With the emergence of unhealthy dietary structures in people’s life， metabolic associated fatty liver disease （MAFLD） has gradually become the most important chronic liver disease in China， and there is also a gradual increase in the cases of MAFLD-associated liver cancer. Adipose tissue not only has the function of energy storage， but also secretes adipokines that play an important role in the development and progression of MAFLD and its associated liver cancer. Studies on the mechanism of adipokines have provided important help for the prevention and treatment of MAFLD， and a large number of studies have shown that the abnormal secretion of adipokines is associated with MAFLD and plays an important regulatory role in the development and progression of liver cancer. Adipokines are not only regulated at the gene level， but they can also interact with genes through specific pathways to co-regulate pathophysiological processes such as inflammation， metabolism， immunity， and cell proliferation in MAFLD and its associated liver cancer. This article reviews the latest studies on the association of adipokines with MAFLD and its associated liver cancer， in order to provide new directions for further research on the pathogenesis of liver cancer.

Objective To investigate the value of serum hepatitis B virus(HBV)RNA for predicting hepatitis B virus e antigen(HBeAg)clearance and seroconversion after nucleoside(acid)analogs(NAs)treatment in patients with chronic hepatitis B(CHB).Methods Serum samples were collected from 178 CHB patients who received NAs monotherapy in Weihai Hospital affiliated to Shandong University of Traditional Chinese Medicine from February 12,2017 to February 21,2019.Serum HBV RNA levels were analyzed by real-time fluorescence-based quantitative PCR at baseline and after NAs treatment.Results The patients with HBeAg clearance and seroconversion showed significantly lower serum HBV RNA levels at baseline,6 months and 12 months of treatment compared with those without HBeAg clearance and seroconversion(P＜0.001).During follow-up,the patients with lower baseline HBV RNA levels had higher rate of cumulative HBeAg clearance(Log Rank x2=11.282,P=0.001)or seroconversion(Log Rank x2=10.739,P=0.001)than the patients with higher baseline HBV RNA levels.Cox regression model analysis indicated that serum HBV RNA levels at baseline,6 months and 12 months of treatment were an independent predictor for HBeAg clearance and seroconversion in CHB patients(P＜0.05).The area under the ROC curve(AUC)of baseline serum HBV RNA level was 0.808(95％CI:0.743-0.872)for predicting HBeAg clearance and 0.824(95％CI:0.763-0.885)for predicting seroconversion.The AUC of HBV RNA level at 6 months of treatment was 0.830(95％CI:0.765-0.894)for predicting HBeAg clearance and 0.732(95％CI:0.657-0.808)for predicting seroconversion.The AUC of HBV RNA level at 12 months of treatment was 0.737(95％CI:0.641-0.833)for predicting HBeAg clearance and 0.757(95％CI:0.671-0.842)for predicting seroconversion.The AUC of baseline HBV RNA level combined with HBV RNA decline at 6 months of treatment was 0.856(95％CI:0.795-0.917)for predicting HBeAg clearance and 0.864(95％CI:0.802-0.926)for predicting seroconversion.The AUC of baseline HBV RNA level combined with HBV RNA decline at 12 months of treatment was 0.881(95％CI:0.826-0.936)for predicting HBeAg clearance and 0.848(95％CI:0.784-0.911)for predicting seroconversion.Conclusions Serum HBV RNA levels have high predictive value for HBeAg clearance and seroconversion after NAs therapy in CHB patients,suggesting that HBV RNA levels are helpful for identifying non-responders and informing combination therapy.

