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Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, affecting about 1/4 th of the global population and causing a huge global economic burden. To date, no drugs have been approved for the treatment of NAFLD, making the correction of unhealthy lifestyles the principle method of treatment. Identifying patients with poor adherence to lifestyle correction and attempting to improve their adherence are therefore very important., Aim: To develop and validate a scale that can rapidly assess the adherence of patients with NAFLD to lifestyle interventions., Methods: The Exercise and Diet Adherence Scale (EDAS) was designed based on compilation using the Delphi method, and its reliability was subsequently evaluated. Demographic and laboratory indicators were measured, and patients completed the EDAS questionnaire at baseline and after 6 months. The efficacy of the EDAS was evaluated in the initial cohort. Subsequently, the efficacy of the EDAS was internally verified in a validation cohort., Results: The EDAS consisted of 33 items in six dimensions, with a total of 165 points. Total EDAS score correlated significantly with daily number of exercise and daily reduction in calorie intake ( P < 0.05 each), but not with overall weight loss. A total score of 116 was excellent in predicting adherence to daily reduction in calorie intake (> 500 kacl/d), (sensitivity/specificity was 100.0%/75.8%), while patients score below 97 could nearly rule out the possibility of daily exercise (sensitivity/specificity was 89.5%/44.4%). Total EDAS scores ≥ 116, 97-115, and < 97 points were indicative of good, average, and poor adherence, respectively, to diet and exercise recommendations., Conclusion: The EDAS can reliably assess the adherence of patients with NAFLD to lifestyle interventions and have clinical application in this population., Competing Interests: Conflict-of-interest statement: The authors of this manuscript have no conflicts of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Direct-acting antivirals (DAAs) revolutionized the treatment of chronic hepatitis C virus (HCV)-associated disease achieving high rates of sustained virological response (SVR). However, whether DAAs can reduce the occurrence of hepatocellular carcinoma (HCC) in patients with HCV-associated cirrhosis who are at high risk have not been concluded., Aim: To investigate the effect of DAAs on the occurrence of HCC in patients with HCV-associated cirrhosis after achieving SVR., Methods: Of 427 inpatients with HCV-associated cirrhosis were enrolled in Tianjin Second People's Hospital from January 2014 to April 2020. 118 patients weren't received antiviral treatment with any reasons named non-antiviral treatment group, and 236 patients obtained from the 309 DAAs treatment patients according to the propensity score matching named DAAs treatment group. Demographic information and laboratory data were collected from baseline and the following up. Kaplan-Meier curve and Log-Rank test were used to compare the incidence and cumulative incidence of HCC between the two groups. Cox proportional risk regression was used to re-evaluate the risk factors for HCC., Results: HCC incidence was 4.68/100PY (95%CI, 3.09-6.81) in the DAAs treatment group, while it was 3.00/100PY (95%CI, 1.50-5.37) in the non-antiviral treatment group, and the relative risk was 1.82 (95%CI, 0.93-3.53, P > 0.05). The incidence of HCC at 12, 24, 36 and 48 months was 3.39%, 6.36%, 8.47% and 10.17% in the DAAs treatment group, and it was 0%, 0%, 3.39% and 9.32% in the non-antiviral treatment group, respectively. Age > 58 [hazard ratio (HR) = 1.089; 95%CI, 1.033-1.147; P = 0.002] and liver stiffness measurement > 27.85 kPa (HR = 1.043; 95%CI, 1.022-1.065; P = 0.000) were risk factors for HCC in all patients ( n = 427), and DAAs treatment didn't show protective efficacy., Conclusion: DAAs treatment seems failed to reduce the incidence of HCC occurrence in HCV-associated cirrhosis in 48 months, and even increased the incidence of HCC in 36 months., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Chronic hepatitis C is a kind of viral hepatitis caused by hepatitis C virus infection, which can further progress to cirrhosis, liver failure, hepatocellular carcinoma, and even death. Presently, there is no preventive vaccine yet. Therefore, preventing infection and safe and effective drug treatment are currently the most effective strategies for dealing with hepatitis C virus infection. Since 2014, the clinical application of direct-acting antiviral drugs has brought revolutionary changes to the treatment of chronic hepatitis C. Direct-acting antiviral drugs have an excellent hepatitis C virus clearance effect, are well tolerated, have a good safety profile, and can significantly improve liver function, metabolic disorders, immune dysfunction, etc. However, some studies have pointed out that even if the hepatitis C virus is cleared during the treatment of chronic hepatitis C-related cirrhosis with direct-acting antiviral drugs, a considerable proportion of patients still have severe liver failure, hepatocellular carcinoma, and even liver disease-related death, so there are still some problems in the treatment of chronic hepatitis C- related cirrhosis with direct-acting antiviral drugs that need to be further explored. This article reviews the research progress of direct-acting antiviral drugs so as to provide meaningful references for the treatment of patients with chronic hepatitis C-related cirrhosis.

Objective: To investigate the clinical and pathological characteristics of chronic hepatitis B (CHB) with metabolic dysfunction-associated fatty liver disease (MAFLD), as well as associations with advanced fibrosis. Methods: CHB patients who underwent liver biopsy at Tianjin Second People's Hospital from June 2016 to September 2019 were included in the study. The patients were divided into two groups based on whether they had concomitant MAFLD; a CHB group and a MAFLD-CHB group. t -tests and Chi-square tests were used to compare pathological characteristics and basic features in the two groups. Logistic regression analysis was used to analyze factors associated with advanced fibrosis. Results: The CHB group included 110 patients, and the MAFLD-CHB group included 272 patients. There were significant differences in smoking, alcohol consumption, hypertension incidence, body metabolic index, alanine aminotransferase, gamma-glutamyl transferase (GGT), high-density lipoprotein, low-density lipoprotein, fasting plasma glucose, and platelets (PLT) between the two groups (all P <0.05). The MAFLD-CHB group had a higher incidence of advanced fibrosis than the CHB group ( P <0.05). In logistic regression analysis MAFLD [odds ratio ( OR )=2.204, 95% confidence interval ( CI ) 1.018-4.774, P =0.045], GGT ( OR= 1.008, 95% CI 1.002-1.013, P= 0.005), and PLT ( OR =0.995, 95% CI 0.991-0.999, P= 0.019) were associated with advanced fibrosis (all P <0.05). In the MAFLD-CHB group type 2 diabetes ( OR =3.281, 95% CI 1.375-7.832, P =0.007), GGT ( OR =1.011, 95% CI 1.003-1.018, P =0.005), and PLT ( OR =0.993, 95% CI 0.988-0.998, P =0.004) were associated with advanced fibrosis ( P< 0.05). Conclusion: Patients with MAFLD-CHB are more likely to develop advanced fibrosis than patients with CHB alone. In the MAFLD-CHB group type 2 diabetes mellitus was associated with advanced fibrosis. It is important to strictly control relevant risk factors in MAFLD-CHB patients, especially in patients with type 2 diabetes.

Non-alcoholic fatty liver disease (NAFLD) is not a benign condition, especially in patients with non-alcoholic steatohepatitis (NASH) combined with liver fibrosis grades F2-4, who have a higher risk of liver-related events and mortality. Thus, this population is considered "at-risk" for developing NASH. China has a large NAFLD patient population, so how to screen for those with liver fibrosis is an important socio-economic concern. At the moment, serological models, liver stiffness detection based on vibration-controlled transient elastography, and magnetic resonance elastography (MRE) are the only non-invasive tests (NITs) for liver fibrosis. The prevention and treatment guidelines for NAFLD at home and abroad are reviewed here, based on the research progress of NITs in recent years, so as to suggest screening, evaluation pathways, and management for liver fibrosis in patients with NAFLD.

Background and Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV)., Methods: Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment., Results: A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), p =0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), p =0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, p =0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, p =0.031)., Conclusions: ETV combined with ALHX increased liver fibrosis regression in CHB patients., Competing Interests: The authors have no conflict of interests related to this publication., (© 2023 Authors.)

Solid-state lithium batteries are promising and safe energy storage devices for mobile electronics and electric vehicles. In this work, we report a facile in situ polymerization of 1,3-dioxolane electrolytes to fabricate integrated solid-state lithium batteries. The in situ polymerization and formation of solid-state dioxolane electrolytes on interconnected carbon nanotubes (CNTs) and active materials is the key to realizing a high-performance battery with excellent interfacial contact among CNTs, active materials and electrolytes. Therefore, the electrodes could be tightly integrated into batteries through the CNTs and electrolyte. Electrons/ions enable full access to active materials in the whole electrode. Electrodes with a low resistance of 4.5 Ω □ -1 and high lithium-ion diffusion efficiency of 2.5×10 -11  cm 2  s -1 can significantly improve the electrochemical kinetics. Subsequently, the batteries demonstrated high energy density, amazing charge/discharge rate and long cycle life., (© 2023 Wiley-VCH GmbH.)

