Animals ; Corticosterone ; blood ; Male ; Rats ; Rats, Wistar ; Stress, Physiological

Agricultural Workers' Diseases ; Humans ; Musculoskeletal Diseases

Adult ; Antineoplastic Agents ; adverse effects ; Comet Assay ; DNA Damage ; Female ; Humans ; Nurses ; Occupational Exposure ; Young Adult

Bone Neoplasms ; Female ; Humans ; Middle Aged ; Nasal Septum ; Nose Neoplasms ; Osteoma

Autosomal dominant polycystic kidney disease (ADPKD) is a most common inherited renal disease, about 50% with a family history, although the exact etiology not yet clear. To date, ADPKD, a multisystem disorder without effective preventive and therapeutic means, has been shown to be detrimental to human health. Recent studies show that severe oligoasthenozoospermia, necrospermia, immotile sperm, azoospermia, epididymal cyst, seminal vesicle cyst, and ejaculatory duct cyst found in male ADPKD patients may lead to male infertility, though the specific mechanisms remain unknown. Structural anomaly of spermatozoa, defect of polycystin, mutation of PKD genes, and micro-deletion of the AZF gene could be the reasons for the higher incidence of abnormal semen quality in male ADPKD patients. Assisted reproductive techniques can increase the chances of pregnancy, whereas the health of the offspring should be taken into consideration. This article presents an overview of reproductive issues concerning infertile male ADPKD patients from the perspective of the morbidity, pathophysiological mechanism, diagnosis, and management of the disease.
Cysts ; pathology ; Ejaculatory Ducts ; pathology ; Female ; Humans ; Infertility, Male ; physiopathology ; Kidney ; pathology ; Male ; Mutation ; Polycystic Kidney, Autosomal Dominant ; physiopathology ; Pregnancy ; Reproductive Techniques, Assisted ; Semen Analysis ; Spermatozoa ; pathology

Objective To investigate radionuclide imaging and routine CT in diagnosing hepatic focal nodular hyperplasia (FNH) and the combined diagnostic value of the two modalities. Methods Thirty-two patients with hepatic FNH were retrospectively studied. All patients underwent routine CT scan. Twenty-four patients were examined by 99Tcm-sulfur colloid (SC) hepatic planar scintigraphy and SPECT/CT imaging, and then patients who had abnormal foci underwent 99Tcm-diethyl iminodiacetic acid (EHIDA) triple-phase hepatobiliary imaging. x2 -test of four-table or Fisher exact probabilities in 2 × 2 table was applied for statistical analysis. Results Of all 32 patients pathologically diagnosed as FNH with single solitary nodule, 25 were classified as classic type and the rest 7 as non-classic type. Although routine CT found all hepatic lesions, only 15 cases were diagnosed pathologically as FNH classic type but the rest were either misdiagnosed or left as indeterminate. On radionuclide imaging (hepatic colloid scintigraphy plus triple-phase hepatobiliary images), 11 patients with big foci (with maximal diameter ＞3 cm) out of 24 patients were correctly diagnosed as FNH, with 7 diagnosed as classic type FNH and 4 as non-classic. Other 13 patients were either misdiagnosed or simply missed. The diagnosing rates of routine CT and radionuclide imaging were60.0% (15/25) and 38.9% (7/18) for FNH classic type, 0/7 and 4/6 for non-classic type,50.0% (10/20) and 73.3% (11/15) for big foci, 41.7% (5/12) and 0/9 forsmall foci (with maximal diameter≤3 cm), respectively. The total diagnosing rate of radionuclide imaging combined with routine CT was significantly higher than that of routine CT or radionuclide imaging alone ( x2 = 4. 48, P ＜ 0. 05;x2 =4.27, P ＜0.05 ). Conclusion Radionuclide imaging in combination with routine CT may improve the diagnostic accuracy for hepatic FNH patients.

Aim of the present study is to investigate activation effect of nobiletin on cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity. CFTR-mediated iodide influx assay and patch-clamp tests were done on FRT cells stably co-transfected with human CFTR and EYFP/H148Q. Nobiletin potently activated CFTR chloride channel activity in a dose- and time-dependent manner. The CFTR blocker CFTR(inh)-172 could completely reverse the effect. Preliminary mechanism study indicated that nobiletin activated CFTR chloride channel through a direct binding way. In addition, ex vivo tests done on mice trachea showed that nobiletin time-dependently stimulated submucosal gland fluid secretion. Nobiletin may be a therapeutic lead compound in treating CFTR-related diseases including disseminated bronchiectasis.

