Vincent Wong

Endogenous ribonucleotides and deoxyribonucleotides are essential metabolites that play important roles in a broad range of key cellular functions. Their intracellular levels could also reflect the action of nucleoside analogues. We investigated the effects of 5-fluorouracil (5-FU) on ribonucleotide and deoxyribonucleotide pool sizes in cells upon exposure to 5-FU for different durations. Unsupervised and supervised artificial neural networks were compared for comprehensive analysis of global responses to 5-FU. As expected, deoxyuridine monophosphate (dUMP) increased after 5-FU incubation due to the inhibition of thymine monophosphate (TMP) synthesis. Interestingly, the accumulation of dUMP could not lead to increased levels of deoxyuridine triphosphate (dUTP) and deoxyuridine diphosphate (dUDP). After the initial fall in intracellular deoxythymidine triphosphate (TTP) concentration, its level recovered and increased from 48 h exposure to 5-FU, although deoxythymidine diphosphate (T...

Calcium is a second messenger which is required for regulation of many cellular processes. However, excessive elevation or prolonged activation of calcium signaling would lead to cell death. As such, selectively regulating calcium signaling could be an alternative approach for anti-cancer therapy. Recently, we have identified an effective analogue of resveratrol, (Z)3,4,5,4'-trans-tetramethoxystilbene (TMS) which selectively elevated the intracellular calcium level in gefitinib-resistant (G-R) non-small-cell lung cancer (NSCLC) cells. TMS exhibited significant inhibitory effect on G-R NSCLC cells, but not other NSCLC cells and normal lung epithelial cells. The phosphorylation and activation of EGFR were inhibited by TMS in G-R cells. TMS induced caspase-independent apoptosis and autophagy by directly binding to SERCA and causing endoplasmic reticulum (ER) stress and AMPK activation. Proteomics analysis also further confirmed that mTOR pathway, which is the downstream of AMPK, wa...

Controlled attenuation parameter (CAP) evaluated with transient elastography (FibroScan) is a recent method for non-invasive assessment of steatosis. Its usefulness in NonAlcoholic Fatty Liver Disease (NAFLD) in unknown. We prospectively investigated the performance of CAP for the diagnosis of steatosis in NAFLD, factors associated discordances between CAP and steatosis grades, and relationships between CAP and clinical or biological parameters. All CAP examinations performed in NAFLD patients with a liver biopsy performed within one week of CAP measurement were included. Liver biopsies were assessed for activity and fibrosis stage, NAFLD activitiy score, and steatosis graded as follows: S0, steatosis < 5%; S1, 5-33%; S2, 34-66%; S3, >66%. 261 patients (59% males, age 56 years) from two ethnic groups were included. No patient had steatosis < 5%. The area under the receiver-operating characteristics curve of CAP for steatosis ≥ S2 and S3 was 0.80, and 0.66 respectively. At a cut-off value of 310 dB/m, the sensitivity, specificity, positive and negative predictive values for ≥ S2 steatosis were 79%, 71%, 86% and 71%, respectively. Discordance of at least one grade between CAP and steatosis was observed in 81 patients. By multivariate analysis, only steatosis S2S3 was associated with no discordance. By multivariate analysis, only BMI ≥ 30 kg/m(2) was significantly associated with CAP > 310 dB/m. The association of CAP with steatosis, especially in patients with nonalcoholic steatohepatitis, and with elevated BMI could be useful for the diagnosis and follow-up of NAFLD patients.

Dietary pattern analysis is an alternative approach to examine the association between diet and nonalcoholic fatty liver disease (NAFLD). This study examined the association of two diet-quality scores, namely Diet Quality Index-International (DQI-I) and Mediterranean Diet Score (MDS) with NAFLD prevalence. Apparently healthy Chinese adults (332 male, 465 female) aged 18 years or above were recruited through a population screening between 2008 and 2010 in a cross-sectional population-based study in Hong Kong. DQI-I and MDS, as well as major food group and nutrient intakes were calculated based on dietary data from a food frequency questionnaire. NAFLD was defined as intrahepatic triglyceride content at ≥5% by proton-magnetic resonance spectroscopy. Multivariate logistic regression models were used to examine the association between each diet-quality score or dietary component and prevalent NAFLD with adjustment for potential lifestyle, metabolic and genetic factors. A total of 220 su...

