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Objectives: In this study we aimed to assess the clinicopathological characteristics and long‐term prognosis of patients with nonalcoholic fatty liver disease (NAFLD) having distinct steatosis distribution patterns. Methods: Clinicopathological data of 238 individuals with biopsy‐confirmed NAFLD were collected. Nonalcoholic steatohepatitis‐clinical research network (NASH‐CRN) and steatosis, activity and fibrosis (SAF)/fatty liver inhibition of progression (FLIP) algorithm were used. Cumulative incidence of liver‐related events (LREs) was compared by Kaplan–Meier analysis. Univariate and multivariate logistic regression analyses were used to identify independent predictors for steatosis distribution. Results: Eligible patients were categorized into three groups based on their steatosis distribution, including azonal steatosis (AS) (62 [26.1%]), perivenular steatosis (PVS) (147 [61.8%]), and the pan‐acinar steatosis (PAS) groups (29 [12.1%]). There were significantly higher ballooning grade and disease activity (P < 0.05), more severe fibrosis (P < 0.001), and a higher cumulative incidence of LREs (hazard ratio [HR] 8.0, 95% confidence interval [CI] 2.34–27.35, P < 0.0001) in the AS group than in the PVS and PAS groups after a median of 3.6‐year follow‐up. Multivariate logistic regression analysis revealed age (odds ratio [OR] 1.11, 95% CI 1.06–1.16, P < 0.001) might be independently associated with AS distribution, and PNPLA3 rs738409 CG/GG genotype (OR 3.36, 95% CI 0.98–11.47, P = 0.053) might also play a role. Conclusions: AS is associated with more severe disease activity and fibrosis stage in NAFLD, and predisposes toward poor prognosis. Age might be an independent predictor for AS in NAFLD, while PNPLA3 rs738409 CG/GG genotype might also play a role. [ABSTRACT FROM AUTHOR]

Background: Postprandial distress syndrome (PDS) is referred to as meal-related functional dyspepsia (FD) and causes a reduced quality of life (QoL) for patients. Several randomized controlled trials (RCTs) have suggested that acupuncture is an effective treatment for FD, but few studies were particularly for PDS. This pilot study was designed to determine the feasibility and efficacy of acupuncture in patients with PDS characterized by postprandial fullness and early satiation according to the Rome III criteria.Methods: This is a multi-center, two-arm, blinded (participants), pilot RCT. Forty-two participants who meet the inclusion criteria will be randomly assigned to the verum acupuncture group or minimal acupuncture group in a 1:1 ratio. Both treatments consist of 12 sessions of 20 min duration over four weeks (three sessions per week). The primary outcome measurement is the proportion of persons who improve as assessed using the global outcome by the overall treatment effect (OTE) at end-of-treatment (EOT) (four weeks after randomization). Global assessment at weeks 8 and 16 after randomization is one of the secondary outcomes. The other secondary outcomes including symptoms, disease-specific QoL, and depression and anxiety will be assessed at weeks 4, 8, and 16 after randomization.Discussion: This pilot study will help determine the feasibility and efficacy of acupuncture in patients with PDS.Trial Registration: ISRCTN Registry, ISRCTN18135146 . Registered on 7 July 2016. [ABSTRACT FROM AUTHOR]

Objective: To explore the mechanism of electroacupuncture (EA) at "Zusanli" (ST36) on improving glucose metabolism disorder in chronic restraint induced depressed rats., Methods: A total of 30 male SD rats were randomly divided into control, model and EA groups, with 10 rats in each group. The depression model was established by chronic restraint 2.5 h each day for 4 weeks. For rats in the EA group, EA stimulation (1 mA, 2 Hz, 30 min) was applied to bilateral ST36 during the modeling period, once a day for 4 weeks. The body weight of the rats was recorded before and after modeling. The behavior of rats was observed by sugar-water preference and forced swimming after modeling. The contents of glucose and glycosylated albumin in serum were determined by biochemical method. The histopathological morphology and liver glycogen content were observed by HE and PAS staining. The expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylated (p)-PI3K (p-PI3K), protein kinase B (Akt), p-Akt, glycogen synthase kinase-3β (GSK3β) and p-GSK3β proteins in liver were determined by Western blot., Results: Compared with the control group, the weight increment and sugar-water preference index decreased ( P <0.01), the immobile swimming time was prolonged ( P <0.01), the glucose and glycosylated albumin contents in serum increased ( P <0.05), the expression of p-Akt protein and the ratio of p-Akt/Akt in liver tissues decreased ( P <0.001), the expression of p-GSK3β protein and the ratio of p-GSK3β/GSK3β in liver tissues increased ( P <0.01, P <0.001) in the model group. Compared with the model group, the weight increment and sugar-water preference index increased ( P <0.05), the immobile swimming time was shortened ( P <0.05), the glucose and glycosylated albumin contents in serum decreased ( P <0.05), the expressions of p-PI3K and p-Akt proteins and the ratio of p-PI3K/PI3K and p-Akt/Akt in liver tissues increased ( P <0.05), the expression of p-GSK3β protein and the ratio of p-GSK3β/GSK3β in liver tissues decreased ( P <0.01) in the EA group. HE staining showed that the structure of the hepatic lobule was intact, no obvious inflammatory cell infiltration or fibrosis was observed in the lobule and interstitium, and no abnormalities were observed in the small bile duct, portal vein and artery in the portal area. PAS staining showed that the intensity of staining from the center of the hepatic lobule to the periphery of the hepatic lobule was gradually enhanced in the blank group, that is, the glycogen-rich granules in the hepatic cells were gradually increased; most of the hepatocytes were light colored and glycogen was lost significantly in the model group; while the intensity of hepatocyte staining increased, the staining intensity of the perilobular zone was weaker than that in the blank group, and the glycogen particles partially recovered in the EA group., Conclusion: EA intervention can regulate glucose metabolism disorder in chronic restraint induced depressed rats through PI3K/Akt/GSK3β signaling pathway.