T_4 was coupled to human serum albumin(HSA)to make the conjugate T_4-HSA,a polyvalent T_4 analogue rather than monovalent T_4 per se alone.A new strategy for sandwich enzyme immunoassay model system of small molecular hapten hormones FT_4 was developed,such as intra-assay CV,inter-assay CV,average recovery, normal and abnormal values were fit for clinical application.The sensitivity was as much as 10 times higher than conventional competitive enzyme immunoassay.

OBJECTIVETo study the effects of Citalopram on the mRNA expression of bax and bel-2 in frontal cortical neurons and on cell apoptosis of rats after stress.

METHODSTwenty-four healthy male SD rats were randomly divided into three groups (n = 8). The control group did no receive any treatment, the stress group was subject to stress and given normal saline and experimental group was given Citalopram irrigation stomach after stress. Rats were forced to swim to establish chronic stress model (15 min/d, 4 weeks), bax, bcl-2 mRNA expression were tested by in situ hybridization technique (ISH), TUNEL assay was used to determine cell apoptosis, Nikon image analysis software were used to measure the number of positive cells in each index.

RESULTSCompared with the control group, the stress group showed a larger number of bax mRNA expressing cells( P < 0.01), a smaller number of bcl-2 mRNA expressing cells (P < 0.01), and the staining intensity of positive cells was significantly reduced( P < 0.01). Compared with the stress group, the experiment group showed more reduced number of bax mRNA positive cells( P < 0.01) and significantly increased bcl-2 mRNA positive cells( P < 0.05), a small amount of positive cells were found, compared with that in the stress group, nuclear condensation in the experimental group was reduced significantly and the staining was obviously weaker( P < 0.01).

CONCLUSIONCitalopram significantly antagonizes bax mRNA and potentiatesbcl-2 mRNA protein expression and inhibits apoptosis of rat prefrontal cortical neurons caused by chronic stress, which might be one possible mechanism of Citalopram for prevention and treatment of psychosis caused by chronic stress.

Animals ; Apoptosis ; Citalopram ; pharmacology ; Male ; Neurons ; drug effects ; metabolism ; Prefrontal Cortex ; cytology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Stress, Physiological ; bcl-2-Associated X Protein ; metabolism

OBJECTIVE Transient outward potassium current (Ito) plays a crucial role in cardiac phase 1 repolarization and the channels are assembled by pore-forming α-subunits (Kv4.2 or Kv4.3) and auxiliary subunits (KChIP2 and DPP6). Previous studies have found that the compound NS5806 increases Ito in canine ventricular cardiomyocytes through slowing current decay. Here, we reported that NS5806 produced an acute inhibitory action on Ito in mouse ventricular cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM). METHODS Whole-cell patch-clamp was used to record Ito in native myocytes and in HEK cells expressing cloned Kv4.x/KChIP2/DPP6 channels; Western-blot detected the channel protein expression. RESULTS In isolated mouse ventricular cardiomyocytes, NS5806 (0.1-30 μmol·L-1) inhibited Ito in a concentration-dependent manner with IC50 of 6.6±1.9 μmol·L-1. The current decay was significantly accelerated with a time constant from 53.8±5.5 to 41.8±3.0 ms at +60 mV (P<0.01). Similarly, NS5806 concentration-dependently reduced the Ito peak current amplitude with an acceleration of current decay. In addition, NS5806 increased IKv4.2/KChIP2 and delayed current decay, but decreased IKv4.2/KChIP2/DPP6 with the acceleration of current decay. The inhibitory action on the current was more potent if DPP6 expression level was increased from Kv4.2/KChIP2/DPP61:1:1 to 1:1:3. Western-blot showed a higher expression of DPP6 protein in mouse heart and in hiPS- CM compared to canine heart. Moreover, specific knock- down DPP6 expression by siRNA antagonized the inhibitory action of NS5806 in hiPS-CM. Our results pointed to an important role of DPP6 subunit in the regulation of NS5806 on the channel. By using molecular docking simulation, five interaction sites with high possibility between KChIP2 and DPP6 were identified. Mutations of those sites changed the inhibitory action of NS58056 into excitatory effect on the current with the delay of current decay. CONCLUSION NS5806 significantly inhibits Ito by accelerating current decay in mouse cardiomyocytes and hiPS-CM. The effect depends on the interaction between DPP6 and KChIP2 subunits.