The growing epidemic of obesity, which causes non-alcoholic fatty liver disease (NAFLD) and the more severe phenotype non-alcoholic steatohepatitis (NASH), has paralleled the increasing incidence of hepatocellular carcinoma (HCC). Accumulating evidence demonstrates that over-nutrition and metabolic pathways can trigger modifications of DNA and histones via deregulation of chromatin modifiers, resulting in aberrant transcriptional activity. However, the epigenetic regulation of HCC development in NAFLD remains obscure. Here we uncover key epigenetic regulators using both dietary and genetic obesity-promoted HCC models through quantitative expression profiling and characterize the oncogenic activities of histone deacetylase HDAC8 in NAFLD-associated hepatocarcinogenesis. HDAC8 is directly upregulated by the lipogenic transcription factor SREBP-1 where they are co-expressed in dietary obesity models of NASH and HCC. Lentiviral-mediated HDAC8 attenutation in vivo reversed insulin resist...

Activation of IκB kinase β (IKK-β) and nuclear factor (NF)-κB signaling contributes to cancer pathogenesis and inflammatory disease; therefore, the IKK-β-NF-κB signaling pathway is a potential therapeutic target. Current drug design strategies focus on blocking NF-κB signaling by binding to specific cysteine residues on IKK-β. However, mutations in IKK-β have been found in patients who may eventually develop drug resistance. For these patients, a new generation of IKK-β inhibitors are required to provide novel treatment options. We demonstrate in vitro that cysteine-46 (Cys-46) is an essential residue for IKK-β kinase activity. We then validate the role of Cys-46 in the pathogenesis of inflammation using delayed-type hypersensitivity (DTH) and an IKK-β C46A transgenic mouse model. We show that a novel IKK-β inhibitor, dihydromyricetin (DMY), has anti-inflammatory effects on WT DTH mice but not IKK-β C46A transgenic mice. These findings reveal the role of Cys-46 in the promotion of i...

Patients with Non-Alcoholic Fatty Liver Disease (NAFLD) and family history of Colorectal Cancer (CRC) are at higher risks but how they should be screened remains uncertain. Hence, we evaluated the cost-effectiveness of CRC screening among patients with NAFLD and family history by different strategies. A hypothetical population of 100,000 subjects aged 40-75 years receive:(1).yearly Faecal Immunochemical Test (FIT) at 50 years;(2).Flexible Sigmoidoscopy (FS) every 5 years at 50 years;(3).colonoscopy 10 yearly at 50 years;(4).colonoscopy 10 yearly at 50 years among those with family history/NAFLD and yearly FIT at 50 years among those without;(5).colonoscopy 10 yearly at 40 years among those with family history/NAFLD and yearly FIT at 50 years among those without;(6).colonoscopy 10 yearly at 40 years among those with family history/NAFLD and colonoscopy 10 yearly at 50 years among those without. The Incremental Cost-Effectiveness Ratio (ICER) was studied by Markov modeling. It was fou...

Traditionally, the LCD driver chip has been play- ing the simple role of signal driving for LCD panels. However, with the recent trends of moving towards highly integrated, com- pact, light-weight, and long-battery life in mobile applications, such as cellular, pager and PHS, both the function and package considerations of the LCD driver chips are becoming critical to fulfil these

