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The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.

This study aims to identify the underlying genetic cause of a Chinese patient with Leber congenital amaurosis (LCA). Detailed clinical data and family history were collected. A medical diagnostic panel sequencing covering 4450 genes was conducted. Two candidate disease-causing mutations detected in CEP290 were then validated with Sanger sequencing and bioinformatic analysis. Reverse transcription polymerase chain reaction (RT-PCR) and cDNA sequencing were performed to understand the effect of the novel CEP290 mutation on CEP290 mRNA splicing. A five-month-old LCA patient with both parents was enrolled. Medical diagnostic panel sequencing revealed that the patient is a compound heterozygote for two potentially pathogenic CEP290 mutations. Among them, c.1666dupA (p.I556NfsX20) was previously reported and has a significant association with LCA phenotype. A novel CEP290 mutation (c.3310–1_3313delGCTTA) was confirmed in both the patient and her father. RT-PCR and cDNA sequencing confirmed that the novel mutation affects the CEP290 mRNA splicing and results in a complete skipping of exon 29. The frameshift resulted in an early stop codon and truncation of the mutant protein by 1371 amino acid residues (p.L1104fsX6). Our report provided a new mutation to the spectrum of CEP290-related diseases. The data suggested that the c.3310–1_3313delGCTTA mutation affects the CEP290 mRNA splicing and the CEP290 protein function. This valuable information is important for future studies on the mRNA splicing of CEP290 and the pathogenesis of CEP290-related diseases.

Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities.The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation.During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits 7 times/week comparing to those 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]).These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

Summary Zoledronic acid (ZOL) is a therapy inhibiting bone resorption. In this study, generic ZOL (Yigu®) showed its clinical efficacy consistency with original ZOL (Aclasta®) in Chinese postmenopausal women with osteoporosis. This study provides a practical basis for the application of Yigu® in Chinese population. Introduction Yigu® has been approved its bioequivalence to Aclasta®. However, the clinical efficacy and safety of Yigu® have not been evaluated yet. Here, we compared the effectiveness and safety between Yigu® and Aclasta® in Chinese postmenopausal women with osteoporosis and assessed the efficacy of intravenous infusion of ZOL. Methods This was a randomized open-label, active-controlled study in postmenopausal women with osteoporosis of 14 clinical centers in China. Postmenopausal women with osteoporosis were recruited and randomized to receive a single infusion of 5 mg Yigu® or Aclasta®. The primary endpoint was the percentage change in bone mineral density (BMD) at lumbar spine after 12 months of treatment and was assessed for equivalence. The secondary endpoint was the percentage change in BMD at proximal femur after 12 months. Additional secondary endpoints were percentage changes in BMD at the above sites after 6 months of treatment and changes in bone turnover biomarkers during ZOL treatment. Safety was also evaluated and compared between two groups. Results A total of 458 postmenopausal women with osteoporosis were enrolled (n = 227, Yigu®; n = 231, Aclasta®). The mean percentage change in the BMD had no statistical difference at the lumbar spine (5.32% vs 5.18%), total hip (2.72% vs 2.83%), and femoral neck (2.37% vs 2.81%) between Yigu® and Aclasta® groups after 12 months of treatment. The mean difference of BMD change at the lumbar spine after 12 months between two groups was 0.15% (95% CI: − 0.71 to 1.00, equivalence margin: − 1.5%, 1.5%), demonstrating the treatments were equivalent. Meanwhile, the decreases in the P1NP and β-CTX showed no difference between two groups after 14 days and 6 and 12 months of treatment. As regards the whole sample, BMD significantly increased after 12 months of treatment. Also, serum C-terminal telopeptide of type 1 collagen (β-CTX) and procollagen 1 N-terminal peptide (P1NP) significantly decreased at each visit period. The overall adverse events were comparable and quite well between two groups. Conclusion Intravenous infusion of zoledronic acid achieved the potent anti-resorptive effects which led to significant increase in BMD of Chinese postmenopausal women with osteoporosis. Yigu® was equivalent to Aclasta® with respect to efficacy and safety.

