Diabetic neuropathic pain(DNP)is one of the most common complications in clinical, which influenced patients’ daily functions greatly, without clear mechanisms and effective methods.P2X3 receptors play a pivotal role in the formation, transmission and conduction of pain under neuropathic pain models, associated with peripheral sensory nerve excitability enhancement.This paper focuses on the establishment of DNP models, and the effects of P2X3 receptors in diabetes mellitus.

Objective To investigate the effects of low frequency electroacupuncture on the P2X3 receptor expres-sion in dorsal root ganglion ( DRG) of rats with type II diabetic neuropathic pain. Methods Part 1:Fifty normal SD rats were randomly divided into normal group (8 rats) and model group (42 rats). The rat model of type II diabetic neuropathic pain was generated by high fat and high sugar diet with a single intraperitoneal injection of streptozotocin ( STZ, 35 mg/kg) . 2 Hz electroacupuncture was administered at ipsilateral acupoints Zusanli and Kunlun for consecutive 7 days. Insulin sensitivity index ( ISI) was measured at 0 w and 5 w, and fasting plasma glucose ( FPG) was measured at 0 w, 5 w, and 7 w. Paw withdrawal threshold (PWT) was measured by mechanical pain threshold, and P2X3 receptor was determined by immunofluorescence. Part 2:Twelve rats with diabetic neuropathic pain (DNP) were divided into EA + vehicle group (6 rats) and EA + αβ?meATP group (6 rats). Rats in the two groups received the same EA treatment as Part 1. Rats in the EA + αβ?meATP group were injected with P2X3 receptor agonistαβ?meATP (0. 6μmol/L, 100μL) into the ventral sur?face of each hind paw every time before EA treatment. Rats in the EA + vehicle group received the same dose of vehicle ( PBS buffer) as a control. Pain threshold of the rats were measured. Results ① Compared with the normal group, the ISI levels of the rats in DNP group was significantly decreased after 5 weeks of the high?fat high?sugar diet (P < 0. 01). Two weeks after STZ injection, the fasting plasma glucose levels in the rats receiving STZ were significantly elevated ( P <0. 01 ) . The type 2 diabetes model was established with a successful rate of 69. 04%. ②PWTs:The PWTs of rats in DNP group were reduced compared with rats in the normal group (P < 0. 01), indicating that the type 2 DNP model was suc?cessfully established. Compared with the PWTs of DNP?controlled rats, the 2 Hz electroacupuncture significantly increased bilateral PWT of rats subjected to DNP from day 3 after treatment (P < 0. 01). P2X3 receptor agonistαβ?meATP greatly reduced bilateral PWT of EA?treated DNP rats compared with that of the EA + vehicle group (P < 0. 01). ③The immu?nofluorescence essay showed that P2X3 receptor expression in bilateral L5 DRGs in the DNP group was significantly in?creased as compared with that in the normal group ( P < 0. 01 ) . The increases were inhibited by 2 Hz EA in L5 DRGs compared with the DNP group (P < 0. 01). Conclusions 2Hz electroacupuncture can effectively treat the type II diabet?ic neuropathic pain by decreasing the expression of L5 DRG P2X3 receptors in rats.

Heat shock factor 1 (HSF1) is the key protein in regulating stress response. It can be activated under heat, oxidative or another stress conditions. Dominant-positive and dominant-negative HSF1 are two types of HSF1 mutants. Both of them gain the DNA binding activity in the absence of stress. In addition, dominant-positive HSF1 acquires transcriptional activity, which dominant-negative HSF1 does not acquire. In this paper, the progress of using these HSF1 mutants in the research of cancer, neurodegenerative disorders and cardiovascular diseases will be discussed.
Genetic Therapy ; Heat-Shock Proteins ; genetics ; therapeutic use ; Humans ; Mutant Proteins ; genetics ; Neoplasms ; therapy ; Neurodegenerative Diseases ; therapy

OBJECTIVETo compare profiles and related factors of irregular bleeding induced by different types of low-dose hormone therapy (HT) and a Chinese formulated herbs products.