Some studies suggest that non-obese patients with nonalcoholic fatty liver disease (NAFLD) may have more severe disease. We aim to study the epidemiology and severity of non-obese NAFLD. A total of 911 community subjects were randomly recruited from the census database of the Hong Kong Government. Intrahepatic triglycerides (IHTG) and liver fibrosis were assessed by proton-magnetic resonance spectroscopy and transient elastography, respectively. The Asian body mass index cutoff of 25 kg/m(2) was used to define non-obese NAFLD. The prevalence of NAFLD was 19.3% in non-obese subjects and 60.5% in obese subjects (P<0.001). Compared with obese NAFLD patients, non-obese NAFLD patients had similar IHTG content (median 9.8% vs. 9.9%; P=0.100) but lower cytokeratin-18 fragments (149 vs. 182 IU/l; P=0.019) and liver stiffness (4.6 vs. 5.6 kPa; P<0.001). The G allele at the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3 rs738409) was more common in non-obese than obese NAFLD patients (78.4% vs. 59.8%; P=0.001). Obesity, high hemoglobin A1c, insulin resistance, hyperferritinemia, and the PNPLA3 G allele were independent factors associated with NAFLD in non-obese subjects. Even among non-obese subjects with normoglycemia, those with NAFLD were more insulin resistant (mean homeostasis model assessment of insulin resistance: 2.0±1.0 vs. 1.1±1.1; P<0.001). One-fifth of the general non-obese Chinese population has NAFLD. Non-obese patients with NAFLD do not have a higher risk of steatohepatitis or advanced fibrosis. Patients with risk factors of advanced fibrosis such as metabolic syndrome and PNPLA3 G allele carriage should be assessed for severe NAFLD.Am J Gastroenterol advance online publication, 28 July 2015; doi:10.1038/ajg.2015.235.

The use of statin in hepatocellular carcinoma (HCC) and death prevention is still uncertain among hepatitis B-infected (HBV) patients. This study aimed to examine the effect of statin on HCC and death in HBV population METHODS: We conducted a hospital-based population study of HBV patients, using the Hospital Authority database in Hong Kong. We defined statin use by landmark analysis to abrogate "immortal time bias" and propensity score (PS) weighting to minimise baseline confounders and "indication bias". Multiple imputations for missing data were performed. The weighted Cox regression analyses was performed for the risk of HCC (adjusting for competing mortality) and death. A total of 73,499 patients with a crude HCC incidence of 1.75 per 100 patient-years were entered into the 2-year landmark analysis. After landmark analysis and PS weighting of baseline covariates, statin users had 32% risk reduction in HCC (weighted sub-hazard ratio (SHR) 0.68; 95% CI 0.48-0.97) compared to non-users. There was no decreased risk of death in statin users (weighted HR 0.92; 0.76-1.11, p=0.386). In subgroup analysis, concurrent statin and nucleos(t)ide analogue (NA) use was associated with 59% risk reduction in HCC (weighted SHR 0.41; 0.19-0.89, p=0.023) compared to NA use alone. In this HBV cohort adjusted for confounders and biases, statin use is associated with reduced HCC risk by 32%. Additive HCC chemopreventive effect was seen with the concomitant use of NA and statin. Further prospective studies are warranted to investigate the potential use of statin in NA users.

In this paper, we propose a novel optimization-based pre-equalization filter (PEF) design for direct-sequence ultra-wideband (DS-UWB) systems with pre-Rake combining. The key feature in our design is that we explicitly take into account the spectral mask constraints that are usually imposed by the telecommunication regulation bodies. This avoids the need for an inefficient power back-off, which is necessary for transmit structures designed solely based on average transmit power constraints. Simulation results confirm that the proposed PEF design leads to significant performance gains over UWB PEF structures without explicit spectral mask considerations.

Absfracf - Most current routing protocols for mobile ad hoc networks consider the shortest path with minimum hop counts 8s the optimal route. However, the minimum end-to-end delay from source to destination may not always be achieved through this shortest path. I n this ...

Hepatocellular carcinoma (HCC) is a worldwide threat to public health, especially in China where chronic hepatitis B virus (HBV) infection is found in 80-90% of all HCCs. The HBV encoded X antigen (HBx) is a trans-regulatory protein involved in virus-induced hepatocarcinogenesis. Although the carboxyl-terminus truncated HBx, rather than the full-length counterpart, is frequently overexpressed in human HCCs, its functional mechanisms are not fully defined. We investigated the molecular function of a naturally-occurring HBx variant which has 35 amino acids deleted at the C-terminus (HBxΔ35). Genome-wide scanning analysis and PCR validation identified growth arrest-specific 2 (GAS2) as a direct target of HBxΔ35 at the transcriptional level in human immortalized liver cells. HBxΔ35 was found to bind the promoter region of GAS2 and attenuate its expression to promote hepatocellular proliferation and tumorigenicity. Further functional assays demonstrated that GAS2 induces p53-dependent ap...

