Objective:To investigate the role of speckle-type POZ(pox virus and zinc finger protein) protein (SPOP) in enterovirus 71 (EV71) infection.Methods:Immunoprecipitation analysis was employed to examine the impact of SPOP on the ubiquitin level of EV71 non-structural protein 2A protease (2A pro), while the phosphorylation level of IFR3 protein was assessed through Western blot. Cells were either overexpressed or knockdown of SPOP, followed by infection with EV71. RT-qPCR was utilized to analyze the transcription level of IFN-β, and the transcription level and protein level of EV71 structural protein VP1 were determined using RT-qPCR and Western blot, respectively. Results:The inhibition of EV71 infection in RD cells was observed following transfection with HA-SPOP. Additionally, it was found that the ubiquitin level of EV71-2A pro increased in a gradient-dependent manner. Subsequent transfection with shSPOP plasmid for endogenous SPOP knockdown resulted in a dose-dependent decrease in the levels of melanoma differentiation-associated gene 5 (MDA5), mitochondrial antiviral signaling (MAVS), and p-IRF3. Conversely, transfection with HA-SPOP plasmid led to a dose-dependent increase in the levels of MDA5, MAVS, and p-IRF3. The expression of SPOP, whether high or low, had an impact on the expression of IFN-β in cells. Additionally, the levels of VP1 mRNA or protein were found to be inhibited or increased. Conclusions:SPOP plays a role in increasing the ubiquitination level of EV71-2A pro, which in turn promotes the phosphorylation level of IRF3 and secretion of IFN-β. This effect is achieved by inhibiting the cleavage of 2A pro against key molecules MAVS and MDA5 in the RLR signaling pathway, ultimately leading to the inhibition of EV71 replication.

Objective: Saposhnikoviae Radix (Fangfeng in Chinese), the roots of Saposhnikovia divaricata, lacks commodity specification and grade standardization in the current market. This study investigated the existing specifications and grades of Saposhnikoviae Radix to provide a standardized scientific reference for its market use. Methods: Based on a textual research of Chinese herbal medicine from the Han Dynasty to the present, medicinal materials of different specifications and grades obtained from Saposhnikoviae Radix in the main producing areas of China were collected and the markets for these materials were investigated. Field investigations were performed in the major producing areas such as Northeast China, Hebei Province, and Inner Mongolia. Four major Chinese herbal medicine markets in China were investigated. Sensory indices were used to categorize the two specifications (wild and cultivated) according to the shape, color, texture, and cross-section. High-performance liquid chromatography was performed to determine the active components. Vernier calipers and measuring tape were used to measure the diameter and length, respectively, of 41 samples. Using Excel and the R Language software, cluster analysis and descriptive statistical analysis were performed to assist in the application of new specifications and grades based on physical characteristics, pharmacological activity, and chemical composition. Results: The two specifications (wild and cultivated) of Saposhnikoviae Radix were divided into three grades each based on the length and diameter. Prim-O-glucosylcimifugin, 5-O-methylvisamminoside, and the length of Saposhnikoviae Radix can be used as a basis for classifying the commodity specifications and grades. The specifications and grade standards of Saposhnikoviae Radix were established based on the following eight aspects: shape, surface characteristics, texture, cross section, taste, prim-O-glucosylcimifugin content, 5-O-methylvisamminoside content and length. Conclusion: The formulation of this standard stipulates the commodity specification level of Saposhnikoviae Radix. It is also suitable for the evaluation of commodity specifications in the process of production, circulation and use of Saposhnikoviae Radix.