Objective: To observe the effect of acupuncture at Weizhong (BL 40) with deqi on bladder urination function., Methods: A total of 60 healthy subjects were randomized into an observation group and a control group, 30 subjects in each group. Under the guidance of ultrasound, acupuncture was applied Weizhong (BL 40) on both sides. In the observation group, the needling depth was reached to the tibial nerve, and lifting-thrusting twirling method was used to induce deqi . In the control group, the needling depth was reached to the superficial fascia, and no manipulation was operated to induce deqi . The needles were retained for 10 min and acupuncture was given once in both groups. The bilateral ureteral ejection frequency and volume of the bladder were observed by ultrasound before and after acupuncture, and the score of clinical evaluation scale of deqi sensation was observed in both groups., Results: After acupuncture, the frequency of bilateral ureteral ejection in the observation group and the bladder volume in the two groups were increased compared before acupuncture ( P <0.05), and the frequency of bilateral ureteral ejection, bladder volume and score of clinical evaluation scale of deqi sensation in the observation group were higher than those in the control group ( P <0.05, P <0.01)., Conclusion: Acupuncture at Weizhong (BL 40) with deqi improves the bladder urination function. Ultrasound visualization improves the standardization and safety of acupuncture, intuitively evaluates the acupuncture effect, and provides an objective basis for the correlation between meridian points specificity and zang - fu organs.

Objective: To observe the clinical efficacy and safety of Jianpi Peiyuan acupoint thread embedding therapy on perimenopausal obesity (PMO)., Methods: Ninety-six patients of PMO were randomly divided into an observation group (48 cases) and a control group (48 cases). The control group received health education and lifestyle intervention. On the basis of the treatment in the control group, the observation group was treated with acupoint thread embedding at the main acupoints of Shangwan (CV 13), Zhongwan (CV 12), Xiawan (CV 10), Yinlingquan (SP 9) and Fenglong (ST 40), etc. as well as the supplementary acupoints in accordance with the syndrome differentiation, once every 2 weeks for 8 weeks (4 times in total). The indexes of obesity (body mass index [BMI], waist circumference, hip circumference and body mass), modified Kupperman score, insomnia severity index (ISI) score, self-rating anxiety scale (SAS) score, and self-rating depression scale (SDS) score of the two groups were observed before and after treatment, and the safety was evaluated., Results: After treatment, BMI, waist circumference, hip circumference and body mass in the two groups were lower than before treatment ( P <0.05), and those in the observation group were lower than the control group ( P <0.05). After treatment, Kupperman, ISI and SAS scores in the observation group were lower than before treatment ( P <0.05), and ISI score in the control group was lower than before treatment ( P <0.05). Kupperman, ISI and SAS scores in the observation group were lower than those in the control group ( P <0.05). There was no significant difference in SDS between the two groups or within groups ( P >0.05). No serious adverse reactions occurred during the experiment., Conclusion: Jianpi Peiyuan acupoint thread embedding therapy can reduce the degree of obesity in PMO patients, and improve patients' the perimenopausal symptoms, insomnia and anxiety, with good safety.

The operation standardization, quantitative standard and safety of acupuncture treatment are important links in the development of acupuncture modernization. In recent years, with the continuous development of ultrasonic imaging technology, ultrasonic medicine has the characteristics of visualization, quantitative analysis and real-time dynamics, which could play a unique role in acupuncture treatment. In this paper, the research progress of the combined application of ultrasonic medicine and acupuncture treatment is described from three aspects: ultrasound guidance helping to standardize acupuncture operation, ultrasound guidance helping to improve and evaluate the clinical efficacy of acupuncture, and ultrasound guidance helping to improve the safety of acupuncture, aiming to providing new ideas for the application of modern medicine in traditional medicine.

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic disorders. This study aimed to explore the role of metabolic disorders in screening advanced fibrosis in NAFLD patients., Methods: A total of 246 histologically-proven NAFLD patients were enrolled across 14 centers. We compared the severity of fibrosis in patients with different components of metabolic disorders. Based on standard noninvasive tests and metabolic disorders, we developed new algorithms to identify advanced fibrosis., Results: Metabolic syndrome (MetS) was frequent in NAFLD patients (133/246, 54%). Patients with MetS had a higher proportion of significant fibrosis ( p =0.014) and higher LSM values (9.2 kPa, vs. 7.4 kPa, p =0.002) than those without MetS. Patients with more metabolic disorders had higher fibrosis stages ( p =0.017). Reduced high-density lipoprotein cholesterol (odds ratio [OR]: 2.241, 95% confidence interval [CI]: 1.004-5.002, p =0.049) and raised fasting glucose (OR: 4.500, 95% CI: 2.083-9.725, p <0.001) were significantly associated with advanced fibrosis. Using these two metabolic disorders as a screening tool, a sensitivity, specificity and accuracy of 92%, 81% and 83% was achieved, respectively. With the new algorithms combining metabolic disorders with noninvasive measurements, the number of patients requiring liver biopsy was reduced, especially in combination with the Fibrosis-4 score and metabolic disorders (36% to 17%, p <0.001). In addition, this stepwise algorithm could achieve a high accuracy (85%) and high negative predictive value (93%)., Conclusions: Metabolic disorders should be taken into consideration in the diagnosis of advanced fibrosis. With further validation and investigation, new algorithms could be recommended in primary care units to spare patients from unnecessary referral and liver biopsies., Competing Interests: BP is an employee of Sanofi. None of the other authors have any potential or real conflicts of interest to declare. The authors did not receive any payment for authoring this publication., (© 2021 Authors.)

Background: This study aimed to assess the association between metabolic syndrome (MetS) and severity of nonalcoholic fatty liver disease (NAFLD), and to discuss the pathological relevance of the diagnostic criteria in metabolic (dysfunction) associated fatty liver disease (MAFLD)., Methods: This was a multicenter, cross-sectional study. Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China. Anthropometric and metabolic parameters were collected to assess the pathological relevance., Results: Of 246 enrolled patients with NAFLD, 150 (61.0%) had the comorbidity of MetS. With the increase of metabolic components, the proportions of nonalcoholic steatohepatitis (NASH) and significant fibrosis were notably increased. The comorbid three metabolic components significantly increased the proportion of NASH, and further increase of metabolic components did not increase the proportion of NASH. However, the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis. Among the 246 patients, 239 (97.2%) met the diagnostic criteria of MAFLD. Although non-MAFLD patients had less NASH, they present with similar proportion of significant fibrosis and cirrhosis. In the diagnostic criteria of MAFLD, BMI ≥ 23 kg/m 2 was related to NASH (Mantel-Haenszel Common Estimate OR: 2.975; 95% CI: 1.037-8.538; P = 0.043), and T2DM was related to significant fibrosis (Mantel-Haenszel Common Estimate OR: 2.531; 95% CI: 1.388-4.613; P = 0.002). The homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.5 was the most significant factor for NASH (OR: 4.100; 95% CI: 1.772-9.487; P = 0.001) and significant factor for liver fibrosis (OR: 2.947; 95% CI: 1.398-6.210; P = 0.004) after the adjustments of the BMI and diabetes., Conclusions: Metabolic dysregulations are important risk factors in NAFLD progression. The insulin resistance status may play a predominant role in the progression in MAFLD patients., (Copyright © 2021. Published by Elsevier B.V.)

Objective: Hepatic steatosis has a high incidence in human immunodeficiency virus (HIV) infected people, and there is no effective non-invasive method to evaluate it. This study aims to evaluate the diagnostic value of non-invasive models for hepatic steatosis in this population. Methods: A single-center retrospective study was applied to evaluate: (1) the diagnostic value of controlled attenuation parameters (CAP) and hepatic steatosis index (HSI) in HIV-infected patients with hepatic steatosis; (2) the ability of the non-invasive model to distinguish hepatic steatosis caused by abnormal glucose and lipid metabolism and hepatic steatosis caused by hepatitis C virus infection; (3) the diagnostic value of the above models for hepatic steatosis in patients co-infected with HIV/hepatitis C virus. The diagnostic value of the model was analyzed and evaluated by diagnostic test and receiver operating characteristic curve. Results: (1) the diagnostic value of hepatic steatosis for HIV-infected patients: when CAP = 232 dB/m, the sensitivity and specificity were 89.2% and 78.1%, respectively; when HSI = 34, the sensitivity and specificity were 79.1% and 83.2%, respectively. (2) The ability to identify the causes of hepatic steatosis in HIV-infected patients: when CAP = 258dB/m, the sensitivity and specificity were 81.5% and 88.2%, respectively; when HSI = 37, the sensitivity and specificity were 70.7% and 92.4%, respectively. (3) The diagnostic value of hepatic steatosis in patients co-infected with HIV/hepatitis C virus: when CAP = 241 dB/m, the sensitivity and specificity were 80% and 71.4%, respectively; when HSI = 32, the sensitivity and specificity were 73% and 68.9%, respectively. Conclusion: CAP and HSI have superior diagnostic value for hepatic steatosis in patients infected with HIV.

