Objective To explore the effects of Qingshen Granules(QSG)on adenine-induced renal fibrosis in mice and in uric acid(UA)-stimulated NRK-49F cells and its mechanism for regulating exosomes,miR-330-3p and CREBBP.Methods A mouse model of adenine-induced renal fibrosis were treated daily with QSG at 8.0 g·kg-1·d-1 via gavage for 12 weeks.An adeno-associated virus vector was injected into the tail vein,and renal tissues of the mice were collected for analyzing exosomal marker proteins CD9,Hsp70,and TSG101 and expressions of Col-Ⅲ,α-SMA,FN,and E-cad using Western blotting and immunofluorescence and for observing pathological changes using HE and Masson staining.In the cell experiment,NRK-49F cells were stimulated with uric acid(400 μmol/L)followed by treatment with QSG-medicated serum from SD rats,and the changes in expressions of the exosomal markers and Col-Ⅲ,α-SMA,FN,and E-cad were analyzed.Dual luciferase reporter assay was employed to examine the targeting relationship between miR-330-3p and CREBBP,whose expressions were detected by RT-qPCR and Western blotting in treated NRK-49F cells.Results The mouse models of adenine-induced renal fibrosis showed significantly increased levels of CD9,Hsp70,and TSG101,which were decreased by treatment with QSG.The expressions of Col-Ⅲ,α-SMA,and FN increased and E-cad decreased in the mouse models but these changes were reversed by QSG treatment.QSG treatment obviously alleviated renal fibrosis in the mouse models.Intravenous injection of adeno-associated viral vector obviously inhibited miR-330-3p,increased CREBBP levels,and reduced fibrosis in the mouse models.Dual luciferase assay confirmed CREBBP as a target of miR-330-3p,which was consistent with the results of the cell experiments.Conclusion QSG inhibits renal fibrosis in mice by regulating the exosomes,reducing miR-330-3p levels,and increasing CREBBP expression.

Objective To explore the effects of Qingshen Granules(QSG)on adenine-induced renal fibrosis in mice and in uric acid(UA)-stimulated NRK-49F cells and its mechanism for regulating exosomes,miR-330-3p and CREBBP.Methods A mouse model of adenine-induced renal fibrosis were treated daily with QSG at 8.0 g·kg-1·d-1 via gavage for 12 weeks.An adeno-associated virus vector was injected into the tail vein,and renal tissues of the mice were collected for analyzing exosomal marker proteins CD9,Hsp70,and TSG101 and expressions of Col-Ⅲ,α-SMA,FN,and E-cad using Western blotting and immunofluorescence and for observing pathological changes using HE and Masson staining.In the cell experiment,NRK-49F cells were stimulated with uric acid(400 μmol/L)followed by treatment with QSG-medicated serum from SD rats,and the changes in expressions of the exosomal markers and Col-Ⅲ,α-SMA,FN,and E-cad were analyzed.Dual luciferase reporter assay was employed to examine the targeting relationship between miR-330-3p and CREBBP,whose expressions were detected by RT-qPCR and Western blotting in treated NRK-49F cells.Results The mouse models of adenine-induced renal fibrosis showed significantly increased levels of CD9,Hsp70,and TSG101,which were decreased by treatment with QSG.The expressions of Col-Ⅲ,α-SMA,and FN increased and E-cad decreased in the mouse models but these changes were reversed by QSG treatment.QSG treatment obviously alleviated renal fibrosis in the mouse models.Intravenous injection of adeno-associated viral vector obviously inhibited miR-330-3p,increased CREBBP levels,and reduced fibrosis in the mouse models.Dual luciferase assay confirmed CREBBP as a target of miR-330-3p,which was consistent with the results of the cell experiments.Conclusion QSG inhibits renal fibrosis in mice by regulating the exosomes,reducing miR-330-3p levels,and increasing CREBBP expression.