OBJECTIVE: To investigate the anti-inflammatory effect and mechanisms of interleukin-35 (IL-35) in inflammatory bowel disease. METHODS: BALB/c mice were divided into three groups with 10 mice in each group:control group, model group (oral administration of 4% glucan sodium sulfate for 7 d) and IL-35-treated group (oral administration of 4% glucan sodium sulfate for 7 d, intraperitoneal injection of 2 μg IL-35 at d2-5). Disease activity index (DAI) was scored every day. After 7 d, the mice were sacrificed, and the serum and intestinal tissue samples were collected. The gross morphology of the colon was observed; HE staining was used to observe the pathological changes of colon tissue; flow cytometry was employed to detect the change of macrophage polarization ratio in colon tissue; the mRNA expression levels of cytokines IL-6, TNF-α, IFN-γ, IL-10 and SHIP1 in colon tissue were determined by real-time quantitative RT-PCR; the expression and distribution of SHIP1 in colon tissue was measured by immunohistochemistry; Western blotting was adopted to detect the expression level of SHIP1 protein in colonic intestinal tissues of each group. RESULTS: The DAI scores of the mice in the model group were higher than those in the control group, while the DAI scores in the IL-35-treated group were lower than those in the model group (all <0.01). Compared with the control group, the colon length was significantly shortened in the model group (<0.05), while the colon length of the IL-35-treated group had an increasing trend compared with the model group, but the difference was not statistically significant (>0.05). Compared with the model group, microscopic inflammatory infiltration score was decreased and microscopic crypt destruction and score was significantly lower in IL-35-treated group (all <0.05). The relative expression of proinflammatory cytokines IL-6, TNF-α and IFN-γ in the colon tissue of IL-35-treated group was decreased compared with the model group, while the relative expression of IL-10 mRNA was higher than that of the model group (all <0.05). Compared with the control group, the proportion of M1 macrophages in the model group increased (<0.05), while the proportion of M1 macrophages in the IL-35-treated group was lower than that in the model group (<0.05). The relative expression of SHIP1 mRNA and protein in the colon tissue of IL-35-treated group was higher than that in the model group (all <0.05). CONCLUSIONS IL-35 can inhibit the polarization of M1 macrophages and regulate inflammatory cytokines to promote anti-inflammatory effect on mice with colitis.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Colitis ; drug therapy ; physiopathology ; Colon ; drug effects ; Cytokines ; genetics ; Disease Models, Animal ; Gene Expression Regulation ; drug effects ; Glucans ; pharmacology ; Interleukin-6 ; genetics ; Interleukins ; pharmacology ; Macrophages ; drug effects ; Mice ; Mice, Inbred BALB C ; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases ; genetics

Objective To explore the potential influence of gender on screening value of aldosterone-renin ratio (ARR) for primary aldosteronism (PA).Methods The biochemical parameters were collected of 451 PA patients and 300 essential hypertension (EH) patients who were diagnosed in the General Hospital of PLA from 1992 to 2014. Each group was then divided into two groups by gender. The clinical characteristics were compared and then the receiver operating characteristic curve (ROC) was conducted to evaluate the best cut-off value.Results The plasma aldosterone concentration (PAC), serum sodium and ARR were much higher, but the plasma rennin activity (PRA), serum potassium and BMI were much lower in PA patients than in EH patients (P<0.01), and no significant difference existed between the two groups in age, duration of hypertension and blood pressure. The PRA was obviously lower in males than in females either in PA or in EH patients, but no signicantcant difference existed between males and females in PAC (P>0.05). The best cut-off value of ARR in male PA patients was 19.11, the relevant area under the curve (AUC) was 0.968, the sensitivity and specicantcity was 92.44% and 93.08%, and the Youden index (YI) was 0.86. The best cut-off value of ARR in female PA patients was 27.26, with AUC 0.956, sensitivity 92.07%, specicantcity 90.00% and YI 0.82, respectively. If the cut-off value was set at 27.26 in males, the specicantcity would rise a little, but the sensitivity and YI would sharply decrease. Similarly, the sensitivity would increase a little but the specicantcity and YI would fall substantially if the cut-off value in females was set at 19.11. The best cut-off value of ARR in men was smaller than the ocantcial value recommended by guidelines.Conclusion Gender is an important factor should be considered while ARR is used in PA screening, and the cut-off value of ARR in screening female PA patients should be setting higher.

Objective To investigate the correlation between body mass index (BMI) and the occurence of papillary thyroid carcinoma (PTC) among the patients with thyroid nodules. Methods This cross-sectional study collected the data of 4 350 patients with thyroid nodules who underwent thyroidectomy in our hospital from January 1994 to December 2013. The patients were divided into normal weight (BMI 18.50~23.9 kg/m 2), overweight (BMI 24.0~27.9 kg/m 2), and obese (BMI≥28.0 kg/m 2) groups according to BMI, as well as benign nodules and papillary thyroid carcinoma groups based on their pathological finding. The differences of age-sex composition, nodule diameter, TSH level, overweight and obese constituent ratio between two groups were also analyzed. Logistic regression method was used to evaluate the risk factors of PTC. Results (1) Compared with the benign nodule group, there was a higher proportion of patients under the age of 40 years (34.1% vs 19.5%, P<0.01) in PTC group, with smaller tumour diameters [ 1.0 (0.7-2.0) cm vs 3.0 (2.0-4.0) cm, P<0.01]and higher TSH levels [ 1.9 (1.2-3.0) mU/L vs 1.6 (0.9-2.5) mU/L, P<0.01]. (2) The proportion of obese patients was higher in PTC group than that in the benign nodule group (28.7% vs 20.7%, P<0.01) among male patients. While the difference was not found among female patients. (3) Stratification analysis according to gender and age showed that the proportion of overweight (49.4% vs 44.1%, P<0.05) or obese (26.5% vs 15.3%, P<0.01) in PTC group was higher than that of benign nodule group among male patients aged≤40 years and the proportion of obese patients in PTC group was higher than that of benign nodule group (30.8% vs 22.2%, P<0.01) among male patient aged 41 to 65 years. (4) A multivariate analysis indicated that overweight (OR=4.947) and obesity (OR=7.648) were all independent risk factors for PTC (P<0.01) among male patients aged≤40 years. Conclusion Overweight and obesity are associated with higher PTC risk for male patients aged 40 years or less.

