OBJECTIVETo observe the therapeutic effect of a drug pair of Radix Astragali and Rehmanniae Radix combined with glucocorticoid (GC) in treating lupus nephritis (LN) patients and its influence on some experimental indices.

METHODSTotally 52 LN patients were randomly assigned to the treatment group (treated by routine Western medicine and a drug pair of Radix Astragali and Rehmanniae Radix, 25 cases) and the control group (treated by Western medicine, mainly by GC and cyclophosphamide, 27 cases). All patients received 6-month therapy. The GC dosage, the withdrawal and reduction dosage of GC, clinical efficacy, systemic lupus erythematosus disease activity index (SLEDAI) score, adverse reactions, and laboratory indicators were recorded.

RESULTS(1) All patients got relieved to some degree with the dosage of GC reduced. The total withdrawal and reduction dosage of GC was slightly higher in the treatment group than in the control group [(50.23 +/- 12.43) mg vs (48.76 +/- 13.61) mg, P > 0.05]. Besides, the prednisone dosage in the treatment group was lower than that in the control group, but without statistical difference (P > 0.05). The ratio of patients in need of adding prednisone for aggravating disease was 24.0%, significantly lower than that in the control group (44.44%, P < 0.05). (2) There was no statistical difference in the SLEDAI score, inflammatory indicators, liver and renal functions, blood electrolytes, blood glucose, blood and urine routines between the two groups (P > 0.05). The 24-h urinary protein count was (1.06 +/- 0.22) g/L in the treatment group, obviously lower than that in the control group (1.43 +/- 0.55 g/L, P < 0.05). (3) There was no statistical difference in the incidence rate of infection, gastrointestinal hemorrhage, psychoneuroses, Cushing's syndrome, cardiovascular anomalies, and femoral head necrosis between the two groups (P > 0.05). But the incidence of adverse reactions such as insomnia, tidal fever, spontaneous sweat, and obesity was less in the treatment group than in the control group (P < 0.05).

CONCLUSIONSUsing a drug pair of Radix Astragali and Rehmanniae Radix combined with GC in treating LN could withdraw the dosage of GC and relieve symptoms it induced. It was advantageous in reducing the dosage of GC and stabilizing patients' conditions.

Adolescent ; Adult ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Glucocorticoids ; therapeutic use ; Humans ; Lupus Nephritis ; drug therapy ; Treatment Outcome ; Young Adult

Background and purpose: Urokinase-type plasminogen activator receptor is related to invasion and metastasis of tumor. Inhibition of uPAR expression in tumor cells results in reducing its metastasis. This study was aimed to construct an expression vector with short hairpin RNA (shRNA) of uPAR, which could pave the way for RNAi-mediated tongue squamous cell carcinoma therapy. Methods: Genome sequences of uPAR gene were retrieved from Genhank and cDNA was designed to code expression of shRNA for uPAR gene. The cDNA was synthesized and inserted into the eukaryotic expression vector pWH1, and the recombinant pWH1-uPAR expression vector was identified by enzyme cutting method. Then, pWH1-uPAR expression vector was transfected into tongue squamous cell carcinoma Ts cells by Lipofectomine 2000. At last, the expression of uPAR in Ts cells transfected with pWH1-uPAR expression vector was observed by RT-PCR, immunocytochemistry staining and Western blot. MTT assay was performed to measure the proliferation of Ts cell. Results: The uPAR shRNA eukaryotic expression vector was successfully constructed. Compared with Ts cells and Ts cells transfected with plasmid pWH1, the Ts cells transfected with pWHI-uPAR expression vector showed a lower mRNA and protein expression of uPAR. The inhibition rate of proliferation was 32.9% of Ts cells by transfected with pWHl- uPAR. Conclusion: The constructed uPAR shR.NA expression vector could inhibit the expression of uPAR in tongue squamous cell carcinoma, which may be helpful for further research on the function of uPAR and provide effective methods for therapy of tongue squamous cell carcinoma.

Adolescent ; Cochlear Implantation ; Cochlear Implants ; Humans ; Male ; Otitis Media, Suppurative ; rehabilitation ; Postoperative Period

Objective To investigate whether and how CD4 + CD25 + regulatory T cells(Tr) affect oxidized low density lipoprotein(oxLDL) induced proinflammatory response in macrophages.Methods Tr were isolated from lymphocyte suspensions by magnetic cell sorting-column and analyzed by flow cytometry.Macrophages were cultured alone,with CD4 + CD25 + Tr or CD4 + CD25 - Tr in the presence of oxLDL for 48 h.The phenotype of macrophages was determined by flow cytometry.NO production was assessed by Griess reaction an iNOS mRNA was isolated by RT-PCR.ELISA were used to measure the production of cytokine/chemokine like MCP-1,MMP-9,TNF-ct,TGF-β and IL-10 in macrophages response to oxLDL.Results Our data showed that with oxLDL challenge,the Tr modulated macrophages have decreased NO production and iNOS expression,decreased HLA-DR and CD86 expression,and down-regulated proinflammatory cytokine/chemokine production.Conclusion Tr can inhibit the proinflammatory properties of macrophages and steer macrophage differentiation toward an anti-inflammatory cytokine producing phenotype.