Objective To explore the clinical characteristics and risk factors of occult pneumonia in advanced elderly patients.Methods A total of 170 advanced elderly patients with community-acquired pulmonary infection in geriatric department of Xijing hospital from January 2014 to October 2017 were enrolled.Patients were divided into two groups:the observation group (with occult pneumonia,n=80)and the control group(without occult pneumonia,n =90).Clinical data of patients were collected,and clinical characteristics and related risk factors of occult pneumonia in elderly patients were analyzed.Results There was no statistically significant difference in the positive rate of sputum culture and the distribution of pathogenic bacteria between the two groups (P ＞ 0.05).Gram-negative bacteria predominated in pathogenic bacteria.The hospitalization time was longer in the observation group than in the control group[(17.3 ± 3.0) d vs.(10.3 ± 3.9) d,P ＜ 0.05].The mortality rate was higher in the observation group than in the control group(10.0 ％ vs.3.3 ％,P ＜ 0.05).The age was older in the observation group than in the control group[(87.0± 1.7) years vs.(82.0± 2.4) years,P ＜ 0.05].The incidences of diabetes,Alzheimer's disease,hypothyroidism and long-term bed rest were higher in the observation group than in the control group (P ＜ 0.05).Multivariate logistic regression analysis showed that age (OR =6.93),dementia (OR =4.32),hypothyroidism(OR =4.89) were independent risk factors for occult pneumonia (P ＜ 0.05).Conclusions The pathogenic bacteria in advanced elderly patients with occult pneumonia are mainly gram-negative bacteria.The positive rate of CT scan confirmed-occult pneumonia is much higher than that by chest X-ray.The advanced elderly patients with occult pneumonia have longer hospitalization time and higher mortality rates.Old age,senile dementia and hypothyroidism are independent risk factors for occult pneumonia in advanced elderly patients.

Objective:To observe the effect of acupuncture in regulating ubiquitin-proteasome pathway (UPP),and discuss the action of acupuncture in intervening heroin-induced brain damage.Methods:Thirty male Sprague-Dawley (SD) rats were divided into a control group,a model group and an acupuncture group by using the random number table.Rats in the model and acupuncture groups received intramuscular heroin injection for successive 8 d at a progressively increased dose.Afterwards,the injection was suspended for 5 d for withdrawal.The heroin relapse rat model was established by repeating the drug addiction and withdrawal process for 3 times.The control group followed the step of the model establishment,but was given intramuscular injection of normal saline at the stage of addiction and no intervention at the stage of withdrawal;the model group was given intramuscular heroin injection at a progressively increased dose at the addiction stage and no intervention at the withdrawal stage;the acupuncture group was dealt in the same way as the model group at the addiction stage,but received acupuncture at Baihui (GV 20) and Dazhui (GV 14) at the withdrawal stage,with the needles retained for 30 min each time,1 session a day,for successive 5 d.On the 39th day,brain tissues were extracted from the hippocampus and ventral tegmental area (VTA) of the three groups of rats.The apoptosis of brain nerve cells was detected by using terminal deoxynucleotidyl transferase-mediated nick and labeling (TUNEL).The mRNA and protein expressions of ubiquitin (Ub),ubiquitin protein ligase (E3) and 26S were examined by immunohistochemistry and quantitative real-time polymerase chain reaction (RT-qPCR).Results:Compared with the model group,rat's hippocampus and VTA in the acupuncture group showed significantly fewer cells positively stained by TUNEL staining (P＜0.01),and its mRNA and protein expressions of Ub,E3,26S were significantly lower (P＜0.01).Conclusion:Reducing nerve cell apoptosis and regulating the mRNA and protein expressions of Ub,E3 and 26S in rat's hippocampus and VTA are possibly one of the action mechanisms of acupuncture in intervening heroin-induced brain damage.

Extracellular acidity has been associated with many pathological states, such as cancer, ischemic stroke, neurotrauma and infection, which makes it an effective target for therapy and diagnosis of such diseases. As a polypeptide vector, pH low insertion peptides (pHLIPs) are endowed with high sensitivity to extracellular acidic environment, which can insert the membrane and deliver payload to pathological cells in a pH dependent manner. Here, theranostic applications of pHLIP in disease, are reviewed in two aspects:pHLIP-mediated single-molecule transporter and nano-sized carrier.