Objective : To investigate the effects of Lin28 overexpression on the proliferation and osteogenic differentiation of human dental pulp stem cells (hDPSCs) through mTOR signaling pathway. Methods : After transfecting lentiviral vectors of Lin28 gene in hDPSCs , the relative expression of Lin28 was detected by Real⁃time PCR. CCK⁃8 assay was applied to detect the effect on cell proliferation. qRT⁃PCR was used to research the expression levels of alkaline phosphatase (ALP) , osteopontin (OPN) and osteocalcin (OCN) . Western blot assay was processed to investigate the effects on the relative expression levels of ALP and OPN proteins. Alizarin red staining was utilized to detect the mineralized nodules. Results : Compared with the control group , the cell proliferation of transfection group was promoted (P < 0. 05) ; The mRNA and protein expression levels of ALP , OPN and OCN in transfection group were significantly lower than those in control group (P < 0. 05) , the expression level of ALP apparently decreased after the addition of mTOR inhibitor rapamycin (P < 0. 05) ; Alizarin red staining showed that the size and number of mineralized nodules formed in transfection group were markedly declined compared with empty carrier group (P < 0. 05) . Conclusion Overexpression of Lin28 can inhibit the osteogenic differentiation of hDP⁃ SCs through suppress mTOR signaling pathway.

Objective:To establish a double antibody sandwich ELISA for detecting the specific antigen of Seoul virus (SEOV) L99 strain and to provide a means for antigen detection in the development, production and verification of vaccine against hemorrhagic fever with renal syndrome (HFRS).Methods:Monoclonal antibodies (McAbs) aganist L99 virus were induced in mice using four hybridoma cell lines and purified by Protein-A affinity chromatography. The purity, titer and specificity of McAbs were determined by SDS-PAGE, indirect ELISA and Western blot, respectively. Four McAbs were paired with each other and the additivity indices of paired McAbs were analyzed. After labeling McAbs with horseradish peroxidase (HRP), the concentrations of the coated and labeled antibodies were optimized by orthogonal test, and then a double antibody sandwich ELISA for virus antigen detection was established. Type Ⅱ HFRS inactivated vaccine standard was used as a quantitative standard to verify the sensitivity, linearity, specificity, accuracy and precision of the developed method. The applicability of the method was verified by testing three batches of vaccine stock solutions.Results:Four McAbs were at titers of greater than 1∶10 6 and their purity was all greater than 98%. The McAbs secreted by 1D5, 3A4 and 5B7 cells could specifically recognize the nucleocapsid protein of SEOV L99. There was cross-reaction between McAb secreted by 1D5 cells and Hantaan virus PS-6. The McAbs secreted by 3A4 and 1D5 were used as coating and labeling antibodies based on the results of antibody pairs. The working concentrations of the coating antibody and the horseradish peroxidase (HRP)-labeled antibody were 20 μg/ml and 1∶4 000, respectively. The minimum detection limit of the established method for the detection of SEOV L99 antigen was 0.078 1 μg/ml, and the linear range was 0.078 1-2.500 0 μg/ml with a R2 value of more than 0.99. There was no cross reaction with other HFRS vaccine. The virus antigen recovery rate was between 95.8% and 108.7%, and the coefficients of variation of precision was less than 10%. Three batches of Type II HFRS inactivated vaccine stocks were detected by this method and the results was dose-dependent. Conclusions:This study successfully established a double antibody sandwich ELISA method for specific detection of SEOV L99 strain antigen in the production of bivalent HFRS vaccines produced from hamster kidney cells.

