Objective:To screen and identify differential proteins, analyze lipid metabolism-related proteins and pathways, and explore their functions and biological processes in liver tissue of patients with alcoholic liver disease using tandem mass tag (TMT) labeling technology.Methods:Liver tissues that met the inclusion criteria were collected. Eight samples from patients with alcoholic cirrhosis and three samples from the normal control group were screened out. The TMT technique was used to screen differential proteins, perform signaling pathway enrichment analysis, and analyze protein interaction networks to explore the biological processes involved in them.Results:Proteomic analysis identified 2 741 kinds of differentially expressed proteins in the two groups of data with statistical significance ( P < 0.05). The standard criteria of P < 0.05 and |log2(foldchange)| > 1 had screened out 106 kinds of differentially expressed proteins. Compared with the control group, the alcoholic liver disease group had 12 kinds of up-regulated proteins and 94 kinds of down-regulated proteins. Among them, there were 2 kinds of up-regulated differential proteins related to lipid metabolism and 14 kinds of down-regulated differential proteins. The results of bioinformatics analysis showed that these proteins were primarily involved in biological processes such as lipid transport, regulation of lipase activity, fatty acid binding, and cholesterol metabolism in lipid metabolism and also had a close link to signal pathways related to lipid metabolism such as peroxisome proliferator-activated receptor signaling pathways, cholesterol metabolism, triglyceride metabolism, and regulation of lipolysis in adipocytes. Conclusion:The 16 kinds of lipid metabolism-related differential proteins may be the key proteins in the pathogenesis of alcoholic liver disease.

Objective:To investigate the clinical value of peripheral blood T lymphocytes in the diagnosis and prognosis of patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation.Methods:The clinical and laboratory data of 50 HCC patients, who received liver transplantation and were followed up in the Liver transplantation Center of Beijing Youan Hospital from January 2014 to December 2016, were retrospectively analyzed. The differences on clinical laboratory indicators and five-year survival were compared between HCC recurrence group ( n=29) and non-recurrence group ( n=21). Spearman correlate analysis was used to analyze the correlation between clinical laboratory indicators and HCC recurrence after liver transplantation. Receiver operator characteristic (ROC) curve was used to analyze the diagnostic value of CD4+T lymphocytes in HCC recurrence after liver transplantation. Kaplan-Meier survival curve was used to compare the survival time of patients with different CD4+T lymphocytes levels post liver transplantation. Results:Compared to non-recurrence group, the level of alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, albumin, lymphocytes, alpha-fetoprotein, protein induced by vitamin K deficiency or antagonist-Ⅱ, CD3+, CD4+and CD8+T lymphocytes were significantly different (all P<0.05). The median recurrence time after liver transplantation was 13.0 (6.0, 24.0) months, and the mortality rate was 100%. The 5-year mortality rate was 0 in the non-recurrence group. During 5-year follow-up, the median survival time of patients in the HCC recurrence group was 18.0 (9.0, 36.0) months, which was significantly lower than that of non-recurrence group [60.0 (60.0, 60.0) months, ( P<0.05)]. Compared with non-recurrence group, the CD3+, CD4+, and CD8+T lymphocytes were significantly lower in the recurrence group (all P<0.05). Spearman correlate analysis showed that HCC recurrence after liver transplantation was negatively correlated with the CD3+, CD8+and CD4+T lymphocytes ( r=-0.43, -0.38, -0.44, all P<0.05). ROC analysis showed that CD4+T lymphocytes at cutoff of≤265.50 cells/μl was valuable for the diagnosis of HCC recurrence after liver transplantation (specificity 100%, sensitivity 48.30%). Survival curve analysis showed that the survival time was significantly lower in the CD4≤265.50 cells/μl group [15.0 (10.0, 36.8) months] than that in the CD4>265.50 cells/μl group [53.0 (19.5, 60.0) months] ( P<0.05). Conclusion:There is a significant negative correlation between CD4+T lymphocytes and HCC recurrence after liver transplantation. CD4+T lymphocytes at cutoff value of≤265.50 cells/μl is valuable for the clinical diagnosis and prognosis evaluation of HCC recurrence after liver transplantation.

