OBJECTIVETo analyze clinical features and genetic mutations in a Chinese family affected with autosomal dominant caveolinopathies.

METHODSClinical data of the proband and her family members were collected. Genomic DNA was extracted from peripheral blood samples with a standard procedure. Next generation sequencing was carried out for the proband, and direct sequencing was employed to detect potential mutation of the CAV gene.

RESULTSThe proband presented with slowly progressing distal muscle weakness and atrophy, especially distal upper limbs and muscular soreness during early childhood, with her CK level moderately elevated and EMG showing myogenic and neurogenic injuries. Her sisters presented mild symptoms with hand muscle atrophy and fasciculation after exercise. A heterozygous missense mutation c.80G>A (p.Arg27Gln), which was reported as being pathogenic, was identified in the CAV3 gene in the proband and her sisters.

CONCLUSIONA heterozygous c.80G>A (p.Arg27Gln) mutation in the CAV3 gene probably underlies the autosomal dominant caveolinopathies in this Chinese family.

Caveolin 3 ; genetics ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Middle Aged ; Muscular Dystrophies ; genetics ; Mutation

Objective:To explore the regulatory effects of Danzhi Jiangtang Capsules on glucose metabolism and mitochondrial oxidative stress levels in db/db mice.Methods:Totally 32 db/db mice were randomly divided into model group, positive control group, and Danzhi Jiangtang Capsule low-, medium- and high-dosage groups; at the same time, 8 same-sex C57BL/6 mice of the same week age were selected as the blank group. The metformin group was filled with metformin solution 0.1 g/kg, and the Danzhi Jiangtang Capsule low-, medium- and high-dosage groups were injected with 0.99, 0.49 and 0.25 g/kg Danzhi Jiangtang Capsule solution respectively. The model group and the blank group received the same volume of physiological saline solution for the gavage, 1 time/d, continuous 12 weeks. The weight and fasting blood sugar (FBG) changes in each group of mice were detected; the serum insulin (FINS) level was detected by ELISA method and the insulin resistance index (HOMA-IR) was calculated; kits were used to detect the pancreatic tissue SOD and MDA levels of each group of mice; HE staining was used to observe pathological morphology of pancreatic tissue. Transmission electron microscopy was used to observe the ultrastructure of pancreatic mitochondria; Western blot method was used to detect the expressions of p-AMPK and AMPK proteins in pancreatic tissue.Results:Compared with the model group, after 8 or 12 weeks of drug administration, the weight of mice in the Danzhi Jiangtang Capsule high-dosage group decreased ( P<0.05 or P<0.01), and the level of FBG decreased ( P<0.01); FINS and HOMA-IR in the Danzhi Jiangtang Capsule high- and medium-dosage groups decreased ( P<0.01), the SOD activity in Danzhi Jiangtang Capsule high- medium- and low-dosage groups increased, and the level of MDA decreased ( P<0.01); the expressions of p-AMPK and AMPK in Danzhi Jiangtang Capsule high-and medium-dosage groups increased ( P<0.01), the expression of AMPK in Danzhi Jiangtang Capsule low-dosage group increased ( P<0.01). Conclusion:Danzhi Jiangtang Capsule can improve SOD activity in pancreatic tissue of db/db mice, reduce MDA content, and activate the AMPK signaling pathway, suggesting that Danzhi Jiangtang Capsule can improve insulin resistance and restore glucose homeostasis by inhibiting oxidative stress levels and improving mitochondrial function.

BACKGROUND: The number of patients diagnosed with hereditary hemolytic anemia (HHA) has increased since the advent of novel diagnostic techniques that accurately identify this disorder. Here, we report data from a survey on the prevalence and characteristics of patients diagnosed with HHA in Korea from 2007 to 2011. METHODS: Information on patients diagnosed with HHA in Korea and their clinical and laboratory results were collected using a survey questionnaire. Globin gene and red blood cell (RBC) enzyme analyses were performed. In addition, we analyzed data collected by pediatricians. RESULTS: In total, 195 cases of HHA were identified. Etiologies identified for HHA were RBC membranopathies, hemoglobinopathies, and RBC enzymopathies, which accounted for 127 (64%), 39 (19.9%), and 26 (13.3%) cases, respectively. Of the 39 patients with hemoglobinopathies, 26 were confirmed by globin gene analysis, including 20 patients with beta-thalassemia minor, 5 patients with alpha-thalassemia minor, and 1 patient with unstable hemoglobin disease. CONCLUSION: The number of patients diagnosed with hemoglobinopathies and RBC enzymopathies has increased considerably since the previous survey on HHA in Korea, dated from 1997 to 2006. This is likely the result of improved diagnostic techniques. Nevertheless, there is still a need for more sensitive diagnostic tests utilizing flow cytometry and for better standardization of test results to improve the accuracy of diagnosis of RBC membranopathies in Korea. Additionally, more accurate assays for the identification of RBC enzymopathies are warranted.
alpha-Thalassemia ; Anemia, Hemolytic, Congenital ; beta-Thalassemia ; Diagnostic Tests, Routine ; Erythrocytes ; Flow Cytometry ; Globins ; Hematology ; Hemoglobinopathies ; Hemoglobins ; Humans ; Korea ; Prevalence ; Spherocytosis, Hereditary ; Thalassemia ; Surveys and Questionnaires

