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Although itch and pain have many similarities, they are completely different in perceptual experience and behavioral response. In recent years, we have a deep understanding of the neural pathways of itch sensation transmission. However, there are few reports on the role of non-neuronal cells in itch. Microglia are known to play a key role in chronic neuropathic pain and acute inflammatory pain. It is still unknown whether microglia are also involved in regulating the transmission of itch sensation. In the present study, we used several kinds of transgenic mice to specifically deplete CX3CR1+ central microglia and peripheral macrophages together (whole depletion), or selectively deplete central microglia alone (central depletion). We observed that the acute itch responses to histamine, compound 48/80 and chloroquine were all significantly reduced in mice with either whole or central depletion. Spinal c-fos mRNA assay and further studies revealed that histamine and compound 48/80, but not chloroquine elicited primary itch signal transmission from DRG to spinal Npr1- and somatostatin-positive neurons relied on microglial CX3CL1-CX3CR1 pathway. Our results suggested that central microglia were involved in multiple types of acute chemical itch transmission, while the underlying mechanisms for histamine dependent and non-dependent itch transmission were different that the former required the CX3CL1-CX3CR1 signal pathway.

This study aimed to characterize the genetic, pathological, and clinical alterations of 17 patients in China presenting with nondystrophic myotonia (NDM) and to analyze the relationship between genotype and clinical phenotype.CLCN1 and SCN4A genes in patients with clinical features and muscle pathology indicative of NDM were sequenced. Furthermore, KCNE3 and CACNA1S genes were assessed in patients with wild-type CLCN1 and SCN4A.Patients may have accompanying atypical myopathy as well as muscle hypertrophy, secondary dystonia, and joint contracture as determined by needle electromyography. All the study participants were administered mexiletine in combination with carbamazepine and showed significant improvements in myotonia symptoms in response to this therapy. CLCN1 gene mutation was detected in 8 cases diagnosed with myotonia congenital using gene screening. The detected mutations included 5 missense, 2 nonsense, 1 deletion, and 2 insertions. Further gene analysis showed 4 mutations in the SCN4A gene in patients diagnosed with paramyotonia congenita.Myotonia congenita and paramyotonia congenita are the predominant forms of NDM in China. NDM may be best diagnosed using genetic analysis in associated with clinical features.

Aims: The aim of this study was to study the relationship between the hypertriglyceridemic-waist (HTGW) phenotype and the risk of carotid artery atherosclerosis (CAA) in Chinese patients with type 2 diabetes. Methods: A total of 2651 consecutive in-patients with type 2 diabetes (mean age 56±11 years, 58% women) were included. CAA was determined by Color Doppler Ultrasonography and defined by the formation of detectable carotid artery plaques. Logistic regression analysis was applied to relate HTGW phenotype to CAA. Results: The prevalence of CAA was 46.3% and 26.2% respectively in patients with and without HTGW. Compared with participants who had no HTGW, those with the HTGW phenotype had higher levels of systolic blood pressure (139.2 mmHg vs. 132.7 mmHg, p < 0.05) , fasting plasma glucose (9.1 mmol/L vs. 8.5 mmol/L, p < 0.05) , HbA1c [73 mmol/mol (8.83%) vs. 63 mmol/mol (7.95%) , p < 0.05], apolipoprotein B (0.95 g/L vs. 0.89 g/L, p < 0.05) , C-reactive protein (8.23 mg/L vs. 4.92 mg/L, p < 0.05) , TNF-α (26.46 pg/ml vs. 16.80 pg/ml, p < 0.05) and mean intima-media thickness (0.85 mm vs. 0.79 mm, p < 0.05) , but lower levels of apolipoprotein A1 (1.21 g/L vs. 1.33 g/L, p < 0.05) . The hypertriglyceridemic-waist phenotype was associated with CAA (OR 1.55, 95% CI 1.07-2.24) , after adjusting for age, sex, duration of diabetes, body mass index, smoking, HbA1c, apolipoprotein B and C-reactive protein. Conclusion: Among patients with type 2 diabetes, simultaneous measurement of waist circumference and triglycerides could be used as an inexpensive and simple approach to identify individuals with CAA. Disclosure L. Zhang: n/a. Y. Yang: None. J. Wang: None. Y. Dong: None.