Widespread and long-term use of oral nucleos(t)ide analogues (NAs) to treat chronic hepatitis B (CHB) brings about the safety data in real-life setting. We aimed to determine the risks of renal and bone side effects in patients receiving/who have received NAs as CHB treatment. A territory-wide cohort study using the database from Hospital Authority, the major provider of medical services in Hong Kong was conducted. We identified CHB patients by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes, diagnosed between 2000 and 2012. The primary events were renal (incident renal failure and renal replacement therapy [RRT]) and bone events (incident hip, vertebral and all fractures). A 3-year landmark analysis was used to evaluate the relative risk of primary outcome in patients with or without NA treatment. 53,500 CHB patients (46,454 untreated and 7,046 treated), who were event-free for 3 years, were included in the analysis. At a median follow-up of 4.9 years, chronic renal failure, RRT, all fractures, hip fractures and vertebral fractures occurred in 0.6%, 0.2%, 0.7%, 0.1% and 0.1% of untreated subjects; and 1.4%, 0.7%, 1.3%, 0.2% and 0.2% of treated subjects. After propensity score weighting, NA therapy did not increase the risk of any of the events (hazard ratios [HR] ranged from 0.79-1.31; P=0.225-0.887). Exposure to nucleotide analogues, compared with nucleoside analogues, increased the risk of hip fracture (HR=5.69, 95% confidence interval 1.98-16.39, P=0.001) but not other events (HR=0.58-1.44; P=0.202-0.823). NA treatment does not increase the risk of renal and bone events in general. Nucleotide analogues may increase the risk of hip fracture, but the overall event rate is low. This article is protected by copyright. All rights reserved.

Diastolic reserve is the ability of left ventricular filling pressures to remain normal with exercise. Impaired diastolic reserve may be an early sign of diabetic cardiomyopathy. We aimed to determine whether diastolic reserve differs in type 2 diabetes (DM) compared with non-DM, and to identify clinical, anthropological, metabolic and resting echocardiographic correlates of impaired diastolic reserve in patients with DM. 237 patients (aged 53±11 years, 133 DM, ejection fraction 68±9%) underwent rest and exercise echocardiography. Mitral E and septal e' were measured at rest, immediately post, and 10 min into recovery. Analysis of covariance (ANCOVA) and binary regression with continuous outcomes were used to model e' and E/e' changes with exercise to identify impaired diastolic reserve defined as post-exercise E/e' ≥15. After adjusting for baseline differences, patients with DM immediately post-exercise had a lower septal e', a lower Δe' (1.2 vs 2.3 cm/s, p=...

Nonalcoholic fatty liver disease (NAFLD) has been associated with reduced growth hormone levels and signaling. Such hormonal changes also occur in metabolic acidosis. Since mild metabolic acidosis can be diet induced, diet-induced acid load may constitute a nutritional factor with possible influence on NAFLD development. This study explored whether a higher diet-induced acid load is associated with an increased likelihood of NAFLD. Apparently healthy Chinese adults (330 male, 463 female) aged 19-72 years were recruited through population screening between 2008 and 2010 in a cross-sectional population-based study in Hong Kong. Estimated net endogenous acid production (NEAP) was calculated using Frassetto's method and potential renal acid load (PRAL) was calculated using Remer's method based on dietary data from a food frequency questionnaire. NAFLD was defined as intrahepatic triglyceride content at >5% by proton-magnetic resonance spectroscopy. Possible advanced fibrosis was defined as liver stiffness at >7.9 kPa by transient elastography. Multivariate logistic regression models were used to examine the association between each measure of dietary acid load and prevalent NAFLD or possible advanced fibrosis with adjustment for potential anthropometric and lifestyle factors. 220 subjects (27.7%) were diagnosed with NAFLD. Estimated NEAP was positively associated with the likelihood of having NAFLD after adjustment for age, sex, body mass index, current drinker status and the presence of metabolic syndrome [OR (95% CI) = 1.25 (1.02-1.52), p = 0.022]. The association was slightly attenuated but remained significant when the model was further adjusted for other dietary variables. No association between PRAL and NAFLD prevalence was observed. Both estimated NEAP and PRAL were not associated with the presence of possible advance fibrosis. Our findings suggest that there may be a modest association between diet-induced acid load and NAFLD. More studies are needed to ascertain the link between diet-induced acid load and NAFLD and to investigate the underlying mechanisms.

