Description: Background: The serious consequences of diabetes mellitus, and the subsequent economic burden, call for urgent preventative action in developing countries. This study explores the clinical and economic outcomes of strategies that could potentially prevent diabetes based on Chinese circumstances. It aims to provide indicators for the long-term allocation of healthcare resources for authorities in developing countries. Methods: A representative sample of Chinese adults was used to create a simulated population of 20,000 people aged 25 years and above. The hybrid decision tree Markov model was developed to compare the long-term clinical and economic outcomes of four simulated diabetes prevention strategies with a control group, where no prevention applied. These preventive strategies were the following: (i) one-off screening for undiagnosed diabetes and impaired glucose tolerance (IGT), with lifestyle interventions on diet, (ii) on exercise, (iii) on diet combined exercise (duo-intervention) respectively in those with IGT, and (iv) one-off screening alone. Independent age-specific models were simulated based on diverse incidences of diabetes, mortalities and health utilities. The reported outcomes were the following: the remaining survival years, the quality-adjusted life years (QALYs) per diabetes or IGT subjects, societal costs per simulated subject and the comparisons between preventions and control over 40 years. Sensitivity analyses were performed based on variations of all assumptions, in addition to the performance and the compliance of screening. Results: Compared with the control group, all simulated screening programmes prolonged life expectancy at the initiation ages of 25 and 40 years, postponed the onset of diabetes and increased QALYs at every initiation age. Along with an assumption of six years intervention, prevention programmes were associated with cost-saving compared with the control group, especially in the population aged 25 years. The savings were at least US$2017 per subject, but no statistically significant difference was observed among the intervention strategies within each age groups. The cost savings were reduced when screening was affected by poor performance and noncompliance. Conclusions: Developing countries have few effective strategies to manage the prevention of diabetes. One-off screening for undiagnosed diabetes and IGT, with appropriate lifestyle interventions for those with IGT are cost saving in China, especially in young adults.

Description: Background: We reported a case of sudden monocular vision loss after calcium hydroxyapatite (CaHA) injection into the nasal tip and dorsum with detailed retina images.Case presentationA healthy, 35-year-old woman received CaHA filler injection for nose augmentation. Ten minutes after the procedure, she developed nausea, vomiting, headache, ptosis, and left periorbital pain. After 30 minutes, she complained of progressively blurring vision in the left eye. The best-corrected visual acuity (BCVA) in her left eye was 30 cm ahead of hand motion. Left exotropia was noted in primary gaze. Limitations in adduction, supraduction, and infraduction of the left eye were also observed. Slit lamp examination of the left eye revealed a pink conjunctiva, a clear cornea, a mild anterior chamber reaction, a sluggish papillary light reflex, and a semi-dilated pupil. A positive relative afferent pupillary defect was observed in the left eye. Fundus examination revealed optic disc edema and some linear whitish opacity over the superior and temporal sites in the left eye, suggesting multiple CaHA emboli in the choroid vessels. Conclusions: Although the majority of adverse reactions are mild and transient, surgeons should be alert about extremely rare serious adverse events such as visual loss.

Description: Background: Thorax is the common place to develop Castleman disease (CD), but there is no systemic clinical analysis for intrathoracic CD. Methods: We conducted a retrospective analysis of 48 intrathoracic CD patients with definite pathological diagnosis who were hospitalized between 1992 and 2012 in a Chinese tertiary referral hospital. Results: The study included 16 cases with unicentric CD (UCD) and 32 cases with multicentric CD (MCD). UCD were younger than MCD (30.5y vs 41.6ys, P 