Objective: To evaluate the clinical effect of acupuncture for the improvements in various dyspeptic symptoms of postprandial distress syndrome., Methods: The secondary analysis on the data of a multi-center randomized controlled trial (RCT) was conducted. 278 patients with postprandial distress syndrome were randomized into an acupuncture group (138 cases) and a sham-acupuncture group (140 cases). In the acupuncture group, acupuncture was applied to Baihui (GV 20), Danzhong (CV 17), Zhongwan (CV 12), Qihai (CV 6), Neiguan (PC 6), Zusanli (ST 36), etc. In the sham-acupuncture group, 6 sites, neither located on meridians nor belonged to meridian acupoints, were selected and punctured shallowly. The duration of treatment was 20 min each time, 3 times a week, for 4 weeks totally in the two groups. The follow-up visit lasted for 12 weeks. The scores of dyspeptic symptoms were compared between the two groups before treatment, during treatment (in week 1, 2, 3 and 4) and during follow-up (in week 8, 12 and 16) separately., Results: Besides the scores of early satiety and vomiting in the sham-acupuncture group in week 1, the scores of the other dyspepsia symptoms during treatment and follow-up were all reduced in the two groups as compared with those before treatment ( P <0.05). In week 2 and 3, the score of early satiety in the acupuncture group was lower than that in the sham-acupuncture group ( P <0.05). In week 3, the scores of postprandial fullness, upper abdominal bloating and belching in the acupuncture group were lower than those in the sham-acupuncture group ( P <0.05). In week 4 and during follow-up, the scores of postprandial fullness, early satiety, upper abdominal bloating and belching in the acupuncture group were all lower than those in the sham-acupuncture group ( P <0.05)., Conclusion: Acupuncture remarkably relieves postprandial fullness, early satiety, upper abdominal bloating and belching in patients with postprandial distress syndrome.

Objective: To verify the clinical effect of acupuncture on knee osteoarthritis (KOA)., Methods: Forty-two patients with KOA were randomly divided into an acupuncture group (21 cases, 1 case dropped off) and a sham acupuncture group (21 cases, 1 case dropped off). The patients in the acupuncture group were treated with routine acupuncture at 5-6 local acupoints [Dubi (ST 35), Neixiyan (EX-LE 4), Heding (EX-LE 2), Yinlingquan (SP 9), Xuehai (SP 10), Zusanli (ST 36), etc.] and 3-4 distal acupoints [Fengshi (GB 31), Waiqiu (GB 36), Xuanzhong (GB 39), Zulinqi (GB 41), etc.]. The patients in the sham acupuncture group were treated with shallow needling technique at non-acupoint. The needles were retained for 30 min in both groups. All the treatment was given three times a week for 8 weeks. Knee injury and osteoarthritis outcome score (KOOS) were recorded before and after treatment and 18-week follow-up., Results: Compared before treatment, the scores of 5 dimensions of KOOS [pain, symptoms (except pain), daily activities, sports and entertainment, and quality of life] were increased after treatment and during follow-up in the two groups ( P <0.05), and the scores of pain and daily activities in the acupuncture group were higher than those in the sham acupuncture group ( P <0.05)., Conclusion: Acupuncture can reduce the pain symptoms and improve daily activities in patients with KOA.