Objective:To investigate the effect of preoperative hemoglobin (Hb) level on the risk of developing acute kidney injury (AKI) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI).Methods:A retrospective study was conducted. The hospitalized patients diagnosed with AMI who underwent PCI from May 2015 to May 2020 in the department of cardiology in the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University were enrolled. According to the serum creatinine (SCr) level before and after interventional therapy, the patients were divided into an AKI group and a non-AKI group. The difference in patients' Hb levels between the AKI and non-AKI groups was compared. Univariate and multivariate Logistic regression analyses were used to analyze the effects of Hb levels on the risk of AKI after interventional therapy in patients with AMI. Kaplan-Meier survival curve was used to evaluate the effects of Hb levels on patients with AMI in all-cause death in the hospital.Results:A total of 922 AMI patients were enrolled in this study, of which 165 patients (17.9%) developed AKI. Compared with the non-AKI group, female patients in the AKI group had a higher proportion [35.8% (59/165) vs. 26.9% (204/757)], older (age: 69.78±14.56 vs. 66.61±13.44), with a lower rate of smoking [42.4% (70/165) vs. 51.7% (391/757)] and a higher prevalence of hypertension [73.3% (121/165) vs. 63.5% (481/757)], however, the patients in AKI group also had a worse cardiac function [the proportion of Killip grade 3 or above was higher: 33.9% (56/165) vs. 13.9% (105/757)], lower Hb level (g/L: 127.61±22.18 vs. 132.79±19.45), and there were less patients using angiotensin converting enzyme inhibitor/angiotensin Ⅱreceptor blocker [ACEI/ARB, 60.0% (99/165) vs. 74.5% (564/757)] and more patients using diuretics [24.8% (41/165) vs. 17.7% (134/757)] in AKI group, the differences were statistically significant (all P < 0.05). Compared with non-AKI group, patients in AKI group had a longer operation time [operation time > 60 minutes: 4.2% (7/165) vs. 1.5% (11/757)] and received more contrast media during the operative procedure [contrast media > 100 mL: 16.4% (27/165) vs. 3.6% (27/757)], the individuals had a higher rate of intra-operative hypotension [16.4% (27/165) vs. 8.2% (62/757)], and more patients were implanted more than 2 stents [8.5% (14/165) vs. 3.6% (27/757), all P < 0.05]. Univariate Logistic regression analysis suggested that each 1 g/L increase in preoperative Hb level was associated with a 1.2% decrease in the risk of postoperative AKI [odds ratio ( OR) = 0.988, 95% confidence interval (95% CI) was 0.980-0.996, P = 0.003]. Meanwhile, for every 1 standard deviation increase in preoperative Hb level, the risk of postoperative AKI decreased by 22.1% ( OR = 0.779, 95% CI was 0.661-0.918, P = 0.003). The patients were divided into low, medium and high concentration groups according to Hb levels (Hb levels were < 110 g/L, 110-150 g/L, ≥ 150 g/L, respectively), and multivariate Logistic regression analysis showed that the risk of AKI was significantly reduced in the high concentration group compared with that in the low concentration group ( OR = 0.463, 95% CI was 0.241-0.888, P = 0.020). The Kaplan-Meier survival curve analysis indicated that the short term survival after coronary intervention in AMI patients with low Hb concentration was significantly lower than that in patients with medium and high Hb concentration (Log-Rank: χ2= 23.215, P < 0.001). Conclusions:Preoperative lower Hb level is an independent risk factor for postoperative AKI in AMI patients. AMI patients with lower Hb levels have an increased risk of all-cause mortality within 1 month after AMI.

Copy number variations (CNVs), which can affect the role of long non-coding RNAs (lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer (BLCA). Messenger RNA (mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Objective:To develop and validate a clinical prediction model for the risk of malignant ventricular arrhythmia in patients with acute myocardial infarction (AMI) during hospitalization, and evaluate the effect of the prediction model.Methods:A retrospective study was conducted. A total of 2 649 patients with AMI admitted to cardiology department of Changzhou No.2 People's Hospital of Nanjing Medical University from December 2012 to August 2020 were enrolled. The clinical characteristics including gender, age, medical history, discharge diagnosis, vital signs during hospitalization, electrocardiogram characteristics at admission, laboratory examination indexes, interventional treatment, drug usage, malignant ventricular arrhythmias [mainly included sustained ventricular tachycardia (VT), ventricular flutter or ventricular fibrillation (VF)], and death were recorded. All patients were divided