Humans ; PPAR gamma/metabolism* ; Multiple Sclerosis ; Transcription Factors/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha

【Objective】 To study the therapeutic effects of tetrahydrocurcumin(THC) via intraperitoneal(i.p.) injection on the respiratory symptoms and inflammatory responses in asthmatic mice. 【Methods】 BALB/c mice were randomly divided into 4 groups, including normal control group, ovalbumin(OVA) -induced model group, positive group and THC administration group. The latter two groups were treated with 2.5 mg/kg of dexamethasone(DEX) or 20 mg/kg of THC via i.p. injection from Day 21 to Day25. The weight changes and nasal symptoms were recorded before and after OVA challenge. The mice were sacrificed at the end of the experiment and the lung tissue and broncho-alveolar lavage fluid(BALF) were collected for assessment of histopathological alterations, Th cell subsets and related cytokine level. 【Results】 After THC treatment via i.p. injection, the asthmatic mice’s rubbing frequencies were reduced(P < 0.05) with a difference of 5.2 between the two means(95% CI = 0.66 to 9.74), lungs’pathological scores were reduced(P < 0.05) with a difference between the two means being 1.6(95% CI = 0.32 to 2.88), mucus production induced by hyperplasia of goblet cells was alleviated(P < 0.0001) with a difference between the two means being 9.56(95% CI = 5.05 to 14.07). Besides, compared with OVA group, the percentages of Th2 and Th17 cells were reduced(P < 0.01) with a difference between the two means being 1.49 and 2.15(95% CI = 0.50 to 2.49 and 0.72 to 3.58), respectively. The levels of interleukin(IL) -4, IL-5, IL-13 and IL-17A in BALF were decreased(P < 0.05) with a difference between the two means being 5.45, 4.13, 5.17 and 2.44 (95% CI = 1.95 to 8.94, 1.08 to 7.19, 0.80 to 9.54 and -0.30 to 5.17), respectively. The further comparison between THC and DEX groups showed no significant difference(P > 0.05) in the lung pathological change, Th17 cells, IL-13, and IL-17A levels. 【Conclusions】 It is concluded that i.p. injection of THC could effectively alleviate the respiratory symptoms and inhibit inflammatory reaction in asthmatic mice in short time with high safety. Therefore, i.p. injection of THC has the potential value to be the alternative therapeutic strategy for asthma.

Objective To identify measles vaccine failures in Tianjin,China using a measles virus IgG avidity assay.Methods The China Information System for Disease Control and Prevention (CISDCP) was used to collect information about measles cases and blood specimens in Tianjin from 2013 to 2015.Measles-specific IgM and IgG antibodies were detected using Enzyme-Linked Immunosorbent Assay (ELISA).Avidity testing for measles IgG was performed using a commercial enzyme immunoassay (EIA).Results A total of 284 confirmed measles cases were identified.Of this total,262 (92.25％) were in patients aged ≥ 20 years.High avidity was exhibited in 172 (60.56％) cases,while 80 (28.17％) cases demonstrated low avidity.High avidity was detected in only 21.43％ of cases in patients aged ＜ 1 year.The proportion of high avidity increased with age,and was significantly higher in patients aged 30-39 years at 70.07％ (x2 =17.27,P =0.002).Of the 52 measles cases in patients with a history of vaccinations,41 (78.85％) cases showed high avidity,indicating secondary vaccine failures (SVF).In these vaccinations,there was no significant difference (P ＞ 0.05) in clinical severity between high avidity and low avidity cases.However,regardless of vaccination status,clinical severity was significantly lower in high avidity cases (P ＜ 0.001) than in low avidity cases.The percentages of positive measles IgM results in high avidity and low avidity cases were 66.28％ and 91.25％,respectively.Geometric Mean Concentration (GMC) was significantly lower in high avidity cases at 33.73 U/mL,compared to 166.07 U/mL in low avidity cases.Conclusions Low clinical severity and inconclusive IgM antibody results are more likely in high avidity measles cases.Measles cases were more common in adults.Therefore,a further dose of vaccines should be recommended for 30-39 years in Tianjin.