Azacitidine ; administration & dosage ; analogs & derivatives ; pharmacology ; Cell Proliferation ; drug effects ; Daunorubicin ; administration & dosage ; pharmacology ; HL-60 Cells ; Humans ; PTEN Phosphohydrolase ; metabolism

According to the existing Provisions for Drug Registration (SFDA Order No. 28), applications for new drugs of traditional Chinese medicine are divided into two parts: the applications for drug clinical trial and for drug production (including new drug certificate). It will last for about 10 years from the application for drug clinical trial to get approving, and it also remains many problems and the low probability to succeed. From the sight of pharmaceutical review, there are mainly two aspects of regulatory compliance and technical issues, mainly for changes without approval of the competent authorities of the country. For example, sample preparation and approval of clinical trial process are significant changes. Technical problems are reporting incomplete data or information submitted does not comply with the technical requirements for review, such as: production process validation does not provide information, the preparation of samples for clinical trials and field inspection, production information, or the information provided does not meet the technical requirements. This paper summarizes the frequently asked questions and to make recommendations to advise applicants concerned, timely detection of problems, avoid risk, improving the quality and efficiency of the application for registration.
China ; Drug Approval ; legislation & jurisprudence ; Drug Evaluation ; legislation & jurisprudence ; Humans ; Legislation, Drug ; Medicine, Chinese Traditional

No abstract available.

Objective To clarify the role of B7-H1 in the immune privilege after corneal transplantation in homogeneity variant mice.Methods We established the experimental animal model of allograft mice by using C57BL/6 mouse as donor and Balb/c mouse as recipient.We allocaated the mice with long time survival (＞50 days) corneal graft into survival group,mice with rejection occurring in 50 days into rejection group,and normal C57BL/6 mice into control group.The transplanted corneal grafts were obtained for future reference at the 8th week after transplantation in survival group,and the time of rejection in rejection group.The expression of B7-H1 mRNA was detected by using immunohistochemistry and real time quantitative PCR (RT-PCR),and the relationship between B7-H1 and the immune privilege after corneal transplantation was analyzed. Results The B7 H1 mRNA was highly expressed in epithelium and endothelium of corneal grafts both in survival and control group,in comparison to an obviously lower expression in rejection group.The relative expression level of B7-H1 mRNA was 200.0 ± 11.5 in survival group,44.7 ± 10.8 in control group,and 6.9 ± 12.0 in rejection group,respectively. There were statistically significant differences among the three groups (F=241.164,P＜0.01 ).The was a significant correlation between the level of B7-H1 mRNA and occurrence rate of rejection in corneal graft (P＜0.01 ).Conclusion The results suggest that the immune privilege after corneal transplantation might be mediated by B7-H1,which plays an important role in maintaining the state of corneal immune privilege.

Background The rejection following keratoplasty still is a leading cause of corneal transplantation failure.Studies showed that the interleukin-22 (IL-22) ,one of the effector molecules of T helper cell 17 (Th17) participated on the rejection after heart,liver and bone marrow transplantation.However,the effect of IL-22 on corneal graft rejection is not well understood.Objective This study was to investigate the expression of IL-22 mRNA in the corneal grafts and the role of IL-22 in the immune rejection after corneal transplantation in rats.Methods Seventy-two Wistar rats were randomized into autologous keratoplasty group,allograft keratoplasty group and anti-rejection group,and other 4 normal Wistar rats served as normal control group.Autologous keratoplasty was operated on the Wistar rats of the autologous keratoplasty group,and allograft keratoplasty were carried out with the 24 SD rats as donors and 48 Wistar rats as recipients.Tobramycin and dexamethasone eye drops were topically administrated after autologous keratoplasty for 2 weeks in the anti-rejection group.The experimental eyes were examined by slit lamp microscope after surgery and graft survival was evaluated based on the rejection scoring criteria of Larkin.Intergroup accumulated survival rates of grafts were compared using Kaplan-Meier analysis.Histopathological examination of grafts was carried out in 5 and 14 days after operation respectively,and the related expression levels of IL-22 mRNA and aryl hydrocar-bon receptor (AhR) mRNA were carried out by real-time fluorescence quantitative PCR.The feeding and use of the experimental animals followed the Guangdong provincial regulations on the management of experimental animals.The experimental design was approved by the ethics committee of Southern Medical University.Results The median survival time of grafts in the allograft keratoplasty group was 10 days,and that in the anti-rejection group was 17 days,showing a significant survival extention in the anti-rejection group (x2=16.442,P =0.000).Significant differences were found among the 4 groups in the related expression levels of IL-22 mRNA in both 5 days and 14 days after surgery (postoperative 5 days : F=2.44,P =0.00;postoperative 14 days: F=267.92, P =0.00), and the related expression levels of IL-22 mRNA were remarkably higher in the allograft keratoplasty group than those in the anti-rejection group at different time points (postoperative 5 days :9.70±0.35 vs.0.46±0.21;postoperative 14 days : 23.12 ± 1.89 vs.3.14±0.94) (both at P＜0.05).The related expression levels of AhR mRNA in the grafts were considerably different among the 4 groups (postoperative 5 days : F =395.73, P =0.00;postoperative 14 days : F =942.37, P =0.00) , and the expression levels were significantly elevated in the allograft keratoplasty group compared with the anti-rejection group at various time points (postoperative 5 days:2.52±0.32 vs.1.89±0.10;postoperative 14 days:7.20±0.25 vs.2.60±0.17) (both at P＜0.05).Conclusions The expression level of IL-22 RNA up-regulates in the grafts with immuno-rejection.Topical administration of tobramycin and dexamethasone eye drops inhibits the rejection after keratoplasty.AhR plays a regulative role to the expression of IL-22 in rats after keratoplasty.