Objective: To observe the effect of the small needle knife through the Zusanli(ST 36) on behavior and hippocampal expression of NLRP3 and IL-1β in myalgia comorbid depressed rats., Methods: The rat models of myalgia comorbid depression were prepared by intraperitoneal injection of acute reserpine. Twenty-four SD male rats were randomly divided into control group, model group, small needle knife group and amitriptyline group, 6 rats in each group. The open field behavior and mechanical pain threshold of each group were detected. The thermal pain threshold was detected by intelligent hot plate test. The expression of NLRP3 and IL-1β in hippocampus of rats was detected by Western blotting., Results: Compared with the model group, the mechanical pain threshold of the foot was significantly improved in the small needle knife group ( P <0.01). Compared with the amitriptyline group, the small needle knife stimulation of Zusanli(ST 36) can significantly increase the thermal pain threshold in rats( P <0.05); in the comparison of the horizontal movement distance and the number of crossings in the open field behavioral rats, the total distance of the open field activity of the small needle knife group was significantly increased( P <0.05). Compared with the model group, the number of crossings in the small needle knife group had no statistically significant difference ( P >0.05). The expressions of NLRP3 and IL-1β in the hippocampus of the model group were significantly increased( P <0.05), and the expression of IL-1β in the small needle knife group was significantly decreased ( P <0.05). The stimulation of small needle knife at Zusanli(ST 36) could inhibit the expression of NLRP3 in hippocampus of rats. However, there was no statistically significant difference compared with the model group ( P >0.05)., Conclusions: Small needle knife can improve the pathological state of myalgia comorbid depression caused by reserpine in rats. The mechanism may be related to the inhibition of NLRP3 inflammasome and IL-1β expression in central hippocampus., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2019 by the China Journal of Orthopaedics and Traumatology Press.)

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder that has been ranked as the 4th leading cause of disability worldwide. Past clinical and laboratory evidence has confirmed that abnormalities of the hypothalamic-pituitary-adrenal (HPA)-axis are involved in MDD development. In this study, we took advantage of corticosterone treatment of PC12 cells as a model to identify genes regulated by HPA-axis hormones. Next-generation RNA-Seq technology was utilized to explore genome-wide differentially expressed gene profiles between control and corticosterone treated PC12 cells. 1,274 genes with at least two-fold expression level change were identified. Gene ontology analysis showed that the top enriched biological processes included response to glucocorticoid signaling, apoptosis, cell division/DNA replication, and neuron projection/axon guidance, highly consistent with phenotypes of PC12 cells treated with corticosterone. Taken together, RNA-seq data is reliable and comprehensive, thus providing a valuable resource for understanding underlying mechanisms of glucocorticoid-induced neuron malfunction., Competing Interests: None., (IJCEP Copyright © 2018.)

The aim of the present study was to determine the protection of allogeneic bone marrow mesenchymal stem cells (BMSCs) on an ischaemia/reperfusion (I/R)‑induced acute kidney injury (AKI) rat model and to investigate the underlying mechanisms. The BMSCs were isolated and cultured from adult Sprague‑Dawley (SD) rats and the I/R‑induced AKI model was established by bilateral clamping of renal pedicles for 60 min. Following successfully establishing the AKI model, 1x106 BMSCs were administered by intrarenal injection. All animals were randomly divided into four groups (n=10 in each): 1 (sham control), 2 (I/R), 3 (I/R+culture medium) and 4 (I/R+BMSCs). Serum levels of creatinine (Cr) and blood urea nitrogen (BUN) were measured in all four groups at 24 and 72 h. Three days post‑surgery, the level of inflammatory factors, including interleukin‑6 (IL‑6), tumour necrosis factor‑α (TNF‑α) and vascular endothelial growth factor (VEGF) in the kidney was analysed by quantitative polymerase chain reaction. Three days following surgery, mRNA expression levels of IL‑6 and TNF‑α were significantly lower, however, the expression level of VEGF was significantly higher in group 4 compared with groups 2 and 3 (P<0.05). By contrast, the immunofluorescence results showed that the injected BMSCs differentiated into vascular endothelial cells. In conclusion, the present study identified that intrarenal administration of BMSCs improved I/R‑induced AKI through the anti‑inflammatory effect and a paracrine mechanism and therefore, may be hypothesised for the use in clinical trials.