Liver fibrosis, liver cirrhosis and hepatocellular carcinoma caused by chronic hepatitis B are still the main diseases that seriously affect the health of Chinese population. Notably, even if serum HBV-DNA cannot be detected after treatment, many patients will still develop liver disease. Therefore, in addition to the quantitative analysis of HBV-DNA and HBsAg, other new serological markers should be sought to facilitate the selection of CHB antiviral drugs and methods, monitoring efficacy and follow-up, efficacy prediction, and the risks of viral rebound after drug withdrawal. This article focuses on three new serological markers, namely HBcrAg, HBV-RNA and anti-HBc, with a view to applying them in clinical practice.

Objective: To investigate the application value of reactive oxygen species (ROS) and adiponectin (ADPN) in the judgment of liver inflammation in chronic hepatitis B virus infection combined with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 159 cases with NAFLD (21 cases), chronic hepatitis B virus infection (57 cases), and chronic hepatitis B virus infection combined with NAFLD (81 cases) were collected between June 2016 to December 2018, and the visited patients diagnosis were confirmed by histopathological examination of the liver. ROS and ADPN level retained in serum was determined by enzyme-linked immunosorbent assay. Histopathological examination of liver tissue was used as the gold standard to discuss the diagnostic value of the serum in patients with chronic hepatitis B virus infection combined with NAFLD for the occurrence of nonalcoholic steatohepatitis. One-way analysis of variance was used for the comparison among multiple groups, and LSD-t test was used for pairwise comparison between groups. Measurement data for non-normal distributions were expressed as M (P25, P75). Comparisons between groups were performed using the Mann-Whitney U or Kruskal-Wallis H test. Chi-square test was used to compare the count data between groups. Correlation analysis was performed using Spearman correlation analysis. Histopathological grouping of liver tissue was used as the gold standard, and the area under the receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the regression formula. Results: (1) In patients with chronic hepatitis B virus infection combined with NAFLD, the levels of ROS in the non-hepatic steatosis group and the mild hepatic steatosis group were significantly lower than those in the moderate and severe hepatic steatosis group, while the ADPN level in the non-hepatic steatosis group was significantly higher than liver steatosis group, P < 0.05. (2) The results of correlation analysis showed that ROS was significantly correlated with NAS score, change in the degree of fatty liver and lobular inflammation (all P < 0.05).There was a significant negative correlation between ADPN and the change in the degree of fatty liver ( P < 0.05). (3) Logistic regression analysis results showed that the diagnostic formula for chronic hepatitis B virus infection combined with nonalcoholic steatohepatitis was 0.02 × controlled attenuation index + 0.584 × white blood cells/10(9) + 0.587 × ROS-10.982. The area under receiver operating characteristic curve of the subject was = 0.896. The sensitivity, specificity, positive and negative predictive value were 97.1%, 71.2%, 64.2%, and 97.9%. Conclusion: ADPN and ROS have certain reference value in differentiating the change in the degree of fatty liver and inflammation in chronic hepatitis B virus infection combined with NAFLD and the diagnostic formula has higher application value in the diagnosis and exclusion of chronic hepatitis B virus infection combined with nonalcoholic steatohepatitis.

Presently, the situation of chronic hepatitis B combined with non-alcoholic fatty liver disease is relatively common in our country, and yet the relationship between them has not reached a consensus. The co-existing fatty liver may affect the efficacy of anti-HBV therapy and increase the all-cause mortality rates in patients. Therefore, it is very important to correctly diagnose and evaluate fatty liver changes, inflammation, and fibrosis for active prevention and treatment.

Objective: Lactulose is effective in the treatment and prevention of overt hepatic encephalopathy (OHE), but there are limited data on its use on microbiota in relations to minimal hepatic encephalopathy (MHE) recovery. The present study aimed to assess the efficacy of lactulose in recovery of MHE in aspects of cognitive function, quality of life, and impact on intestinal microbiota., Methods: This multicenter, open-label randomized controlled trial was conducted in 11 teaching hospitals in China. Participants were randomly allocated on a 2:1 basis to receive lactulose (Gp-L) or no therapy as control (Gp-NL) for 60 days. The primary endpoint was the MHE reversal rate. Gut microbiota were compared between MHE patients and healthy volunteers, as well as lactulose-responders and non-responders., Results: A total of 98 cirrhotic patients were included in the study, with 31 patients in the Gp-NL group and 67 patients in the Gp-L group. At day 60, the MHE reversal rate in Gp-L (64.18%) was significantly higher than that in Gp-NL (22.58%) (P = .0002) with a relative risk of 0.46 (95% confidence interval 0.32-0.67). Number needed to treat was 2.4. Further, there was significantly more improvement in physical functioning in Gp-L (4.62 ± 6.16) than in Gp-NL (1.50 ± 5.34) (P = .0212). Proteobacteria was significantly higher in MHE patients compared with healthy volunteers (12.27% vs 4.65%, P < .05). Significant differences were found between lactulose responders and non-responders in Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria., Conclusions: Treatment with lactulose significantly improves MHE recovery rate, and gut microbiota change in MHE patients can modulate the effectiveness of this therapy. Chinese Clinical Trial Register (ChiCTR) (ID: ChiCTR-TRC-12002342)., (© 2019 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Liver stiffness measurement (LSM) by transient elastography is a noninvasive method for the diagnosis of hepatic fibrosis. The impact of hepatic steatosis on LSM remains to be explored., Aim: To determine whether LSM is affected by hepatic steatosis in patients with chronic hepatitis B (CHB)., Methods: Consecutive patients with biopsy-proven CHB were prospectively enrolled. Hepatic steatosis was classified by pathology as none (S0, <5%), mild (S1, 5%-33%), and moderate-severe (S2-3, >33%), and quantitatively by controlled attenuation parameter (CAP) as CAP S0 (≤247 dB/m), CAP S1 (248-267 dB/m) and CAP S2-3 (≥268 dB/m). Liver fibrosis was assessed by METAVIR classification and noninvasively by LSM., Results: The prevalence of non-alcoholic fatty liver disease (n = 223) in CHB patients (n = 593) was 37.6%. Forty-eight belonged to S2-3 and 127 belonged to CAP S2-3. In patients without significant fibrosis (F0-1), the median LSM (kPa) was 7.4 in S2-3 and 7.1 in CAP S2-3, which was significantly higher than that in S0/S1 (P = 0.005) and CAP S0/S1 (P = 0.003). No significant difference was found in significant fibrosis (F2-4). For LSM identifying significant fibrosis (F2-4), the negative predictive value was higher in CHB patients with CAP ≥ 268 compared to those with CAP < 268 (0.81 vs 0.73); the positive predictive value was lower in CAP ≥ 268 than its counterpart (0.65 vs 0.76)., Conclusions: Moderate-severe steatosis increased the LSM value in CHB patients without significant fibrosis. A CAP ≥ 268 did not affect LSM for ruling out, but it slightly affected LSM for ruling in significant fibrosis., Trial Registration: ChiCTR-DDT-13003983., (© 2019 John Wiley & Sons Ltd.)

