Summary Background Early intensive insulin therapy in patients with newly diagnosed type 2 diabetes might improve β-cell function and result in extended glycaemic remissions. We did a multicentre, ...randomised trial to compare the effects of transient intensive insulin therapy (continuous subcutaneous insulin infusion CSII or multiple daily insulin injections MDI) with oral hypoglycaemic agents on β-cell function and diabetes remission rate. Methods 382 patients, aged 25–70 years, were enrolled from nine centres in China between September, 2004, and October, 2006. The patients, with fasting plasma glucose of 7·0–16·7 mmol/L, were randomly assigned to therapy with insulin (CSII or MDI) or oral hypoglycaemic agents for initial rapid correction of hyperglycaemia. Treatment was stopped after normoglycaemia was maintained for 2 weeks. Patients were then followed-up on diet and exercise alone. Intravenous glucose tolerance tests were done and blood glucose, insulin, and proinsulin were measured before and after therapy withdrawal and at 1-year follow-up. Primary endpoint was time of glycaemic remission and remission rate at 1 year after short-term intensive therapy. Analysis was per protocol. This study was registered with ClinicalTrials.gov , number NCT00147836. Findings More patients achieved target glycaemic control in the insulin groups (97·1% 133 of 137 in CSII and 95·2% 118 of 124 in MDI) in less time (4·0 days SD 2·5 in CSII and 5·6 days SD 3·8 in MDI) than those treated with oral hypoglycaemic agents (83·5% 101 of 121 and 9·3 days SD 5·3). Remission rates after 1 year were significantly higher in the insulin groups (51·1% in CSII and 44·9% in MDI) than in the oral hypoglycaemic agents group (26·7%; p=0.0012). β-cell function represented by HOMA B and acute insulin response improved significantly after intensive interventions. The increase in acute insulin response was sustained in the insulin groups but significantly declined in the oral hypoglycaemic agents group at 1 year in all patients in the remission group. Interpretation Early intensive insulin therapy in patients with newly diagnosed type 2 diabetes has favourable outcomes on recovery and maintenance of β-cell function and protracted glycaemic remission compared with treatment with oral hypoglycaemic agents. Funding 973 Programme from the Chinese Government, the Natural Science Foundation of Guangdong Province Government, Novo Nordisk (China), and Roche Diagnostics (Shanghai).
Purpose To measure the density of the superficial retinal small vessel network (SRSVN), superficial retinal capillary network (SRCN), deep retinal capillary network (DRCN) and choriocapillaris, and ...the size of the foveal avascular zone (FAZ) in the superficial retinal layer in normal eyes. Design Prospective observational cross-sectional study. Methods In healthy Chinese volunteers, the retinal and choroidal vasculature was visualized by split-spectrum amplitude decorrelation angiography associated optical coherence tomography (RTVueXR Avanti device; Optovue Inc., Fremont, CA, USA). Results Among 105 healthy participants (age:35.9±13.8 years) mean FAZ measured 0.35±0.12mm2 , and mean density of SRSVN, SRCN, DRCN and choriocapillaris was 8.54±0.92%, 31.8±2.6%, 45.8±3.3%, 44.4±3.3% and 44.5±2.7%, respectively. In multivariate analysis, higher SRSVN density was associated with younger age ( P =0.001;standardized regression coefficient β:-0.28;), male gender ( P =0.008; β:-0.23), lower SRCN density ( P <0.001; β:-0.40), and larger mean choriocapillaris vessel diameter ( P =0.001;β:0.30). Higher SRCN density was correlated with male gender ( P =0.007; β:-0.19), lower SRSVN density ( P <0.001; β:-0.44), and higher density of the radial peripapillary capillary density ( P =0.004; β:0.20). Higher DRCN density was correlated with younger age ( P <0.001; β:-0.31), female gender ( P =0.002; β:0.22), higher SRCN density ( P <0.001; β:0.38), and higher choriocapillaris density ( P <0.001; β:0.39). Higher choriocapillaris network density in the central region was associated with higher DRCN density ( P <0.001; β:0.43) and lower radial peripapillary capillary density ( P =0.005; β:-0.26). All retinal vascular parameters were not significantly correlated with axial length or subfoveal choroidal thickness. Conclusions The density of the macular vascular networks decreases with older age and is independent of axial length and subfoveal choroidal thickness in healthy individuals.
Background and Aims The use of endoscopic submucosal dissection (ESD) for management of widespread superficial esophageal squamous carcinoma is closely associated with esophageal stenosis. We ...investigated the efficacy and feasibility of endoscopic injection of botulinum toxin type A (BTX-A) for preventing esophageal strictures after ESD for superficial esophageal squamous carcinoma. Methods Sixty-seven patients with superficial esophageal squamous cell carcinomas with mucosal defects that exceeded one half of the circumference of the esophagus after ESD treatment were enrolled and randomly divided into 2 groups (group A, n = 33; group B, n = 34). Patients in group A (BTX-A group) were immediately injected with BTX-A after ESD, whereas patients in group B (control group) received ESD only. Endoscopy was performed when patients reported dysphagia symptoms and at 12 weeks post-ESD in patients without symptoms. Patients who experienced post-ESD esophageal strictures in both groups received bougie dilation. Results The number of patients who experienced esophageal strictures in group A (per protocol analysis, 6.1%, 2/33; intention to treat analysis, 11.4%, 4/35) was significantly less than that seen in group B (per protocol analysis, 32.4%, 11/34; intention to treat analysis, 37.8%, 14/37) ( P < .05). Moreover, the number of bougie dilation procedures was significantly lower in group A (mean, 1.5; range, 0-2) than in group B (mean, 2.8; range, 0-5) ( P < .05). Conclusions Endoscopic injection of BTX-A was effective in preventing post-ESD esophageal strictures and decreasing the times of bougie dilation procedures. (Clinical trial registration number: ChiCTR-TRC-12003188.)