Objective: To investigate chronic hepatitis B (CHB) patients infected with the antiviral-resistant rtA181 mutation hepatitis B virus (HBV) who have been unresponsive to general therapy to determine the effects of individualized therapy., Methods: Fifty-four patients with confirmed rtA181 mutation and who experienced virological breakthrough during nucleus(t)ide analogue (NUC) treatment were enrolled in this prospective cohort study. Their serum levels of HBV DNA, hepatitis B surface antigen (HBsAg), and alanine transaminase (ALT) were tested. Each patient was genotyped by pyrosequencing for 10 mutation sites in the HBV P gene that have been previously correlated to NUC efficacy. Each patient's antiviral therapy and response history was analyzed in regard to their particular mutation pattern. The serological index was determined for carriers of the rtA181T/V mutation. The secondary individualized treatment included adding/switching to entecavir (ETV; group A) or adding telbivudine (LdT; group B) upon confirmation of drug resistance. Effect of individualized treatment was analyzed by T test and Mann-Whitney U test for continuous variables with normal or skewed distributions, respectively. Categorical variables were analyzed by the Chi-squared ( x² ) or Fisher's exact tests., Results: The rtA181T mutation was found in 64.8% (35/54) of patients with rtA181 mutation HBV. The most frequent previously administered medications were adefovir dipivoxil (ADV) and lamivudine (LAM). Multi-site rtA181 mutations occurred more frequently in the patients with multi-NUCs history (57.6%) than in those with single NUCs history (28.6%) (x²=4.342, P less than 0.05). Serum HBV DNA level at virological breakthrough was lower than that at baseline of the first antiviral treatment (5.66+/-1.01 vs. 6.75+/-0.81 log10 copies/ml; t=-4.210, P less than 0.01). The serum HBsAg level was higher in carriers of the rtA181T mutation than in carriers of the rtA181V mutation (3.80+/-0.45 vs. 3.46+/-0.60 log10 IU/ml; t=2.109, P less than 0.05). In patients with serum HBV DNA more than or equal to 6 log10 copies/ml at viral breakthrough, 100% (8/8) of patients in the secondary treatment group A and 75% (3/4) patients in the secondary treatment group B exhibited virological response at week 24 after intervention. Undetectable HBV DNA was achieved in three patients of group A and one patient of group B. In patients with serum HBV DNA less than 6 log10 copies/ml at viral breakthrough, 100% (14/14) of patients in group A and 71.4% (5/7) of patients in group B exhibited biological response at week 24 after intervention. The serum HBV DNA level decreased to undetectable levels in 12 patients of group A and four patients of group B., Conclusion: The rtA181 mutation pattern correlates with previous antiviral therapy response. In addition, multi-site rtA181 mutations occur more frequently in patients with a history of multi-NUCs therapy. Adding or switching rtA181 carriers to ETV produces a more robust virological suppression than adding LdT.

Objective: To investigate the association of thrombin activatable fibrinolysis inhibitor (TAFI) and its encoding gene CPB2 polymorphism in patients with coronary heart disease (CHD)., Methods: The CPB2 gene polymorphisms of Thr325Ile and Thr147Ala were analyzed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in patients of acute myocardial infarction (n=100), acute angina pectoris (n=110) and a control group (n=190). The antigen (Ag) and activity (Act) of the TAFI were determined by sandwich enzyme link immunosorbent assay specific for human TAFI and chromogenic assay for activated human TAFI in plasma, respectively. The relationship between Thr325Ile and Thr147Ala gene polymorphism and TAFI Ag and Act were also analyzed., Results: Plasma TAFI Act and TAFI Ag in acute myocardial infarction group and acute angina pectoris group (CHD patients group) were both significantly higher than those of the control group. The genotype frequencies of Thr325Ile (C1040T) and Thr147Ala (G505A) were as the following: C1040C (Thr325Thr) 67 (31.9%) and 64 (33.6%); C1040T (Thr325Ile) 109 (51.9%) and 92 (48.4%); T1040T (Ile325Ile) 34 (16.2%) and 34(17.8%); G505G (Ala147 Ala) 75 (35.7%) and 72 (37.8%); G505A(Thr147Ala) 112 (53.3%) and 96 (50.5%); A505A(Thr147Thr)23 (10.9%) and 22 (11.7%), in the CHD patients and control respectively. Chi-square analysis showed no significant difference in the Thr325Ile and Thr147Ala polymorphism distributions (P > 0.05). In addition, at the 325 position, the TAFI antigen of the Thr325Thr was higher than that of the other genotypes (Thr325Ile and Ile325Ile, P < 0.05). There was no statistical significance between the TAFI antigen of the Thr325Ile and Ile325Ile (P > 0.05). No significant correlation was found between the TAFI Act and the Thr325Ile polymorphism. At the position 147, significant correlation between the polymorphism of the Thr147Ala and TAFI Ag and Act was not found., Conclusion: TAFI plays an important role in anti-fibrinolysis. It might be a risk factor for acute myocardial infarction and acute angina pectoris. The Thr325Ile polymorphism had obvious effect on TAFI antigen levels, but the Thr325Ile and Thr147Ala polymorphism had no association with coronary heart disease.

