evaluate the value of high-resolution magnetic resonance imaging of the vessel wall (VWI) for differentiating moyamoya disease (MMD) from atherosclerotic moyamoya syndrome (AS-MMS). MATERIALS AND METHODS: Twenty-one patients with MMD or AS-MMS were assessed retrospectively by two independent raters regarding and magnetic resonance angiography (MRA) stage grading score; collateral development in the lateral fissure and basal ganglia on MRA; and pattern of the thickening of the arterial wall; presence, degree, and pattern of enhancement; presence and distribution of deep tiny flow voids (DTFVs) and collateral development in the lateral fissure and basal ganglia on VWI. After univariate analysis between the two groups, logistic regression models based on imaging findings of MRA or VWI were implemented respectively, and receiver operating characteristic (ROC) curves were generated to compare the discriminatory power of the two imaging methods for diagnosis of MMD. Interrater agreement was analysed using an unweighted Cohen's κ or interclass correlation coefficient (ICC). RESULTS: MMD manifested as more concentric thickening, more homogeneous enhancement, higher presence of DTFV, smaller outer-wall boundary area of stenosis or occlusion, and smaller remodelling index on VWI. After Bonferroni-Holm correction for multiple comparisons, for AS-MMS, collaterals in both the lateral fissure and basal ganglia were not usually present on either MRA or VWI. The diagnostic performance of the multivariate logistic regression model based on VWI with an accuracy of 87.1% for classification was higher than MRA. Interrater agreement was moderate or substantial for all the imaging findings. CONCLUSIONS: VWI might be a useful and feasible method for differentiating MMD from AS-MMS and a prospective tool for guiding first-line treatment.

Clinical and radiological characteristics of COVID-19: a multicentre, retrospective, observational study.

BACKGROUND: Multicentre cohort investigations of patients with coronavirus disease 2019 (COVID-19) have been limited. We investigated the clinical and chest computed tomography characteristics of patients with COVID-19 at the peak of the epidemic from multiple centres in China. METHODS: We retrospectively analysed the epidemiologic, clinical, laboratory, and radiological characteristics of 189 patients with confirmed COVID-19 who were admitted to seven hospitals in four Chinese provinces from 18 January 2020 to 3 February 2020. RESULTS: The mean patient age was 44 years and 52.9% were men; 186/189 had ≥1 co-existing medical condition. Fever, cough, fatigue, myalgia, diarrhoea, and headache were common symptoms at onset; hypertension was the most common co-morbidity. Common clinical signs included dyspnoea, hypoxia, leukopenia, lymphocytopenia, and neutropenia; most lesions exhibited subpleural distribution. The most common radiological manifestation was mixed ground-glass opacity with consolidation (mGGO-C); most patients had grid-like shadows and some showed paving stones. Patients with hypertension, dyspnoea, or hypoxia exhibited more severe lobe involvement and diffusely distributed lesions. Patients in severely affected areas exhibited higher body temperature; more fatigue and dyspnoea; and more manifestations of multiple lesions, lobe involvement, and mGGO-C. During the Wuhan lockdown period, cough, nausea, and dyspnoea were alleviated in patients with newly confirmed COVID-19; lobe involvement was also improved. CONCLUSIONS: Among patients with COVID-19 hospitalised at the peak of the epidemic in China, fever, cough, and dyspnoea were the main symptoms at initial diagnosis, accompanied by lymphocytopenia and hypoxaemia. Patients with severe disease showed more severe lobe involvement and diffuse pulmonary lesion distribution.

[Expression of CD200 and INSM1 in gastrointestinal and pancreatic neuroendocrine neoplasms and its diagnostic values].