METHODSApplied with open-labeled, randomized, and clinical trial design, 136 postmenopausal women were assigned into four groups: group A: estradiol valerate (E2 V) 1 mg/d + medroxyprogesterone acetate (MPA) 2 mg/d; group B: conjugated equine estrogen 0.45 mg/d + MPA 2 mg/d; group C: tibolone 1.25 mg/d; group D: a Chinese formulated herbs product (Kuntai) 4# tid. Each subject took element calcium 400 mg/d and vitamin D 200 IU/d concomitantly. Modified Kupperman scores were assessed on baseline and every 3 months thereafter and irregular bleeding was recorded on menopausal diary every day. The duration of this study was 1 year. Results The efficacies were similar in three HT-managed groups, but was better than in group D, although the latter was also effective in alleviating menopausal symptoms. Hazard ratio (HR) of irregular bleeding was 1.00 in group C, 2.43 in group A (95% CI: 1.08-5.46), 3.12 in group B (95% CI: 1.42-6.88), and 0.73 in group D (95% CI: 0.26-2.04). Most cases initially experienced bleeding in the first 3 months but such initiation was a bit later in group C. Endometrium, as detected by B-mode ultrasound, increased approximately 1 mm in HT groups, while it was a bit thicker in group C. Long periods in reproductive age and short time since menopause were high risk factors for irregular bleeding.

CONCLUSIONProfiles of irregular bleeding in 3 commonly used types of low-dose HT are different and some factors such as long period in reproductive age and short time since menopause may contribute to bleeding initiation.

Adult ; Aged ; Double-Blind Method ; Estradiol ; administration & dosage ; analogs & derivatives ; Estrogen Replacement Therapy ; adverse effects ; Estrogens, Conjugated (USP) ; administration & dosage ; Female ; Humans ; Medroxyprogesterone Acetate ; administration & dosage ; Metrorrhagia ; etiology ; Middle Aged ; Norpregnenes ; administration & dosage ; Phytotherapy ; adverse effects ; Postmenopause ; Risk Assessment

OBJECTIVETo investigate the DNA and chromosome damage in peripheral blood lymphocyte of workers occupationally exposed to formaldehyde (FA).

METHODSAll 151 workers occupationally exposed to FA from two plywood factories and 112 workers without occupational FA exposure working in a machine manufactory were recruited into this study. Comet assay and cytokinesis-block micronucleus technique was used to evaluate the DNA and chromosomal damage of peripheral blood lymphocyte. The air FA samples were collected with SKC 224-PCXR8 air samplers. Gas chromatography was used to analyze the FA level. Personal information including occupational history, age, sex, smoking and drinking status was collected by the questionnaire.

RESULTSThe time weighted average concentration (TWA) of FA in the working environment of FA-exposed workers (range 0.10 - 7.88 mg/m(3)) was higher than those in controls (< 0.01 mg/m(3)). The olive tail moment (Olive TM) in low FA-exposed workers [3.03 (2.49 - 3.67)] was lower than that in high FA-exposed workers [3.95 (3.53 - 4.43)], but higher than that in controls [0.93 (0.78 - 1.10)], the differences were statistical significant (P < 0.05). Comet trail length in FA-exposed workers were significantly higher than that in controls [6.78 (6.05 - 7.60)], but no significant differences ware found between the high FA-exposed workers [12.59 (11.80 - 13.43)] and the low FA-exposed workers [11.25 (10.12 - 12.50)]. The frequency of micronuclei per 100 binucleated cells in low FA-exposed workers (0.41 +/- 0.25) was lower than that in high FA-exposed workers (0.65 +/- 0.36), but higher than that in controls (0.27 +/- 0.13), the differences were statistical significant (P < 0.05). The increased tendencies with the exposure levels were found in those three indices. In stratification analysis, the same results were found.