into two groups according to whether VT/VF occurred during their hospitalization. Independent risk factors for VT/VF during hospitalization were evaluated by multivariate Logistic regression analysis, and a clinical prediction model was constructed. The receiver operating characteristic curve (ROC curve) was plotted, and the area under ROC curve (AUC) was calculated to evaluate the accuracy of the prediction model.Results:A total of 2 649 eligible patients with AMI were enrolled, of whom 134 (5.06%) developed VT/VF during hospitalization. The in-hospital mortality rate in VT/VF group was significantly higher than that in non-VT/VF group (38.1% vs. 1.7%, P < 0.01). Compared with the non-VT/VF group, the patients in the VT/VF group with lower systolic blood pressure [SBP (mmHg, 1 mmHg = 0.133 kPa): 125.9±28.2 vs. 132.0±24.2], higher random blood glucose (mmol/L: 8.6±4.8 vs. 7.4±3.7), worse cardiac function [Killip heart function grade ≥ 3: 36.6% vs. 10.7%, left ventricular ejection fraction (LVEF) < 0.50: 56.7% vs. 33.6%, frequent premature ventricular contractions: 12.7% vs. 1.2%] and more hypokalemia (46.3% vs. 17.3%), with significant differences (all P < 0.05). Multivariate Logistic regression analysis showed that Killip classification of cardiac function ≥ 3 [odds ratio ( OR) = 3.540, 95% confidence interval (95% CI) was 2.336-5.363], random blood glucose > 11.1 mmol/L ( OR = 1.841, 95% CI was 1.171-2.893), LVEF < 0.50 ( OR = 0.546, 95% CI was 0.374-0.797), frequent premature ventricular contractions ( OR = 12.361, 95% CI was 6.077-25.144), potassium < 3.5 mmol/L ( OR = 4.268, 95% CI was 2.910-6.259), SBP < 90 mmHg ( OR = 0.299, 95% CI was 0.150-0.597) and creatinine (Cr) > 100 μmol/L ( OR = 2.498, 95% CI was 1.170-5.334) were independent risk factors for VT/VF in patients with AMI (all P < 0.05). The clinical prediction model of VT/VF risk was constructed based on the variables selected by multivariate regression analysis. The ROC curve analysis showed that the AUC of the model in predicting VT/VF was 0.779 (95% CI was 0.735-0.823, P < 0.001); the optimal cut-off value of the model was 17, the sensitivity was 76.1%, the specificity was 67.3%. Conclusions:The incidence of VT/VF during hospitalization of AMI patients significantly increases the risk of in-hospital death. The independent risk factors of VT/VF are Killip grade ≥ 3, random blood glucose > 11.1 mmol/L, LVEF < 0.50, frequent ventricular premature beats, potassium < 3.5 mmol/L, SBP < 90 mmHg and Cr > 100 μmol/L. The newly constructed clinical prediction model has certain predictive value for the occurrence risk of VT/VF.

Objective:To explore the application effect and feedback of online pediatrics teaching for the clerkship and internship stage of medical students of clinical medicine eight-year program.Methods:In this study, 38 clerkship medical students and 12 internship medical students of clinical medicine eight-year program in pediatrics department of Peking University First Hospital from February to March, 2020 were selected as research objects. They had two weeks of online teaching, including online flipped classroom, case-based learning (CBL), and problem-based learning (PBL). The effect of online teaching, and the feedback from these students were all investigated through the questionnaire survey.Results:All students were satisfied with the overall arrangement of the online teaching and believed that the results exceed [42% (21/50)] or meet [58% (29/50)] their expectations. According to the feedback, network congestion [82% (41/50)] was the biggest problem in online teaching, followed by the inability of effective interaction [20% (10/50)]. Students all believed that the online teaching arrangement was most helpful for the cultivation of theoretical knowledge (Total scores 4.58±0.50), autonomous learning ability (Total scores 4.42±0.58) and clinical reasoning (Total scores 4.42±0.58), but had minimal impact on the skills operation (Total scores 2.68±0.87) and scientific research ability (Total 2.98±0.98). For the ability of communication between doctors and patients, the scores of clerkship students (3.79±0.99) were significantly higher than those of internship students (3.08±0.67), ( P<0.05). Clerkship students considered that online flipped classroom was the most helpful teaching mode, while internship students believed online CBL teaching was the most helpful one. Majority of the students (94%) think it's necessary to keep online teaching in the future. Conclusion:Online teaching of pediatrics is approved by the medical students of clinical medicine eight-year program in the stage of clerkship and internship, and plays an important role in the cultivation of the ability of medical students, but it can't completely replace offline clinical practice.