Objective To analyze the molecular epidemiology characteristic of neonatal deafness susceptibility genes .Methods Hearing screening and deafness susceptibility genes screening were performed in 1 674 cases of newborn to analyze the epidemiolog‐ical characteristics .Results Among 1 674 cases of neonatus ,37 cases were with deafness susceptibility gene abnormalities ,inclu‐ding 2 cases of 176 del 16 mutations ,5 cases of 299 del AT heterozygous mutation ,16 cases of 235 del C mutation ,9 cases of IVS7‐2A>G heterozygous mutations ,1 case of 2168A> G mutation ,2 cases of 538C> T heterozygous mutation ,2 cases of 1494C> T mutation ,and the positive rate was 2 .21% .Conclusion Hearing screening combined with deafness susceptibility gene screening could detect possible hearing loss children from molecular level ,providing favorable reference for the early detection ,predict and in‐terventions .

Objective To investigate the apoptosis of neuron surrounding the hematoma in intracerebral hemorrhage(ICH)rats.Methods 64 male SD rats were randomly divided into two groups,trial group(ICH,n=56)and control group(sham operated,n=8).The brains of the rats were removed 6 h,12 h,24 h,48 h,72 h,7 d,14 d after ICH.Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-bioti in situ nick end-labeling(TUNEL)was used to detect deoxyribonucleic acid(DNA)fragmentation.The activation of caspase-3 was measured with immunohistochemistery.The electron microscope were used to observe histological changes surrounding the hematoma.Results Under transmission electronic microscope,shrunken neuron and glial cell with pre-apoptotic signs of intensely stained cytoplasm and abnormally dense nucleus,swollen blood vessel were found.TUNEL-positive cells appeared in the periphery of the hematoma and increased from 6 h to 14 d after ICH.Little TUNEL-positive cells could be found in the control group.The change of the caspase-3-positive cells was similar to TUNEL,but the peak of caspase-3-positive cells was more early than that of TUNEL.Conclusion The apoptosis of neuron occurred surrounding the hematoma in ICH rats and it may related to caspase-3.

Objective To investigate the effect of gastrointestinal Roux-en-Y gastric bypass surgery on blood sugar and insulin function of patients with type-2 diabetes mellitus.Methods Twenty-seven cases of gastric cancer patients with type-2 diabetes and undergone Roux-en-Y bypass the gastrointestinal treatment in the centre hospital of Cangzhou were selected as our subject.Body mass index (BMI),Glycosylated hemoglobin (HBA1c),Fasting and glucose (FPG),fasting insulin (FINS),Fasting C-peptide (FCP) levels were measured.Glucose (2 hPG),insulin (2 hINS) and C-peptide (2 hCP) levels were detected after 2 h for oral use 75 g glucose.Homeostasis model was applied to assess insulin resistance index (HOMA-IR).Results No significant change was seen in terms of BMI between before and after surgery.Compared to before surgery,the levels of FPG((7.58 ±0.84) mmol/L),2 hPG((10.43 ± 1.88) mmol/L),HbA1c((7.56 ± 1.15)％) and HOMA-IR(4.55 ±0.76) were lower in patients at 3 months after surgery ((9.93 ± 1.57) mtmol/L,(13.89± 2.13) mtmol/L,(9.88 ± 1.66) ％,(4.55 ± 0.76),respectively,P ＜ 0.05 or P ＜ 0.01).FPG ((6.56± 0.80) mmol/L),2 hPG ((8.57 ± 1.32) mmol/L),HbA1 c ((6.37 ± 1.24) ％),HOMA-IR (4.03 ± 0.45)of patients after 6 months were lower than that of before surgery and 3 months after surgery (P ＜ 0.05 or P＜0.01).However,the levels of FINS ((13.67 ± 1.96) mU/L),FCP((2.62 ±0.87) μg/L),2 hINS((49.91± 5.14) mU/L) and 2 hCP ((6.28 ± 1.65) μg/L) were higher in patients with 3 months after surgery compared to that of before surgery ((11.08 ± 1.69) mU/L,(1.78 ± 0.61) μg/L,(36.05 ± 4.03) mU/L,(4.28 ± 1.48) μg/L,P ＜ 0.01).Meanwhile those indices after 6 months (FINS:(15.88 ± 2.05) mU/L,FCP:(3.30 ±0.68) μg/L,2 hINS:(67.40 ±5.68) mU/L,2 hCP:(9.39 ± 1.52) μg/L) were higher than that of before surgery and 3 months after surgery(P ＜ 0.01).Conclusion Roux-en-Y gastrointestinal bypass can effectively reduce blood sugar level and improve the situation of Pancreatic Beta-cell function of gastric cancer patients with type-2 diabetes.