Background Environmental factors may play important roles in asthma, but findings have been inconsistent. Objective The goal of this study was to determine the associations between early life ...exposures, environmental factors, and asthma in urban and rural children in southeast China. Methods A screening questionnaire survey was conducted in 7,164 children from urban Guangzhou and 6,087 from rural Conghua. In the second stage, subsamples of 854 children (419 from Guangzhou, 435 from Conghua) were recruited for a case-control study that included a detailed questionnaire enquiring on family history, early life environmental exposures, dietary habits, and laboratory tests (including histamine airway provocation testing, skin prick tests, and serum antibody analyses). House dust samples from 76 Guangzhou families and 80 Conghua families were obtained to analyze levels of endotoxins, house dust mites, and cockroach allergens. Results According to the screening survey, the prevalence of physician-diagnosed asthma was lower in children from Conghua (3.4%) than in those from Guangzhou (6.9%) ( P < .001). A lower percentage of asthma was reported in rural subjects compared with urban subjects (2.8% vs. 29.4%; P < .001) in the case-control study. Atopy (OR, 1.91 95% CI, 1.58-2.29), parental atopy (OR, 2.49 95% CI, 1.55-4.01), hospitalization before 3 years of age (OR, 2.54 95% CI, 1.37-4.70), high consumption of milk products (OR, 1.68 95% CI, 1.03-2.73), and dust Dermatophagoides farinae group 1 allergen (OR, 1.71 95% CI, 1.34-2.19) were positively associated with asthma. Living in a crop-farming family at < 1 year of age (OR, 0.15 95% CI, 0.08-0.32) and dust endotoxin levels (OR, 0.69 95% CI, 0.50-0.95) were negatively associated with asthma. Conclusions Rural children from an agricultural background exhibited a reduced risk of asthma. Early life exposure to crop farming and high environmental endotoxin levels might protect the children from asthma in southern China.
Summary While vascularized iliac crest flap is widely used for mandibular reconstruction, it is often challenging to predict the clinical outcome in a conventional operation based solely on the ...surgeon’s experience. Herein, we aimed to improve this procedure by using computer-assisted techniques. We retrospectively reviewed records of 45 patients with mandibular tumor who underwent mandibulectomy and reconstruction with vascularized iliac crest flap from January 2008 to June 2015. Computer-assisted techniques including virtual plan, stereomodel, pre-bending individual reconstruction plate, and surgical navigation were used in 15 patients. The other 30 patients underwent conventional surgery based on the surgeon’s experience. Condyle position and reconstructed mandible contour were evaluated based on post-operative computed tomography. Complications were also evaluated during the follow-up. Flap success rate of the patients was 95.6% (43/45). Those in the computer-assisted group presented with better outcomes of the mandibular contour (p=0.001) and condyle position (p=0.026). Further, they also experienced beneficial dental restoration (p=0.011) and postoperative appearance (p=0.028). The difference between postoperative effect and virtual plan was within the acceptable error margin. There is no significant difference in the incidence of post-operative complications. Thus, computer-assisted techniques can improve the clinical outcomes of mandibular reconstruction with vascularized iliac crest flap.
To investigate the associations of IL17A, IL17F, IL23A, and IL23R copy number variants (CNVs) with Vogt-Koyanagi-Harada (VKH) syndrome and Behçet's disease (BD) and the possible mechanisms involved.
...Two-stage case-control and functional studies.
A total of 1159 VKH patients, 1036 BD patients, and 2050 controls were enrolled.
TaqMan real-time polymerase chain reaction assay was used for genotyping of copy number variant. Cell proliferation was measured by colorimetric assay.
Association of CNVs in IL17A, IL17F, IL23A, and IL23R with BD and VKH syndrome and the functional roles of IL17F CNVs.
Increased frequencies of more than 2 copies of IL17F and IL23A were found in BD patients as compared with controls (IL17F: P=4.17×10(-8); odds ratio OR, 2.2; IL23A: P=2.86×10(-11); OR, 2.8, respectively). A similar result was found for VKH syndrome (IL17F: P=2.84×10(-13); OR, 2.7; IL23A: P=4.46×10(-17); OR, 3.4, respectively). Interestingly, the association of IL17F and IL23A with BD was found only in male patients (IL17F: P=1.06×10(-6); OR, 2.3; IL23A, P=3.81×10(-8); OR, 2.8, respectively), but not in female patients. No association of CNVs in IL17A and IL23R was found for BD and VKH syndrome. IL17F protein levels were correlated positively with gene copy numbers (P=3.43×10(-7)). Individuals with high IL17F copies showed enhanced peripheral blood mononuclear cells (PBMC) proliferation (P=5.67×10(-3)).