This study aims to identify the underlying genetic cause of a Chinese patient with Leber congenital amaurosis (LCA).Detailed clinical data and family history were collected. A medical diagnostic panel sequencing covering 4450 genes was conducted. Two candidate disease-causing mutations detected inA five-month-old LCA patient with both parents was enrolled. Medical diagnostic panel sequencing revealed that the patient is a compound heterozygote for two potentially pathogenicOur report provided a new mutation to the spectrum of

The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.

Objective: To investigate gene mutations associated with three different types of corneal dystrophies (CDs), and to establish a phenotype-genotype correlation. Methods: Two patients with Avellino corneal dystrophy (ACD), four patients with lattice corneal dystrophy type I (LCD I) from one family, and three patients with macular corneal dystrophy type I (MCD I) were subjected to both clinical and genetic examinations. Slit lamp examination was performed for all the subjects to assess their corneal phenotypes. Genomic DNA was extracted from peripheral blood leukocytes. The coding regions of the human transforming growth factor β-induced (TGFBI) gene and carbohydrate sulfotransferase 6 (CHST6) gene were amplified by polymerase chain reaction (PCR) and subjected to direct sequencing. DNA samples from 50 healthy volunteers were used as controls. Results: Clinical examination showed three different phenotypes of CDs. Genetic examination identified that two ACD subjects were associated with homozygous R124H mutation of TGFBI, and four LCD I subjects were all associated with R124C heterozygous mutation. One MCD I subject was associated with a novel S51X homozygous mutation in CHST6, while the other two MCD I subjects harbored a previously reported W232X homozygous mutation. Conclusions: Our study highlights the prevalence of codon 124 mutations in the TGFBI gene among the Chinese ACD and LCD I patients. Moreover, we found a novel mutation among MCD I patients.

To explore intervention with electromagnetic noise for co-suppression effect on gap-junctional intercellular communication (GJIC) induced or strengthened by low intensity magnetic field with carcinogen 12-O-tetradecanoylphorbol-13-acetate (TPA).Fibroblast cells from NIH 3T3 mice were exposed to extremely low intensity magnetic field (MF) 0.2 mT, 0.2 mT + TPA or/and electromagnetic noise with the same intensity of MF for 24 h, and GJIC was determined using fluorescence recovery analysis after photobleaching (FRAP) with a laser-scanning confocal microscope (Leica, Germany).GJIC function could be co-suppressed by MF of 0.2 mT with TPA, with fluorescence recovery of (23 +/- 11)%, lower than that in the control group [(46 +/- 19)%] and in the group with TPA only [(34 +/- 17) %] (P0.01), indicating 0.2 mT MF plus TPA could co-inhibit GJIC (P0.01). Superposition of 0.2 mT noise MF could get a fluorescence recovery of (35 +/- 19)% and significantly antagonize its co-suppression by TPA.Electromagnetic noise of 0.2 mT could block the intensifying effect of power frequency magnetic field on TPA-induced GJIC inhibition.

OBJECTIVE: To evaluate the relationship between katG gene mutation and isoniazid (INH) resistance and to develop a rapid screening method of point mutation in the katG gene associated with MTB resistance. METHODS: Twenty-four clinical isolates of MTB with 8 INH resigtance isolates and 16 INH-sensitive isolates were analyzed by PCR-RFLP, with the H(37)Rv reference strain as the control. RESULTS: G--C point mutations were detected in 7 of 8 isoniazid-resistant strains and no gene mutation was shown in 16 isoniazid-sensitive isolates. The sensitivity and specificity were 87.5 % and 100 % respectively. No katG gene sequence deletion was observed in any specimen. CONCLUSION: Our results suggest katG gene mutation is one of the most important mechanisms of INH-resistant TB. PCR-RFLP may be useful in detection of katG gene mutation.