Objective Pemetrexed and β-elemene can inhibit the growth of tumor cells .This study was to investigate the effect of pemetrexed combined with β-elemene on the proliferation and apoptosis of cervical cancer HeLa cells. Methods Cervical cancer HeLa cells were treated with pemetrexed at the concentrations of 38, 76, 152, 228, and 304μg/mL, and at 24 and 48 hours of treatment subjected to MTT for detection of their proliferation .The experiment included four groups , with the cells treated with β-elemene ( 125μg/mL) , pemetrexed ( 76 μg/mL ) , β-elemene ( 125 μg/mL ) +pemetrexed (76μg/mL), and nothing (blank control) for 24 hours, followed by determination of their proliferation and apoptosis by MTT and flow cytometry, respectively. Results Pemetrexed at 38, 76, 152 and 228μg/mL inhibited the proliferation of the HeLa cells in a concentration-dependent manner, with the inhibition rates of (7.24 ±3.78), (7.94 ±4.37), (11.10 ±2.86) and (15.88 ± 3.38)%at 24 hours, and (16.69 ±0.95), (22.54 ±1.53), (24.48 ±0.92) and (25.54 ±3.61)%at 48 hours, both with statis-tically significant differences between any two groups (P<0.05).Significant differences were also found in the proliferation rate of the same concentration of pemetrexed at the two time points (P<0.05).The combination of pemetrexed and β-elemene showed an inhibi-tion rate of (49.95 ±5.76)%at 24 hours, remarkably higher than (24.36 ±5.59)%in theβ-elemene group and (10.69 ±1.37)%in the pemetrexed group (P<0.01). Conclusion Pemetrexed combined with β-elemene can significantly inhibit the proliferation and synergistically accelerate the apoptosis of HeLa cells .

OBJECTIVETo evaluate the clinical efficacy and safety of treatment of chronic primary glomerulopathy (CPG) patients of Shen deficiency and dampness heat syndrome (SDDHS) by Yishen Qingli Granule (YQG) combined with low-dose Tripterygium Wilfordii multiglycoside Tablet (TWT).

METHODSTotally 231 CPG patients of SDDHS were enrolled in this study (including 60 patients from First Affiliated Hospital of Nanjing University of Chinese Medicine, 58 from First Affiliated Hospital of Nanjing Medical University, 46 from Xinqiao Hospital of Third Military Medical University, 35 from First Affiliated Hospital of Guangzhou University of Chinese Medicine, 14 from First Affiliated Hospital of Soochow University, and 18 from Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine). They were randomly assigned to the control group (116 cases) and the trial group (115 cases) according to block group method. There were 217 cases in the safety analysis set (109 cases in the trial group vs 108 cases in the control group), and 203 cases in the full analysis set (99 cases in the trial group vs 104 cases in the control group). All patients received basic treatment such as ACEI/ARB. Furthermore, YQG (consisting of raw astragalus 10 g, prepared Polygonum Multiflorum 10 g, Pyrrosia 10 g, 1.5 g each package, containing 10 g of crude drugs) was additionally given to patients in the trial group, each package, twice daily. The TWT (10 mg) was given, twice a day. The TWT dose was adjusted according to 24 h urinary total protein (UTP). The placebos of YQG and TWT were administered to those in the control group. The treatment course consisted of 24 weeks and the follow-up visit lasted for 24 weeks. The biochemical indices were observed before and after treatment including 24 h UTP, urine red cell count (U(RBC)), renal functions (BUN, SCr), blood routine test (WBC), and liver functions (SGPT, SGOT). Reverse reactions such as gastrointestinal discomfort, skin rash, and irregular menstruation were also observed.

RESULTSCompared with the control group, the total effective rate was better in the trial group (82.83% vs 61.54%, P < 0.01). Results of stratified comparison of UTP showed better efficacy in the trial group (0.8-3.0 g/24 h, P < 0.01). The UTP decline occurred in the trial group after 8 weeks of treatment, with stable action, showing statistical difference when compared with the control group (P < 0.01). In the trial group, U(RBC) level decreased after treatment but changed more significantly. But there was no statistical difference in the changes when compared with the control group (P > 0.05). After treatment, there were no statistical difference in safety indicators such as WBC, SGPT, and SGOT between the two groups after treatment (P > 0.05).

CONCLUSIONOn the basis of basic treatment such as ACEI/ARB, application of YQG combined with low-dose TWT had better effect in controlling proteinuria of CPG patients, and could help stabilizing their conditions with less adverse reactions.

Adult ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Kidney Diseases ; diagnosis ; drug therapy ; Kidney Glomerulus ; pathology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; methods ; Treatment Outcome ; Tripterygium

BACKGROUNDA multi-center large scale study is needed to confirm the efficacy and safety of domestic peritoneal dialysis (PD) solutions. Some researchers believe that 6 L/d is enough for adequate dialysis, but there is no multi-center prospective study on Chinese population to confirm this. In this study, we evaluated the efficacy and safety of domestic PD solution (Changfu) and its difference between 6 L and 8 L dosage.

METHODSAdult PD patients who had taken PD therapy for at least one month were selected and divided into four groups according to two dialysis solution brands and two dialysis dosages, i.e., 6 L dose with Changfu dialysis solution, 6 L dose with Baxter dialysis solution, 8 L dose with Changfu dialysis solution, and 8 L dose with Baxter dialysis solution. After 48 weeks, the changes of primary and secondary efficacy indices were compared between different types and different dosages. We also analyzed the changes of safety indices.