Objective: By means of the detection of the numbers of CD34(+) cells and eosinophils (EOS), and the level of IL-5 in peripheral blood from normal controls and patients with allergic rhinitis pre- or post-treatment, the role of EOS-stem cells paths for treatment effect in allergic rhinitis (AR) was studied so as to find the convenient and quick indicators which could be used to evaluate the clinical therapeutic effect and adjust the methods of the hormone therapy., Methods: There were 2 groups. (1) experimental group: 44 patients, including 24 males and 20 females with a age range of 7 to 68 years old. The patients received the treatment of fluticasone spurt for four weeks. (2) CONTROL GROUP: 30 cases, from normal health examination. The EOS numbers, CD4(+) cell numbers and the IL-5 level were examined in control group as well as before and after therapy in experimental group., Results: The IL-5 level and CD numbers before therapy in experimental group were (88.25 +/- 33.47) ng/L, (9.24 +/- 2.15)/10(5), significantly higher than that after therapy and experimental group which were (44.34 +/- 16.32) ng/L, (6.31 +/- 1.83)/10(5) and (31.24 +/- 8.43) ng/L, (3.47 +/- 1.32)/10(5) respectively. The IL-5 level was positively correlated with the CD34(+) number pre-and post treatment in experimental group (r = 0.64, P <0.01; (r = 0.61, P <0.01). The EOS number was positively correlated with the level of IL-5 (r = 0.64, P <0.01)., Conclusions: IL-5 and CD34(+) cells can be regarded as indicators to evaluate the therapeutic effect. The EOS, CD34(+) cells and the level of IL-5 in the peripheral blood are correlated with the pathogenesis of AR, suggesting that there is a related path between the local nasal tissue of AR patients and the marrow.

Objective: The purpose of this study was to observe the association between chronic glomerulonephritis (CGN) and human leukocyte antigen (HLA) on DNA level in order to identify susceptible and protective genes and to further explain the possible pathogenesis of CGN., Methods: 1073 renal transplantation patients with Han ethnicity were included in this study. All patients were recruited from three provincial Hospitals during the past ten years. The control group contained 7418 healthy Han volunteer donors from Shandong Hematopoietic Stem Cell Data Bank of China. We collected data about the polymorphism of HLA-I , II and DRB1. Gene frequency (GF), relative risk (RR) and correlation test were analyzed using statistical software. Some patients carrying the susceptible genes were followed up for 1,3 and 5 years, and compared their survival rate respectively., Results: The frequency of HLA-A23, A25,B15, B40, B53 and DRB1 * 18 alleles increased significantly in CGN patients than in controls, showing that they might be the suspicious susceptibility genes of CGN. After the follow-up periods, the prognosis of patients with the susceptible genes was worse than the controls. The frequency of haplotypes of A23-B44-DRB1 * 18, A25-B15-DRB1 * 07, A3-B70-DRB1 * 11, A68-B13-DRB1 * 04, A11-B10-DRB1 * 12 increased significantly in CGN patients than in controls. There were 8 lower frequencies alleles (including A20, A22, A35, A36, A38, B21, B73 and B78) in CGN patients that were not found in the control group. The frequencies of the HLA-A32, A33, B50, B58, B60, B71, DRB1 * 16 alleles decreased significantly in CGN patients than in controls, showing that they might be the protective genes of CGN., Conclusion: Our data showed that there might be corresponding susceptibility and protective genes of CGN in Han population, in Shandong. There was significant association between the five common haplotype and CGN in Shandong population. However, the prognosis of the patients with the susceptibility genes was worse than the controls.

Objective: To investigate the factors affecting the survival and to predict the survival time of glioma., Methods: Graph method was applied to fit the type of probability distribution of patients' postoperative survival time. As one suitable model, Weibull regression model tested by residual analysis was used to identify prognostic factors for postoperative survival and to predict patients' post-operative survival time., Results: In multivariate analysis of Weibull regression model, following characteristics showed significant influence on postoperative survival time including: sex, age, epilepsy, type of glioma, density of glioma, type of surgery, times of surgery and mode of postoperative therapy. According to predictive value, patients were clustered into three groups. The survival probability of one year for the first group was less than 50% and that of five years for the second group about 50%, for the third group around 80%., Conclusion: Sex, age, epilepsy, type of glioma, density of glioma, type of surgery, times of surgery and mode of postoperative therapy were important risk factors and Weibull regression model might help to predict patients' postoperative survival time.