Type 2 diabetes is an important risk factor for non-alcoholic fatty liver disease (NAFLD), but current guidelines provide conflicting recommendations on whether diabetic patients should be screened for NAFLD. We therefore studied the strategy of screening diabetic patients by FibroScan. Liver fat and fibrosis were assessed by controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) by FibroScan at a diabetic centre for patients from primary care and hospital clinics. Probe-specific LSM cut-offs were used to detect advanced fibrosis. Of 1918 patients examined, 1799 (93.8%) had valid CAP and 1884 (98.2%) had reliable LSM (1770 with the M probe and 114 with the XL probe). The proportion of patients with increased CAP and LSM was 72.8% (95% CI 70.7% to 74.8%) and 17.7% (95% CI 16.0% to 19.5%), respectively. By multivariable analysis, female gender, higher body mass index, triglycerides, fasting plasma glucose and alanine aminotransferase (ALT) and non-insulin use we...

In this paper, we propose a distributed random medium access control (MAC) algorithm for wireless ad hoc networks based on the framework,of network utility maximization (NUM). Compared,with the related algorithms proposed in the literature, our algorit hm achieves the optimal network performance without frequent explicit message passing among wireless users. This is of critical importance in practice, since any

Approximately one-quarter of patients with Barcelona Clinic Liver Cancer (BCLC) stage 0/A hepatocellular carcinoma (HCC) suffer from tumor relapse within the first year after surgical resection. Little data is available for inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI), in predicting the clinical outcome of patients with very early/early stage HCC who underwent curative surgery. A retrospective cohort study of 324 patients with BCLC stage 0/A primary HCC undergoing surgical resection was conducted to investigate the prognostic impacts of NLR, PLR, and PNI. The low-PNI group (<45) had an adverse overall survival (1-year survival rate of 92 vs. 97 %; 5-year survival rate of 57 vs. 82 %; p < 0.001) and disease-free survival (1-year survival rate of 69 vs. 85 %; 5-year survival rate of 39 vs. 63 %; p < 0.001). It was an independent predictor for disease-specific death, and early and late tumor relapses, with hazard ratios of 2.78 (p < 0.001), 1.82 (p = 0.011), and 2.55 (p = 0.013), respectively. Neither NLR nor PLR had any prognostic significance. The PNI is a significant prognostic factor for OS and DFS of patients with very early/early stage HCC receiving curative surgery.

Serum albumin and bilirubin are the most significant independent prognostic factors to predict hepatic events in patients with primary biliary cirrhosis (PBC). We aimed to investigate the prognostic significance of a new prognostic score, the albumin-bilirubin (ALBI) score, among PBC patients. In a retrospective longitudinal cohort of 61 Chinese PBC patients with follow-up period up to 18.3 years, the prognostic performance of the ALBI in prediction of hepatic events was compared with other well-established prognostic scores: Child-Pugh score, Model for End-stage Liver Disease, Mayo risk score, Yale, European and Newcastle models. Fifteen patients (24.6%) developed hepatic events during follow-up. The c-index (0.894) and χ2 by likelihood ratio test (36.34) of the ALBI score were highest in comparison to other models. The ALBI score was the only independent prognostic factor by multivariate analysis and its adjusted hazard ratio of developing hepatic event was 27.8 (P<0.001). Ther...

Flat supercontinuum (SC) generation with less than 1 dB fluctuation in the telecommunication band is demonstrated using a regenerative active mode-locked fiber laser together with a dispersion-flattened highly nonlinear fiber. Such SC is highly desirable in the context of a photonic time-stretched ADC system due to its flatness, bandwidth and brightness. Experimental results presented here agree well with the simulations.

Abstract—In wireless sensor networks (WSNs), when a stim-ulus or event is detected within a particular region, data reports from the neighboring sensor nodes (sources) are sent to the sink or destination. Data from these sources are usually aggregated along their way to the ...