Description: Background: Itai-itai disease primarily results from cadmium (Cd) exposure and is known as one of the four major pollution diseases in Japan. Cd pollution is more serious in several areas of China than in Japan. However, there is still a lack of information regarding the threshold level of Cd exposure for the adverse health effects in the general Chinese population. This study aims to evaluate the reference value of urinary Cd (UCd) for renal dysfunction in a Chinese population as the benchmark dose lower confidence limit (BMDL) based on a large sample survey. Methods: A total of 6103 participants who lived in five Cd polluted areas of China participated in this study. We analyzed UCd levels as a biomarker of exposure and urinary β 2 -microglobulin (Uβ 2 -MG) levels as a renal tubular effect biomarker. The BMD studies were performed using BMD software. The benchmark response (BMR) was defined as a 10 % additional risk above the background. Results: There was a positive correlation between the UCd levels and the prevalence of Uβ 2 -MG. The BMD of UCd for Uβ 2 -MG was estimated for each province. The findings showed that the BMD levels were related to the participants’ geographic region, which may be partially due to the large differences in Cd exposure level, ethnic group, lifestyle and diet of the sample population in these study areas. The reference level of UCd for the renal effects was further evaluated by combining the five sets of data from all 6103 subjects. The overall BMDLs of UCd for Uβ 2 -MG with an excess risk of 10 % were 2.00 μg/g creatinine (μg/g cr) in males and 1.69 μg/g cr in females, which were significantly lower than the World Health Organization (WHO) threshold level of 5 μg/g cr for Cd-related renal effects. Conclusions: The selection of the sample population and geographic region affected the BMDL evaluation. Based on the findings of this survey of a large sample population, the UCd BMDLs for Uβ 2 -MG in males with BMRs at 10 % were 2.00 μg/g cr. The BMD was slightly lower in females, which indicated that females may be relatively more sensitive to Cd exposure than males.

Description: Background: Delirium is a common complication in elderly patients after surgery and associated with increased morbidity and mortality. Studies suggest that deep anesthesia and intense pain are important precipitating factors of postoperative delirium. Neuraxial block is frequently used in combination with general anesthesia for patients undergoing major thoracic and abdominal surgery. Compared with general anesthesia alone and postoperative intravenous analgesia, combined epidural-general anesthesia and postoperative epidural analgesia decreases the requirement of general anesthetics during surgery and provided better pain relief after surgery. However, whether combined epidural-general anesthesia plus epidural analgesia is superior to general anesthesia plus intravenous analgesia in decreasing the incidence of postoperative delirium remains unknown.Methods/designThis is a multicenter, open-label, randomized, parallel-controlled clinical trial. One thousand eight hundred elderly patients (age range 60–90 years) who are scheduled to undergo major thoracic or abdominal surgery are randomized to receive either general anesthesia plus postoperative intravenous analgesia or combined epidural-general anesthesia plus postoperative epidural analgesia. The primary outcome is the 7-day incidence of postoperative delirium. Secondary outcomes include the duration of postoperative delirium, the intensity of pain during the first three days after surgery, the 30-day incidences of postoperative non-delirium complications, the length of stay in hospital after surgery and 30-day all-cause mortality.DiscussionResults of the present study will provide information to guide clinical practice in choosing appropriate anesthesia-analgesia method for elderly patients undergoing major thoracic and abdominal surgery.Trial registrationThe study is registered on ClinicalTrials.gov NCT01661907 and Chinese Clinical Trial Registry ChiCTR-TRC-12002371.

Description: Bone destruction and low immunity function always occurr in multiple myeloma(MM) patients. In this study, we explore the changes of osteoblasts and cellular immunity function and the relationship between them in MM patients. The quantity of osteoblasts from MM patients was less than that of normal controls. The calcium depositions of MM patients were less than those of normal controls. The quantity of osteoblasts cultured in vitro with MM patients' serum was less than that without MM patients' serum. Bortezomib could increase osteoblasts in MM patients. The ratio of CD4+/CD8+Dendritic cells(DC) 1/DC2CD8+CD25+/CD3+T in the peripheral blood of MM patients were reduced, and the helper T cell (Th)1/Th2 was significantly decreased; the percentages of CD4+CD25+/ CD3+T and CD4+CD25+CD127low/CD4+T were significantly higher. Some of them were correlated with the quantity of osteoblasts. The level of IL-7 in the serum of MM patients was higher than that of normal controls. The expression of BMP2 mRNA was seen in the normal osteoblasts and MM patients' osteoblasts cultured with bortezomib, but not seen in those cultured without bortezomib. Our data indicated that the proliferation and osteogenic potential of OBs from MM patients were decreased. There were down-regulations of quantity and function of cellular immunity while the regulatory T cells relatively raised. Some of the cellular immunity parameters were correlated with the quantity of OBs.