Objective:To analyze the factors influencing prognosis of intrahepatic cholangiocarcinoma (ICC) after surgical resection.Methods:The clinical data of patients diagnosed with ICC and who underwent surgical resection from December 2015 to December 2019 at the Fifth Medical Center of PLA General Hospital were retrospectively analyzed. Of 39 patients who were included in this study, there were 23 males and 16 females, with age of (54.1±7.2) years old. The body mass index, hepatitis B virus infection status, tumor diameter, degree of differentiation, microvascular tumor thrombus, lymph node metastasis, and serum levels of carbohydrate antigen 19-9 (CA19-9) were analyzed as risk factors affecting postoperative recurrence and survival.Results:The median times to recurrence were significantly better in patients with a tumour length <5 cm (11 vs. 5 months), patients without microvascular tumor thrombus (54 vs. 6 months) and patients without lymph node metastasis (8 vs. 5 months) (all P<0.05). The median survival of patients with CA19-9≥100 U/ml was significantly shorter than that of patients with CA19-9<100 U/ml, (9 vs. 27 months, P<0.05). Tumor diameter>5 cm, microvascular tumor thrombus, lymph node metastasis, and CA19-9 ≥100 U/ml are risk factors affecting the recurrence time after ICC resection, CA19-9 ≥100 U/ml is a risk factor affecting survival time after ICC resection. Conclusion:Tumor diameter, microvascular tumor thrombus, lymph node metastasis and CA19-9 can be used to estimate the risk of ICC recurrence, and CA19-9 level can be used to estimate postoperative survival of ICC patients after resection.

The etiology and pathogenesis of autoimmune liver diseases has always been a hot area of research. Pathogen infections can elicit an autoimmune response and often become the key pathogenic factor of immune diseases. Based on the literature data and the author's clinical experience, this review will briefly introduce the role and influence of pathogen infections in the development and progression of autoimmune liver diseases from the aspects such as molecular mimicry mechanism, in order to further understand the pathogenesis of autoimmune liver diseases.

ObjectiveTo investigate the differentially expressed proteins in the plasma exosome of acute-on-chronic liver failure (ACLF) patients with different prognoses, to analyze their functions and biological processes, and to provide a basis for clinical diagnosis. MethodsA prospective study was performed for 10 ACLF patients who were hospitalized and diagnosed in Beijing YouAn Hospital, Capital Medical University, from July 2019 to October 2019, and the patients were followed up for 90 days. The patients who died or received liver transplantation were enrolled as liver transplantation/death group (5 patients), and the patients who survived were enrolled as survival group (5 patients). The Mann-Whitney U test was used for comparison of general data between the two groups. The label-free quantitative proteomic method was used for identification and quantitative analysis of plasma exosome proteins to screen out differentially expressed proteins, and a functional enrichment analysis was performed. R-3.5.1 software was used to perform a hierarchical cluster analysis of differentially expressed proteins to analyze the biological processes involving these proteins. ResultsA total of 860 proteins were identified by the exosome proteomic analysis, and according to the criteria of upregulation ＞1.2 folds or downregulation ＞1.2 folds (P＜0.05), there were 116 differentially expressed proteins. Compared with the liver transplantation/death group, the survival group had 62 upregulated proteins and 54 downregulated proteins. The bioinformatics analysis showed that these differentially expressed proteins mainly participated in immune reaction, signal transduction, vesicle-mediated transport, cell death, and cell proliferation and were closely associated with the signaling pathways including inflammatory response, carbohydrate and amino acid metabolism, hepatocyte injury, and hepatocyte regeneration. ConclusionDifferentially expressed proteins screened out by the label-free quantitative proteomic method can be used as serological markers for the early diagnosis and prognostic evaluation of ACLF.