Objective:To study the effect of ulinastatin combined with early enteral nutrition on severe acute pancreatitis and its effect on nuclear factor-κB(NF-κB) and Toll-like receptor 4 (TLR4).Methods:Ninety severe acute pancreatitis patients who were treated in Central Hospital of Lijin County from January 2016 to January 2020 were selected and were divided into U+EEN group (ulinastatin combined with early enteral nutrition therapy) and EEN group (early enteral nutrition therapy) by random number table method, with 45 patients in each group. Curative effect, complications, nutritional indicators, immunoglobulins and inflammatory factors were detected and compared with analysis of variance. Western blot was used to detect the expression of NF-κB and TLR4 in pancreatic tissue in two groups.Results:The hospitalization time, ICU admission time, intestinal ventilation time, hospitalization costs and organ failure rate, pancreatic cysts, diabetes, chronic pancreatitis, incidence of sepsis in U + EEN group were lower than those in EEN group: (2.1 ± 0.4) months vs. (2.4 ± 0.6) months, (16.9 ± 2.1) d vs. (21.7 ± 2.8) d, (23.7 ± 3.8) d vs. (27.4 ± 4.1) d, (11.4 ± 1.5) thousand Yuan vs. (14.1 ± 2.1) thousand Yuan and 8.9%(4/45) vs. 20.0%(9/45), 13.3%(6/45) vs. 28.9%(13/45), 11.1%(5/45) vs. 24.4%(11/45), 8.9%(4/45) vs. 26.7%(12/45), 6.7%(3/45) vs. 22.2%(10/45), and the differences were statistically significant ( P<0.05). The levels of prealbumin (PA), albumin (ALB) and total protein (TP) after treatment in U + EEN group were higher than those in EEN group: (107.4 ± 6.5) mg/L vs. (102.8 ± 4.7) mg/L, (46.1 ± 3.5) g/L vs. (43.4 ± 2.8) g/L, (55.9 ± 3.4) g/L vs. (53.7 ± 3.1) g/L, and the differences were statistically significant ( P<0.05). The levels of IgG, IgA, IgM after treatment in U+EEN group were higher than those in EEN group: (10.5 ± 1.6) g/L vs. (9.5 ± 1.3) g/L, (8.9 ± 1.4) mg/L vs. (8.3 ± 1.2) mg/L, (60.5 ± 3.6) mg/L vs. (55.9 ± 3.4) mg/L, the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 in U+EEN group were lower than those in EEN group: (25.1 ± 2.9) mg/L vs. (30.6 ± 4.1) mg/L, (20.1 ± 1.9) mg/L vs. (24.6 ± 1.5) mg/L, (17.8 ± 1.9) mg/L vs. (20.1 ± 2.3) mg/L, and the differences were statistically significant ( P<0.05). The expressions of NF-κB and TLR4 protein in pancreatic tissue of patients in U + EEN group were significantly lower than those in EEN group (0.3 ± 0.2 vs. 0.5 ± 0.2, 0.2 ± 0.1 vs. 0.5 ± 0.1, P<0.05). Conclusions:Ulinastatin combined with early enteral nutrition can significantly improve the nutritional status and immune function and improve the prognosis of patients with severe acute pancreatitis, which may be related to ulinastatin′s reduction effect of NF-κB and TLR4′s expressions.