Objective To investigate the trends in the clinicopathological characteristics of thyroid cancer patients undergoing surgery from 1994 to 2013. Methods A retrospective analysis was conducted on the clinical data of inpatients with thyroid nodular diasease undergoing thyroidectomy with pathology results from January 1994 to December 2013. The trends in the pathogenic constituent of thyroid nodule and the clinicopathological characteristics of 3 399 patients with thyroid cancer were analyzed. Results (1) Over the past 20 years, the proportion of patients diagnosed as thyroid cancer was gradually increased, especially those with papillary thyroid cancer (PTC). Whereas the proportions of benign nodule and other rare thyroid cancer were gradually decreased(P<0.01). (2) The average age of patients with thyroid cancer was (44.30±11.72) years, with the peak incidence at 30~59 years. The incidence of thyroid cancer was increasing in both males and females, especially more evident in the absolute increase in women(P<0.05). (3) Among 3 399 patients with thyroid cancer, 56.20%(1 910/3 399)underwent subtotal lobectomy. 20.74%(705/3 399)underwent total/near total thyroidectomy, showing an increase trend (P<0.01). Ultrasound-guided aspiration biopsy for thyroid nodule were performed in 48.87% (1 661/3 399)patients before operation. The proportion of aspiration biopsy was gradually increased since 2004. (4) An increase in thyroid cancer of tumor sizes less than 2.0 cm was observed, especially those size≤1.0 cm(P<0.01). 83.96%(2 854/3 399)patients revealed TNM Ⅰ~Ⅱ stage, and the proportion of patients with TNM Ⅲ~Ⅳ stage was gradually decreased since 2006(P<0.01). Conclusion Over the past 20 years, the proportion of thyroid cancer, especially papillary thyroid microcarcinoma reveals an ascending tendency. The percentages of patients undertaking total/near total thyroidectomy and ultrasound-guided aspiration biopsy before operation are on the rising.

Objective To summarize the current status and trend of hypoglycemic agents of diabetic inpatients in different departments of Chinese PLA General Hospital.Methods The clinical data of diabetic patients admitted to Chinese PLA General Hospital from January 2000 to May 2014 were collected(those hospitalized in the department of endocrinology were excluded).A total of 10 041 patients were selected by stratified random sampling.The type of hypoglycemic agents in different departments and the variation on anti-hyperglycemic drugs with time were retrospectively analyzed.Results Of all the patients in non-endocrinological wards, 50.2% were treated with insulin, 36.9% with metformin, 21.3% with α-glycosidase inhibitor, and 18.9% with sulfonylureas.Metformin, α-glucosidase inhibitors, pre-mixed 30R, and insulin glargine were more commonly used than other anti-hyperglycemic agents, accounting for 36.9%, 21.0%, 14.0%, 8.7%, respectively.Metformin, sulfonylureas, α-glucosidase inhibitor, and different types of insulin were more widely applied in internal medicine while insulin therapy was more frequently used in surgical department.During the past 15 years, the proportions of insulin, glinides, α-glucosidase inhibitor, and thiazolidinediones application were gradually increased, while the proportions of sulfonylureas and metformin treatment were on the decline trend.Conclusion Most of the inpatients were treated with oral antidiabetic drugs.Metformin, α-glucosidase inhibitor, pre-mixed 30R, and insulin glargine were the most frequently prescribed agents for the inpatients.

Objective To analyze the relationship between the brain functional alterations of patients with Cushing's disease (CD) and patients' mental symptom by applying the Evaluating Emotional Scales and task functional magnetic resonance imaging (Task fMRI).Methods Task fMRI was performed on 8 patients with diagnosed CD admitted in the Department of Endocrinology of Chinese PLA General Hospital from Nov. 2015 to Nov. 2016 and 21 healthy people with matched age, gender and education level as control. Meanwhile, Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Positive and Negative Affective Scale (PANAS) and Cushing Quality of Life Scale (Cushing QOL) were obtained to assess the brain functions.Results Significant depression and anxiety were observed in patients with CD, and their positive affective score was substantially lower while the negative affective score was relatively higher compared with that in the controls. Task fMRI revealed that, when watching the positive pictures, the activation degree of left cerebellum and right postcentral gyrus weakened in CD patients than in the controls, and the positive correlations existed between the activation degree of left cerebellum and the 16 o'clock adrenocorticotrophic hormone (ACTH) level, and between the activation degree of right postcentral gyrus and the urinary free cortisol (UFC) level in CD patients. In contrast, when watching the negative pictures, the activation degree of left cerebellum, bilateral parahippocampal gyrus and left inferior frontal gyrus was weakened in CD patients than in the controls, and the activation degree of left cerebellum was negatively correlated to the 0 o'clock cortisol level and SAS score, but is positively correlated to the UFC level. When watching the neutral pictures, the activation degree of left cerebellum and left parahippocampal gyrus was weakened in CD patients than in the controls.Conclusions CD patients may have impaired brain function with depression and anxiety mental symptoms. By Task fMRI, it can be found that the weakened activation degree of left inferior frontal gyrus, right postcentral gyrus, bilateral parahippocampal gyrus and left cerebellum may be related to CD patients' mental symptoms.