The aim of the present study was to uncover the role of leukocytic DNA methylation in the evaluation of nonalcoholic fatty liver disease (NAFLD). Patients with biopsy-proven NAFLD (n=35) and normal controls (n=30) were recruited from Chinese Han population. Their DNA methylation in peripheral leukocytes was subjected to genome-wide profiling. The association between differential methylation of CpG sites and NAFLD was further investigated on the basis of histopathological classification, bioinformatics, and pyrosequencing. A panel of 863 differentially methylated CpG sites dominated by global hypomethylation, characterized the NAFLD patients. Hypomethylated CpG sites of Acyl-CoA synthetase long-chain family member 4 (ACSL4) (cg15536552) and carnitine palmitoyltransferase 1C (CPT1C) (cg21604803) associated with the increased risk of NAFLD [cg15536552, odds ratio (OR): 11.44, 95% confidence interval (CI): 1.04‑125.37, P=0.046; cg21604803, OR: 6.57, 95% CI: 1.02-42.15, P=0.047] at cut-off β-values of <3.36 (ACSL4 cg15536552) and <3.54 (CPT1C cg21604803), respectively, after the adjustment of age, sex, body mass index (BMI) and homeostasis model assessment of insulin resistant (HOMA-IR). Their methylation levels also served as biomarkers of NAFLD (ACSL4 cg15536552, AUC: 0.80, 95% CI: 0.62-0.98, P=0.009; CPT1C cg21604803, AUC: 0.78, 95% CI: 0.65-0.91, P=0.001). Pathologically, lowered methylation level (β-values <3.26) of ACSL4 (cg15536552) conferred susceptibility to nonalcoholic steatohepatitis (NASH). Taken together, genome-wide hypomethylation of peripheral leukocytes may differentiate NAFLD patients from normal controls. The leukocytic hypomethylated ACSL4 (cg15536552) was suggested to be a biomarker for the pathological characteristics of NAFLD.

Objective: To compare the clinical value of FibroScan, FIB-4, APRI and AAR diagnosing hepatic fibrosis in chronic hepatitis B virus (HBV) carriers. Methods: A total of 213 patients with chronic HBV carriers diagnosed by clinical and liver biopsy were selected. And according to HBeAg status, 149 patients were divided into HBeAg-positive group and 64 patients were divided into HBeAg-negative group. The liver stiffness measurements (LSM) was measured by FibroScan (FS), FIB-4, APRI and AAR values were calculated using FIB-4, APRI and AAR formula. And all patients underwent liver biopsy in the same period. According to the degree of hepatic fibrosis in Knodell, one decision point was set: significant hepatic fibrosis (S ≥ 2). The Spearman correlation analysis method was used to analyze the correlation of indicators and the area under receiver operator characteristic curves (AUROCs) of LSM, FIB-4, APRI and AAR were drawn according to liver biopsy pathology results as gold standard. The value of LSM, FIB-4, APRI and AAR diagnosing hepatic fibrosis in chronic HBV carriers was retrospectively analyzed. Retrospective analysis of FS, FIB-4, APRI and AAR were divided into 149 HBeAg-positive chronic HBV carriers (HBeAg-positive group) and 64 HBeAg-negative chronic HBV carriers (HBeAg) in 213 patients with chronic HBV carriers and HBeAg Negative group) in the diagnosis of liver fibrosis. Results: The LSM of 213 patients with chronic HBV carriers, 149 patients with HBeAg-positive chronic HBV carriers and 64 patients with HBeAg-negative chronic HBV carriers were significantly correlated with liver fibrosis grade≥ 2 ( P < 0.001). Regardless of HBeAg status, only LSM in the three groups had moderate evaluation efficacy for evaluating significant fibrosis(S≥2), and the positive predictive value was more than 94%, but the diagnostic accuracy was not high, the minimum was 46.31% (HBeAg-positive group), the maximum value of 67.19% (HBeAg-negative group), while the remaining three kinds of serum noninvasive liver fibrosis diagnostic model indicators and diagnostic efficacy are low. The LSM in the three groups showed a significant positive correlation with liver fibrosis grade (S)≥2. Conclusion: LSM is more accurate than FIB-4, APRI and AAR in diagnosing chronic HBV carriers. Dynamically monitoring changes of LSM can earlier understand the progress of liver fibrosis than the three kinds of serology noninvasive diagnostic model and is contributed to the choice of liver biopsy timing.

Background: Liver fibrosis is often accompanied by steatosis, particularly in patients with non-alcoholic fatty liver disease (NAFLD), and its non-invasive characterisation is of utmost importance. Vibration-controlled transient elastography is the non-invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis., Aim: To determine how to use CAP in interpreting liver stiffness measurements., Methods: This is a secondary analysis of data from an individual patient data meta-analysis on CAP. The main exclusion criteria for the current analysis were unknown aetiology, unreliable elastography measurement and data already used for the same research question. Aetiology-specific liver stiffness measurement cut-offs were determined and used to estimate positive and negative predictive values (PPV/NPV) with logistic regression as functions of CAP., Results: Two thousand and fifty eight patients fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV, 51% significant fibrosis ≥ F2). Youden optimised cut-offs were only sufficient for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity-optimised cut-offs, NPV for ruling out significant fibrosis was moderate (70%) and could be improved slightly through consideration of CAP. PPV for significant fibrosis and cirrhosis were 68% and 55% respectively, despite specificity-optimised cut-offs for cirrhosis., Conclusions: Liver stiffness measurement values below aetiology-specific cut-offs are very useful for ruling out cirrhosis, and to a lesser extent for ruling out significant fibrosis. In the case of the latter, Controlled Attenuation Parameter can improve interpretation slightly. Even if cut-offs are very high, liver stiffness measurements are not very reliable for ruling in fibrosis or cirrhosis., (© 2018 John Wiley & Sons Ltd.)

Aims: To evaluate the value of noninvasive tools for diagnosis of hepatic steatosis in patients with chronic hepatitis B (CHB)., Methods: Consecutive treatment-naïve patients with CHB with body mass index less than 30kg/m 2 who underwent liver biopsy, ultrasound and FibroScan ® were enrolled. The diagnostic performance of controlled attenuation parameter (CAP), hepatic steatosis index (HSI) and ultrasound for hepatic steatosis compared with liver biopsy was assessed. The areas under receiver operating characteristics curves (AUROCs) were calculated to determine the diagnostic efficacy, with comparisons using the DeLong test., Results: CAP and HSI accuracies were significantly higher than that of ultrasound to detect patients with biopsy-proven mild steatosis (S1, 65.3%, 56.5%, respectively, vs. 17.7%, χ 2 =46.305, 31.736, both P<0.05)and moderate-severe (S2-3) steatosis (92.3%, 100%, respectively, vs. 53.8%, χ 2 =4.887, 7.800, P=0.037, 0.007, respectively). Both CAP and HSI had lower underestimation rates of steatosis grade than ultrasound (12%, 14.8%, respectively, vs. 29.5%, χ 2 =9.765, 6.452; P<0.05 for both), but they exhibited higher overestimation rates (30.5%, 38.2%, respectively, vs. 12.4%, χ 2 =39.222, 70.986; both P<0.05). The AUROCs of CAP and HSI were 0.780 (95% confidence intervals [CIs] 0.735-0.822) and 0.655 (95%CI 0.604-0.704) for S ≥1, 0.932 (95%CI 0.902-0.956) and 0.755 (95%CI 0.707-0.799) for S ≥2, 0.990 (95%CI 0.974-0.998) and 0.786 (95% CI 0.740-0.827) for S3, respectively., Conclusion: CAP might be more accurate for detecting hepatic steatosis than HSI and ultrasound in patients with CHB, but further studies are needed to reduce the overestimation rates., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: The prevalence of fatty liver underscores the need for non-invasive characterization of steatosis, such as the ultrasound based controlled attenuation parameter (CAP). Despite good diagnostic accuracy, clinical use of CAP is limited due to uncertainty regarding optimal cut-offs and the influence of covariates. We therefore conducted an individual patient data meta-analysis., Methods: A review of the literature identified studies containing histology verified CAP data (M probe, vibration controlled transient elastography with FibroScan®) for grading of steatosis (S0-S3). Receiver operating characteristic analysis after correcting for center effects was used as well as mixed models to test the impact of covariates on CAP. The primary outcome was establishing CAP cut-offs for distinguishing steatosis grades., Results: Data from 19/21 eligible papers were provided, comprising 3830/3968 (97%) of patients. Considering data overlap and exclusion criteria, 2735 patients were included in the final analysis (37% hepatitis B, 36% hepatitis C, 20% NAFLD/NASH, 7% other). Steatosis distribution was 51%/27%/16%/6% for S0/S1/S2/S3. CAP values in dB/m (95% CI) were influenced by several covariates with an estimated shift of 10 (4.5-17) for NAFLD/NASH patients, 10 (3.5-16) for diabetics and 4.4 (3.8-5.0) per BMI unit. Areas under the curves were 0.823 (0.809-0.837) and 0.865 (0.850-0.880) respectively. Optimal cut-offs were 248 (237-261) and 268 (257-284) for those above S0 and S1 respectively., Conclusions: CAP provides a standardized non-invasive measure of hepatic steatosis. Prevalence, etiology, diabetes, and BMI deserve consideration when interpreting CAP. Longitudinal data are needed to demonstrate how CAP relates to clinical outcomes., Lay Summary: There is an increase in fatty liver for patients with chronic liver disease, linked to the epidemic of the obesity. Invasive liver biopsies are considered the best means of diagnosing fatty liver. The ultrasound based controlled attenuation parameter (CAP) can be used instead, but factors such as the underlying disease, BMI and diabetes must be taken into account. Registration: Prospero CRD42015027238., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the serum lipidomic profile in patients with nonalcoholic fatty liver disease (NAFLD), and to analyze the lipid metabolism characteristics of NAFLD. Methods: The subjects were divided into control group (23 patients) and pathologically confirmed NAFLD group (42 patients), and ultra-high-performance liquid chromatography-tandem mass spectrometry was used to measure serum lipidomic metabolites. The partial least squares-discriminant analysis (PLS-DA) model was established to analyze the differences in lipid metabolism with reference to the univariate analysis. The t-test and Mann-Whitney U test were used for data analysis. Results: A total of 239 lipids were identified and qualitative and quantitative analyses were performed. The PLS-DA model (R2 = 0.753, Q2 = 0.456) and the univariate analysis showed that 77 lipids were metabolized differentially between the NAFLD group and the control group (VIP > 1, P < 0.05), including free fatty acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, lysophosphatidylcholine, lysophosphatidylinositol (LPI), choline plasmalogen (PlsCho), ethanolamine plasmalogen (PlsEtn), ceramide (Cer), sphingomyelin, and triglyceride (TG). Compared with the control group, the NAFLD group had significant increases in monounsaturated fatty acids (increased by 39%, t = -3.954, P < 0.05) and TGs (increased by 36%, Z = -2.662, P < 0.05), mainly TGs with low numbers of carbon atoms and unsaturated bonds, while there were reductions in TGs with high numbers of carbon atoms and unsaturated bonds. In addition, compared with the control group, the NAFLD group had significant increases in the levels of LPI (increased by 223%, t = -3.858, P < 0.05) and Cer (increased by 21%, t = -2.481, P < 0.05) and significant reductions in PlsCho (reduced by 18%, t = 3.184, P < 0.05) and PlsEtn (reduced by 20%, t = 2.363, P < 0.05). Conclusion: There is a significant difference in lipid metabolism profile between NAFLD patients and healthy people, and a serum lipidomic analysis of NAFLD helps to further clarify the characteristics of lipid metabolism in patients with NAFLD.