Aims: The study aimed to investigate the relationship between components of metabolic syndrome (MS) and risk of cancer in patients with type 2 diabetes (T2DM) . Methods: We enrolled 6587 patients with T2DM who were hospitalized in Qingdao Endocrine and Diabetes Hospital from Feb 2005 to Jan 2016. According to the number of MS component each patient had, they were divided into isolated T2DM, T2DM plus 1 component,2 components, 3 components and 4 components, respectively. The IDF Worldwide Definition of the Metabolic Syndrome was applied. Information on the diagnosis of cancer was obtained by matching ICD-10 codes recorded in local Healthcare medical records database. Prevalence of cancer was compared using Chi-square test. Logistic regression model was used to evaluate risk of cancer associated with MS. Results: The prevalence of cancer was 4.2% among 6587 patients with T2DM. Female patients had higher prevalence than did male in total or in the MS subgroup. The prevalence of cancer were 3.8%, 3.9%, 3.8%, 5.1% and 5.0% in isolated DM, T2DM plus 1 component of MS, T2DM plus 2, T2DM plus 3 and T2DM plus 4 components, respectively (P for trend Conclusions: A cluster of metabolic disorders consisting of increased waist, elevated TG and decreased HDL-C seems to be oncogenic among Chinese patients with T2DM. For patients in combination with 3 or 4 MS components, it is important to conduct early cancer screening and prevention. Disclosure L. Zhang: n/a. J. Wang: None. Y. Yang: None. Y. Dong: None.

The aim of the current study is to investigate the prevalence of vitamin D deficiency among patients with type 2 diabetes (T2DM) in a Chinese cohort. We enrolled 3025 patients with T2DM (aged 30-91 yrs) who were hospitalized in Qingdao Endocrine and Diabetes Hospital from Jan 2018 to Jan 2019. The exclusion criteria were as follows: (1) with other types of diabetes; (2) pregnant or lactating females; (3) with acute complications of diabetes or other stress states, such as surgery and trauma; (4) with rheumatologic, serious hepatic, cardiac, renal failure, malignancy, and endocrine diseases that affect the metabolism of vitamin D. Serum level of 25-OH-vitamin D ≥ 30 ng/mL was defined as normal, 20 ng/mL ≤ 25-OH-vitamin D < 30 ng/mL as vitamin D insufficiency (VDI) , and serum 25-OH-vitamin D < 20 ng/mL as vitamin D deficiency (VDD) . The chi-square test was used for group comparison of VDD or VDI prevalence. In all subjects, the prevalence of VDI was 35%. Male patients had higher prevalence of VDI than female patients (40.0% vs. 28.9%, P In conclusion, VDI and VDD is prevalent in patients with type 2 diabetes. Poor glucose control is related to lower serum level of vitamin D. Future studies are required to verify if vitamin D supplementation could be beneficial in patients with diabetes. Disclosure L. Zhang: n/a. J. Wang: None. Y. Yang: None. Y. Dong: None.

BACKGROUND In China, ischemic heart disease is the main cause of mortality. Having cardiac rehabilitation and a secondary prevention program in place is a class IA recommendation for individuals with coronary artery disease. WeChat-based interventions seem to be feasible and efficient for the follow-up and management of chronic diseases. OBJECTIVE This study aims to evaluate the effectiveness of a tertiary A-level hospital, WeChat-based telemedicine intervention in comparison with conventional community hospital follow-up on medication adherence and risk factor control in individuals with stable coronary artery disease. METHODS In this multicenter prospective study, 1424 patients with stable coronary artery disease in Beijing, China, were consecutively enrolled between September 2018 and September 2019 from the Fuwai Hospital and 4 community hospitals. At 1-, 3-, 6-, and 12-month follow-up, participants received healthy lifestyle recommendations and medication advice. Subsequently, the control group attended an offline outpatient clinic at 4 separate community hospitals. The intervention group had follow-up visits through WeChat-based telemedicine management. The main end point was medication adherence, which was defined as participant compliance in taking all 4 cardioprotective medications that would improve the patient’s outcome (therapies included antiplatelet therapy, β-blockers, statins, and angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers). Multivariable generalized estimating equations were used to compare the primary and secondary outcomes between the 2 groups and to calculate the relative risk (RR) at 12 months. Propensity score matching and inverse probability of treatment weighting were performed as sensitivity analyses, and propensity scores were calculated using a multivariable logistic regression model. RESULTS At 1 year, 88% (565/642) of patients in the intervention group and 91.8% (518/564) of patients in the control group had successful follow-up data. We matched 257 pairs of patients between the intervention and control groups. There was no obvious advantage in medication adherence with the 4 cardioprotective drugs in the intervention group (172/565, 30.4%, vs 142/518, 27.4%; RR 0.99, 95% CI 0.97-1.02; P=.65). The intervention measures improved smoking cessation (44/565, 7.8%, vs 118/518, 22.8%; RR 0.48, 95% CI 0.44-0.53; PP CONCLUSIONS The tertiary A-level hospital, WeChat-based intervention did not improve adherence to the 4 cardioprotective medications compared with the traditional method. Tertiary A-level hospital, WeChat-based interventions have a positive effect on improving lifestyle, such as quitting drinking and smoking, in patients with stable coronary artery disease and can be tried as a supplement to community hospital follow-up. CLINICALTRIAL ClinicalTrials.gov NCT04795505; https://clinicaltrials.gov/ct2/show/NCT04795505