Objective: To investigate the expression and diagnostic values of CD200 and insulinoma associated protein 1 (INSM1) in gastrointestinal and pancreatic neuroendocrine neoplasm (GIP-NEN). Methods: The expression of CD200, INSM1, Syn and CgA was detected in 69 cases of GIP-NEN, 66 cases of gastrointestinal and pancreatic non-neuroendocrine neoplasm (GIP-nonNEN) and 16 cases of metastatic neuroendocrine neoplasm by immunohistochemistry, to compare the values of CD200, INSM1, Syn, CgA and their combinations in diagnosing GIP-NEN. Receiver operating characteristics (ROC) curve was used. Results: The immunoreactivity of CD200 was present in the cytoplasma and/or membrane of the neoplasms cells, the positive expression rates in GIP-NEN and GIP-nonNEN were significantly different (P<0.01). The sensitivity and specificity of CD200 for diagnosing GIP-NEN were 95.7% and 78.8%, respectively. There was significant difference of the positive rates of CD200 between neuroendocrine tumor and neuroendocrine carcinoma (P=0.05). The immunoreactivity of INSM1 was present in the nuclei of neoplasms cells. The positive expression rates in GIP-NEN and GIP-nonNEN were significantly different (P<0.01). The sensitivity and specificity of INSM1 for diagnosis of GIP-NEN were 85.5% and 95.5%, respectively. There were also significantly different positive rates of INSM1 between neuroendocrine tumor and neuroendocrine carcinoma, as well as between G1 and G3 neuroendocrine tumors (P<0.05). There was no difference in the area under ROC curve (AUC) of single stain of CD200, INSM1, Syn or CgA (0.857, 0.907, 0.890 and 0.833, respectively, P>0.05). The sensitivity of combined CD200+INSM1 stains for diagnosing GIP-NEN was significantly higher than that of Syn+CgA (85.5% vs. 63.8%, P<0.05). The AUC of two combinations were 0.962 and 0.925, respectively, which were not statistically different (P>0.05). Conclusions: CD200 and INSM1 are two novel markers of neuroendocrine neoplasm, which aid to diagnosis for GIP-NEN and exclude its mimickers. They are associated with tumor grades. Combining both as an immunohistochemical panel shows high sensitivity and specificity. Thus, the combined panel can be utilized as useful supplement for Syn and CgA.

[Application of artificial intelligence-assisted diagnosis for cervical liquid-based thin-layer cytology].

Objective: To explore the application value of artificial intelligence-assisted diagnosis system for TBS report in cervical cancer screening. Methods: A total of 16 317 clinical samples and related data of cervical liquid-based thin-layer cell smears, which were obtained from July 2020 to September 2020, were collected from Southern Hospital, Guangzhou Huayin Medical Inspection Center, Shenzhen Bao'an People's Hospital(Group) and Changsha Yuan'an Biotechnology Co., Ltd. The TBS report artificial intelligence-assisted diagnosis system of cervical liquid-based thin-layer cytology jointly developed by Southern Medical University and Guangzhou F. Q. PATHOTECH Co., Ltd. based on deep learning convolution neural network was used to diagnose all clinical samples. The sensitivity,specificity and accuracy of both artificial intelligence-assisted diagnosis system and cytologists using artificial intelligence-assisted diagnosis system were analyzed based on the evaluation standard(2014 TBS). The time spent by the two methods was also compared. Results: The sensitivity of artificial intelligence-assisted diagnosis system in predicting cervical intraepithelial lesions and other lesions (including endometrial cells detected in women over 45 years old and infectious lesions) under different production methods, different cytoplasmic staining and different scanning instruments was 92.90% and 83.55% respectively, and the specificity of negative samples was 87.02%, while that of cytologists using artificial intelligence-assisted diagnosis system was 99.34%, 97.79% and 99.10%, respectively. Moreover, cytologists using artificial intelligence-assisted diagnosis system could save about 6 times of reading time than manual. Conclusions: Artificial intelligence-assisted diagnosis system for TBS report of cervical liquid-based thin-layer cytology has the advantages of high sensitivity, high specificity and strong generalization. Cytologists can significantly improve the accuracy and work efficiency of reading smears by using artificial intelligence-assisted diagnosis system.

[Evaluation of infrahepatic inferior vena cava clamping in robot-assisted laparoscopic liver resection].

Objective: To evalutate the safety and efficacy of infrahepatic inferior vena cava clamping robot-assisted laparoscopic liver resection. Methods: All data about 24 patients with robotic liver resection at Hepatic Surgery Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology between February 2015 and December 2017 were collected and analyzed. These patients were divided into two groups based on different methods to decrease central venous pressure. Eight patients(6 males and 2 females,aged 49 years(range:50 to 56 years)) were applied with infrahepatic inferior vena cava clamping,and the other 16 matched cases (15 males and 1 female,aged 53 years(range:38 to 69 years)) were categorized into lowering central venous pressure group. Intraoperative blood loss,blood transfusion,intraoperative hemodynamic parameters,postoperative complications,and renal function were compared by t-test,non-parametric test,χ2 test,or Fisher exact test. Results: There was significantly difference in the intraoperative blood loss between the infrahepatic vena cava clamping group and the lowering central venous group(200(220) ml (range:100 to 400 ml) vs. 750(800) ml (range:100 to 2 000 ml),Z=‒2.169,P=0.030). The clamping time of portal triad and infrahepatic inferior vena cava were 24 (18) minutes and 29 (20) minutes in the infrahepatic inferior vena cava clamping group, and portal triad clamping time was 23 (23) minutes in the low central venous group. There was no significant difference between the two groups (Z=‒0.323, P=0.747). There was no intraoperative blood transfusion in the infrahepatic inferior vena cava clamping group, and 5 cases in the low central venous group, with a transfusion volume of 1.5(1.5)U. The difference between the two groups was statistically significant (Z=‒3.353, P=0.001). However, the mean arterial pressure in the infrahepatic vena cava clamping group decreased from (88.6±4.9) mmHg to (67.4±3.8) mmHg(1 mmHg=0.133 kPa), which was lower than that of lowering central venous group (72.4±3.3) mmHg (t=2.315,P=0.003). And there were no significant differences related to postoperative complications rate or hepatic and renal function in both groups. Conclusion: The infrahepatic inferior vena cava technology is safe and feasible to decrease central venous pressure during robotic liver resections,which will not affect the recovery of hepatic and renal functions.

