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.

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.

The diagnosis of insomnia includes not only complaints of dissatisfaction with sleep quantity or quality, but also accomplished with daytime dysfunction.Cognitive impairment is one of the daytime dysfunction that insomnia patients often complain about, but the objective measures of cognitive function have no obtained consistent results.Executive functions consist of three core areas, including inhibitory control, working memory and cognitive flexibility.Executive functions represent advanced cognitive processes and are related to daily activities and academic achievement.Executive functions are sensitive to insufficient sleep.However, the relationship between insomnia and executive functions has not attracted enough attention, and it is unclear whether insomnia is related to impairment of executive functions.This article reviews the influence of insomnia on executive functions.The potential mechanism and the role of hyperarousal on executive functions impairment in patients with insomnia is also discussed.

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 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 investigate the therapeutic effect of fibular head composite flap in repairing the bone and skin defect of radiocarpal joint. Methods: From Aug.2009 to Dec.2016, 9 cases with bone and skin defects at radiocarpal joint were reconstructed with fibular head composite flaps pedicled with lateral inferior genicular vascular bundle. The skin defect size was (3-7) cm×(5-10) cm.The joint function was assessed by the Gartland-Werley standard score. Results: All 9 patients were followed up for 6 months to 3 years, with an average of 18 months.Primary wound healing was achieved in all cases without infection.Bony union of the transplanted fibular head was observed .The range of motion (ROM) of the wrist joint and forearm was assessed as following: the mean extension range of motion was 32.9° (range 29°-41°), flexion 24.5° (range 18°-33°), pronation 75° (range 56°-83°)and supination 65.4° (range 40°-78°). The average grip strength was 78% of that on the healthy side. Mayo wrist score was 85 on average, ranging from 58 to 91.By the Gartland-Werley standard score, the wrist function was rated as excellent in 3 case, good in 5 cases and fair in 1 case, with an excellent to good rate of 88.9%.All patients could cope with daily life and work, with good wrist stability and no motion-related pain. Conclusions The fibular head composite tissue flap has a good therapeutic effect in repairing the bone and skin defect of radiocarpal joint.

Objective: To investigate the effect of Δ40p53, an alternative spliced isoform of p53 lacking the N-ter minus, on the pro-apoptotic function of p53. Methods: The wild-type p53 was ectopically expressed in HCT116-p53^-/- (endogenous Δ40p53 expression), HCT116-p53^{+ /+} (wild-type p53) and H1299 (p53-null) cells by adenoviral delivery, while Δ40p53 plasmid were transfected into these cells to overexpress Δ40p53. The levels of Δ40p53 and p53 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR) and quantitative PCR. The expression of related proteins was deter mined by Western blotting. The interaction of p53 and Δ40p53 was observed by co-immunoprecipitation assay. Calcein-AM/propidium iodide (PI) staining and flow cytometry were used to detect the apoptotic rate of tested cells in each group. Results: HCT116-p53^-/- cells expressed endogenous Δ40p53 isoform. Neither transcription nor protein expression of wild-type p53 was interfered by the increased expression of Δ40p53. Full length p53 and Δ40p53 could bind to each other. Calcein-AM/PI staining showed that the apoptotic rates of H1299-Control, HCT116-p53^-/- -Control, H1299+ p53, HCT116-p53^-/-+ p53, H1299+ oxaliplatin (Oxa), HCT116-p53^-/-+ Oxa, H1299+ p53+ Oxa and HCT116-p53^-/-+ p53+ Oxa groups were (2.50±0.47)%, (2.40±0.32)%, (5.20±0.58)%, (4.10±0.18)%, (22.40±1.73)%, (19.30±1.11)%, (29.90±1.15)% and (39.30±2.26)%, respectively. It was statistically significant between H1299+ p53+ Oxa and HCT116-p53^-/-+ p53+ Oxa groups (t=3.721, P=0.0205). Moreover, the apoptotic rates of H1299-Control, H1299+ Δ40p53, H1299+ p53, H1299+ p53+ Δ40p53, H1299+ Oxa, H1299+ Δ40p53+ Oxa, H1299+ p53+ Oxa and H1299+ p53+ Δ40p53+ Oxa groups were (2.60±0.35)%, (2.20±0.17)%, (4.80±0.49)%, (4.90±1.10)%, (20.30±1.10)%, (19.60±1.45)%, (27.90±1.39)%, (35.20±1.43)%, respectively. Furthermore, flow cytometry assay showed that the apoptotic rates of above cells were (2.70±0.32)%, (2.20±0.24)%, (4.60±0.48)%, (3.90±0.67)%, (19.30±1.11)%, (17.70±0.66)%, (28.30±2.76)% and (37.50±1.51)%, respectively. H1299+ p53+ Δ40p53+ Oxa cells showed higher cell apoptosis than H1299+ p53+ Oxa cells (t=2.930, P=0.042). Conclusion Δ40p53 isoform can bind to full-length p53, and enhance its pro-apoptotic function in tumor cells.

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.

Objective To analyze the role of cysteinyl aspartate specific proteinase-1 (caspase-1) in a mouse model of D-galactosamine (D-GalN) and lipopolysaccharide (LPS) induced acute liver failure (ALF) and to study the possible mechanism. Methods C57BL/ 6 mice were randomly divided into four groups including control group, Z-WEHD-FMK (caspase-1 inhibitor) treatment group, ALF model group and Z-WEHD-FMK-treated ALF group. The mouse model of ALF was established by intraperitoneally injec-ting the mice with D-GalN (450 mg/ kg) and LPS (10 μg/ kg). The damages in liver tissues were evaluated based on the histopathological examination and the levels of alanine transaminase (ALT) and aspartate trans-aminase (AST) in serum samples. Western blot assay was performed to analyze the expression of caspase-1 and the phosphorylation of glycogen synthase kinase 3β (GSK-3β). The qRT-PCR was used to measure the expression of inflammatory cytokines at transcriptional level. Results The expression of caspase-1 at both mRNA and protein levels were gradually increased during the development of ALF. Compared with the mice with ALF, those in the Z-WEHD-FMK-treated ALF group showed less severe liver damages on histopatholog-ical examination and decreased levels of ALT and AST in serum samples [ALT: (479. 2±39. 5) U/ L vs (998. 5±60. 4 ) U/ L, P<0. 05; AST: ( 478. 5±28. 6) U/ L vs ( 1 180. 7±91. 4) U/ L, P<0. 05]. The expression of TNF-α, IL-1β, IL-18 and IL-33 at transcriptional level were significantly suppressed in mice with ALF upon the Z-WEHD-FMK intervention. Results of the Western blot assay indicated that Z-WEHD-FMK suppressed the activities of GSK-3β by enhancing its phosphorylation. Conclusion This study demon-strated that caspase-1 could promote the activation of GSK-3β resulting in the development of inflammation responses and liver damages during the development of ALF in mice.