Background Cooking oil fumes are closely related to immune response, and adipose tissue also plays an important role in immune regulation. At present, the biological effect and mechanism of inflammation of adipose tissue induced by oil fume exposure are not clear yet. Objective To investigate the inflammatory effect of different exposure duration of cooking fumes on adipose tissue in mice and explore the role of Nod-like receptor pyrin domain 3 (NLRP3)/cysteinyl aspartate specific proteinase 1 (Caspase 1)/interleukin (IL)-1β signaling pathway. Methods Forty 8-week-old female C57BL/6J mice were randomly divided into 3-day control group (CON₃ group), 7-day control group (CON₇ group), 3-day oil fume exposure group (COF₃ group), and 7-day oil fume exposure group (COF₇ group), with 10 mice in each group. The mice were exposed to oil fumes in a cooking oil fume formation and exposure equipment (COFFEE) for 20 min, followed by a 10-min pause, 1 h a day for consecutive 3 d or 7 d. General condition of mice was observed and body weight was measured every day. After exposure, blood was sampled from the eyeball. Serum levels of IL-6, IL-27, and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). The adipose tissue of mice was collected and observed after hematoxylin-eosin (HE) staining. The percentages of CD4⁺ and CD8⁺T cells in adipose tissue were detected by flow cytometry. Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of nuclear factor-κB (NF-κB), NLRP3, Caspase 1, and IL-1β in adipose tissue. Western blot was used to detect the expression levels of NLRP3, Caspase 1, and IL-1β in adipose. Results Compared with the corresponding control group, serum IL-6, IL-27, and IL-1β contents in the COF₃ group and the COF₇ group were significantly increased (P<0.05) except IL-6 in the COF₃ group, and the levels in the COF₇ group were significantly higher than those in the COF₃ group (P<0.05). Vacuolar lipid droplets in adipocytes decreased, cytoplasm shrank, and inflammatory cells infiltrated in the COF₇ group after HE staining. The flow cytometry results showed that the proportions of CD4⁺ and CD8⁺T cells in adipocytes of the COF₃ group and the COF₇ group were increased compared to the corresponding control group, with a significant increase in the COF₇ group (P<0.05), and the CD4⁺/CD8⁺T ratio also significantly increased progressively in the two groups (P<0.05). The results of RT-qPCR showed that compared with the corresponding control group, the mRNA expression levels of NF-κB, NLRP3, Caspase 1, and IL-1β in adipose tissue of mice in the COF₃ group and the COF₇ group were significantly increased (P<0.05, P<0.01). The mRNA expression levels of mice in each exposure group gradually increased over time. The Western blot results showed that compared with the corresponding control group, the protein expressions of NLRP3 and Caspase 1 in the COF₃ group were significantly increased (P<0.01), and the expression of IL-1β protein also increased but without statistical significance. The protein expressions of NLRP3, Caspase 1, and IL-1β in the COF₇ group were significantly higher than those in the CON₇ group (P<0.05, P<0.01). Conclusion Acute exposure to cooking oil fumes can induce significant inflammatory response in adipose tissue, and the effect gradually increases with the extension of exposure time. The mechanism of action may be related to the activation of NLRP3 inflammasome signaling pathway.

PURPOSE: Interleukin-17 (IL-17) is a proinflammatory cytokine that plays important roles in inflammation, autoimmunity, and cancer. The purpose of this study was to determine if IL-17 indirectly regulates macrophage differentiation through up-regulation of cyclooxygenase-2 (COX-2) expression in the cancer cell lines. MATERIALS AND METHODS: Human cervical cancer HeLa, human lung cancer A549, and mouse prostate cancer Myc-CaP/CR cell lines were treated with recombinant IL-17; Western blot analysis, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction analysis were utilized to examine the cellular responses. RESULTS: IL-17 up-regulated expression of COX-2 mRNA and protein in HeLa, A549, and Myc-CaP/CR cell lines. IL-17's effects were mediated through nuclear factor-kappaB and ERK1/2 signaling pathways as the inhibitors of these pathways could inhibit IL-17-induced COX-2 expression. The conditional medium obtained from the cancer cells contained prostaglandin E2, the levels of which were increased by IL-17 treatment. When treated with the conditional medium, particularly with the IL-17-induced conditional medium, mouse RAW264.7 macrophages and human THP-1 monocytes expressed higher levels of IL-10 (a marker of M2 macrophages) than inducible nitric oxide synthase or tumor necrosis factor alpha (markers of M1 macrophages). In contrast, when RAW264.7 and THP-1 cells were treated directly with IL-17, expression of these marker genes was not markedly changed. CONCLUSION: The results of this study suggest that IL-17 indirectly promotes M2 macrophage differentiation through stimulation of the COX-2/PGE2 pathway in the cancer cells, thus IL-17 plays an indirect role in regulating the tumor immune microenvironment.
Animals ; Autoimmunity ; Blotting, Western ; Cell Line ; Cyclooxygenase 2 ; Dinoprostone ; Enzyme-Linked Immunosorbent Assay ; Humans ; Inflammation ; Interleukin-10 ; Interleukin-17* ; Lung Neoplasms ; Macrophages* ; Mice ; Monocytes ; Nitric Oxide Synthase Type II ; Prostatic Neoplasms ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Tumor Microenvironment ; Tumor Necrosis Factor-alpha ; Up-Regulation ; Uterine Cervical Neoplasms

