Liver cirrhosis is the advanced stage of various chronic liver diseases,and its complications include portal hypertension,esophageal and gastric varices,hepatocellular carcinoma,etc. Transient elastography( TE),a noninvasive method for liver stiffness measurement( LSM),has been used widely to detect liver fibrosis qualitatively and quantitatively. Recently,correlations were observed for LSM with liver cirrhosis and its complications. This article reviewed the studies focused on these correlations,as well as the clinical application of TE.

Background:Fibroscan is the noninvasive method widely used to evaluate quantitatively the liver fibrosis and monitor the long-term efficacy of anti-fibrosis therapy. Aims:To study the use of Fibroscan for evaluating the efficacy of combined therapy with FuFang BieJia RuanGan tablet and antiviral drugs in patients with hepatitis B virus( HBV)-related cirrhosis. Methods:A total of 90 patients with HBV-related cirrhosis from March 2013 to September 2014 at Shanghai Ren Ji Hospital were recruited,and divided into treatment group and control group. Patients in treatment group received FuFang BieJia RuanGan tablet,and patients in control group received conventional liver-protective drugs,all the patients took nucleoside antiviral drugs at the same time. The treatment courses in both groups were 6 months. Liver stiffness measurement( LSM)was detected by Fibroscan before and after treatment. Biochemical parameters,width of portal vein and clinical symptoms were recorded. Results:After treatment,LSM was significantly decreased in both groups( P <0.05). Liver function,width of portal vein and Child-Pugh score were improved in both groups(P <0. 05),and no significant differences were found between the two groups(P>0. 05). LSM was closely associated with Child-Pugh score both before and after treatment(r=0. 484,P<0. 01;r=0. 523,P<0. 01). Patients with Child-Pugh A had lower LSM than those with Child-Pugh B or Child-Pugh C(P<0. 01). Conclusions:FuFang BieJia RuanGan tablet combined with oral antiviral drugs can remarkably improve the liver function of cirrhotic patients and prevent progression of cirrhosis. Dynamic detection of LSM can be used for monitoring drug efficacy and disease progression in patients with cirrhosis.

Objective: This study aims to explore the effect of lipid-induced macrophage M1/M2 polarization on lipid metabolism in hepatocytes. Methods: RAW264.7 macrophages were incubated with different kinds of fatty acids including saturated fatty acids-palmitic acid (PA), monounsaturated fatty acids-oleic acid (OA) and polyunsaturated fatty acids-docosahexaenoic acid (DHA), and cell culture supernatants were collected to prepare conditioned medium (CM). Hepatocytes were isolated by in situ perfusion of the liver with collagenase in mice, and a macrophage-hepatocyte CM co-culture system was established. Macrophage M1/M2 phenotype markers were detected by Real-time PCR. Lipid synthesis and decomposition related mRNA and protein expressions in hepatocytes were detected by Real-time PCR and Western Blot. Lipid depositions in hepatocytes were detected by oil red O staining. An analysis of variance was used for comparison of means between multiple groups. Results: Compared with control groups, PA polarized macrophages to a M1 phenotype (expression of TNF-α and IL-6 significantly increased, F≥22.68, P < 0.01), OA polarized macrophages to a M1/M2 mixed phenotype (expression of IL-6, Mrc2 and IL-10 increased F≥4.94, P < 0.05) and DHA polarized macrophages to a M2 phenotype (expression of Mrc2 and IL-10 significantly increased, F≥4.94, P < 0.01). CM-PA significantly increased lipid synthesis related genes, including SREBP1C, ACC1 mRNA expression (F≥5.66, P < 0.01) and FASN, ACC1 protein expression (F≥38.34, P < 0.05) in hepatocytes, and decreased lipid decomposition gene ACOX1 protein expression (F=154.48, P < 0.01). CM-OA affected several lipid metabolism genes expression. CM-DHA significantly increased CPT1A mRNA expression (F = 10.30, P < 0.01) and ACOX1, CPT1A protein expression (F≥47.06, P < 0.05), and decreased SREBP1C, ACC1 protein expression (F≥65.84, P < 0.05) in hepatocytes. Massive lipid droplets were deposited in hepatocytes in CM-PA treated hepatocytes, and a few amount of lipid droplets were deposited in CM-DHA treated hepatocytes. Conclusion Different fatty acids affect the balance of lipid metabolism in hepatocytes and liver by inducing macrophage M1 / M2 polarization, thus promoting or delaying the progression of non-alcoholic fatty liver disease.

Objective To explore the relationship between the serum neuropeptide Y (NPY) levels and the pathogenesis,therapeutic intervention of schizophrenia. Methods One hundard twenty-five patients with schizophrenia (case group) with no medication for at least 4-week and 136 healthy controls (control group) were evaluated by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Positive and Negative Syndrome Scala (PANSS). Simultaneously blood tests were performed to detect serum NPY levels. In the case group, PANSS was evaluated and blood collected again after 4 weeks of treatment with olanzapine. Result At the baseline,the serum NPY concentration was significantly lower in the case group than in control group (t=-5.79, P<0.01). The scores of RBANS and its factors were significantly lower in the case group than in control group (all P<0.01). The concentration was positively correlated with the score of the attention factor for RBANS scale (r=0.20, P=0.04). After treatment with olanzapine for 4 weeks,the serum NPY level in the case group was significantly increased (t=-2.23,P=0.03).The scores of PANSS total scale and subscale were significantly decreased(all P<0.01).There was no significant correlation between alterations of the serum level of NPY and PANSS total or subscale scores from baseline to 4-week (all P>0.05). Conclusion The present study has revealed a significant decrease in serum NPY levels in patients with schizophrenia which can be attenuated by treatment of Olanzapine.The action of Olanzapine may be related to the mechanism of action of Olanzapine.However,there is no correlation between alterations of the serum level of NPY and the improvement in the patientˊs clinical symptoms.