Objective: To evaluate the significance of serum 8-hydroxy-deoxyguanosine acid(8-OHdG) in the diagnosis of nonalcoholic steatohepatitis (NASH). Methods: Patients or healthy subjects were enrolled at the Second Hospital of Tianjin Medical University and the Second People's Hospital of Tianjin from May 2013 to December 2015. A total of 41 patients with nonalcoholic fatty liver disease were enrolled in the study, including 20 nonalcoholic simple fatty liver (NAFL) patients and 21 NASH patients whose diagnosis were proven by liver biopsy. The other 32 healthy subjects were studied as controls. Serum 8-OHdG, ALT, AST and GGT were tested. Nonalcoholic fatty liver disease activity score (NAS) and expression of 8-OHdG in liver was investigated between NAFL patients and NASH patients. The correlations between serum 8-OHdG and serum ALT, AST, GGT, and 8-OHdG in liver tissue in NASH group were investigated. In addition, the receiver operating characteristic (ROC) curve analyses for ALT and 8-OHdG levels were performed in NAFL patients and NASH patients, and the cut-off value was determined. Results: Serum 8-OHdG values in healthy controls, NAFL and NASH patients were (0.19±0.16) μg/L, (0.22±0.16) μg/L, (0.42±0.21) μg/L respectively. The serum 8-OHdG and serum ALT, GGT and 8-OHdG in liver tissue were all positively correlated in NASH group with respective correlation coefficient r values as 0.454 7, 0.382 9, and 0.497 6. AUC of 8-OHdG was 0.901 with cut-off value 0.39 μg/L. Its sensitivity was 88.3% and specificity was 81.5%, which were higher than those of ALT. Conclusion: The value of serum 8-OHdG would be used as a marker for the diagnosis of NASH.

PNPLA3 polymorphisms serve as the genetic basis of hepatic steatosis in normal population and lead to dysregulated glucose metabolism. Whether it underlies the hepatic steatosis and glucose homeostasis in chronic hepatitis B patients remains uncertain. Here, we investigated the PNPLA3 polymorphisms in biopsy-proven chronic hepatitis B patients with (CHB+HS group, n = 52) or without hepatic steatosis (CHB group, n = 47) and non-CHB subjects with (HS group, n = 37) or without hepatic steatosis (normal group, n = 45). When compared to the TT genotype, C-allele at PNPLA3 rs1010023 (CC and TC genotypes) conferred higher risk to hepatic steatosis in chronic hepatitis B patients (odds ratio (OR) = 1.768, 95% confidence interval (CI): 1.027-3.105; P = 0.045) independent of age, gender, and body mass index. In contrast to their role in hepatic steatosis, CC and TC genotypes of PNPLA3 rs1010023 were correlated to significant improvement of homeostasis model assessment index (HOMA-IR) as compared to TT genotype in the CHB+HS group. Downregulated fasting blood glucose also characterized the CHB+HS patients with C-allele at PNPLA3 rs1010023 (CC/TC versus TT: 4.81 ± 0.92 mmol/L versus 5.86 ± 2.11 mmol/L, P = 0.02). These findings suggest that PNPLA3 rs1010023 may predispose chronic hepatitis B patients to hepatic steatosis but protects them from glucose dysregulation by attenuating insulin resistance.

Objective: To investigate the differences and similarities between drug-induced liver injury (DILI) and autoimmune hepatitis (AIH) in serum biochemical parameters and liver pathology, and to provide some thoughts for clinical diagnosis and differentiation of these two diseases. Methods: A retrospective analysis was performed for the biochemical, immunological, autoantibody, and liver pathological data of 106 DILI patients and 63 AIH patients who were hospitalized, diagnosed, and treated in our hospital from January 2012 to October 2014. The patients' general data, biochemical parameters, immunological data, Ishak score, and qualitative changes in liver tissue were analyzed and compared. The Kruskal-Wallis test was used for comparison of nonparametric data between multiple groups, the Nemenyi test was used for comparison of nonparametric data between any two groups, the Wilcoxon rank sum test was used for comparison of Ishak scores, and the chi-square test was used for comparison of constituent ratio of categorical data. Results: There were significant differences between AIH group and DILI hepatocyte injury group/mixed-type DILI group in the following serum biochemical parameters: alanine aminotransferase (187.2 U/Lvs 1 326.5 U/L and 455.6, P < 0.05), aspartate aminotransferase (172.2 U/L vs 759.5 U/L and 349.5 U/L, P <0.05), alkaline phosphatase (209.3 U/L vs 157.3 U/L and 169.4 U/L, P < 0.05), gamma-glutamyl transferase (254.8 U/L vs 176.5 U/L and 170.5 U/L, P < 0.05), total bilirubin (37.2μmol/L vs 95.8μmol/L and 52.6μmol/L, P < 0.05), serum iron (18.9μmol/L vs 36.2μmol/L and 23.9μmol/L, P < 0.05), serum ferritin (122.5μmol/L vs 410.4μmol/L and 186.5μmol/L, P < 0.05), immunoglobulin G (18.4 g/L vs 12.6 g/L and 12.3 g/L, P < 0.05), and immunoglobulin M (1.8 g/L vs 1.3 g/L and 1.1 g/L, P < 0.05). There were also significant differences between AIH group and DILI hepatocyte injury group/mixed-type DILI group in the Ishak score for interface inflammation (2.2±0.8 vs 1.3±0.7 and 1.3±0.6, P < 0.05), Ishak score for portal inflammation (2.3±0.9 vs 1.5±0.7 and 1.4±0.8, P < 0.05), and fibrosis score (2.8±1.1 vs 1.5±0.7 and 1.3±0.7, P < 0.05). There were significant differences between AIH group and DILI hepatocyte injury group/mixed-type DILI group in the proportion of wax-like deposition (0 vs 29.2% and 34.5%, P <0.05) and proportion of iron deposition (11.1% vs 52.1% and 25.9%, P < 0.05). Conclusion: There are differences in biochemistry, immunology, and liver histology between DILI and AIH patients. AIH patients have more serious interface inflammation and portal inflammation and a higher fibrosis degree compared with DILI patients, while DILI patients have greater proportions of wax-like deposition and iron deposition compared with AIH patients.