ObjectiveTo explore the potential mechanism of Banxia Xiexin Decoction （半夏泻心汤， BXD） in the treatment of diabetic gastroparesis （DGP）. MethodsA total of 29 SD rats were randomly divided into four groups， blank group （5 rats） and model group， BXD group and metformin group （8 rats in each group）. Except for the blank group， rats were administered intraperitoneally with 1% streptozotocin （STZ） solution and were fed a high-sugar， high-fat diet to establish the DGP rat model. After successful modeling， the BXD group was treated with BXD at 6.68 g/（kg·d） by gavage， the metformin group was treated with metformin hydrochloride at 105 mg/（kg·d） by gavage， and the blank group and the model group were treated with normal saline at 6.68 ml/（kg·d） by gavage， for 8 weeks. After the last administration， fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， total cholesterol （TC）， triglycerides （TG） were measured and gastric emptying rate was calculated. ELISA was used to detect the levels of gastrointestinal hormones motilin （MTL） and gastrin （GAS）， as well as inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β） and interleukin-10 （IL-10） in gastric tissue. Oil red O staining was performed to observe liver pathological morphology. Hematoxylin and eosin （HE） staining was used to observe gastric antrum tissue morphology. Immunofluorescence staining was used to detect liver X receptor α （LXRα） levels in the liver. Western Blot was used to detect the protein levels of LXRα in liver tissue， and of janus kinase 2 （JAK2）， phospho-janus kinase 2 （p-JAK2）， signal transducer and activator of transcription 3 （STAT3） and phospho-signal transducer and activator of transcription 3 （p-STAT3） in gastric antrum tissue. Quantitative real-time polymerase chain reaction （qPCR） was used to measure the mRNA expression of LXRα in liver tissue and JAK2， STAT3 in gastric antrum tissue. ResultsCompared with the blank group， the model group showed significant hepatic fatty degeneration， gastric antrum tissue structure destruction， and increases in FBG， HbA1c， TC， and TG levels； the average fluorescence intensity， protein level， and mRNA expression of LXRα in liver tissue were reduced； the gastric emptying rate and gastric tissue GAS and MTL levels decreased； inflammatory factors including TNF-α， IL-6， IL-1β in gastric tissue increased， IL-10 decreased； in gastric antrum tissue， the mRNA expression of p-JAK2/JAK2， p-STAT3/STAT3， and JAK2 and STAT3 increased （P＜0.01）. Compared with the model group， both the BXD group and the metformin group showed improved liver and gastric antrum tissue pathology； FBG， HbA1c， TC， and TG levels decreased， while LXRα fluorescence intensity， protein level， and mRNA expression in liver tissue significantly increased； the gastric emptying rate and the levels of GAS and MTL in gastric tissue were markedly higher； the levels of TNF-α， IL-6， and IL-1β decreased， whereas IL-10 levels increased， p-JAK2/JAK2， p-STAT3/STAT3， and the mRNA expression of JAK2 and STAT3 in gastric antrum tissue decreased （P＜0.05 or P＜0.01）. The BXD group showed higher level than the metformin group in FBG， HbA1c， and TG levels， lower level in gastric emptying rate and gastric tissue GAS content， and higher level in gastric tissue TNF-α， IL-6， IL-1β levels； there was also a decrease in IL-10 levels， and a reduction in LXRα fluorescence intensity and mRNA expression in liver tissue， as well as in p-JAK2/JAK2 levels in gastric antrum tissue （P＜0.05 or P＜0.01）. ConclusionBXD can reduce blood glucose and lipid levels in DGP model rats while improving gastric function and alleviating gastric tissue inflammation. Its mechanism may be related to the regulation of LXRα expression in liver tissue and the JAK2/STAT3 pathway in gastric antrum tissue.