Background Pegylated interferon (PEG-IFN) alfa-2b is recommended for chronic hepatitis B (CHB). We aimed to investigate the sustainability of off-treatment responses among Chinese HBeAg-positive CHB patients treated with PEG-IFN alfa-2b from a randomized trial. Methods Eligible Chinese patients (n = 322) were followed up by one visit after a median of 6 years (LTFU) following their participation in a randomized trial evaluating the efficacy of three PEG-IFN alfa-2b dosing regimens (1.0 or 1.5 μg/kg/wk. 24 weeks or 1.5 μg/kg/wk. 48 weeks). Primary endpoints at the LTFU were sustained SR and CR (SR/CR at the end of original study [EOS] and at the LTFU). SR was defined as HBeAg loss and seroconversion to anti-HBe and CR as HBeAg loss and seroconversion to anti-HBe and HBV-DNA

Although microRNA-425-5p (miR-425-5p) has been previously revealed to be upregulated in cervical cancer, the cellular function of miR-425-5p in cervical cancer remains unknown. The aim of the current study was to investigate the cellular function of miR-425-5p and its underlying mechanism in cervical cancer. Reverse transcription-quantitative polymerase chain reaction was used to measure miR-425-5p expression in several cervical cancer cell lines. TargetScan bioinformatics analysis was used to predict apoptosis-inducing factor mitochondria-associated 1 (AIFM1) as a novel target of miR-425-5p, and this was verified by dual-luciferase reporter assay. Furthermore, cell transfections were used to investigate the role of miR-425-5p in cervical cancer. The effect of miR-425-5p on cell viability and apoptosis in HeLa cells was detected by MTT assay and flow cytometry, respectively. The present study demonstrated that miR-425-5p was significantly upregulated in cervical cancer cell lines. In addition, AIFM1 was identified as a direct target of miR-425-5p and negatively regulated by miR-425-5p. Downregulation of miR-425-5p inhibited HeLa cell viability and induced cell apoptosis. Furthermore, downregulation of miR-425-5p significantly increased the protein and mRNA expression levels of cytochrome c, caspase-3, caspase-9 and DNA damage regulated autophagy modulator 1. The effects of miR-425-5p inhibition on HeLa cell viability and apoptosis were significantly reversed by AIFM1 knockdown. In conclusion, the present study demonstrated that miR-425-5p was upregulated in cervical cancer, and downregulation of miR-425-5p inhibited cervical cancer cell growth by targeting AIFM1.

Background: The aim of our study was to characterize the genetic, pathological and clinical alterations of 17 patients in China presenting with non-dystrophic myotonia (NDM). Methods: We first sequenced the CLCN-1 gene in patients having clinical features and muscle pathology indicative of NDM. If no mutations were detected, we subsequently analyzed the SCN4A, KCNE3 and CACNA1S genes. Results: As determined by needle electromyography, patients may have accompanying atypical myopathy as well as muscle hypertrophy, secondary dystonia and joint contracture All participants in this study were administered mexiletine in combination with carbamazepine and showed significant improvements in their myotonia symptoms. Routine pathological examinations showed mild abnormalities in muscle pathology. Oxidative enzyme activity was decreased in many fibers. ATPase studies of fiber subtypes demonstrated a predominance of type 2A fibers and a complete absence of type 2B muscle fibers in patients with CLCN-1 mutations. CLCN-1 gene mutations were found in 8 cases diagnosed with myotonia congenital by gene screening. The detected mutations included 5 missense, 2 nonsense, 1 deletion and 2 insertions, and these CLCN-1 mutations were concentrated in exons 8 and 12. Further gene analysis showed 4 mutations in the SCN4A gene in patients diagnosed with paramyotonia congenita. One of these mutations was consistent with a previously reported mutation, whereas 3 mutations were novel. All of these novel mutations occurred within “hot spots” of exons 22 and 24. Five patients with NDM lacked any identifiable mutations in CLCN-1, SCN4A, CACNA1S or KCNE3. Conclusions: Myotonia congenita and paramyotonia congenita are the predominant forms of NDM in China. NDM may be best diagnosed using genetic analysis in combination with clinical features. New mutations of the CLCN-1 and SCN4A genes in patients with NDM were detected, we postulate that novel pathogenic genes for NDM occur in China.