Background and Aim: The association between nonalcoholic fatty liver disease (NAFLD) and apolipoprotein C3 gene (APOC3) promoter region single-nucleotide polymorphisms (SNPs) rs2854117 and rs2854116 is controversial. The aim of this study was to investigate the relationship between other polymorphisms of APOC3 and NAFLD in Chinese., Methods: Fifty-nine liver biopsy-proven NAFLD patients and 72 healthy control subjects were recruited to a cohort representing Chinese Han population. The polymorphisms in the exons and flanking regions of APOC3 and patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphisms were genotyped., Results: Among the five SNPs (rs4225, rs4520, rs5128, rs2070666, and rs2070667) in APOC3, only rs2070666 (c.179 + 62 T/A) was significantly different in genotype and allele frequency (both p < 0.01) between groups of NAFLD and control. After adjusting for sex, age, serum triglycerides, total cholesterol, body mass index, and the PNPLA3 rs738409 polymorphism, the APOC3 rs2070666 A allele was an independent risk factor for NAFLD with an odds ratio (OR) of 3.683 and 95 % confidence interval (CI) of 1.037-13.084. The APOC3 rs2070666 A allele was linked to the fourth quartile of the controlled attenuation parameter values (OR 2.769, 95 % CI 1.002-7.651) in 131 subjects, and also linked to the significant histological steatosis (OR 4.986, 95 % CI 1.020-24.371), but neither to liver stiffness measurement values nor to hepatic histological activity and fibrosis in NAFLD patients., Conclusions: The APOC3 rs2070666 A allele is a risk factor for NAFLD independent of obesity, dyslipidemia, and PNPLA3 rs738409, and it might contribute to increased liver fat content in Chinese Han population.

Objective: To investigate the value of a two-step approach with cytokeratin-18 (CK-18) and controlled attenuation parameter (CAP) in the noninvasive diagnosis of nonalcoholic steatohepatitis (NASH)., Methods: A total of 65 patients with biopsy-proven nonalcoholic fatty liver disease were enrolled, including 30 patients with NASH. The M30 and M65 enzyme-linked immunosorbent assay kits were used to measure serum CK-18, and FibroScan was used to measure CAP. The receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUROC) was used to determine the value of noninvasive diagnosis. The binary logistic regression model was used to calculate the predicted probability of combined diagnosis. The maximum Youden index, a sensitivity of >90%, and a specificity of > 90% were used to determine the optimal cut-off value, the low value, and the high value, respectively., Results: The results of the multivariate analysis showed that M65 (OR = 1.004, 95% CI 1.002-1.007, P = 0.003) and CAP (OR = 1.017, 95% CI 1.001-1.033, P = 0.036) were independent predictors of NASH. The AUROC of M65+CAP was 0.851 (95% CI 0.761-0.942), higher than 0.808 (95% CI 0.702-0.913) of M65 and 0.677 (95% CI 0.545-0.808) of CAP alone. A two-step approach with high (820.8 U/L) and low (527.7 U/L) values for M65 and the optimal cut-off value (293.5 dB/m) for CAP was used for the differential diagnosis of NASH, with a positive predictive value of 85.7%, a negative predictive value of 100%, and a coincidence rate of 92.0%., Conclusion: A two-step approach with M65 and CAP can improve the value of noninvasive diagnosis of NASH, and a high negative predictive value can avoid unnecessary liver biopsy.

Theta-burst stimulation (TBS) over human primary motor cortex evokes plasticity and metaplasticity, the latter contributing to the homeostatic balance of excitation and inhibition. Our knowledge of TBS-induced effects on primary somatosensory cortex (SI) is limited, and it is unknown whether TBS induces metaplasticity within human SI. Sixteen right-handed participants (6 females, mean age 23 yr) received two TBS protocols [continuous TBS (cTBS) and intermittent TBS (iTBS)] delivered in six different combinations over SI in separate sessions. TBS protocols were delivered at 30 Hz and were as follows: a single cTBS protocol, a single iTBS protocol, cTBS followed by cTBS, iTBS followed by iTBS, cTBS followed by iTBS, and iTBS followed by cTBS. Measures included the amplitudes of the first and second somatosensory evoked potentials (SEPs) via median nerve stimulation, their paired-pulse ratio (PPR), and temporal order judgment (TOJ). Dependent measures were obtained before TBS and at 5, 25, 50, and 90 min following stimulation. Results indicate similar effects following cTBS and iTBS; increased amplitudes of the second SEP and PPR without amplitude changes to SEP 1, and impairments in TOJ. Metaplasticity was observed such that TOJ impairments following a single cTBS protocol were abolished following consecutive cTBS protocols. Additionally, consecutive iTBS protocols altered the time course of effects when compared with a single iTBS protocol. In conclusion, 30-Hz cTBS and iTBS protocols delivered in isolation induce effects consistent with a TBS-induced reduction in intracortical inhibition within SI. Furthermore, cTBS- and iTBS-induced metaplasticity appear to follow homeostatic and nonhomeostatic rules, respectively., (Copyright © 2016 the American Physiological Society.)

Background & Aims: Controlled attenuation parameter (CAP) is a non-invasive method for evaluating hepatic steatosis. However, larger skin capsular distance (SCD) can affect the accuracy. The aim of this study was to investigate the impact of SCD on the diagnostic performance of CAP and liver stiffness measurement (LSM)., Methods: Of 101 patients with non-alcoholic fatty liver disease (NAFLD) and 280 patients with chronic hepatitis B (CHB) who underwent liver biopsy were prospectively recruited. CAP, LSM and SCD were performed using FibroScan with M probe. The areas under receiver operating characteristics curves (AUROCs) were calculated to determine the diagnostic efficacy. The optimal thresholds were defined by the maximum Youden index., Results: SCD (B 30.34, P < 0.001) and hepatic steatosis (B 23.04, P < 0.001) were independently associated with CAP by multivariate analysis. The AUROCs were slightly higher for SCD <25 mm compared to those for SCD ≥25 mm for steatosis ≥5% (0.88 vs. 0.81), >33% (0.90 vs. 0.85) and >66% (0.84 vs. 0.72). For SCD <25 mm, the optimal CAP cut-offs for differentiating steatosis ≥5%, >33% and >66% were 255.0 dB/m, 283.5 dB/m and 293.5 dB/m. However, cut-offs were elevated by approximately 60-70 dB/m for SCD ≥25 mm. When stratified by fibrosis grade, LSM was significantly affected by SCD ≥25 mm for advanced fibrosis (≥F3) in NAFLD, but not in CHB., Conclusion: CAP is a promising tool for detecting and quantifying hepatic steatosis. SCD ≥25 mm may cause overestimation of steatosis. Similarly, SCD ≥25 mm affects the detection of advanced fibrosis by LSM in NAFLD patients., (© 2015 The Authors. Liver International Published by John Wiley & Sons Ltd.)

Aim: To investigate the association of PNPLA3 polymorphisms with concurrent chronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD)., Methods: A cohort of Han patients with biopsy-proven CHB, with or without NAFLD (CHB group, n = 51; CHB + NAFLD group, n = 57), and normal controls (normal group, n = 47) were recruited from Northern (Tianjin), Central (Shanghai), and Southern (Zhangzhou) China. Their PNPLA3 polymorphisms were genotyped by gene sequencing. The association between PNPLA3 polymorphisms and susceptibility to NAFLD, and clinical characteristics of NAFLD were evaluated on the basis of physical indices, liver function tests, glycolipid metabolism, and histopathologic scoring. The association of PNPLA3 polymorphisms and hepatitis B virus (HBV) load was determined by the serum level of HBV DNA., Results: After adjusting for age, sex, and body mass index, we found that four linked single nucleotide polymorphisms (SNPs) of PNPLA3, including the rs738409 G allele (CHB + NAFLD group vs CHB group: odds ratio [OR] = 2.77, 95% confidence interval [CI]: 1.18-6.54; P = 0.02), rs3747206 T allele (CHB + NAFLD group vs CHB group: OR = 2.77, 95%CI: 1.18-6.54; P = 0.02), rs4823173 A allele (CHB + NAFLD group vs CHB group: OR = 2.73, 95%CI: 1.16-6.44; P = 0.02), and rs2072906 G allele (CHB + NAFLD group vs CHB group: OR = 3.05, 95%CI: 1.28-7.26; P = 0.01), conferred high risk to NAFLD in CHB patients. In patients with both CHB and NAFLD, these genotypes of PNPLA3 polymorphisms were associated with increased susceptibility to nonalcoholic steatohepatitis (NASH) (NAFLD activity score ≥ 3; P = 0.01-0.03) and liver fibrosis (> 1 Metavir grading; P = 0.01-0.04). As compared to those with C/C and C/G at rs738409, C/C and C/T at rs3747206, G/G and G/A at rs4823173, and A/A and A/G at rs2072906, patients in the CHB + NAFLD group with G/G at rs738409, T/T at rs3747206, A/A at rs4823173, and G/G at rs2072906 showed significantly lower serum levels of HBV DNA (P < 0.01-0.05)., Conclusion: Four linked SNPs of PNPLA3 (rs738409, rs3747206, rs4823173, and rs2072906) are correlated with susceptibility to NAFLD, NASH, liver fibrosis, and HBV dynamics in CHB patients.