RESULTSChanges of Kt/V from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of creatinine clearance rate (Ccr). Normalized protein catabolic rate (nPCR) from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of net ultrafiltration volume (nUF) and estimated glomerular filtration rate (eGFR). Changes of nPCR from baseline to 48 weeks between 6 L and 8 L showed no statistical differences; so did those of nUF and eGFR. The decline of Kt/V from baseline to 48 weeks in 6 L group was more than that in 8 L group. Change of Ccr was similar. During the 48-week period, the mean Kt/V was above 1.7/w, and mean Ccr was above 50 L×1.73 m(-2)×w(-1). More adverse events were found in Changfu group before Changfu Corporation commenced technology optimization, and the statistical differences disappeared after that.

CONCLUSIONSThe domestic PD solution (Changfu) was proven to be as effective as Baxter dialysis solution. During 48-week period, a dosage of 6 L/d was enough for these patients to reach adequate PD. Clinical study promotes technological optimization, further helps to improve the safety indices of the medical products.

Adolescent ; Adult ; Aged ; Dialysis Solutions ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Peritoneal Dialysis ; methods ; Young Adult

OBJECTIVETo explore the clinical significance and diagnostic value of GP73 in early-stage primary hepatocelluar carcinoma (PHC).

METHODSGP73 levels in 50 healthy controls, 65 cases of liver cirrhosis and 40 early stage PHC were detected by ELISA. The areas under ROC, sensitivities and specificities were also compared. The relationship between GP73 and liver function parameters was analyzed.

RESULTSThe median of serum GP73 in early PHC was 291.3 µg/L, significantly higher than that in the cirrhosis group 211.8 µg/L and in the control group 58.3 µg/L (all P<0.01). The sensitivity of GP73 (72.5%) was significantly higher than that of AFP (50.0%), P<0.05. The specificity of GP73 (70.4%) was lower than that of AFP (95.7%), P<0.05. The sensitivity and specificity in combination for diagnosis were 77.5% and 79.1%, and the area under ROC curve in the combining form was 0.838 (95% CI:0.760-0.917). In the early PHC patients, the median of GP73 in the Child C group was 365.2 µg/L, significantly higher than that in the Child B group 310.6 µg/L and Child A group 266.4 µg/L, P = 0.002. In patients with liver cirrhosis, the median of GP73 in the Child B group was 307.3 µg/L, significantly higher than that in the Child A group 176.6 µg/L, P = 0.031. The level of serum GP73 was positively correlated with ALT, AST, negatively with ABL, A/G, and with no significant correlation with AFP, TBLB, DBLB, IBLB, and GGT.

CONCLUSIONSGP73 has a superior sensitivity in detecting early-stage PHC in liver cirrhosis patients. The sensitivity can be further increased by combining with AFP. The changes of GP73 expression may be related with the decline of liver function.

Aged ; Biomarkers, Tumor ; blood ; Carcinoma, Hepatocellular ; blood ; diagnosis ; Female ; Humans ; Liver Cirrhosis ; blood ; diagnosis ; Liver Neoplasms ; blood ; diagnosis ; Male ; Membrane Proteins ; blood ; Middle Aged ; Neoplasm Staging ; ROC Curve ; Sensitivity and Specificity ; alpha-Fetoproteins ; metabolism

Pannexin-1 (Panx1) forms nonselective large channel in cell plasma membrane and has been shown to be associated with NLRP3 inflammasome activation, ATP release and phagocytes recruitment. In the current study, by manipulation of Panx1 expression in human myeloid cells and application of Panx1 deficient mice, we failed to find a correlation between Panx1 and NLRP3 inflammasome activation, although an interaction between these two proteins was evident. However, in thioglycollate induced peritonitis, Panx1 deficient mice showed much more phagocytes infiltration. Further analyses showed that mice deficient for Panx1 exhibited enlarged F4/80(low)Gr1(-)Ly6C(-)cell population in the peritonea. Our study thus reveals an important role for Panx1 in regulation of peritoneal cell population and peritonitis development.
Animals ; Carrier Proteins ; metabolism ; Cell Line ; Connexins ; antagonists & inhibitors ; deficiency ; genetics ; metabolism ; HEK293 Cells ; Humans ; Inflammasomes ; metabolism ; Macrophages ; cytology ; metabolism ; Mice ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nerve Tissue Proteins ; antagonists & inhibitors ; deficiency ; genetics ; metabolism ; Peritoneal Cavity ; cytology ; Peritonitis ; chemically induced ; metabolism ; pathology ; RNA Interference ; RNA, Small Interfering ; metabolism ; Thioglycolates ; toxicity

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