Aims: The study aimed to investigate the relationship between metabolic syndrome (MS) and risk of cancer in patients with type 2 diabetes (T2DM). Methods: We enrolled 6587 patients with T2DM who were hospitalized in Qingdao Endocrine and Diabetes Hospital from Feb 2005 to Jan 2016. According to the number of MS component each patient had, they were divided into isolated T2DM, T2DM plus 1 component,2 components, 3 components and 4 components, respectively. The IDF Worldwide Definition of the Metabolic Syndrome was applied. Information on the diagnosis of cancer was obtained by matching ICD-10 codes recorded in local Healthcare medical records database. Prevalence of cancer was compared using Chi-square test. Logistic regression model was used to evaluate risk of cancer associated with MS. Results: The prevalence of cancer was 4.2% among 6587 patients with T2DM. Female patients had higher prevalence than did male in total or in the MS subgroup. The prevalence of cancer were 3.8%, 3.9%, 3.8%, 5.1% and 5.0% in isolated DM, T2DM plus 1 component of MS, T2DM plus 2, T2DM plus 3 and T2DM plus 4 components, respectively (P for trend Conclusions: A cluster of metabolic disorders consisting of increased waist, elevated TG and decreased HDL-C seems to be oncogenic among Chinese patients with T2DM. For patients in combination with 3 or 4 MS components, it is important to conduct early cancer screening and prevention. Disclosure L. Zhang: None. Y. Yang: None. W. Meng: None. J. Wang: None. S. Chen: None. Y. Dong: None.

Objectives: Adult-onset autoimmune diabetes, defined as having latent autoimmune diabetes in adults (LADA), is characterized by a less intensive autoimmune process, in which a lymphocytic infiltration of the exocrine pancreas is involved. immunosuppressive agents may have potential therapeutic benefit. This is a pilot study examining the therapeutic effects of ciclosporin A on insulin secretion in patients with LADA. Methods: The study was an open label, single arm, pilot trial. A total of 18 patients (12 men and 6 women with mean age of 40.6 yrs old) diagnosed with LADA were prospectively evaluated. All patients underwent insulin treatment at least for 3 months without any oral anti-hyperglycemic agent. All patients were prescribed ciclosporin A (50mg/day) for 12 weeks. Serum C-peptide concentrations were measured at baseline and 3 months after ciclosporin A intervention. We also evaluated total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (Cre) before and after ciclosporin A treatment. The primary outcome of the study was the change in serum C-peptide concentrations. Results: A total of 17 patients completed the study. One patient was withdrawn at day 32 due to discontinuation of medication. Serum fasting C-peptide concentrations significantly increased from 0.12 ng/ml up to 0.32 ng/ml (P0.05), DBIL (4.70 vs. 4.65 umol/L, P>0.05), AST (17.41 vs. 17.82 U/L, p>0.05), ALT (18.19 vs. 18.08 U/L, p>0.05), or Cre (67.40 vs. 67.53 umol/L, P>0.05) compared with the corresponding baseline levels. Conclusions: This pilot study demonstrates the potential therapeutic effects of oral administration of ciclosporin A for patients with LADA. Larger, controlled studies are needed to verify the findings. Disclosure L. Zhang: None. W. Meng: None. S. Chen: None. Y. Yang: None. J. Wang: None. Y. Dong: None.

Nonalcoholic fatty liver disease (NAFLD) is independently associated with cardiovascular disease and chronic kidney disease. Among patients with type 2 diabetes (T2DM), the relationship between NAFLD and diabetic macrovascular and microvascular complications is unclear. The study population consisted of 2504 patients (M/F: 1520/984, mean age 60.8 ± 10.4 years) with T2DM who have been hospitalized between 2007 and 2011. All subjects had data on anthropometric parameters, total cholesterol (TC), low-density lipoprotein cholesterol, HbA1C, creatinine (Scr), tumor necrosis factor- α (TNF-α), and 24h urine albumin exerting rate (24hUAER). Doppler ultrasound examination was used to diagnose fatty liver and to measure carotid artery intima-media thickness (IMT). Carotid artery intimal thickening was diagnosed as IMT≧1mm. Diabetic nephropathy (DN) was diagnosed if 24hUAER≧30mg/24h. NAFLD accounted for 57.4% of all patients. After adjusting for age, gender, disease duration, systolic blood pressure (SBP), waist and other factors, patients with NAFLD had increased carotid artery IMT (1.11 ± 0.25 vs. 0.87 ±0.18 mm, P Disclosure L. Zhang: None. N. Wang: None. J. Wang: None. X. Yin: None. Y. Yang: None. W. Gao: None. Y. Dong: None.

