Homozygous familial hypercholesterolemia in China: Genetic and clinical characteristics from a real-world,multi-center,cohort study

BackgroundThere is a lack of large-scale data on the clinical and genotype characteristics of homozygous familial hypercholesterolemia (HoFH) patients in Asia.ObjectiveTo define the characteristics of phenotypic and genetic HoFH probands from mainland China.MethodsWe collected data from patients with suspected HoFH from ten clinical hospitals across mainland China from 2003 to 2019. Clinical data and DNA testing were obtained in all patients. The Kaplan-Meier method was used to generate survival curves, and the groups were compared with the log-rank test.ResultsA total of 108 unrelated probands with suspected HoFH (mean age 14.9 years) were included. The three most common variants were W483X (c.1448 G>A), A627T (c.1879 G>A), H583Y (c.1747 C>T). The majority (64.8%) were compound heterozygotes (n = 70), 23 (21.3%) were true HoFH patients. True HoFH showed higher LDL-C levels compared to compound HoFH (16.8±3.6 mmol/L vs. 15.0±3.1 mmol/L, P = 0.022). During follow-up, only 21.2% patients exhibited an LDL-C reduction of more than 50%. Kaplan-Meier analysis showed that the true HoFH probands had significantly worse survival rates compared to other genotype probands (13-year survival; 20.3% vs. 76.7%, respectively; P = 0.016). In addition, true HoFH shows that 2.8-fold (P = 0.022) increase any death and 3.0-fold (P = 0.023) increase cardiovascular death risk in relative to other FH.ConclusionsThis report shows that HoFH has devastating consequences, and that patients are often only diagnosed after they have been exposed to severely elevated LDL-C for years. Systematic screening and early intensive treatment are an absolute requirement for these young individuals with HoFH.     

Engineered glove to evaluate hand disability in rheumatoid arthritis: A pilot-study

ObjectiveThe Hand Test System (HTS) is an engineered-sensorized glove that has been originally developed in the neuroscientific field for the evaluation of hand fingers’ speed movement. This pilot-study aimed to evaluate the reproducibility of HTS analysis in rheumatoid arthritis (RA), correlating glove-derived parameters with clinical disease activity indexes, self-reported disability-related questionnaires and hand strength.MethodsFifty-five RA patients and fifty age and sex matched healthy controls (HCs) performed HTS analysis. The glove recognized the touch speed between the finger tips during standard sequences of movements, providing three quantitative parameters: touch duration (TD), inter-tapping interval (ITI) and movement rate (MR). These variables were correlated with Health Assessment Questionnaire (HAQ), Health Assessment Questionnaire-Disease Index (HAQ-DI), Hand Disability Index (HDI), Hand Grip Strength (HGS), DAS28-CRP, CDAI and SDAI.ResultsIntraclass correlation coefficient was 0.93 (CI: 0.92, 0.95). RA patients showed significantly slower TD, ITI and MR than HCs, for all classes of disease activity (P < 0.001). All HTS parameters correlated significantly with HAQ, HAQ-DI, HDI, HGS, DAS28-CRP, SDAI, CDAI (between P < 0.05 and P < 0.001). Of note, also RA patients in clinical remission showed a significantly higher TD compared with HCs (P < 0.001).ConclusionHTS seems a new safe and fast tool to evaluate rheumatoid hand's functionality, measuring the speed of finger movements. Furthermore, the HTS parameters significantly correlate with quality of life, disease activity, hand strength and perceived hand disability, evaluating also potential hand motor impairment in RA clinical remission.     

Antifungal sensitivity and species of yeasts in oral mucosa of street mixed-breed dogs

The aim of this research is to verify the yeast species isolated from oral mucosa in street mixed-breed dogs and to determine the antifungal profiles. After capturing and sedating the animals, oral mucosa samples were collected from fifty dogs and the materials were inoculated on Sabouraud dextrose agar with chloramphenicol. Forty-three yeast strains were isolated and identified trough the API-20C AUX method. Thirty-seven (86.1%) of the yeasts belonged to genus Candida, five (11.6%) to genus Trichosporon and only one strain (2.3%) to genus Malassezia. The sensitivity profiles to anifungals (amphotericin B, itraconanole, ketoconazole, fluconazole and variconazole) were determined through Etest® method. This study found resistance of some yeasts to amphotericin B and a good susceptibility to voriconazole and ketoconazole. Some of these antifungals are used in veterinary medical practice. This research is the first investigation on street mixed-breed dogs regarding yeast identifications and antifungals profiles.     