The worldwide threat from tuberculosis (TB) has resulted in great demand for new drugs, particularly those that can treat multidrug-resistant TB. We synthesized novel pleuromutilin derivatives with N-benzylamine side chain substituted at the C14 position and evaluated their activity in vitro against a virulent strain of Mycobacterium tuberculosis (H37Rv). The primary assay results showed that five compounds inhibited the H37Rv at 20μM, with a MIC of one of the analogues as low as 7.2μM., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background and Aim: The controlled attenuation parameter (CAP) using transient elastography (TE) was validated in chronic hepatitis C to evaluate hepatic steatosis; however, limited data are available on chronic hepatitis B (CHB). Therefore, we assessed the accuracy and the efficacy of CAP for the detection of steatosis in CHB., Methods: Consecutive CHB patients underwent liver biopsy and liver stiffness measurements (LSM) with simultaneous CAP determination using the M probe of the TE. The area under the receiver operating characteristics curve (AUROC) was used to evaluate the performance of CAP in diagnosing steatosis compared with biopsy., Results: A total of 340 patients were included: 60 % were male, the median age was 37 years; the body mass index (BMI) was ≥ 28 kg/m(2) for 14 % of the subjects; and the distribution of the steatosis grade was S0 58.2 %, S1 34.2 %, S2 5.0 % and S3 2.6 %. The median (range) of CAP was 218 (100-400) dB/m, and CAP correlated with the BMI (ρ = 3.622) and steatosis grade (ρ = 29.203) according to a multivariate analysis (both P < 0.001). CAP could detect the different grades of steatosis: ≥ S1 with AUROC of 0.81 at a cutoff of 224 dB/m, ≥ S2 with AUROC of 0.90 at a cutoff of 236 dB/m and ≥ S3 with AUROC of 0.97 at a cutoff of 285 dB/m. Furthermore, the LSM and fibrosis and activity grades on biopsy did not influence the CAP performance., Conclusions: CAP presented excellent diagnostic performance for severe steatosis with high sensitivity and specificity in Chinese patients with CHB.

Objective: To systematically review and meta-analyze the relation between maternal fever in the first trimester and congenital heart defect (CHD) in offspring., Study Design: We searched PubMed (1977-2012), Embase (1974-2012) and the Cochrane Library (2012) databases to identify relevant articles. Random effects model were performed, with the conduction of subgroup analysis., Result: Meta-analysis yielded a pooled odds ratio of 1.53 (95% confidence interval=1.36 to 1.73) for the magnitude of the relation between maternal fever in the first trimester and CHD in offspring. As to subgroup analysis, it is associated with ventricular septal defects (VSDs) and right obstructive defects., Conclusion: Our analysis suggests that maternal fever in the first trimester is the risk factor of congenital heart diseases in offspring. Through the subgroup analysis, we find that exposure to maternal fever is the risk factor of VSD and right obstructive defects.

Chinese herbal medicine Jinlianqingre Effervescent Tablets (JET) are the recommended control measure for uncomplicated hand, foot, and mouth disease (HFMD) by the Ministry of Health of China. However, high-quality evidence to support this recommendation is limited. A total of 288 patients ranging in age from 1 to 13 years were randomly assigned to JET in combination with conventional therapy (mainly including the reduction of temperature by applying physical cooling paste or warm bathing), or conventional therapy with placebo group for 7 days. The objective was to test the hypothesis that JET combination therapy is more effective than conventional therapy for uncomplicated HFMD. A randomized, double-blind, placebo-controlled trial was designed. Our study showed that, compared with conventional therapy, the median time to fever resolution was significantly shorter in the JET combination therapy (8 vs. 80 h; p < 0.0001); the risk of fever resolution increased in the JET combination therapy [hazard ratio, 19.8; 95% confidence interval (CI), 12.8 to 30.7]; the median healing time of rash or oral ulcer was significantly shorter in the JET combination therapy (14 vs. 74 h; p < 0.0001); and the median symptom score for skin or oral mucosa lesions improved more rapidly in the JET combination therapy during the follow-up period. The median duration of hospital stay was 6 days in the JET combination therapy and 7 days in the conventional therapy (p < 0.0001). No significant adverse events and complications were found in both groups. The addition of JET to conventional therapy reduced fever clearance time, healing time of skin or oral mucosa lesions, and duration of hospital stay in children with uncomplicated HFMD.

Aim: To evaluate the performance of a novel non-invasive controlled attenuation parameter (CAP) to assess liver steatosis., Methods: This was a multi-center prospective cohort study. Consecutive patients (aged ≥ 18 years) who had undergone percutaneous liver biopsy and CAP measurement were recruited from three Chinese liver centers. Steatosis was categorized as S0: < 5%; S1: 5%-33%; S2: 34%-66%; or S3: ≥ 67%, according to the nonalcoholic fatty liver disease (NAFLD) activity score. The FibroScan(®) 502 equipped with the M probe (Echosens, Paris, France) was used to capture both CAP and liver stiffness measurement values simultaneously. Receiver operating characteristic curves were plotted, and the areas under the curves were calculated to determine the diagnostic efficacy. The accuracy of the CAP values at the optimal thresholds was defined by maximizing the sum of sensitivity and specificity (maximum Youden index)., Results: A total of 152 patients were recruited, including 52 (34.2%) patients with NAFLD and 100 (65.8%) with chronic hepatitis B (CHB) virus infection. After adjustment, the steatosis grade (OR = 37.12; 95%CI: 21.63-52.60, P < 0.001) and body mass index (BMI, OR = 6.20; 95%CI: 2.92-9.48, P < 0.001) were found independently associated with CAP by multivariate linear regression analysis. CAP was not influenced by inflammation, fibrosis or aetiology. The median CAP values and interquartile ranges among patients with S0, S1, S2 and S3 steatosis were 211 (181-240) dB/m, 270 (253-305) dB/m, 330 (302-360) dB/m, and 346 (313-363) dB/m, respectively. The cut-offs for the CAP values in all patients with steatosis ≥ 5%, ≥ 34% and ≥ 67% were 253 dB/m, 285 dB/m and 310 dB/m, respectively. The areas under the curves were 0.92, 0.92 and 0.88 for steatosis ≥ 5%, ≥ 34% and ≥ 67%, respectively. No significant differences were found in the CAP values between the NAFLD group and the CHB group in each steatosis grade., Conclusion: CAP appears to be a promising tool for the non-invasive detection and quantification of hepatic steatosis, but is limited by BMI.

Aim: To investigate the prevalence of minimal hepatic encephalopathy (MHE) and to assess corresponding health-related quality of life (HRQoL) in hospitalized cirrhotic patients in China., Methods: This multi-center cross-sectional study included 16 teaching hospitals, which were members of "Hepatobiliary Cooperation Group, Society of Gastroenterology, Chinese Medical Association", from different areas of China carried out between June and October in 2011. All the eligible hospitalized cirrhotic patients (n = 538) were required to complete triplicate number connection tests combined with one digit symbol test for diagnosing MHE. Patients' clinical examination data were complemented by a modified questionnaire assessing HRQoL. Written informed consent was obtained from each patient., Results: Male was predominant (68.6%) in 519 patients who met the criteria of the study, with a mean age of 49.17 ± 11.02 years. The most common cause of liver cirrhosis was chronic hepatitis B (55.9%). The prevalence of MHE was 39.9% and varied by Child-Pugh-Classification score (CPC-A: 24.8%, CPC-B: 39.4% and CPC-C: 56.1%, P < 0.01). MHE (P < 0.01) and higher CPC scores (P < 0.01) were associated with a high HRQoL scores (reflecting poorer quality of life). The prevalence of MHE was proportionate to CPC (P = 0.01) and high quality of life scores (P = 0.01)., Conclusion: Hospitalized cirrhotic patients have a high prevalence of MHE that is proportionate to the degree of liver function and HRQoL impairment.