Vitamin D deficiency is not only related to bone-related diseases but also associated with cardiovascular disease, diabetes, cancer and autoimmune diseases. Previous studies show that vitamin D deficiency increases risk of diabetic peripheral neuropathy (DPN). Data is limited among Chinese patients with type 2 diabetes. In this cross-sectional study, we enrolled 5362 patients (2359 men and 3003 women aged 30 to 89 years) with type 2 diabetes from Jan 1, 2016 to Oct 31, 2018. Serum 25-hydroxyvitamin D (25(OH)D) level was measured by electrochemiluminescence assay. Vitamin D deficiency was defined as Serum 25(OH)D level < 20 ng/mL according to the Endocrine Society Clinical Practice Guideline 2011. Diabetic peripheral neuropathy was diagnosed by motor/sensory nerve conduction velocity. Patients with diabetic peripheral neuropathy had lower serum 25(OH)D concentration (16.81±3.83 ng/mL vs. 18.05±4.11 ng/mL, P Disclosure L. Zhang: None. Y. Gu: None. Y. Yang: None. Y. Zhu: None. X. Yin: None. Y. Dong: None.

The study aimed to investigate the effect of 7-point or 5-point glucose monitoring on medical costs, glycemic control and the incidence of hypoglycemia in hospitalized patients with type 2 diabetes (T2DM). A total of 4002 patients with T2DM (1490 male and 2512 female cases) with complete medical records were included between 2012 and 2017. The average age was 61.5 years and the mean disease duration 8.68 years. According to the frequency of daily monitoring of blood glucose during hospitalization, patients were divided into 2 subgroups of 5-point group and 7-point group. Patients in 5-point group received fasting blood glucose (FBG), 2h blood glucose (2hBG) after breakfast, 2hBG after lunch, 2hBG after dinner and bedtime blood glucose tests. Patients in 7-point group received additional tests of pre-lunch glucose and pre-dinner blood glucose. Blood glucose monitoring was performed using Johnson & Johnson SureStep blood glucose meter. Comparison of two groups includes duration of in-hospital stay, medical costs, glycemic control and the incidence of hypoglycemia. Patients in 7-point glucose monitoring group had significantly shorter hospital stay (14.4 vs. 16.6 days, P0.05). At discharge, both fasting and 2-h glucose decreased significantly compared with baseline levels in either 5-point or 7-point group. In 7-point group, FPG decreased by 2.41mmol/L and 2hPG by 3.9mmol/L. In the 5-point group, the corresponding figures were 2.07mmol/L and 3.6mmol/L, respectively. The incidence of hypoglycemia were 24.2% in 7-point group and 33.1% in 5-point group (P Disclosure L. Zhang: None. Y. Gu: None. Y. Yang: None. N. Wang: None. W. Gao: None. J. Wang: None. X. Yin: None. Y. Dong: None.

Adult-onset autoimmune diabetes, defined as having latent autoimmune diabetes in adults (LADA), is characterized by a less intensive autoimmune process, in which a lymphocytic infiltration of the exocrine pancreas is involved. Immunosuppressive agents may have potential therapeutic benefit. This is a pilot study examining the therapeutic effects of oral administration of ciclosporin A on insulin secretion in patients with LADA. The study was an open label, single arm, pilot trial. A total of 12 patients (8 men and 4 women with mean age of 40.2 years old) diagnosed with LADA were prospectively evaluated. All patients underwent insulin treatment at least for 3 months without any oral anti-hyperglycemic agent. Serum C-peptide concentrations were measured at baseline and after ciclosporin A intervention. We also evaluated clinical parameters including total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (Cre) before and after ciclosporin A treatment. The primary outcome of the study was the change in serum C-peptide concentrations. A total of 12 patients completed the study. No patient was withdrawn. Serum fasting C-peptide concentrations significantly increased from 0.10 ng/ml up to 0.32 ng/ml, following treatment with ciclosporin A (50mg/day) for 4 weeks (P Disclosure L. Zhang: None. J. Wang: None. N. Wang: None. Y. Yang: None. X. Yin: None. Y. Dong: None.

Patients with diabetes (DM) are at high risk for restenosis after coronary stenting. Information relating the outcome of percutaneous transluminal coronary angioplasty (PTCA) to prediabetes is, however, limited. The study objective was to investigate the relationship between restenosis after PTCA and baseline glucose categories. We retrospectively analyzed data of 1003 patients (mean age 58.5±4.2 years, 61.5% of men, mean history of coronary heart disease 9.5±1.1 years) who undertook PTCA at Emergency Department between Jan 2008 and Dec 2011. Baseline measures included blood pressure (BP), fasting plasma glucose, lipid profile, HbA1c, C-reactive protein (C-RP), and 2-hour capillary glucose. All patients had follow-up coronary angiography 2 year after PTCA. Restenosis was defined as ≧ 50% stenosis in stent or within 5 mm adjacent to stent. The rate of restenosis was compared among patients with normal glucose tolerance (NGT, n=436), impaired glucose regulation (IGR, n=275), and DM (n=292) according to their baseline glucose levels or prior history of DM. Patients with DM had highest levels of body mass index (BMI), BP, triglycerides (TG), and C-RP, followed by those with IGR and NGT (P8% had increased rate of restenosis (14.6% vs. 11.2%, P Disclosure L. Zhang: None. Y. Gu: None. X. Yin: None. J. Wang: None. N. Wang: None. Y. Yang: None. Y. Dong: None.