Risk of tuberculosis reactivation during interleukin-17 inhibitor therapy for psoriasis: a systematic review.

Immunosuppressive therapies, effective in treating inflammatory disorders such as psoriasis, increase the risk of serious infections, such as tuberculosis (TB). For example, tumour necrosis factor (TNF)-alpha inhibitors significantly increase the risk of TB reactivation in patients with latent TB infection (LTBI), which has led clinicians to routinely test for TB prior to initiation of these medications. This protocol has since extended to other, newer immunomodulatory therapies for psoriasis, such as interleukin (IL)-17 inhibitors, including secukinumab, ixekizumab and brodalumab. We conducted a systematic review to examine whether there is any evidence that IL-17 inhibitor therapy for psoriasis increases the risk of TB reactivation. Using PubMed and EMBASE, our literature search resulted in 139 total articles. After manually reviewing each article for the discussion of IL-17 inhibitors for psoriasis, with data originating from clinical trials, and assessment for incidence of TB reactivation, 23 articles met the full inclusion criteria for our review. Overall, we found no cases of TB reactivation in patients treated with IL-17 inhibitors for psoriasis. This suggests that IL-17 inhibitors may be safely used in psoriasis patients with LTBI who receive appropriate LTBI treatment. However, long-term real-world studies are warranted to further evaluate this risk.

[Early efficacy of islet transplantation in the treatment of adult advanced diabetes].

Objective: To evaluate the safety and efficacy of islet transplantation for patients with advanced diabetes. Methods: Five cases of islet allotransplantation were performed on 4 adult recipients. The same blood type adult brain-dead pancreas donors were selected and the islets were prepared in GMP laboratory. The prepared islet suspension was slowly injected into the liver of the recipients within 30-60 minutes. The immunosuppressive regimen was a combination of basiliximab, tacrolimus and mycophenolate mofetil and TNF-alpha monoclonal antibody was used to reduce the post-transplant inflammatory response. Insulin was temporarily applied to control blood glucose after surgery, and the dosage of insulin was adjusted to decrease according to the blood glucose level until it was discontinued. Results: A total of 5 islet transplants were performed in 4 patients, including 1 patient who received the second islet transplantations. All operations were succeed and the blood glucose and portal pressure were stable during the operation. Exogenous insulin was continued to keep blood glucose level stable (4-12 mmol/L) after surgery. Four cases (including the one who received two islet transplantation) started to stop using insulin at the third to fourth week, and the insulin dosage of the other case was 74% lower than that before the operation, and no hypoglycemic reaction occurred in all patients after islet transplantation. The C-peptide level in 3 patients reached the normal range, and the level in one patient with type I diabetes (without insulin release) remained at 0.45-0.6 µg/L (0.15-0.2 nmol/L). In addition, one patient showed a rise in blood glucose again and continued to use insulin half a year after insulin discontinuation. Then, he was performed the second islet transplantation which showed good effect and stopped taking insulin in 10 days after surgery. There were 3 cases of liver puncture bleeding after opeation, of which 2 cases were treated with ultrasound radiofrequency ablation to stop bleeding, 1 case stopped spontaneously, and no other complications were found. Conclusions: Islet transplantation is effective in the treatment of advanced diabetes patients with small trauma and high safety, which is worthy of more promotion. Long-term efficacy and maintenance therapy still need further investigation.

[Construction and evaluation of a novel diagnosis pathway for 2019-Corona Virus Disease].