Objective To investigate the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in endometriosis (EMS) and its diagnostic value.Methods The information of EMS gene expression was collected from Gene-Cloud of Biotechnology Information (GCBI) and analyzed,in which MALAT1 gene was screened out accordingly.The total RNAs were extracted from tissues and serum samples of the patients with ovarian endometriosis and non-endometriosis and the expression of MALAT1 was detected by real-time quantitative PCR.The correlation between MALAT1 expression level and menstrual cycle was analyzed.The differential diagnostic efficacy of serum MALAT1 levels was analyzed by receiver operating characteristic (ROC) curve.Results Compared with the non-EMS group the expression of MAL4T1 gene was down-regulated by 1.35-fold (t =-3.27,P ＜ 0.01) in EMS group according to gene information analysis of GCBI.The relative expression levels of MALAT1 in ectopic and eutopic endometrium of patients with ovary endometriosis (0.41 ±0.18 and 0.61 ± 0.12) were significantly lower than those in non-endometriosis patients (1.05 ±-0.34,t =5.87 and 4.48,P ＜ 0.01).However,the expression level of MALAT1 was not related with menstrual cycle of the patients with ovarian endometriosis and non-endometriosis (t =1.54 and 1.52,P ＞ 0.05).The expression of MALAT1 in ectopic ovarian cysts was significantly lower than that in eutopic endometrium of ovary endometriosis (t =3.77,P ＜ 0.01).The relative expression of serum MALAT1 in ovary endometriosis (0.60 ±0.18) was significantly lower than that in non-endometriosis (1.05 ± 0.32,t =5.18,P ＜ 0.01).The area under the curve (AUCsOc) was 0.88.When the cut-off value of serum MALAT1 level was set as 0.74,the sensitivity and specificity of expression level of MALAT1 were 82.4％ and 92％ respectively,and Youden's index was 74.4％.Conclusion Low expression of MALAT1 in endometriosis may be related with occurrence and development of endometriosis.Serum MALAT1 level may have certain differential diagnostic value for EMS.

Objective To investigate the effect of diabetes on clinical efficacy of transcatheter arterial chemoembolization (TACE) in the treatment of non-viral hepatitis hepatocellular carcinoma (HCC). Methods Retrospectively analyzed the clinical data of 367 non-hepatitis virus HCC patients treated by TACE, included 153 diabetes mellitus cases (test group) and blood glucose of 214 patients was normal (control group). To assess the treatment effect after 1 month of TACE based on response evaluation criteria in solid tumors, include complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), and calculate the disease control rate. Through 6 to 75 months follow-up to observed long-term efficacy, record the time to progression (TTP) and overall survival (OS) time. Survival rate were analyzed using Kaplan-Meier method and Log-rank analysis by SPSS 16.0. The single-factor analysis was used to analyze variables which variables that differed were analyzed by Cox regression. Results The disease control rate of test group was 69.9%(107/153) and control group was 74.3%(159/214), the difference was no statistically significant (P=0.125). The median time to progression (mTTP) and median overall survival (mOS) of test group were 10.0 and 15.0 months;and the mTTP and mOS of control group were 14.0 and 19.0 months, the difference were statistically significant (P=0.023 and P= 0.026). Tumor diameter ≥4.5 cm, numbers of tumor ≥3, invasion of blood vessels, α-fetoprotein≥200 μg/L, Eastern Cooperative Oncology Group score and diabetes were risk factors for OS of HCC patients. Conclusion Diabetes is unfavorable factors for overall survival of non-hepatitis HCC tread by TACE.

Objective To propose a design method of isothermal chamber for tidal volume testing equipment. Methods According to the State Equation of Ideal Gas, the gas volume was accurately calculated and injected into an airtight chamber, and then the pressure and temperature changes in the chamber were measured. To keep constant temperature, the fine copper wire was padded into the chamber to absorb the heat produced by the gas compressed during the injection. Results For the chamber of 1L, 300 g/L copper should be filled at least and with not more than 100 mL gas to keep the temperature inside the chamber isothermal. The experiment system was then connected with ventilator to compare the measured tidal volume and given tidal volume. The results showed that the experimental error was within 2%, which proved the accuracy of this testing equipment. Conclusions The establishment of the physical model of isothermal chambers can accurately detect the tidal volume of ventilator, which provides a theoretical basis and data support for factory inspection and supply more choices for ventilator maintenance in clinic.

OBJECTIVETo investigate the clinical features of thyroid disease occurring in response to antiviral therapy in patients with chronic hepatitis C (CHC).