Summary Maintaining homeostasis of Ca 2+ stores in the endoplasmic reticulum (ER) is crucial for proper Ca 2+ signaling and key cellular functions. The Ca 2+ -release-activated Ca 2+ (CRAC) channel is responsible for Ca 2+ influx and refilling after store depletion, but how cells cope with excess Ca 2+ when ER stores are overloaded is unclear. We show that TMCO1 is an ER transmembrane protein that actively prevents Ca 2+ stores from overfilling, acting as what we term a "Ca 2+ load-activated Ca 2+ channel" or "CLAC" channel. TMCO1 undergoes reversible homotetramerization in response to ER Ca 2+ overloading and disassembly upon Ca 2+ depletion and forms a Ca 2+ -selective ion channel on giant liposomes. TMCO1 knockout mice reproduce the main clinical features of human cerebrofaciothoracic (CFT) dysplasia spectrum, a developmental disorder linked to TMCO1 dysfunction, and exhibit severe mishandling of ER Ca 2+ in cells. Our findings indicate that TMCO1 provides a protective mechanism to prevent overfilling of ER stores with Ca 2+ ions.

// Bin Yan 1, * , Zhongsheng Lu 1, * , Zhizheng Ge 2 , Side Liu 3 , Xuegang Guo 4 , Dean Tian 5 , Yuxiu Yang 6 , Xiaobo Li 2 , Wei Gong 3 , Zhiguo Liu 4 , Mei Liu 5 , Bingxi Zhou 6 , Kabing Zhao 1 , Jing Yang 1 and Yunsheng Yang 1 1 Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, China 2 Department of Gastroenterology and Hepatology, Renji Hospital, Shanghai, China 3 Department of Gastroenterology and Hepatology, Nanfang Hospital, Guangzhou, Guangdong Province, China 4 Department of Gastroenterology and Hepatology, Xijing Hospital, Xian, Shanxi province, China 5 Department of Gastroenterology and Hepatology, Tongji Hospital, Wuhan, Hubei province, China 6 Department of Gastroenterology and Hepatology, Henan Provincial People’s Hospital, Zhengzhou, Henan Province, China * These authors contributed equally to this work Correspondence to: Yunsheng Yang, email: sunny301ddc@126.com Keywords: randomized clinical trial; endoscopic submucosal dissection; ulcer; lansoprazole; rebamipide Received: September 29, 2017 Accepted: November 15, 2017 Published: January 02, 2018 ABSTRACT Objective: To evaluate the healing efficacy of rebamipide and lansoprazole combination therapy with lansoprazole alone for endoscopic submucosal dissection (ESD)–induced ulcers and clarify the ulcer healing-associated factors. Materials and Methods: Three hundred patients were randomized into control and experimental groups after undergoing ESD. The patients received intravenous pantoprazole (30 mg) every 12 hours and oral rebamipide (100 mg, experimental group) or placebo (control group) three times daily on days 1–3. On days 4–56, patients received oral lansoprazole (30 mg daily) and rebamipide (100 mg) or placebo three times daily. Endoscopic evaluations were performed at postoperative 4 and 8 weeks. Results: At week 4, the ulcer reduction rate was significantly higher in the experimental than in the control group (0.94 ± 0.078 vs. 0.97 ± 0.034; P < 0.001). The ulcer healing (20.3% vs 18.2%; P = 0. 669) and ulcer improvement rates (88.7% vs 94.2%; P = 0. 109) in the two groups were not significantly different. At week 8, the ulcer healing and ulcer improvement rates were 90.6% and 100%, respectively, in both groups. Multivariate analysis showed that the combination treatment was an independent factor associated with ulcer area reduction after ESD. The maximum diameter of the initial ulcer (≥ 35.5 mm vs. < 35.5 mm) was an independent factor associated with the ulcer improvement rate after ESD. Conclusions: The rebamipide and lansoprazole combination therapy can help accelerate the reduction rate of post-ESD ulcer compared with the lansoprazole monotherapy at four weeks of therapy.