It was reported that pancreatic arteries constricted during the early phase of bile salt-induced acute pancreatitis (AP), leading to pancreatic microcirculatory disturbance. We conducted this experiment to verify whether the above-mentioned finding was true. AP was induced with intraductal injection of taurodeoxyholate. Small pancreatic artery pressure in dogs was recorded. Functional capillaries were counted and calibrated by multiplying wet weight of pancreas. Pancreatic perfusion was measured with Laser Doppler flowmeter. Pancreatic arterioles of rats dilated during the initial 20 min of AP, and pancreatic arterial pressure declined during the early phase of AP in dogs (from 104.5 +/- 4.8 mmHg to 54.6 +/- 5.6 mmHg). The hematocrit of blood from inferior vena cava was significantly lower than that of portal vein at 5 min after pancreatitis induction. The "true" pancreatic functional capillary density increased. The early pancreatic microcirculatory disturbance coincided with a marked increase of portal vein pressure (PVP) as high as 9.18 +/- 0.78 mmHg. Reduction of PVP to baseline level was followed by a marked increase of pancreatic perfusion (by 1.4-fold). Arterial dilatation, but not constriction, occurred during the early phase of bile salt-induced AP. The pancreatic microcirculatory disturbance was due to a marked rise in PVP that greatly reduced the pressure difference in the pancreatic blood vessels and increased plasma extravasation which led. to local hemoconcentration.
Animals ; Bile Acids and Salts ; adverse effects ; Hypertension, Portal ; complications ; Male ; Microcirculation ; drug effects ; physiology ; Pancreas ; blood supply ; Pancreatitis ; etiology ; physiopathology ; Portal Pressure ; Portal Vein ; physiopathology ; Rats ; Rats, Sprague-Dawley

Background It is unclear if there is any combined effect of air pollutants and non-optimal temperature on metabolic syndrome, or any molecular mechanisms of related signaling pathways in the process, which requires urgent systematic research. Objective To observe the effects of combined exposure to PM_2.5 and non-optimal temperature on metabolic damage at gene and protein levels in mice, and elucidate the role of related signaling pathway in crucial organs. Methods A total of 60 six-week-old male C57BL/6J mice were randomly divided into six groups: a normal temperature-filter air group (T_N-FA), a normal temperature-concentrated PM_2.5 group (T_N-PM), a heat-filter air group (T_H-FA), a heat-concentrated PM_2.5 group (T_H-PM), a cold-filter air group (T_C-FA), and a cold-concentrated PM_2.5 group (T_C-PM). The Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) was used to provide combined exposure settings of air types [concentrated PM_2.5 and filter air (FA)] and temperatures [normal (22°C), cold (4°C), and heat (30°C)] for 4 weeks. Skeletal muscle and white adipose tissue (WAT) of the mice were sampled at the end of exposure, and transcriptomics and Western blot (WB) assay were adopted to observe selected gene and protein expression levels in the samples respectively. Results The transcriptomics results indicated that the PM_2.5 exposure enhanced the number of differentially expressed genes. Specifically, 4820 genes were differentially expressed in the T_N-PM mice compared to the T_N-FA mice at normal temperature, and 1143 genes were differentially expressed in the Tc-PM mice compared to the Tc-FA mice in the cold environment. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and the endoplasmic reticulum protein processing pathway were identified as the most significant pathways in metabolic injury resulting from combined exposure to PM_2.5 and non-optimal temperature exposure. The WB results showed that exposure to PM_2.5 in the normal temperature and the cold environments led to a significant increase in the expression of p-AKT in WAT (P<0.01, P<0.05) and a significant decrease in the expression of GLUT4 (P<0.05, P<0.01). In skeletal muscle, exposure to PM_2.5 led to a significant decrease in GLUT4 (P<0.05) in all environments, with a consistent trend of change as observed in WAT. Conclusion Cold/heat exposure might promote PM_2.5-induced metabolic disorder through suppression of the AKT/GLUT4 pathway, aggravating metabolic damage.

OBJECTIVETo analyze the clinical features of clonal evolution of acquired aplastic anemia (AA) into myelodysplastic syndrome/acute myeloid leukemia (AML) and review of literatures.

METHODSAA developing MDS/AML patients between December 1994 and December 2011 enrolled into this study to analyze their clinical characteristics.

RESULTSDuring the median follow-up of 49(15-97) months, 19 patients evolved to MDS/AML, of whom 10, 8 and 1 were from VSAA, SAA and NSAA subgroups, respectively. The median G-CSF therapy was 270(29-510) days. There were monosomy 7 in 11(57.9%) of 19 patients with AA evolved to MDS/AML. The median AA evolved to MDS/AML was 33(11-88) months. The median MDS/AML transformation in responders (54.2 months) was significantly longer than of non-responders (25.7 months, P<0.01).

CONCLUSIONAA patients could evolved into MDS/AML concomitant with abnormal karotype and worse prognosis.