High gene copy numbers of IL17F and IL23A were associated with BD and VKH syndrome. Enhanced IL17F protein production and PBMC proliferation were associated with high IL17F copy numbers.
Purpose To evaluate the effectiveness of decompression as the primary treatment of odontogenic cystic lesions of the jaw involving factors that affect relative shrinking speed and bone regeneration. ...Patients and Methods A total of 32 patients with odontogenic cystic lesions of the jaw underwent decompression with customized thermoplastic resin stents. Clinical examinations and pre- and postdecompression panoramic radiographs were analyzed. Results The mean relative speed of shrinkage of radicular cysts (RCs; 3.37 cm2 /month) was faster than those of keratocystic odontogenic tumors (KCOTs; 2.87 cm2 /month) and unicystic ameloblastomas (UABs; 2.71 cm2 /month). The relative shrinking size increased linearly in a time-dependent manner for KCOTs ( r = 0.849, P < .001), RCs ( r = 0.681, P = .319), and UABs ( r = 0.146, P = .730); a similar relation was detected between the primary radiolucent area of cystic lesions before decompression and relative shrinking speed after decompression in KCOTs ( r = 0.481, P = .032), RCs ( r = 0.260, P = .673), and UABs ( r = 0.370, P = .366), but patient age did not affect the relative speed of shrinkage ( P > .05). Furthermore, the increase in bone density was more significant in RCs than in KCOTs ( P = .026) and UABs ( P = .012) after decompression. Conclusion Decompression was effective in reducing odontogenic cystic lesions of the jaw and increasing bone density. For aggressive lesions, secondary definitive surgery was necessary.
Abstract Background Vandetanib (ZD6474) is an orally available inhibitor of 3 signaling pathways important in tumor progression: vascular endothelial growth factor receptor, epidermal growth factor ...receptor, and rearranged during transfection tyrosine kinase activity. Current development of vandetanib is focused on the treatment of non–small-cell lung cancer and other tumor types, including thyroid cancer. This study was conducted as a requirement for regulatory submission for vandetanib in China. Objective To determine the pharmacokinetics of vandetanib in Chinese patients with advanced, solid, malignant tumors and to compare these with data obtained in Japanese and Western populations. Methods Phase I consisted of a nonrandomized, open-label, single-center study conducted in Guangzhou, China. Adult patients (12 per treatment) who had tumors refractory to standard treatments or for whom no appropriate therapies existed received oral vandetanib (100 mg every other day, 100 mg once daily, or 300 mg once daily) until disease progression or discontinuation in the study. The initial cohort was dosed at 100 mg every other day. Once at least 3 patients had received this dose of vandetanib for 28 days without experiencing dose-limiting toxicity, a second cohort at 100 mg once daily was started. Following the same criteria, the third cohort received 300 mg once daily. Pharmacokinetics, tolerability, and tumor response were assessed. The pharmacokinetics of vandetanib in Chinese, Western, and Japanese patients were compared through a combined population pharmacokinetic model. Tolerability was assessed by recording adverse events and monitoring physical examination, body weight, performance status, vital signs, urinalysis, biochemistry, hematology, and 12-lead electrocardiogram. Results Thirty-six patients were enrolled (age range 21−82 years, 56% male, body mass index range 17.6−33.0 kg/m2 ). Thirty-three of 36 patients (92%) were World Health Organization performance status 0−1. Vandetanib pharmacokinetics were linear over the dose range studied with AUCss for the 300 mg once daily group (38611 ng/h/mL) being 3.6-fold higher than that for the 100 mg once daily group (10826 ng/h/mL). Absorption was relatively slow following a single 100- or 300-mg dose, with Tmax ranging from 2 to 10 hours. Interpatient variability in Cmax SS and AUCSS was relatively high, with the coefficient of variation ranging from 29.1% to 40.6%. Vandetanib plasma clearance was slow (7.8–9.2 L/h) and was independent of dose. The most common drug-related adverse events were rash (42%) and diarrhea (39%). No QTC prolongation was observed. Hypertension was reported as an adverse event in 3 patients. There were no clinically relevant changes in hematology, urinalysis, or World Health Organization performance status. Elevation of alanine aminotransferase was reported as an adverse event in 1 patient. One patient with medullary thyroid cancer showed a partial tumor response. Population pharmacokinetic analysis suggests that vandetanib pharmacokinetics appear to be comparable in Chinese, Western, and Japanese patients. Conclusions The pharmacokinetic properties of vandetanib in these Chinese patients were characterized by low plasma clearance of approximately 8 L/h, a long half-life of approximately 8 to10 days, and an accumulation of approximately 8−fold to 15-fold on multiple dosing. In these Chinese patients, the pharmacokinetic profile of vandetanib appeared to be comparable with that observed in Japanese and Western populations. Oral doses up to 300 mg once daily appeared to be well tolerated.
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