Reactive oxygen species (ROS) encompass a variety of partially reduced metabolites of oxygen, including superoxide anion (O2−·), hydroxyl radical (·OH),and hydrogen peroxide (H2O2). In the past ROS that were generated intracellularly or derived from outside sources were considered to be harmful to cells and tissues. Previous studies have shown that a high ROS level is associated with aging and various degenerative diseases, including macular degeneration and cataracts. In the case of the cornea, damage of the corneal epithelium has been observed due to prolonged use of contact lenses or UVB irradiation1.2 In recent years, a growing number of studies have shown that ROS can be generated by a variety of extracellular stimuli such as integrin engagement3–5 and cytokine or growth factor binding of the receptor in many nonphagocytic cells, including endothelial cells,6 chondrocytes,7 epidermoid cells,8 lens epithelial cells,9 and corneal epithelial cells.10 This physiological low ROS level is used to regulate cell signaling and mediate a variety of cellular functions, including cell proliferation, differentiation, and cell adhesion and migration. This newly found ROS function is known as redox signaling, in which ROS act as a second messenger in intracellular signaling pathway by activating protein tyrosine kinases and /or inhibiting protein tyrosine phosphatase and regulating redox-sensitive gene expression.11,12 These studies have shed new light on the wide spectrum of biochemical effects elicited by various concentrations of ROS, indicating that maintaining redox homeostasis in cells and tissues is the key to health in general. More notably, it was recently demonstrated that corneal epithelial cells produced ROS in response to EGF stimulation, and the ROS generated were essential in mediating cell proliferation, adhesion, migration, and wound healing.10 Chiarugi and colleagues12,13 elucidated in fibroblast and other cell types that ROS were produced on integrin engagement and ROS were responsible for the direct activation of tyrosine kinase Src by oxidizing its two conserved cysteine (Cys) moieties. The oxidized and activated Src subsequently transphosphorylated epidermal growth factor receptor (EGFR) in a ligand-independent manner, allowing the prosurvival signals to be elicited and escaping from anoikis, or apoptosis due to failed integrin-ECM contact.14 Src is widely recognized as an early mediator in integrin-triggered signaling and plays a pivotal role in cytoskeletal organization and focal adhesion assembly.15,16 Activation of EGFR is absolutely required for induction of proliferation and motility in many epithelia, including the corneal epithelium and the epidermis after wounding.17–19 Although endogenous ROS has been proved to play an instrumental role in various cell functions, little work has been carried out to determine whether or not extracellular ROS may also provide beneficial effects on cells. A few reports in the literature have addressed H2O2-induced cell proliferation and differentiation,9,20,21 but far fewer in examining the benefit of H2O2 for cell adhesion and migration or even wound healing. Understanding whether extracellular ROS can assist such cellular functions, especially in the case of cornea wound healing, is of great ocular therapeutic interest. Corneal epithelium may be impaired by mechanical or chemical damage or be destroyed by microbial, such as bacterial or fungal, infection. Self-regeneration of the epithelium is essential to maintain corneal transparency and normal vision of the human eye. Typically, the healing takes place within 2 to 3 days after wounding of the corneal epithelium. It starts from basal cell renewal via cell division and migration of stem cells from the limbus that flatten and form a new cover on the basement membrane. Then a more pronounced proliferation occurs, resulting in an increase in thickness and formation of its normal layers. Corneal epithelial cell adhesion and migration likely rely on the extracellular matrix (ECM)-integrin system and are the most important processes during re-epithelialization and wound healing.22,23 ECM proteins, such as type IV collagen, laminin, and fibronectin, are components of the corneal basement membrane.24 When corneal injury results in destruction of the basement membrane, fibronectin is synthesized and deposited at the site of the epithelial defect and serves as a temporary matrix for epithelial cell adhesion and migration.25,26 In view of the importance in understanding corneal wound healing, we investigated the probable role of exogenous ROS, namely, H2O2, at low concentrations in cell adhesion, migration, and wound healing using cultured primary rabbit corneal epithelial (RCE) cells in the absence of serum growth factor and cytokine, the ex vivo model of pig eye cornea, and the in vivo model of mouse eye cornea. We have found that H2O2 at 20 μM in the absence of serum growth factor and cytokine showed no adverse effect on cell viability but actually stimulated adhesion and migration in cultured cells on an Fn-coated plate and enhanced pig eye cornea wound healing ex vivo as well as mouse cornea wound healing in vivo.