CONCLUSIONIn the current FA exposure levels, the DNA and chromosomal damage in peripheral blood lymphocyte might be induced by FA exposure, and be increased with the levels of exposure.

Adult ; Alcohol Drinking ; Comet Assay ; DNA Damage ; Formaldehyde ; analysis ; poisoning ; Humans ; Lymphocytes ; drug effects ; metabolism ; Micronucleus Tests ; Occupational Exposure ; analysis ; Smoking ; Young Adult

OBJECTIVETo investigate the clinical characteristics,diagnosis and treatment of intestinal heterotopic gastric mucosa resulting in alimentary tract hemorrhage.

METHODSEleven cases of intestinal heterotopic gastric mucosa with alimentary tract hemorrhage during the past 24 years in our hospital were reviewed and the clinical data were analyzed retrospectively.

RESULTSThe median age was 29 years old. Nine cases had abdominal pain, and radionuclide (99m)Tc-pertechnetate scan revealed bleeding lesion in 6 cases preoperatively. Segmental resection of the intestine with bleeding lesion were performed in all patients, postoperative pathology confirmed heterotopic gastric mucosa. The lesion was located in the jejunum in five cases and in the ileum in six cases. All lesions were complicated with diverticulum, or inflammatory mass on the intestinal wall, or abnormity of intestinal duplication.

CONCLUSIONSIntestinal heterotopic gastric mucosa is difficult to be diagnosed preoperatively, and radionuclide (99m)Tc-pertechnetate scan plays a role in preoperative diagnosis.

Adolescent ; Adult ; Choristoma ; complications ; diagnosis ; surgery ; Female ; Gastric Mucosa ; Gastrointestinal Hemorrhage ; diagnosis ; etiology ; surgery ; Humans ; Intestinal Diseases ; complications ; Intestines ; Male ; Middle Aged ; Young Adult

This study was to investigate the protective effects of puerarin on myocardial ischemia/reperfusion (MI/R) injury and the underlying mechanism. The MI/R-model was established by ligating the left anterior descending artery (LAD) for 60 min followed by 24 h reperfusion, puerarin (10, 30, and 100 mg·kg^-1) was orally administered 20 min before reperfusion. Cardiac function, myocardial infarct index, cardiac damage markers, inflammatory cytokines, and apoptosis index were measured to evaluate the protective effects of puerarin on MI/R injury. The activation of Nod-like receptor protein 3 (NLRP3) inflammasome and Toll like receptor 4 (TLR4)/myeloid differentiation factor 88 (Myd88)/nuclear factor kappa B (NF-κB) pathway were determined by Western blot. All animal experimental procedures were approved by the ethics committee of the Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences. The results showed that puerarin could significantly improve cardiac function, reduce myocardial infarct size, decease the levels of lactic dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase-MB (CK-MB), and cardiac troponin T (cTnT) and suppress cardiomyocyte apoptosis. Meanwhile, puerarin could notably decrease the levels of inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Western blot analysis revealed that puerarin could downregulate the expression of TLR4, Myd88, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved-caspase 1, cleaved-gasdermin-D (GSDMD), IL-1β, and IL-18, as well as the phosphorylation levels of inhibitor of NF-κB α (IκBα), IκB kinase β (IKKβ), and NF-κB. These findings demonstrated that puerarin could alleviate MI/R injury by suppressing NLRP3 inflammasome activation, possibly via TLR4/Myd88/NF-κB pathway.

OBJECTIVETo prospectively study the relationship between risk factors and stroke incidence and mortality in the Chinese elderly.

METHODSAn analytic study in a cohort population of 1,268 male retired cadres in a military setting. A health-screening program was carried out for all cadres aged 55 years or older in Xi'an in February 1987. Baseline data on smoking, cholesterol, triglyceride, blood pressure, body mass index (BMI), histories of hypertension, hyperlipidemia and coronary heart disease (CHD), stroke, diabetes and family histories of cardiovascular disease were investigated. Main outcome measures were stroke incidence, stroke and all-cause mortality.