Objective: To explore clinical and pathological features of chronic hepatitis B (CHB) with hepatic steatosis., Methods: Retrospective analysis of hepatic steatosis in patients with liver biopsy-proven CHB between January 2005 and June 2008. Detailed clinical, laboratory and pathological data of CHB patients with steatosis were compared with those in sex-, age- matched CHB patients without steatosis. Patients co-infected hepatitis C virus or HIV or suffering from liver diseases of other causes were excluded., Results: Histological hepatic steatosis was found in 33.4% of the 1263 CHB patients. The prevalence of steatosis was increased with time in the study period (20.3%, 28.2%, 32.6%, 65.4%, in trend analysis, P values less than 0.05). Body mass index, fasting plasma glucose, serum triglyceride and total cholesterol level in CHB patients with hepatic steatosis (n = 114) were significantly higher than those in 113 patients without steatosis (t values were 6.811, 2.733, 3.063, 2.340, respectively, P values less than 0.01 or 0.05). Compared to patients without steatosis, serum hepatitis B virus DNA titer in patients with steatosis was significantly lower (x2 = 6.154, P less than 0.05) and reduced sharply with the increased degree of hepatic steatosis (x2 = 4.941, P less than 0.05). There were no differences in liver biochemical test (t values were 0.744, 1.390, -0.029, -1.175, 1.393, respectively, P values more than 0.05), hepatic inflammation grade and fibrosis stage between CHB patients with and without steatosis (x2 = 1.434, 0.106, respectively, P more than 0.05), and these parameters were not associated with different degree of hepatic steatosis (x2 = 2.447, 2.911, respectively, P more than 0.05)., Conclusions: Hepatic steatosis is common in patients with CHB, and is related to metabolic disorders. Hepatic steatosis does not affect the severity of CHB. The reverse association of hepatitis B virus titer with the degree of hepatic steatosis needs further investigation.

Objective: To compare therapeutic effects of acupuncture at pain points and massage combined with medicine on myofascial pain syndrome (MPS)., Methods: One hundred and fifty cases were randomly divided into an observation group (n=90) and a control group (n=60). The observation group was treated with needle-sticking method combined with single-finger meditation pushing therapy at pain points, and the control group with local application of Votalin Emulgel combined with Tuina. All the patients were treated for 1 course and followed up after 3 months and their therapeutic effects were compared., Results: There were significant differences in cumulative scores of symptoms before and after treatment in the two groups (both P < 0.01), and there were no significant differences in the pain and pressure pain between the two groups (P > 0.05), and there were significant differences in the muscle spasm and joint range of motion between the two groups (P < 0.05); after treatment, the markedly effective rate and the total effective rate in the observation group were 57.8% and 94.4% respectively, and were 31.7% and 73.3% respectively in the control group, with a significant difference between the two groups (both P < 0.05)., Conclusion: Needle-sticking method combined with single-finger meditation pushing therapy at pain points can effectively alleviate pain and pressure pain in the patients with MPS and it has better therapeutic effect in the markedly effective rate and the total effective rate as well as improvement of muscle spasm and joint range of motion than local application of Votalin Emulgel combined with Tuina.

Objective: To explore the mechanism of acupuncture for treatment of lumbar nerve root compression injury., Methods: Fifty healthy SD rats were randomly divided into 5 groups, a normal group, a model group treated by saline, a medication group treated with Caerulein, an acupuncture group treated with acupuncture at L5, L6 Jiaji (EX-B 2) and a warm needle group treated with acupuncture and moxibustion at L5, L6 Jiaji (EX-B 2). The lumbar nerve root compress injury model was made by placing microsilica gel tablet. After they were treated for 14 days, the compressed nerve root was taken and the ultra-microstructure changes of the injured nerve root were observed by electron microscope and changes of nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP) expressions were investigated by ELISA assay., Results: The changes of ultra-microstructure of the nerve root were the most obvious in the model group and the changes in the medication group, the acupuncture group and the warming needle group reduced in order; the NOS activity and CGRP content in the nerve root tissue of the compressed area in the warm needle group were significantly reduced as compared with the model group (P < 0.05), but with no significant difference as compared with those in the normal group (P > 0.05)., Conclusion: Warm needle treatment can effectively maintain cellular form, and ultra-microstructures of nerve root dorsal root ganglia, and effectively inhibit the release of inflammatory factors NOS and CGRP.

Objective: To investigate the mortality and predictors of outcome of children with acute respiratory distress syndrome (ARDS) in pediatric intensive care unit (PICU)., Methods: ARDS cases were selected from the 12 018 patients admitted in 25 pediatric intensive care units in China from January 1 to December 31, 2004, aged 29 days to 14 years, using the Chinese Pediatric Critical Index of Severity (PCIS) and American Guidelines for Admission and Discharge Policies for PICU. ARDS was diagnosed according to the 1994 American-European Consensus Conference criteria., Results: 105 of the 12 018 patients (1.44%) were diagnosed as with ARDS. The overall mortality of ARDS was 61.0% (64/105), 9 times as high as that of the 7269 severe cases in PICU. Logistic regression analysis showed that infiltration shadows in 2 - 3 quadrants, pediatric critical illness score (PCIS), and partial pressure of carbon dioxide (PaCO2) at the onset of ARDS were independently associated with the mortality., Conclusion: ARDS has a high risk of death, and the infiltration shadows in 2-3 quadrants, PCIS, and PaCO2 are independently associated with mortality.

Objective: To study the relationship between HBeAg expression and HBV-DNA in serum and peripheral blood mononuclear cells (PBMCs)., Methods: 208 patients with chronic hepatitis B were included in this present study. HBV-DNA in the PBMCs were performed by polymerase chain reaction (PCR), with the serum HBV-DNA level being determined by the way of fluoresces quantities PCR (FQ-PCR). Meanwhile, HBV-GM was also detected via enzyme-linked immunosorbent assay (ELISA)., Results: There were 106 patients for positivity in the HBV-DNA level of PBMCs with 102 for negativity, in which the HBV-DNA high levels (HBV DNA load > or = 1.0E5) in serum were 91.5%, 45.1% (chi2=52.12, P>0.01) respectively, with 76.4% and 50.9% (chi2=21.55, P>0.01) for the positive percentage of HBeAg expression., Conclusion: A significantly positive correlation was found between HBV-DNA in PBMCs and serum HBV-DNA along with the positive percentage of HBeAg, indicating that obvious PBMCs' increase infected by HBV in patients with positivity of HBeAg and high level of serum HBV-DNA.

Objective: To study the relationship between TCM syndrome type and HBV-DNA in serum and peripheral blood mononuclear cells (PBMCs) in chronic hepatitis B (CHB) patients., Methods: The serum HBV markers,HBV-DNA levels in serum and PBMCs, were quantitatively detected in 220 CHB patients by PCR method, and TCM syndrome type of 205 patients were differentiated., Results: Arranged from low to high, the percentages of CHB patients with the serum HBV-DNA > or = 1.0 x l0(5) copy/mL (high viral loading) in the five syndrome types were as follows: damp-heat retention in middle-jiao syndrome (DHRS, 55.2%), blood stasis blocking collateral syndrome (BSBC), Gan-Shen yin deficiency syndrome (GSYS), Pi-Shen yang deficiency syndrome (PSDS) and Gan stagnation with Pi deficiency syndrome (GSPS, 82.5%), the difference was significant between DHRS and GSPS; those with HBV-DNA in PBMCs infection were: GSYS (27.3%), DHRS (34.3%), BSBC (53.1%) and GSPS (77.2%). The percentage in GSPS was the highest, which was significantly different to that in other syndromes., Conclusion: Amount of serum HBV-DNA and PBMCs HBV-DNA infection has certain correlation with the TCM syndrome type of CHB. The highest percentage of patients with HBV-DNA > or = 1.0 x l0(5) copy/mL and PBMCs HBV-DNA infection presented in CHB patients of GSPS type. We should pay more attention to strengthen genuine qi to eliminate pathogenic factors in treatment of CHB.

Objective: To search for an effective method for treatment of obesity and to study the mechanism of acupuncture slimming treatment., Methods: The cases of obesity were randomly divided into a diet group of 40 cases and an acupuncture group of 80 cases. Their therapeutic effects and changes of TC, TG, LDL-C, HDL-C contents before and after treatment were observed., Results: The effective rate of 76.3% in the acupuncture group was better than 27.5% in the diet group, and acupuncture could decrease serum TC, TG, LDL-C contents and increase HDL-C content., Conclusion: Acupuncture combined with diet therapy is an effective method for reducing weight at present, and metabolism of lipids is involved in acupuncture slimming mechanism.