Objective To explore risk factors of recurrence in papillary thyroid microcarcinomas ( PTMC ) and papillary thyroid carcinomas with 1-2 cm diameter. Methods From January, 2008 to December, 2010 in PLA General Hospital, 323 eligible patients received first surgery and diagnosed pathologically with papillary thyroid cancer≤2 cm were analyzed retrospectively. According to rumor size, patients were divided into PTMC and PTC of 1-2 cm, which were investigated recurrence factors. Results Finally we indentified 320 PTC≤2 cm, including 218 (68.1%)PTMCand102(31.9%)PTCof1-2cmwithamedianfollow-uptimeof72.5(55-90)months.32cases (10%)of patients relapse, includig 22 cases(10%)in PTMC and 10 cases(9. 8%)in PTC of 1-2 cm. In the clinical characteristics analyses of PTC≤2 cm, the PTC of 1-2 cm was different from PTMC in age, lymph node metastasis and TNM stage. The univariate analysis showed that tumor location and lymph node metastasis influenced recurrence of PTMC and PTC of 1-2 cm,while tumor foci and extrathytoidal extension were risk factors of recurrence in PTMC but not in PTC of 1-2 cm. Lymph node metastasis was independent factor which influenced the recurrence of PTMC and PT C of 1-2 cm according to COX multivariate analysis. Conclusion Disease recurrence did not differ significantly between the PTMC and PTC of 1-2 cm and lymph node metastasis was an independent recurrence factor.

BACKGROUNDAberrant epithelial repair has been observed in chronic rhinosinusitis (CRS) patients; however, the mechanism of epithelial cell repair regulation is unclear. Epidermal growth factor (EGF) plays an important role in regulating epithelial cell repair in lower airway and may be a critical factor in the remodeling processes of CRS. The objective of our research is to evaluate the differences between CRS and normal subjects and between chronic rhinosinusitis without nasal polys (CRSsNP) and chronic rhinosinusitis with nasal polys (CRSwNP) in the regulation of EGF pathways and the regulating proliferative position of classic Ras/Raf/MEK/ERK pathways.

METHODSWe evaluated the proliferation rates of ethmoidal mucosal cells before and after stimulation with EGF, epidermal growth factor receptor (EGFR) kinase inhibitor AG1478, and extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 using MTT assays. We also analyzed the sinonasal epithelial cells collected from control subjects and patients with CRS subtypes CRSsNP and CRSwNP for the expression of ERK1/2, phosphorylated ERK1/2, P21, P15, and P27 using western blotting analyses.

RESULTSThe proliferation rates of sinonasal epithelial cells before and after EGF stimulation were lower in CRS patients than in the controls. AG1478 or PD98059 inhibitor treatment of control epithelial cells did not result in a significant difference in proliferation. Although, AG1478 and PD98059 inhibited the proliferation of CRS cells, the degree of proliferation inhibition was markedly different in CRSsNP. AG1478 suppressed the proliferation of CRSwNP epithelial cells, whereas PD98059 had no effect. The ratio of ERK1/2 phosphorylation in CRS cells was lower than that of the control cells. Cyclin-dependent kinase inhibitors were highly expressed in CRS cells compared with that of control cells. ERK1/2 and P27 showed differential expression in CRSsNP and CRSwNP.

CONCLUSIONSDifferences existed in EGF pathways in CRS patients and normal subjects as well as in CRSsNP and CRSwNP. Classical Ras/Raf/MEK/ERK pathway may assume absolute superiority in control cells. Ras/Raf/MEK/ERK classical pathway and other pathways might be active at the same time to stimulate epithelial cell proliferation in CRSsNP. The function of Ras/Raf/MEK/ERK classical pathway was weaker in CRSwNP than in CRSsNP and when the classical pathway was blocked in CRSwNP, some other pathway could have completely compensated the proliferation induced by the Ras/Raf/MEK/ERK pathway.

Adult ; Aged ; Cell Proliferation ; drug effects ; Cells, Cultured ; Epidermal Growth Factor ; pharmacology ; Epithelial Cells ; cytology ; drug effects ; Female ; Humans ; Male ; Middle Aged ; Nasal Mucosa ; cytology ; Sinusitis ; metabolism