Abstract—In this paper, we consider deployment of energy consumption scheduling (ECS) devices in smart meters for autonomous demand side management within a neighborhood, where several buildings share an energy source. The ECS devices are assumed to be built inside smart ...

The analysis of tumor-derived circulating cell-free DNA opens up new possibilities for performing liquid biopsies for the assessment of solid tumors. Although its clinical potential has been increasingly recognized, many aspects of the biological characteristics of tumor-derived cell-free DNA remain unclear. With respect to the size profile of such plasma DNA molecules, a number of studies reported the finding of increased integrity of tumor-derived plasma DNA, whereas others found evidence to suggest that plasma DNA molecules released by tumors might be shorter. Here, we performed a detailed analysis of the size profiles of plasma DNA in 90 patients with hepatocellular carcinoma, 67 with chronic hepatitis B, 36 with hepatitis B-associated cirrhosis, and 32 healthy controls. We used massively parallel sequencing to achieve plasma DNA size measurement at single-base resolution and in a genome-wide manner. Tumor-derived plasma DNA molecules were further identified with the use of chro...

Abstract In this paper, we show analytically for the first time that the complementary phase properties of a polarization modulator can be utilized to cancel the dispersion-induced second-order distortions in a Time-Stretched Analog-to-Digital Converter (TSADC). Using ...

Abstract—In this paper, we consider a smart power infras-tructure, where several subscribers share a common energy source. Each subscriber is equipped with an energy consumption controller (ECC) unit as part of its smart meter. Each smart meter is connected to not only the power ...

Though extensive research has been performed on primary biliary cirrhosis (PBC) in Caucasian patients, little is known about the disease in the Asian population. This was a retrospective study of Chinese patients with biopsy-proven PBC. Electronic records of results from all liver biopsies (n = 1,021) performed between January 1996 and April 2004, together with records of patients labeled as "biliary cirrhosis," were retrieved. Patients with biopsy-proven PBC were identified, and their medical notes were reviewed. The demographic, clinical, biochemical, and histological parameters of these patients were analyzed for mortality predictors. Thirty-nine patients with biopsy-proven PBC and a median follow-up of 44 (range: 5-114) months were identified. Twelve patients (30.8%) were asymptomatic at diagnosis. The patients were approximately equally divided into one-thirds at stages I, II, and III of the histological disease. Hepatic decompensation or hepatocellular carcinoma deve...

We aimed to study the predictive ability of model for end-stage liver disease (MELD) for short-term mortality in chronic hepatitis B. All patients admitted from 1996 to 2003 because of chronic hepatitis B and its related complications were identified by electronic search of the hospital database. MELD and Child-Turcotte-Pugh (CTP) scores on initial admissions were calculated. Cox proportional hazard model was used to determine the factors associated with mortality. The area under receiver operator characteristics curve (AUC) was used to determine the predictive abilities of the two models for 3-month and 1-yr mortalities. A total of 2,073 patients was admitted because of liver-related problems and 506 patients had chronic hepatitis B-related complications. Two hundred fifty-six (51%) patients died and 16 (3%) patients underwent liver transplantation. In multivariate analysis, MELD and CTP scores were independent predictors of 3-month and 1-yr mortality. Other independent predictors ...

We report a case of sigmoid colon perforation in a patient with Crohn's disease undergoing computed-tomographic (CT) colonography. A 70-year-old patient with Crohn's disease with terminal ileitis and sigmoid stricture underwent CT colonography after incomplete conventional colonoscopy. During the procedure, the colon was inflated by air insufflation and the patient developed abdominal pain with radiological evidence of retroperitoneal and intraperitoneal free gas. Hartmann's operation was performed. This case highlights that CT colonography is not risk-free. The risk of perforation may be higher in patients with inflammatory bowel disease.