BackgroundIn mainland China, peginterferon (PEG-IFN) alfa-2b 1.0μg/kg/wk for 24 weeks is the approved treatment for HBeAg-positive chronic hepatitis B.ObjectiveThis multicenter, randomized trial evaluated the safety and efficacy of regimens utilizing increased dose or treatment duration in treatment-naive Chinese patients with chronic hepatitis B.Study design670 HBeAg-positive patients from China, Malaysia, Taiwan area, Singapore, and Thailand were enrolled. Patients received PEG-IFN alfa-2b 1.0μg/kg/wk (arm A) or 1.5μg/kg/wk (arm B) for 24 weeks, or 1.5μg/kg/wk for 48 weeks (arm C). The primary end point was loss of HBeAg 24 weeks after end of treatment.ResultsAt the end of follow-up, HBeAg loss was significantly greater in arm C compared with arm A (31.3% vs. 17.3%; P=0.001) and arm B (31.3% vs. 18.1%; P=0.001). No significant difference in the rate of HBeAg loss was observed between arms A and B. The proportions of patients with HBe seroconversion, HBV DNA levels

OBJECTIVES: To evaluate the healing efficacy of rebamipide and lansoprazole combination therapy with lansoprazole alone for endoscopic submucosal dissection (ESD)–induced ulcers and clarify the ulcer healing-associated factors. METHODS: Three hundred patients were randomized into control and experimental groups after they underwent ESD. The patients received intravenous pantoprazole (30 mg) every 12 hours and oral rebamipide (100 mg, experimental group) or placebo (control group) 3 times daily on days 1–3. On days 4–56, patients received oral lansoprazole (30 mg daily) and rebamipide (100 mg) or placebo 3 times daily. Endoscopic evaluations were performed at postoperative weeks 4 and 8. RESULTS: At week 4, the ulcer reduction rate was significantly higher in the experimental than in the control group (0.97 ± 0.034 vs. 0.94 ± 0.078; P < 0.001). The ulcer healing (18.2% vs 20.3%; P = 0.669) and ulcer improvement rates (94.2% vs 88.7%; P = 0.109) in the 2 groups were not significantly different. At week 8, the ulcer healing and ulcer improvement rates were 90.6% and 100%, respectively, in both groups. Multivariate analysis showed that the combination treatment was an independent factor associated with ulcer area reduction after ESD. The maximum diameter of the initial ulcer (≥35.5 mm vs

Nonalcoholic steatohepatitis (NASH) has similar clinical pathological changes to alcoholic hepatitis. It shows increased incidence and young trend year by year. Polyene phosphatidyl choline (PPC) is widely used in clinic for liver disease treatment. The effect and mechanism of PPC on NASH have not been fully elucidated. Thirty healthy male Wistar rats were randomly equally divided into control, NASH group, and PPC group. NASH model was established by high fat diet. PPC was intraperitoneal injected to NASH rat from the second week at 80 mg/kg·d for three weeks. Body weight, liver weight index, ALT, AST, TG, and TC were tested. TNF-α and IL-1β levels were detected by ELISA. NF-κB mRNA and protein expression in liver tissue were determined by real time PCR and Western blot. SOD activity and ROS content were measured by colorimetry. NASH rat presented significantly elevated body weight and liver weight index, increased ROS content, declined SOD activity, enhanced liver function and inflammatory factors expression, and upregulated NF-κB mRNA and protein levels compared with control (P < 0.05). PPC intervention obviously reduced body weight and liver weight index, declined ROS content, amplified SOD activity, decreased liver function, weakened inflammatory factor TNF-α and IL-1β expression, and downregulated NF-κB mRNA and protein levels compared with NASH group (P < 0.05). PPC can play a treatment effect on NASH through regulating oxidative balance, inhibiting inflammatory factors and NF-κB signaling pathway.

This study aimed to investigate the presence of plasma minichromosome maintenance complex component 6 (MCM6) mRNA and protein levels in hepatocellular carcinoma (HCC) patients and evaluate their diagnostic value for HCC.Blood samples were collected from 61 HCC and 29 cirrhotic patients, and 30 healthy individuals. Circulating RNA was extracted from plasma of all samples. The mRNA for MCM6 were amplified and quantified by real-time polymerase chain reaction. Plasma MCM6 and α-fetoprotein (AFP) protein levels were measured by enzyme-linked immunosorbent assay.In HCC patients, MCM6 mRNA and protein levels were significantly increased over the cirrhotic and healthy controls. The levels of MCM6 mRNA and protein in the plasma of HCC patients correlated to vascular invasion (P 0.01). Higher MCM6 protein levels also correlated with tumor stage progression and lymph node metastasis. The MCM6 protein has sensitivity of 67.2% and specificity of 89.8% in differentiating total HCC from non-HCC individuals. In the AFP negative HCC group, MCM6 mRNA and protein could both detect 76.9% of HCC patients; combining the two of them increased the detection rate to 84.6%. In small HCC patients, MCM6 mRNA and protein could detect 64.3% and 71.4% of patients, respectively; combining AFP, MCM6 mRNA and MCM6 protein could detect 85.7% of small HCC patients.Our results suggest that MCM6 mRNA and protein levels in plasma can be promising independent biomarkers for HCC, especially in AFP negative and small HCC patients.