METHODSEighty-two patients diagnosed with CHC were recruited for study from our hospital between 2009 and 2010. All patients were given a 48-week course of antiviral combination therapy with pegylated-interferon (Peg-IFN; 180 mug qw ih) and ribavirin (RBV; 15 mg/kg bw). Patient sera was collected prior to treatment (baseline), at treatment weeks 24 and 48, and post-treatment week 24, and used to detect changes in levels of thyroid function markers, thyroid-specific and other autoantibodies, complement factors, and immunoglobulins (Igs). Differential expression of biomarkers was assessed between patients who developed thyroid disorder and those who did not.

RESULTSAt treatment week 48, 13.4% (11/82) of cases developed hypothyroidism, 3.7% (3/82) developed hyperthyroidism, 20.7% (17/82) tested positive for thyroglobulin antibody, and 22.0% (18/82) tested positive for thyroid peroxidase antibody. The patients who did not develop thyroid disease had significantly higher post-treatment levels (vs. baseline) of IgG (14.84 +/- 2.61 vs. 12.95 +/- 3.32 g/L, F = 10.458, P = 0.002) and C4 (0.26 +/- 0.09 vs. 0.22 +/- 0.08 g/L, F = 6.835, P = 0.011) and significantly lower IgM (0.86 +/- 0.48 vs. 1.00 +/- 0.42 g/L, F = 9.106, P = 0.003). The patients who developed thyroid disease showed no significant differences in the baseline and post-treatment levels of IgG, C4, or IgM. When the two groups of patients who did or did not develop thyroid disease were compared, there was no difference in the amount of patients who achieved sustained virological response.

CONCLUSIONAntiviral-induced thyroid disease in patients with refractory hepatitis C manifests as clinically-detectable abnormalities in serum levels of thyroid autoantibody and markers of hypothyroidism. Levels of other autoantibodies and Igs do not correlate with the development of thyroid disease in these patients, and thyroid disease does not appear to affect the efficacy of Peg-IFN + RBV antiviral therapy.

Antiviral Agents ; therapeutic use ; Drug Therapy, Combination ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Polyethylene Glycols ; therapeutic use ; Ribavirin ; therapeutic use ; Thyroid Diseases ; chemically induced

Cancer cell vaccine-based immunotherapy has received increasing interest in many clinical trials involving patients with breast cancer. Combining with appropriate adjuvants can enhance the weak immunogenic properties of tumor cell lysates (TCL). In this study, diphtheria toxin (DT) and two tandem repeats of mycobacterial heat shock protein 70 (mHSP70) fragment 407-426 (M2) were conjugated to TCL with glutaraldehyde, and the constructed cancer cell vaccine was named DT-TCL-M2. Subcutaneous injection of DT-TCL-M2 in mice effectively elicited tumor-specific polyclonal immune responses, including humoral and cellular immune responses. High levels of antibodies against TCL were detected in the serum of immunized mice with ELISA and verified with Western blot analyses. The splenocytes from immunized mice showed potent cytotoxicity on Ehrlich ascites carcinoma cells. Moreover, the protective antitumor immunity induced by DT-TCL-M2 inhibited tumor growth in a mouse breast tumor model. DT-TCL-M2 also attenuated tumor-induced angiogenesis and slowed tumor growth in a mouse intradermal tumor model. These findings demonstrate that TCL conjugated with appropriate adjuvants induced effective antitumor immunity in vivo. Improvements in potency could further make cancer cell vaccines a useful and safe method for preventing cancer recurrence after resection.
Adjuvants, Immunologic ; Animals ; Bacterial Proteins ; genetics ; immunology ; Cancer Vaccines ; immunology ; Carcinoma, Ehrlich Tumor ; immunology ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Diphtheria Toxin ; genetics ; immunology ; Female ; HSP70 Heat-Shock Proteins ; genetics ; immunology ; Immunoglobulin G ; immunology ; Immunotherapy ; Mice ; Neovascularization, Pathologic ; Peptide Fragments ; genetics ; immunology ; Recombinant Fusion Proteins ; genetics ; immunology ; T-Lymphocytes, Cytotoxic ; immunology ; Tandem Repeat Sequences