Objective. Sclerostin plays a major role in regulating skeletal bone mass, but its effects in articular cartilage are not known. The purpose of this study was to determine whether genetic loss or pharmacologic inhibition of sclerostin has an impact on knee joint articular cartilage.Methods. Expression of sclerostin was determined in articular cartilage and bone tissue obtained from mice, rats, and human subjects, including patients with knee osteoarthritis (OA). Mice with genetic knockout (KO) of sclerostin and pharmacologic inhibition of sclerostin with a sclerostin-neutralizing monoclonal antibody (Scl-Ab) in aged male rats and ovariectomized (OVX) female rats were used to study the effects of sclerostin on pathologic processes in the knee joint. The rat medial meniscus tear (MMT) model of OA was used to investigate the pharmacologic efficacy of systemic Scl-Ab or intraarticular (IA) delivery of a sclerostin antibody-Fab (Scl-Fab) fragment.Results. Sclerostin expression was detected in rodent and human articular chondrocytes. No difference was observed in the magnitude or distribution of sclerostin expression between normal and OA cartilage or bone. Sclerostin-KO mice showed no difference in histopathologic features of the knee joint compared to age-matched wild-type mice. Pharmacologic treatment of intact aged male rats or OVX female rats with Scl-Ab had no effect on morphologic characteristics of the articular cartilage. In the rat MMT model, pharmacologic treatment of animals with either systemic Scl-Ab or IA injection of Scl-Fab had no effect on lesion development or severity.Conclusion. Genetic absence of sclerostin does not alter the normal development of age-dependent OA in mice, and pharmacologic inhibition of sclerostin with Scl-Ab has no impact on articular cartilage remodeling in rats with posttraumatic OA.

KCNQ1 has been identified as a susceptibility gene of type 2 diabetes mellitus (T2DM) in Asian populations through genome-wide association studies. However, studies on the association between gene polymorphism of KCNQ1 and T2DM complications remain unclear. To further analyze the association between different alleles at the single nucleotide polymorphism (SNP) rs2237892 within KCNQ1 and TD2M and its complications, we conducted a case-control study in a Chinese Han population. The C allele of rs2237892 variant contributed to susceptibility to T2DM (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.20–1.75). Genotypes CT (OR, 1.97; 95% CI, 1.24–3.15) and CC (OR, 2.49; 95% CI, 1.57–3.95) were associated with an increased risk of T2DM. Multivariate regression analysis was performed with adjustment of age, gender, and body mass index. We found that systolic blood pressure (P = 0.015), prevalence of hypertension (P = 0.037), and risk of macrovascular disease (OR, 2.10; CI, 1.00–4.45) were significantly higher in subjects with the CC genotype than in the combined population with genotype either CT or TT. Therefore, our data support that KCNQ1 is associated with an increased risk for T2DM and might contribute to the higher incidence of hypertension and macrovascular complications in patients with T2DM carrying the risk allele C though it needs further to be confirmed in a larger population.

Abstract.A case-control study was conducted with the aim of identifying the predominant haplogroups associated with type 2 diabetes mellitus (T2DM) and its complications. In addition, the role of N9a in T2DM risk and complications was analyzed. Sequencing of the entire mitochondrial DNA was conducted in 235 patients and 244 controls in cohort 1, and six haplogroups (F, B4, D4, D5, M8a and N9a) associated with T2DM were classified. The frequency of N9a was further determined in cohort 2 (440 patients and 244 controls) and examined in two combined cohorts, including 675 patients with T2DM and 649 non-diabetic controls. Multivariate logistic regression analysis and association analysis were performed to investigate the association between genotypes, T2DM and diabetic nephropathy. M8a [P=0.011; odds ratio (OR), 3.49; 95% confidence interval (CI), 1.26-9.69] and haplogroup N9a (P=0.023; OR, 2.60; 95% CI, 1.11-6.05) were associated with an increased risk of T2DM. The frequency of N9a was higher in T2DM patients compared with that in the controls (6.2% vs. 4.3%) and associated with a mild risk (P=0.10; OR, 1.51; 95% CI, 0.92-2.49). N9a was significantly associated with an increased risk of diabetic nephropathy (P=0.024; OR, 2.15; 95% CI, 1

Aim This study aimed to evaluate the association between cardiovascular autonomic neuropathy (CAN) and left ventricular diastolic dysfunction (LVDD) in type 2 diabetes patients. Methods 315 type 2 diabetes patients from inpatients of Drum Tower Hospital were included and classified into no CAN (NCAN), possible CAN (PCAN), and definite CAN (DCAN) based on cardiovascular autonomic reflex tests. The left ventricular diastolic function was assessed by tissue Doppler imaging echocardiography. Results The distribution of NCAN, PCAN, and DCAN was 11.4%, 51.1%, and 37.5%, respectively. The proportion of LVDD increased among the groups of NCAN, PCAN, and DCAN (39.4%, 45.3%, and 68.0%, P = 0.001). Patients with DCAN had higher filling pressure (E/e′ ratio) (10.9 ± 2.7 versus 9.4 ± 2.8, P = 0.013) and impaired diastolic performance (e′) (6.8 ± 1.7 versus 8.6 ± 2.4, P = 0.004) compared with NCAN. CAN was found to be an independent risk factor for LVDD from the multivariate regression analysis (OR = 1.628, P = 0.009, 95% CI 1.131–2.344). Conclusions Our results indicated that CAN was an independent risk marker for the presence of LVDD in patients with diabetes. Early diagnosis and treatment of CAN are advocated for preventing LVDD in type 2 diabetes.

The aim of the present study was to compare the safety of the application of painless gastroscopy and ordinary gastroscopy for chronic hypertension patients combined with early gastric cancer. A total of 123 patients with early gastric cancer were selected at the Dongying People's Hospital from June, 2014 to August, 2016. The patients were randomly divided into the painless (n=63) and ordinary (n=60) gastroscopy groups. Proper pretreatment was performed according to whether anesthesia was performed or not. Arterial pressure, heart rate, and blood oxygen saturation were detected and compared before anesthesia, when gastroscope passed through the esophageal entrance plane, and after recovery from anesthesia. The incidence of nausea and vomiting, cough, dysphoria, throat discomfort and other adverse reactions during and after surgery were recorded and compared. Compared with the levels before anesthesia, the mean arterial pressure, heart rate and blood oxygen saturation were significantly reduced in painless gastroscopy when the gastroscope passed through the esophageal entrance plane (P<0.05). In the ordinary gastroscopy group, the mean arterial pressure, heart rate and blood oxygen saturation were significantly increased when the gastroscope passed through the esophageal entrance plane compared with the levels before anesthesia (P<0.05). Blood pressure decreased in the painless gastroscopy group whereas it increased in the ordinary gastroscopy group after anesthesia. The decrease in the painless gastroscopy group was lower than in the ordinary group. The incidence of intraoperative and postoperative adverse reactions including nausea, vomiting, cough, dysphoria, pharyngeal discomfort and other adverse reactions was significantly decreased in the painless gastroscopy group than in the ordinary gastroscopy group (P<0.05). The results suggest that the application of painless gastroscopy in chronic hypertension patients can significantly reduce the incidence of intraoperative and postoperative adverse reactions compared with that of the Gastric cancer ordinary gastroscopy. Thus, painless gastroscopy is safer than ordinary gastroscopy.

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