Objective: To construct and evaluate a diagnosis pathway (Xiangya pathway) for Corona Virus Disease 2019 (COVID-19). Methods: Consecutive subjects aged ≥12 years old who were screened for COVID-19 were included in Xiangya Hospital of Central South University from January 23 to February 3, 2020, and the subjects were further divided into the inception cohort and the validation cohort. The gender, age, onset time of disease of the subjects were recorded. The information of epidemiological history, fever, and the declined blood lymphocytes were collected as clinical indicators, CT scan was used to evaluate the possibility of COVID-19 and range of lung involvement. According to the current Chinese national standards, throat swabs of suspected cases were collected and the nucleic acid of COVID-19 was detected by reverse transcription-polymerase chain reaction (RT-PCR). The Xiangya pathway was constructed with multi-indexes, compared with clinical indicators, CT results and Chinese national standards, their effectiveness of detecting confirmed cases were verified in the inception and validation cohort. Results: A total of 382 consecutive adults who was screened for COVID-19 were included, and 261 cases were in the inception cohort and 121 cases were in the validation cohort. Among the 382 cases, 192 were males (50.3%) and 190 were females (49.7%), with a median age of 35 years (range: 15-92 years). There were 183 cases (47.9%) with epidemiological history, 275 cases (72.0%) with fever, 212 cases (55.5%) with decreased peripheral blood lymphocytes, 114 cases (29.8%) with positive CT findings, 43 cases (11.3%) with positive CT-COVID-19, and 30 cases (7.9%) with positive virus nucleic acid by throat swab. Compared with clinical indicators, the sensitivity and specificity of CT were 0.950 and 0.704, respectively. The accuracy of CT to make a definite diagnosis was higher than that of epidemiological history, fever, and declined blood lymphocyte count (0.809 vs 0.660, 0.532, 0.596, P=0.001, 0.002, 0.003, respectively). The sensitivity of this pathway and the pathway recommended by the Health Commission of China were both high (all were 1.000), while the specificity and accuracy of the Xiangya pathway were higher than the one recommended by the Health Commission (0.872 vs 0.765, 0.778 vs 0.592, both P<0.001). The CT-COVID-19 reduced the missed diagnosis rate caused by false negative of nucleic acid test (31 vs 64), with difference rate of 51.6%, and the positive rate of nucleic acid test was 64.5% (20/31). In validation cohort, the specificity and accuracy of the Xiangya pathway was 0.967, the positive rate of nucleic acid test was 76.9%(10/13). Conclusions: The Xiangya pathway can predict the nucleic acid test results of COVID-19, and can be applied as a reliable strategy to screen patients with suspected COVID-19 among people aged ≥12 years in areas other than Hubei during the epidemic period of COVID-19. The cohort size needs to be increased for further validation.

[Association between parental socioeconomic status and preschoolers' consumption of sugar-sweetened beverages].

Objective: To explore the association between parental socioeconomic status (SES) and preschoolers' consumption of sugar-sweetened beverages (SSB). Methods: In June 2018, all preschoolers from 15 kindergartens were selected from the jurisdiction of Education Commission in Dongcheng District of Beijing by using an equal-proportion stratified cluster sampling method in the study. A self-designed questionnaire was used to investigate the parents of preschoolers to obtain the basic information of preschoolers and parents, the consumption situation of preschoolers' sugar-sweetened beverages and the perception of parents to SSB. A tatol of 3 217 preschoolers were finally included in the analysis. A generalized structural equation model was used to analyze the relationship between preschoolers' consumption of sugar-sweetened beverages and their parents' socioeconomic status and the mediating effect of their cognition of sugar-sweetened beverages. The size of mediating effect was estimated by using deviation correction non-parameter percentile Bootstrap method. Results: The age of 3 217 preschoolers was (4.23±0.67) years, of which 52.6% (n=1 692) were boys, and 77.62% (n=2 497) were SSB consumers. Among the parents of 3 217 preschoolers, fathers and mothers accounted for 24.90% (n=801) and 75.10% (n=2 416), and the M (P25, P75) scores of SES were 66.7 (62.5, 69.5) and 69.5 (64.6, 71.4), respectively. The proportion of parents who took the initiative to learn about their children's consumption of SSB, lacked confidence in restricting preschooler's consumption of SSB and read nutrition labels before purchasing food was 74.08% (n=2 383), 82.90% (n=2 667) and 36.24% (n=1 166), respectively. The generalized structural equation model showed that after adjusting for preschoolers' gender, age, body mass index (BMI) of preschoolers and their parents, preschoolers' consumption of SSB was negatively associated with their parents' SES score [path coefficient (95%CI):-4.69×10-2 (-6.56×10-2,-2.69×10-2) ]. The mediating effect of parents' perception of SSB consumption could explain 48.71% of the total effect [path coefficient (95%CI):-2.28×10-2 (-3.54×10-2, -1.10×10-2)]. Conclusion: The consumption of SSB in preschoolers is negatively associated with their parent's SES, and this relationship is partially mediated by parent's perception of SSB consumption.

CAFs secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelial-mesenchymal transition in colorectal cancer.

BACKGROUND: Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) metastasis and chemoresistance have not been fully characterized. METHODS: CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1. RESULTS: CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/ß-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients. CONCLUSIONS: CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.