Although empirical antisecretory drug therapy is recommended to young dyspeptic patients without alarming features, the effectiveness of this approach remains undetermined. We evaluated the long-term effects of an initial 12-wk course of lansoprazole in young dyspeptic patients without Helicobacter pylori (H. pylori) infection. Patients who were less than 45 yr and presented with at least 3 months of dyspepsia in the absence of alarming features were eligible. They were offered (13)C-urea breath test (UBT) to determine H. pylori status and all symptomatic patients with negative UBT were randomized to receive lansoprazole 30 mg daily or placebo for 12 wk. Those who had previous endoscopy or positive UBT were excluded. Primary end point was the proportion of patients with treatment failure, defined as worsening of global dyspeptic symptom, while on study medication. Patients were followed up for 26 wk for global dyspeptic symptom as determined by 7-point Likert scale. Quality-of-life ...

The long-term efficacy of lamivudine treatment for patients suffering from severe acute exacerbation of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B is unknown. Consecutive patients with severe acute exacerbation of HBeAg-positive chronic hepatitis B were prospectively recruited from 1999 to 2004 and treated with lamivudine. All patients had alanine aminotransferase (ALT) and serum bilirubin levels 10x and 3x above the upper limit of normal, respectively. HBeAg-positive patients without severe acute exacerbation served as controls. Forty-five patients with severe acute exacerbation and 31 controls were treated with lamivudine for a median of 2.8 (range 1.0-7.1) years and 3.8 (range 3.5-8.4) years, respectively. Compared with controls, patients with severe acute exacerbation had higher HBeAg seroconversion rates (78% versus 52%; P=0.02) and lower risk of virological breakthrough. However, 33% of patients with severe acute exacerbation still developed lamivudine resistan...

The incidence of ulcerative colitis (UC) in Asia is increasing but reports on its long-term course are few. We set out determine the incidence, prevalence, and survival rate of UC in the Chinese population and phenotypic stability by longitudinal follow-up. A cohort of Chinese UC patients were followed up in a tertiary referral center in Hong Kong between 1985 and 2006. Clinical data were prospectively collected since 2001. Population statistics were obtained from the Census and Statistics Department of Hong Kong for the calculation of age-specific incidence, prevalence, and survival. The disease phenotypes at diagnosis and upon follow-up were documented. A total of 172 patients (51.7% men) with a median age at diagnosis of 37.0 years (range: 12.0-85.0) were included. The cohort was observed for a total of 1,393 person-years with a median follow-up duration of 7.0 years (range: 0.5-22.0). The age-standardized incidence and prevalence rates of UC per 100,000 were 2.1 (95% confidence ...

The off-treatment durability of nucleos(t)ide analogue therapy in Asian hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) and the role of hepatitis B surface antigen (HBsAg) levels in predicting off-treatment durability has not been well investigated. Following Asia-Pacific Association for the Study of the Liver guidelines, entecavir was stopped in Asian HBeAg negative patients treated for ≥2 years with undetectable HBV DNA levels on ≥3 separate occasions 6 months apart before treatment cessation. HBsAg and HBV DNA levels were prospectively monitored every 6-12 weeks for 48 weeks. Entecavir was restarted if there was virologic relapse (defined as HBV DNA >2000 IU/mL). 184 patients (mean age 53.9 years, 67.9% male) were recruited. The cumulative rate of virologic relapse at 24 and 48 weeks was 74.2% and 91.4%, respectively. The median HBV DNA level at virologic relapse was 11 000 (range 2115 to >1.98×10(8)) IU/mL. 42 (25.8%) patients had elevated alanine aminotra...

Resistance of cancer cells to chemotherapy is a significant problem in oncology, and the development of sensitising agents or small-molecules with new mechanisms of action to kill these cells is needed. Autophagy is a cellular process responsible for the turnover of misfolded proteins or damaged organelles, and it also recycles nutrients to maintain energy levels for cell survival. In some apoptosis-resistant cancer cells, autophagy can also enhance the efficacy of anti-cancer drugs through autophagy-mediated mechanisms of cell death. Because the modulation of autophagic processes can be therapeutically useful to circumvent chemoresistance and enhance the effects of cancer treatment, the identification of novel autophagic enhancers for use in oncology is highly desirable. Many novel anti-cancer compounds have been isolated from natural products; therefore, we worked to discover natural, anti-cancer small-molecule enhancers of autophagy. Here, we have identified a group of natural al...

