Objective To determine the expression of interleukin-21 (IL-21) in patients infected with hepatitis B virus (HBV) and its association with HBV-DNA and ALT. Methods Clinical dates and blood specimen were collected from 25 unrelated healthy controls (HC) and 101 independent chronic HBV infected patients, including 25 patients in immune tolerant phase (IT), 25 in immune clearance phase (IC), 26 patients in inactive HBV carrier state (IA) and 25 patients in immune reactive phase (IR). Serum IL-21 levels were measured by Cytometric Bead Array (CBA). IL-21 mRNA and IL-21 receptor mRNA were measured by real-time PCR. Results Chronic HBV-infected patients had higher levels of serum IL-21 and IL-21 mRNA , with P <0.001 for both. In subgroup analysis, both serum IL-21 and IL-21 mRNA levels in IC, IR were higher than those in IT, IA and HC (all P < 0.001). Serum IL-21 level in IA was higher than that in HC and IT (P <0.001, P = 0.036). IL-21R mRNA levels were different between groups. Serum IL-21 level was associated with HBV-DNA (r = -0.472, P < 0.001), but not with ALT. Conclusion IL-21, up-regulated in chronic HBV infection, is associated with immune activity and may play a key role in HBV control.

Objective To explore the prevalence of nonalcoholic fatty liver disease(NAFLD)in patients with polycystic ovary syndrome(PCOS).MethodsA case-control study employing 60 non pregnant patients with PCOS and 60 non-pregnant patients without PCOS as control was conducted to compare the prevalence of NAFLD.Resuits The aminotransferase(ALT),fasting insulin and homeostasis model assessment of insulin resistance(HOMA-IR)levels were(29±15)U/L,(19±12)mU/L and 0.47±0.29 in PCOS group,which were significantly higher(P＜0.05)than corresponding parameters in control group[(15±13)U/L,(11±8)mU/L and 0.31±0.21)].The occurrence of insulin resistance and NAFLD was 63％(38/60)and 42％(25/60),higher than those in control group[35％(21/60)and 20％(12/60),P＜0.05].The increment of ALT was 40％(24/60)in PCOS group,higher than that of 3％(2/60)in control group(P＜0.01).Compared with patients witIlout NAFLD,patients with NAFLD had significantly increased body mass index(P＜0.01),waist-hip ratio,AIJT,C-reaction protein,fasting insulin,insulin and HOMA-IR levels 2 hours after oral glucose tolerance test(P＜0.05).Conchsion The increased prevalence of NAFLD in PCOS patients suggests an association between these two conditions and the necessity of hepatic screening among PCOS patients for potential NAFLD.

Aims The purpose of this study is to investigate thediagnostic value of SWEfor fibrosis in patients with CHBand the factorsinfluencing the accuracy. Methods From July 2013 to October 2015, 261 patients with CHB were recruited from the First Affiliated Hospital of Sun Yat-sen University.All patients received SWE, anthropometry measurement, blood cell count, liver function test and virological indicators measurement. Liver fibrosis was staged from F0 to F4 by METAVIR scorebased onliver biopsy results of 133 CHB patients , while 128 patients were diagnosed as decompensated cirrhosis. Diagnostic accuracyof SWE were evaluated by Receiver Operating Characteristic Curve (ROC) using liver hepatic pathology and decompensated cirrhosis as gold standards. Logistic model was used to find out confounding factors that influence the accuracy of SWE. Results The Area Under ROC (AUC) for liver stiffness measurement with SWE were 0.891, 0.932 and 0.910 for the diagnosis of significant fibrosis (≥ F2), advanced fibrosis (≥F3) and cirrhosis (F4), respectively. A multifactor logistic regression combined modelwas built and showed that hepatic steatosis will decrease the accuracy of SWE. Conclusion SWE could be a valuable method for the noninvasive liver fibrosis assessment. The accuracy of SWE may be influenced by hepatic steatosis.

There is a high prevalence of nonalcoholic fatty liver disease (NAFLD) around the world, and early diagnosis and evaluation of liver fatty degeneration and fibrosis degree play important roles in the early treatment and prognostic evaluation of patients with NAFLD. This article reviews the principles, diagnostic accuracy, influencing factors, and practicability of various imaging techniques applied in liver fat quantification and fibrosis prediction. Studies have shown that radiological fat quantitative diagnosis based on ultrasound and magnetic resonance and liver fibrosis evaluation based on elastography have a high level of accuracy and promising prospects; however, such techniques lack standard cut-off values and operating procedures which may provide a reference for clinical application.

Abnormal uric acid metabolism is closely associated with the development and progression of nonalcoholic fatty liver disease (NAFLD). This article describes the relationship between uric acid and the prevalence and severity of NAFLD, and point out that uric acid metabolic disorders directly affect the development and progression of NAFLD through complicated pathways such as insulin resistance, oxidative stress, direct influence on the expression of lipid synthetase, and inflammatory response. Control of uric acid is expected to become one of the multimodality therapies for NAFLD.