Objective: To investigate the effectiveness of preoperative 3D-CTA in assisting the preparation of free thinned anterolateral thigh lobulated perforator flap with nerve in repairing soft tissue defect of limb. Methods: Between February, 2010 and May, 2018, free super-thin anterolateral thigh lobulated perforator flap with nerve was transferred to repair soft tissue defect of limbs in 11 cases. There were 8 males and 3 females with an average age of 35 (range, 22-56) years. The defect area was 8.0 cm×11.0 cm-9.0 cm×23.0 cm. Preoperation CT scan of the free flap donor site was performed to obtain 3D images of the region with arterial blood supply by digital 3D reconstruction CT, and to determine the origin, direction, classification, length, diameter and the position of pedicle perforator. Postoperative regular followed-up was carried according to the Upper Limb Function Evaluation Trial Standards of Chinese Medical Association of Hand Surgery and Enneking Evaluation System. Results: All 11 flaps survived. No vascular crisis happened. All 11 cases were followed-up for 3 to 12 (average, 5) months. The flaps were supple and elastic with near normal color. There was no bulkiness. Sensory function was recovered well and two point discrimination was 3.0-6.0 mm. According to the Upper Limb Function Evaluation of Upper Limb of Chinese Medical Association of Hand Surgery, the results were excellent in 1 case, good in 3 cases and fair in 1 case. The Enneking system was used to assesse the lower limbs recovery. The average score was 21, an average of 70% of limb function restored. Conclusion The free super-thin anterolateral thigh lobulated perforator flap with nerve offers advantages to the traditional anterolateral thigh flap. The survived flaps are ideal in terms of covering limb defects and restoring functions. Preoperative 3D-CTA in the anterolateral thigh perforator flap transplantation is an accurate and useful method. It helps a safer and successful operation with optimal outcome.

Objective To investigate the sensitivity difference between CT angiography (CTA)and MR angiography (MRA)in detecting portal hypertension,and explore the diagnostic value of the two methods for portal hypertension.Methods The imaging data of portal hypertension patients who were diagnosed by surgical exploration or vascular intervention in our hospital were collected,the accuracy and sensitivity of CTA and MRA in portal hypertension diagnosis were analyzed.Results A total of 351 portal hypertension patients were included in our study,prehepatic portal hypertension were 89 cases,intrahepatic portal hypertension were 121 cases,posterior portal hypertension were 131 cases.The detective cases about prehepatic portal hypertension,intrahepatic portal hypertension and posterior portal hypertension in MRA group were 85 cases,101 cases and 97 cases,in CTA were 79 cases,120 cases and 128 cases. The portal hypertension detection rate of CTA was 93.16%,there was significant difference with surgical exploration or interventional angiography (P1,3＜0.000 1＜0.05).The portal hypertension detection rate of MRA was 80.63%,there was significant difference with surgical exploration or interventional angiography (P1,2＜0.000 1＜0.05),the differences between MRA and CTA was significant (P2,3＜0.000 1＜0.05). Conclusion The sensitivity of CTA is much higher than MRA,which is a non-invasive examination,and worthy of clinical promotion.

Objective: To evaluate the therapeutic effect and security of Buyang Huanwu decoction in treatment of the ischemic stroke recovery. Methods: We retrieved the relevant articles of random and semi- random control trials in treating ischemic stroke recovery using Buyang Huanwu decoction, published in China National Knowledge Infrastructure (CNKI), the Wanfang Data, the Weipu Information Resources System, the Chinese Biomedical Literature Database (CBM), Cochrane Library, PUBMED and MEDLINE from the date of establishment until to March 2018. The quality of studies was evaluated according to the Cochrane Reviewers?? handbook 5.1, and the study was carried out using Cochrane system assessment methods. Statistical analysis was performed with Rev Man 5.3. Results: Altogether 39 studies and 3539 cases of ischemic stroke recovery were enrolled. In terms of clinical efficacy, the difference between Buyang Huanwu Decoction and Western Medicine conventional therapy in the treatment of ischemic stroke was significantly different from that of conventional western medicine therapy [RR =1.26, 95％CI (1.20, 1.31), Z =10.05, P ＜ 0.00001], and the difference between Buyang Huanwu Decoction and other Chinese patent medicines was statistically significant [RR =1.12, 95％CI(1.06, 1.19), Z =3.82, P =0.0001]; neurological deficit NIHSS score [MD =-2.55, 95％CI (-3.10, -2.01), Z =9.20, P ＜ 0.00001]; clinical neurological deficit score (CSS) [MD =-3.85, 95％CI (-5.21, -2.50), Z =5.56, P ＜ 0.00001]; limb motor function score (FMA) [MD =6.10, 95％CI (1.19, 11.01), Z =2.43, P =0.01]; Barthel Index of Daily Living Activity Scale [MD =9.09, 95％CI (6.95, 11.23), Z =8.33, P ＜ 0.00001]; In terms of improving blood rheology index, serum peroxide lipid (LPO), serum superoxide dismutase (SOD) and other biochemical indicators, due to the small number of studies, it may have a certain effect. Most studies did not report adverse reactions. Conclusion: Based on the existing clinical evidence, combination of Buyang Huanwu decoction and western medicine has higher clinical efficacy than western medicine alone for the ischemic stroke recovery. Due to the limited methodological quality of the included studies, more high- quality RCTs with large scale are needed to increase the strength of the above evidence.