CD24 is reported to be up-regulated in the tissues of HCC patients when compared with normal liver tissues. We aim to determine whether CD24 protein is also overexpressed in the plasma of HCC patients, and its diagnostic value for HCC.Plasma levels of CD24 protein and AFP were measured by enzyme linked immunosorbent assay (ELISA) in the plasma of 90 patients with hepatocellular carcinoma and 30 healthy controls. The sensitivity and specificity were calculated and the relationship between the expression of CD24 and clinical pathological parameters was analyzed.Both plasma CD24 protein and AFP levels in HCC patients were higher than those in healthy controls (p0.05). There was no correlation between plasma levels of AFP and CD24 in 90 patients with HCC (r=-0.084, p=0.430). The best cut-off value of CD24 was 3.31ng/mL, which yielded a sensitivity and specificity of 83.3% and 93.3%, respectively, for screening HCC; and plasma CD24 level was not associated with gender, age, hepatitis infection status, tumor size and histological differentiation and TNM stage (p0.05).Plasma CD24 protein might serve as a novel tumor marker in differentiating HCC patients from normal individuals as well as monitor HCC status in AFP negative HCC patients.

Summary Influenza pandemics are a serious threat to public health in today's world. In the past 10 years, the outbreak of three forms of severe influenza – H5N1, H1N1, and H7N9 – has caused tremendous loss of life and property. In order to better cope with pandemics, antivirals such as oseltamivir are being stockpiled in great quantities, placing a substantial burden on government budgets and potentially resulting in massive waste because of the uncertainty as to when an influenza pandemic will strike and whether emerging virus strains will be resistant to the stockpiled drugs. Complementary and alternative medicine (CAM) is generally available, affordable, and commonly used in China and many other countries and CAM has a long track record of fighting influenza. The Chinese Government appropriated funds to intensively investigate herbal medicines in accordance with the principles of evidence-based medicine in order to identify effective, inexpensive, and easily stockpiled medicines. Thus far, several drugs including Shufeng Jiedu capsules, Lianhua Qingwen capsules, Maxing Shigan decoction, Yinqiao powder, and Jinhua Qinggan granules have demonstrated effectiveness in fighting influenza. In the future, CAM is expected to make greater contribution in controlling the prevalence of influenza pandemics.

Analysis of the efficacy and timing of plasma exchange (PE) in the treatment of acute fatty liver of pregnancy (AFLP).The clinical data of 39 cases of AFLP treated with PE from September 2004 to March 2011 include symptoms, physical signs, adverse effects, and all relevant laboratory test results before and after PE.(1) Adverse reactions during PE were generally mild and tolerable, and no patients discontinued treatment due to adverse events; symptoms, physical signs, and liver and kidney functions improved significantly after PE (P0.05); (2) of the 39 cases treated, 37 were cured, 2 died, with a cure rate of 94.87%; (3) of the 37 cases cured, the sooner a patient received PE the faster the recovery and the fewer number of PEs needed for a complete recovery (P0.01).Treatment of AFLP by PE is safe and effective, and timely application of PE in the early phase of the disease can effectively halt and reverse the progression of AFLP.

Background This study aimed to evaluate the predictive values of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) levels in 171 Chinese patients with chronic hepatitis B who received a 48-week course of pegylated interferon alfa-2b therapy at 1.5 mcg/kg. Methods HBsAg, HBeAg, and hepatitis B virus (HBV) DNA levels were measured at baseline and weeks 12, 24, 48, and 72. Clinical responses were defined as a combined response (CR, HBeAg seroconversion [sustained response, SR] combined with HBV DNA level 1.5 logIU/mL at week 12 had a 54.5 % chance. Patients with HBsAg >20,000 IU/mL at weeks 12 and 24 had a 93.8 and 100.0 % chance, respectively, of not achieving a CR. An HBsAg level or changes at weeks 12 and 24, combined with HBeAg or HBV DNA, increased the chance for a SR and CR. Conclusions On-treatment HBsAg quantification, alone or in combination with HBeAg or HBV DNA, predicted off-treatment SR and CR after 48 weeks of PEG-IFNα-2b therapy, and thus, may guide clinicians in making a therapeutic decision to continue or terminate the therapy.