Isoflurane preconditioning ameliorates electromagnetic pulse-induced neural damage by shifting microglia polarization toward anti-inflammatory phenotype via upregulation of SOCS1

With the speedy technological advances during the past few decades, human exposure to the electromagnetic field (EMF) has become increasingly common. Exposure to EMF may induce neural injuries and dysfunction of various organs, likely involving neuroinflammation and activation of microglial cells. Isoflurane preconditioning (IP) is shown to provide neuroprotection in various neurological diseases by inhibiting excessive neuroinflammatory responses. Brain samples harvested from rats exposed to electromagnetic pulse (EMP) with or without IP were subjected to qPCR, Western blot assay, and immunohistochemistry to determine the expression of pro-inflammatory/anti-inflammatory microglia markers and a variety of pro- and anti-inflammatory mediators. Suppressor of cytokine signaling 1 (SOCS1) siRNA was used in cultured N9 microglia cells to examine the roles of SOCS1 in the effect of IP. In both in vivo and in vitro experiments, EMP-exposed microglia were predominantly pro-inflammatory microglia, accompanied by increased expression of pro-inflammatory cytokines and chemokines, and activation of TLR4 pathway, leading to neuronal death. IP reversed the changes induced by EMP and switched the activated microglia to an anti-inflammatory phenotype. SOCS1 siRNA abolished the beneficial effects of IP. IP ameliorates EMP-induced neural injuries by shifting microglia polarization from pro-inflammatory to anti-inflammatory phenotype via upregulation of SOCS1.     

The Hepatorenal Toxicity and Tumor Response of Chemotherapy With or Without Aidi Injection in Advanced Lung Cancer: A Meta-Analysis of 80 Randomized Controlled Trials

PurposeChemotherapy-induced hepatorenal toxicity often decreases tolerance for further therapies and results in poor quality of life and prognosis for patients with lung cancer. In this meta-analysis, all related studies were systematically re-evaluated to determine whether Aidi injection relieves hepatorenal toxicity and improves tumor response, and to determine its threshold and the optimal treatment regimen for obtaining the desired responses.MethodsAll studies regarding Aidi injection with chemotherapy were gathered from Chinese and English databases (from inception until January 2019). Their bias risk was evaluated and the data were synthesized using meta-analysis; the quality of evidence of all outcomes was rated by using the Grades of Recommendation Assessment, Development, and Evaluation approach.FindingsEighty randomized controlled trials containing 6279 patients were included in the study. Most of the trials showed unclear risk of bias. Aidi injection with chemotherapy increased the objective response rate (risk ratio [RR], 1.32; 95% CI, 1.25–1.40) and the disease control rate (RR, 1.15; 95% CI, 1.12–1.17) and resulted in a lower incidence of hepatotoxicity (RR, 0.61; 95% CI, 0.55–0.69) and nephrotoxicity (RR, 0.62; 95% CI, 0.53–0.72) than that of chemotherapy alone. Subgroup analyses showed that treatment with 50 mL per time, 10 to 14 days per cycle, and 2 to 3 cycles of Aidi injection with chemotherapy resulted in a low incidence of hepatorenal toxicity. All of the results were robust, and their quality was moderate.ImplicationsThe moderate evidence indicates that Aidi injection with chemotherapy may improve tumor response and result in a low incidence of hepatorenal toxicity in patients with lung cancer. Aidi injection may relieve hepatorenal toxicity and exhibit an important protective effect against chemotherapy-induced hepatorenal toxicity. Based on the subgroup analysis results, Aidi injection seems to lower the threshold for chemotherapy. Treatment with 50 mL per time, 10 to 14 days per cycle, and 2 to 3 cycles may be the optimal usage for attaining a decrease in hepatorenal toxicity.