OBJECTIVE:To provide reference for further promoting the clinical application of chronopharmacology and rational drug use.METHODS:The self-designed questionnairea was used to conduct on-site investigation among participants from 40 hospitals in Anhui province by dint of a meeting.The survey data were analyzed statistically.RESULTS:Totally 170 questionnaires were distributed,and 166 were retrieved,the total response rate was 97.65％.93.37％ of the interviewed pharmacists were aware of the circadian rhythms,and 87.35％ were aware of the circadian rhythms of more than two kinds;interviewed pharmacists expressed better awareness of indicators like gastric acid secretion (75.30％),blood pressure (67.47％) and growth hormone (66.87％) etc.while their awareness of other diseases like anaphylactic rhinitis (66.87％),gastric ulcer (50.60％) and migraine (50.00％) remained to improve.All the interviewed pharmacists recognized the better therapeutic efficacy (84.34％) and lower side effect (81.33％) of chronopharmacology-referred medication;chronopharmacology characteristics of glucocorticoid drugs were best known (34.34％),followed by antihypertensive drugs (25.30％).CONCLUSIONS:Pharmacists in Anhui province have certain knowledge of chronopharmacology such as biological rhythms,biological process or indicators,biological rhythms of disease and advantage of chronopharmacology-referred medication.It indicates that there has been a foundation for popularizing the concept of chronopharmacology in clinical medication in China;but not often contacted physiological processes or indexes,the understanding of biological rhythm of uncommon diseases are still insufficient,and the understanding of chronopharmacology characteristics of various drugs are far from ideal.

Objective: To investigate the genetic characteristics of Lamivudine-resistant mutation patterns and HBV S gene mutants in patients with chronic hepatitis disease of different disease progression. Methods: Blood samples of LAM-resistant patients with chronic hepatitis disease were collected. HBV RT gene nucleotide sequences were obtained, and then differences in drug-resistant mutation patterns, drug susceptibility and HBV S gene mutants characteristics between the two groups were analyzed. Results: Forty-seven chronic hepatitis B (CHB) patients and 16 HBV-related liver cirrhosis (LC)/HBV-related hepatocellular carcinoma (HCC) patients were included in this study. M204I single point mutation and L180M+ M204I/V were the most common pattern during patients with chronic hepatitis disease (35/63, 55.56%). The numbers of resistant to three nucleos(t)ide analogues in LC/HCC group was higher than CHB group’s (62.50% vs 34.04%, P=0.046). In HBV S gene, more immune associated HBsAg-escape mutations were detected in LC/HCC group than that in CHB group (62.50% vs 31.91%, P=0.031). I126T/V and G145A (for LCC/HCC group, 60%), I126S/T and S117T (for CHB group, 46.67%) were showed as the most common form for HBsAg escape mutations in the two groups. The two groups both detected RT mutations concomitantly with stop codon mutations in S gene (rtA181T/sW172* and rtM204I/sW196*). Conclusions Different characteristics in Lamivudine-resistant mutations and associated HBV S gene mutants were found in patients with chronic hepatitis disease of different disease progression, and LC/HCC patients exhibit more multi-drug resistant variants and immune associated HBsAg-escape mutants than CHB patients.