RESULTSThe cohort was followed up until June 30, 2001 and a total number of follow-up person-year was 15,546. During the follow-up period, there were 113 new stroke cases identified and the adjusted incidence was 727 per 100,000 person-year. Forty-five deaths were due to stroke and the adjusted mortality was 289 per 100,000 person-year. Using Cox model analysis, after adjustment on age, total cholesterol, triglyceride, smoking, drinking and physical exercise, we noticed that the systolic pressure, BMI, history of CHD and hyperlipidemia were independent risk factors for stroke incidence and morality.

CONCLUSIONThe incidence and mortality of stroke in this cohort were lower than those in the same age group of general population. Monitoring and controlling body mass index and blood pressure level seemed to be important factors for the prevention of stroke in the elderly.

Aged ; Aged, 80 and over ; Blood Pressure ; Body Mass Index ; Cohort Studies ; Coronary Disease ; complications ; Humans ; Hyperlipidemias ; complications ; Hypertension ; complications ; Incidence ; Male ; Middle Aged ; Military Personnel ; Risk Factors ; Stroke ; epidemiology ; etiology ; mortality

OBJECTIVETo investigate the difference in urinary proteome between patients with bladder urothelial carcinoma (BUC) and healthy volunteers and to provide a basis for the early diagnosis of BUC.

METHODSThe urine samples from BUC patients and healthy volunteers (controls) were treated by 25% ethanol precipitation and two-dimensional gel electrophoresis (2-DE), and the obtained urinary proteins were subjected to Coomassie brilliant blue staining and analysis by PDQuest 8.0 (2-DE image analysis software); the differentially expressed proteins were sequenced by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry and identified using the Swiss-Prot database; the differential expression of these proteins was verified by western blot.

RESULTSHigh-resolution and high-reproducibility 2-DE images were obtained from the urine samples of BUC patients and controls, with 789 ± 18 and 762 ± 14 protein spots, respectively. Compared with the control group, the BUC grouP had significantly decreased expression of 6 protein spots and significantly increased expression of 11 protein spots. The mass spectrometry revealed five proteins with increased expression in the BUC group, including fibrinogen, lactate dehydrogenase B, apolipoprotein A1, clusterin, and haptoglobin, and the results were confirmed by western blot.

CONCLUSIONThere is significant difference in urinary proteome between BUC patients and healthy volunteers; the identification of differentially expressed proteins in urine lays the foundation for identifying potential molecular markers in early diagnosis of BUC.

Aged ; Case-Control Studies ; Early Detection of Cancer ; Female ; Humans ; Male ; Middle Aged ; Proteomics ; methods ; Urinary Bladder Neoplasms ; diagnosis ; urine

Objective To discuss the optimal clinical diagnosis and treatment of ectopic ACTH syndrome with occult tumors. Methods Clinical features, imaging examinations and treatment of 17 patients with ectopic ACTH syndrome were described and compared. Results All patients illustrated the typical clinical features of Cushing’s syndrome. They had hypokalemic alkalosis, elevated serum cortisol and plasma ACTH levels. In the high-dose dexamethasone suppression tests, most patients failed to suppress serum cortisol and 24-hour urinary cortisol. CT and MRI are useful imaging modalities to localize the ACTH-secreting tumor in patients with ectopic ACTH syndrome. The patients with overt ACTH-secreting tumors had surgical curative resection soon after diagnosis. Among patients with occult ACTH-secreting tumors, three underwent subtotal bilateral adrenalectomy, two underwent right adrenalectomy, four received inhibitor of steroidogenesis aminoglutethimide. Their hypercortisolism was controlled. Conclusion Surgical curative resection is the optimal treatment of ectopic ACTH syndrome with overt ACTH-secreting tumor. Bilateral adrenalectomy, right adrenal ectomy or chemotherapy to control hypercortisolism is an available treatment of ectopic ACTH syndrome with occult ACTH-secreting tumors.