The high prevalence of chronic hepatitis B in Asian countries produces a substantial economic burden. Peginterferon has immunomodulatory effects and a finite course for treatment of hepatitis B, but also a high cost and side effects. The recent introduction of a 12-week stopping rule (stopping treatment after 12 weeks) has increased its appeal as a first-line treatment for hepatitis B. We aimed to determine the cost effectiveness of the 12-week stopping rule for peginterferon in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. We used Markov modeling, with data from the Hong Kong population, to compare the cost effectiveness of peginterferon therapy with a 12-week stopping rule vs conventional therapy (48 weeks) and with other antiviral agents. For HBeAg-positive patients, stopping peginterferon therapy after 12 weeks had the lowest cost-effectiveness ratio (CER), of $9501/quality-adjusted life-year (QALY), compared with no treatment, making it the most cost-effec...

Micro-albuminuria has been established as a marker for micro-vascular disease. Spot urine albumin-to-creatinine ratio (UACR), even in the high normal range, predicts future cardiovascular events. The value of UACR in women with gestational diabetes mellitus (GDM) during pregnancy is uncertain. The objectives of this study were to assess the associations between UACR (performed at the time of GDM diagnosis) and various maternal parameters and to evaluate its correlation with pregnancy outcomes. We conducted a retrospective review of women with GDM who attended antenatal clinics at a single centre between March 2010 and September 2013. Among 1015 women included in this study, high UACR levels were associated with advancing maternal age, maternal obesity, gestational hypertension, elevated glycosylated haemoglobin (HbA1c) and high fasting glucose level. After adjustments for various maternal factors, only advancing age, HbA1c and fasting glucose level were associated with UACR. In term...

As there is no effective treatment for irritable bowel syndrome (IBS), many patients turn to traditional Chinese medicine (TCM) for possible cure. We investigated the therapeutic efficacy of an ancient herbal Chinese formula in patients with diarrhea-predominant IBS. This was a randomized double-blinded placebo-controlled trial. Chinese IBS patients with predominant diarrhea symptoms that fulfilled Rome II criteria were recruited. The diagnosis was verified by a TCM herbalist using TCM criteria. Eligible patients were randomized to receive a standard preparation of TCM extracts that contained 11 herbs or placebo with similar appearance and taste for 8 wk after a 2-wk run-in period. Patients were followed up for an additional 8 wk post-treatment. Primary outcome was patient's global symptom assessment. Other outcome measures included individual IBS symptom scores and health-related quality of life (short form 36). One hundred nineteen patients were randomized: 60 to receive TCM and 59 to receive placebo. There was no significant difference in the proportion of patients with global symptom improvement between the TCM and placebo groups at week 8 (35% vs 44.1%, p = 0.38) and at week 16 (31.7% vs 33.9%, p = 0.62). Moreover, there was no difference in individual symptom scores and the quality-of-life assessment between the two groups at all time points. The use of this herbal formulation for diarrhea-predominant IBS did not lead to global symptom improvement. Further controlled clinical studies may be necessary to characterize the role of TCM in the management of IBS.

The survival benefit of surveillance for hepatocellular carcinoma (HCC) is controversial. We aimed to examine the survival benefit of HCC surveillance in chronic viral hepatitis. Survivals of HCC patients related to chronic viral hepatitis from the Hepatology Clinic (surveillance group) were compared with those referred from other hospitals/clinics (no-surveillance group). Lead-time and length-time biases were adjusted based on tumour volume doubling times. Among 579 patients (91% hepatitis B), 472 (82%) patients had HCC and 79 (17%) of these patients were referred from the surveillance programme. HCC was smaller (4.2 vs. 7.7 cm; P<0.001) and fewer in numbers (2.6 vs. 3.8, P=0.03) in the surveillance group vs. the no-surveillance group. Treatment by surgery (20 vs. 10%, P=0.007) and local ablative therapy (46 vs. 19%, P<0.001) were more frequent in the surveillance group than that in the no-surveillance group. The median survival of the surveillance group (88 weeks) was significantly longer than that of the no-surveillance group (26 weeks) (P<0.001). The adjusted cumulative survival at 2 years was significantly longer in the surveillance group if the tumour volume doubling time was <90 days (P=0.0352). HCC surveillance can improve the survival of patients with chronic viral hepatitis B.