Description: Background: Hypericum japonicum Thunb. ex Murray is widely used as an herbal medicine for the treatment of hepatitis and tumours in China. However, the molecular mechanisms of its effects are unclear. Our previous research showed that extracts of H. japonicum can induce apoptosis in leukaemia cells. We also previously systematically analysed and isolated the chemical composition of H. japonicum. Methods: The fluorescence polarisation experiment was used to screen for inhibitors of Bcl-2 proteins which are proved as key proteins in apoptosis. The binding mode was modelled by molecular docking. We investigated the proliferation attenuating and apoptosis inducing effects of active compound on cancer cells by MTT assay and flow cytometry analysis. Activation of caspases were tested by Western blot. A broad-spectrum caspase inhibitor Z-VAD-FMK was used to investigate the caspases-dependence. In addition, co-immunoprecipitation was performed to analyse the inhibition of heterodimerization between anti-apoptotic Bcl-2 proteins with pro-apoptotic proteins. Moreover, in vivo activity was tested in a mouse xenograph tumour model.Result: Jacarelhyperol A (Jac-A), a characteristic constituent of H. japonicum, was identified as a potential Bcl-2 inhibitor. Jac-A showed binding affinities to Bcl-xL, Bcl-2, and Mcl-1 with Ki values of 0.46 muM, 0.43 muM, and 1.69 muM, respectively. This is consistent with computational modelling results, which show that Jac-A presents a favorable binding mode with Bcl-xL in the BH3-binding pocket. In addition, Jac-A showed potential growth inhibitory activity in leukaemia cells with IC50 values from 1.52 to 6.92 muM and significantly induced apoptosis of K562 cells by promoting release of cytochrome c and activating the caspases. Jac-A also been proved that its effect is partly caspases-dependent and can disrupt the heterodimerization between anti-apoptotic Bcl-2 proteins with pro-apoptotic proteins. Moreover, Jac-A dose-dependently inhibited human K562 cell growth in a mouse xenograph tumour model with low toxicity. Conclusion: In this study, a characteristic constituent of H. japonicum, Jac-A, was shown to induce apoptosis in leukaemia cells by mediating the Bcl-2 proteins. Therefore, we propose a new lead compound for cancer therapy with a low toxicity, and have provided evidence for using H. japonicum as an anti-cancer herb.

Description: Background: Diabetic nephropathy is a serious complication of diabetes whose development process is associated with inflammation, renal hypertrophy, and fibrosis. Coreopsis tinctoria Nutt, traditionally used as a healthcare tea, has anti-inflammatory, anti-hyperlipidemia, and glycemic regulation activities. The aim of our study was to investigate the renal protective effect of ethyl acetate extract of C. tinctoria Nutt (AC) on high-glucose–fat diet and streptozotocin (STZ)-induced diabetic rats. Methods: A diabetic rat model was induced by high-glucose–fat diet and intraperitoneal injection of 35 mg/kg STZ. After treatment with AC at a daily dose of 150, 300 or, 600 mg/kg for 4 weeks, metabolic and renal function parameters of serum and urine were examined. Degree of renal damage, renal proinflammatory cytokines, and fibrotic protein expression were analyzed by histopathology and immunohistochemistry. Renal AMP-activated protein kinase (AMPK) and transforming growth factor (TGF)-β1/Smad signaling pathway were determined by western blotting. Results: Diabetic rats showed obvious renal dysfunction, inflammation and fibrosis. However, AC significantly reduced levels of blood glucose, total cholesterol, triglyceride, blood urea nitrogen, serum creatinine and urinary albumin, as well as expression of kidney proinflammatory cytokines of monocyte chemoattractant protein-1 and intercellular adhesion molecule-1. AC also ameliorated renal hypertrophy and fibrosis by reducing fibronectin and collagen IV and suppressing the TGF-β1/Smad signaling pathway. Meanwhile, AMPKα as a protective cytokine was markedly stimulated by AC. Conclusion: In summary, AC controls blood glucose, inhibits inflammatory and fibrotic processes, suppresses the TGF-β1/Smad signaling pathway, and activates phosphorylation of AMPKα in the kidneys, which confirms the protective effects of AC in the early stage of diabetic kidney disease.

Description: Neurogenic neuroprotection is a promising approach for treating patients with ischemic brain lesions. Fastigial nucleus stimulation (FNS) has been shown to reduce the tissue damage resulting from focal cerebra...

Description: Gastric cancer is the fourth most common cancer and the second most deadly cancer worldwide. Study on molecular mechanisms of carcinogenesis will play a significant role in diagnosing and treating gastric canc...