Objective:To explore the application effect of case-based learning (CBL), teaching mode combined with 3D printing in clinical teaching of sacral tumors.Methods:A total of 108 undergraduate interns and standardized residency training students who studied in our hospital from 2017 to 2018 were divided into the CBL teaching group ( n = 53) and the CBL combined with 3D printing teaching group ( n = 55) according to their study time. The combined teaching group used computer tomography (CT) data to reconstruct and print out a 3D model of sacral tumors based on CBL, and performed preoperative teaching on the invasion of the surrounding tissues of the tumor. The scores of the students in the two groups were evaluated respectively, and the students were surveyed by self-identification questionnaire (learning interest, self-learning ability, teamwork ability, comprehensive analysis ability and clinical thinking ability). The t-test (one-sided) was used for comparison between groups using stata 14.0. Results:The score of CBL teaching group (75.90±6.70) was lower than that of CBL combined with 3D printing teaching group (83.60±7.40). In terms of critical thinking ability evaluation, self-learning ability, learning interest, comprehensive analysis ability and clinical thinking ability, the CBL combined 3D printing teaching group was superior to the CBL teaching group, and the difference was statistically significant ( P<0.001). In terms of teamwork ability, there was no statistical difference between the two groups. Conclusion:The CBL teaching mode combined with 3D printing can improve academic performance, students' learning interest and clinical thinking ability of sacral tumors in the teaching of undergraduate interns and standardized residency training students.

Single-cell transcriptome sequencing (scRNA-seq) can resolve the expression characteristics of cells in tissues with single-cell precision, enabling researchers to quantify cellular heterogeneity within populations with higher resolution, revealing potentially heterogeneous cell populations and the dynamics of complex tissues. However, the presence of a large number of technical zeros in scRNA-seq data will have an impact on downstream analysis of cell clustering, differential genes, cell annotation, and pseudotime, hindering the discovery of meaningful biological signals. The main idea to solve this problem is to make use of the potential correlation between cells and genes, and to impute the technical zeros through the observed data. Based on this, this paper reviewed the basic methods of imputing technical zeros in the scRNA-seq data and discussed the advantages and disadvantages of the existing methods. Finally, recommendations and perspectives on the use and development of the method were provided.
Cluster Analysis ; Transcriptome

BackgroundThe etiopathogenesis of major depressive disorder （MDD） is strongly associated with neuroinflammation. MDD is a highly heterogeneous psychiatric disorder， and the disease subtyping is an essential step for the identification of biological markers. The presence of psychomotor retardation seriously affects the prognosis of MDD， whereas the underlying mechanism is not yet completely clear. A potential involvement of granulocyte colony-stimulating factor （G-CSF） and macrophage colony-stimulating factor （M-CSF） in the pathogenesis of MDD with psychomotor retardation has been suggested in previous studies， but little detailed research has been completed. ObjectiveTo analyze the correlation of plasma G-CSF and M-CSF levels with psychomotor retardation in patients with MDD， and to explore the potential biological underpinnings of psychomotor retardation in MDD. MethodsA total of 50 MDD patients who met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） and attended the outpatient clinics of Shanghai Mental Health Center from April 2018 to April 2019 were included. The severity of symptoms was assessed using the Hamilton Depression Scale-17 item （HAMD-17）. According to the retardation factor in HAMD-17， patients with a score of ≥8 were included in retardation group （n=22）， and those with a score below 8 were included in non-retardation group （n=28）. Another 22 age- and sex-matched healthy controls were concurrently recruited. Plasma G-CSF and M-CSF levels were measured in all subjects using Luminex liquid suspension chip technology. Spearman correlation analysis was adopted to verify the correlation of retardation factor score in HAMD-17 with plasma G-CSF and M-CSF levels in MDD patients. ResultsPlasma G-CSF levels were decreased in MDD patients compared with healthy controls ［57.34（39.24， 83.15）pg/mL vs. 71.47（61.20， 79.99）pg/mL， Z=-2.098， P<0.05］. A statistical difference was found in plasma G-CSF level ［63.92（54.60， 89.43）pg/mL vs. 47.80（33.41， 74.66）pg/mL vs. 71.47（61.20， 79.99）pg/mL， H=8.247， P=0.016］ and plasma M-CSF level ［20.05（16.05， 22.23）pg/mL vs. 13.05（11.43， 17.50）pg/mL vs. 18.95（14.59， 22.88）pg/mL， H=7.620， P=0.022］ among retardation group， non-retardation group and healthy control group. The post hoc pairwise comparisons using Bonferroni correction indicated that plasma G-CSF level was lower in non-retardation group compared with healthy control group （adjusted P<0.05）， and plasma M-CSF level was higher in retardation group compared with non-retardation group （adjusted P<0.05）. The retardation factor score in HAMD-17 was positively correlated with plasma M-CSF level in MDD patients （r=0.348， P<0.05）. ConclusionThe prevalence of psychomotor retardation in MDD patients may be related to abnormally elevated plasma M-CSF level. ［Funded by Shanghai "Science and Technology Innovation Action Plan" Project in Medical Innovation Research Field （number， 21Y11905600）； Shanghai "Science and Technology Innovation Action Plan" Project in Natural Science Field （number， 21ZR1455100）； Shanghai Mental Health Center Scientific Research Project （number， 2021-YJ02）］