Hepatorenal syndrome (HRS) is one of the common serious complications in patients with end-stage liver disease and has poor prognosis and high mortality, and in-depth studies on its pathogenesis will help to achieve precise prevention and treatment. Although the exact pathogenesis of HRS has not yet been fully elucidated, achievements have been made in the pathogenesis of HRS. The classic mechanism of the hypothesis of visceral vasodilation continues to be enriched and perfected, and new understandings have been gained for the role of systemic inflammation and intestinal bacterial translocation in pathogenesis. In addition, a new concept of cardiorenal syndrome is put forward for the involvement of cardiac dysfunction in HRS, and renal pathology has been questioned and challenged. This article reviews the research advances in the pathogenesis of HRS in recent years and related implications for clinical work.

Poor dietary habit is an important cause of the global prevalence of metabolic associated fatty liver disease (MAFLD), and the adjustment of dietary pattern is the cornerstone of MAFLD management. In recent years, a large number of new dietary intervention methods have been proposed and applied in the treatment of MAFLD, including calorie restrict diet, low-carbohydrate diet, low-glycemic index diet, low free sugar diet, intermittent fasting pattern, high protein diet, and Mediterranean diet, and these new methods have different effects in clinical practice. This article introduces the treatment concepts and practical methods of these new dietary treatment strategies and the evidence of their benefits in the treatment of MAFLD in China and globally, so as to provide a new perspective for clinicians to guide patients to achieve individualized nutritional therapy.

Background: Excessive delivery of free fatty acids (FFAs) to the liver promotes steatosis and insulin resistance (IR), with IR defined as reduced glucose uptake, glycogen synthesis and anti-lipolysis stimulated by normal insulin levels. Whether the associations between FFAs and diabetes development differ between patients with and without nonalcoholic fatty liver disease (NAFLD) remains unclear. Methods: Consecutive subjects (2,220 NAFLD subjects and 1,790 non-NAFLD subjects according to ultrasound imaging) were enrolled from the First Affiliated Hospital of Sun Yat-sen University between 2009 and 2019. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Results: There was an approximate J-shaped relationship between FFA levels and HOMA-IR in the NAFLD group. Higher FFA concentration quartiles were associated with higher risks of IR (odds ratio [OR], 9.24; 95% confidence interval [CI], 6.43 to 13.36), prediabetes (OR, 10.48; 95% CI, 5.66 to 19.39), and type 2 diabetes mellitus (T2DM; OR, 19.43; 95% CI, 12.75 to 29.81) in the NAFLD group but not in the non-NAFLD group. The cut-off points for the FFA levels increased in a stepwise manner in discriminating IR, prediabetes and T2DM (573, 697, and 715 μmol/L) in the NAFLD group but not in non-NAFLD individuals. Conclusion A distinct dose-dependent relationship of FFA levels was found with IR, prediabetes and T2DM in NAFLD patients. Screening serum FFA levels in NAFLD patients would be valuable in preventing diabetes development.

Background: Excessive delivery of free fatty acids (FFAs) to the liver promotes steatosis and insulin resistance (IR), with IR defined as reduced glucose uptake, glycogen synthesis and anti-lipolysis stimulated by normal insulin levels. Whether the associations between FFAs and diabetes development differ between patients with and without nonalcoholic fatty liver disease (NAFLD) remains unclear. Methods: Consecutive subjects (2,220 NAFLD subjects and 1,790 non-NAFLD subjects according to ultrasound imaging) were enrolled from the First Affiliated Hospital of Sun Yat-sen University between 2009 and 2019. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Results: There was an approximate J-shaped relationship between FFA levels and HOMA-IR in the NAFLD group. Higher FFA concentration quartiles were associated with higher risks of IR (odds ratio [OR], 9.24; 95% confidence interval [CI], 6.43 to 13.36), prediabetes (OR, 10.48; 95% CI, 5.66 to 19.39), and type 2 diabetes mellitus (T2DM; OR, 19.43; 95% CI, 12.75 to 29.81) in the NAFLD group but not in the non-NAFLD group. The cut-off points for the FFA levels increased in a stepwise manner in discriminating IR, prediabetes and T2DM (573, 697, and 715 μmol/L) in the NAFLD group but not in non-NAFLD individuals. Conclusion A distinct dose-dependent relationship of FFA levels was found with IR, prediabetes and T2DM in NAFLD patients. Screening serum FFA levels in NAFLD patients would be valuable in preventing diabetes development.

The application of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) can be limited due to a lack of compatible protospacer adjacent motif (PAM) sequences in the DNA regions of interest. Recently, SpRY, a variant of Streptococcus pyogenes Cas9 (SpCas9), was reported, which nearly completely fulfils the PAM requirement. Meanwhile, PAMs for SpRY have not been well addressed. In our previous study, we developed the PAM Definition by Observable Sequence Excision (PAM-DOSE) and green fluorescent protein (GFP)‍-reporter systems to study PAMs in human cells. Herein, we endeavored to identify the PAMs of SpRY with these two methods. The results indicated that 5'-NRN-3', 5'-NTA-3', and 5'-NCK-3' could be considered as canonical PAMs. 5'-NCA-3' and 5'-NTK-3' may serve as non-priority PAMs. At the same time, PAM of 5'-NYC-3' is not recommended for human cells. These findings provide further insights into the application of SpRY for human genome editing.
CRISPR-Associated Protein 9/metabolism* ; CRISPR-Cas Systems ; DNA ; Gene Editing/methods* ; Humans ; Streptococcus pyogenes/metabolism*