Aim To investigate the curative effects of resveratrol on OVA induced allergic rhinitis in mice and the underlying immune mechanisms. Methods Balb/c mice (female, 6 weeks) were divided randomly into normal control ( NC) group, allergic rhinitis (AR) group, high dose resveratrol treatment group (RH), low dose resveratrol treatment group (RL), and dexamethasone treatment group ( Dex). RL, RH and Dex group were oral administered with resveratrol 30 mg • kg"1, resveratrol 100 mg • kg"1 and dexamethasone 10 mg • kg"1, respectively. After the treat-ment , the sneezing and nasal rubbing behaviors of mice in all the group were recorded and HE was performed to assess the inflammatory cell infiltration in nasal tissues. The sera levels of allergic cytokines were determined with ELISA assay. The percentage of CD4+ GA- TA3 + T cells in spleen of each group was further recorded by flow cytometry. Results Compared with AR group, treatment with resveratrol (100 mg - kg"1) reduced the sneezing and nasal rubbing behaviors signifi-cantly and improved inflammatory cell infiltration in nasal tissues. The up-regulated sera levels of IL-4, IL- 13 and OVA-sIgE in AR group were reversed by RH, and ratios CD4+ GATA3 + Th2 cells in spleen of RH were also down-regulated parallelly. Conclusions RH treatment could improve the allergic related symptoms of OVA-induced allergic rhinitis, which is associated with down-regulated sera levels of IL-4, IL-13 and OVA-sIgE and ratios of CD4+ GATA3 + Th2 cells in spleen of mouse model.

Objective To investigate the kinetics and the magnitude of intragraft gene expression of interleukin-2 (IL-2), interferon-gamma (IFN-y), perforin and granzyme B, and intragraft expression of interieukin-2 receptor (IL-2R) and intercellular adhesion molecule-1 ( ICAM-1 ) during acute rejection episodes, and to analyze the changes in apoptosis in small intestinal allograft rejection. Methods Heterotopic small intestine transplantation was performed with inbred rats F344/N (RT11) and Wistar/A (RT1-Ak, RT1-Ed). All recipients were divided into four groups: group 1 : Wistar, native control; group 2: Wistar→Wistar; group 3: F344→Wistar and group 4: F344→Wistar + cyclosporine A (6 mg·kg-1 ·d-1 I.M. ). The grafts were harvested on postoperative days (PODs) 3, 5 and 7. All samples were examined pathologically. Intragraft mRNA expression of IL-2, IFN-γ, perforin and granzyme B were detected with reverse transcriptase polymerase chain reaction (RT-PCR) and intragraft expression of IL-2R and ICAM-1 were stained using immunohistochemistry. We also analyzed the change in apoptosis rejection with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Results Mild acute rejection occurred on POD 3 in the ailograft group, moderate acute rejection on POD 5, and severe acute rejection on POD 7, while none of the isografts had histological evidence of acute rejection. Cyclosporine A could effectively control rejection. Gene expression was virtually negative in the native control. Only on POD 5 was IL-2 mRNA expression of ailografts significantly higher than that of isografts ( P ＜ 0.05). IFN-γ mRNA expression was significantly higher than that of the control groups ( P ＜ 0.01 ) on PODs 3, 5 and 7, and the level of perforin and granzyme B mRNA expression reached significantly higher levels than in the other two control groups on POD 5 and POD 7. Intragraft IL-2R expression of the allograft was significantly higher than that of the other three control groups. Only on POD 3 was intragraft ICAM-1 expression of allografts significantly higher than isografts. The number of apoptotic cells per crypt of allografts was significantly higher than that of the other three control groups on POD 3 and POD 5 ( P ＜ 0.01 ). Conclusion Transcription of IL-2, IFN-γ, perforin and granzyme B, and expression of IL-2R and ICAM-1 as well as apoptosis of epithelial cells of the grafts play an important role in small intestine allograft rejection. Intragraft gene expression of IFN-γ and intragraft expression of IL-2R as well as apoptotic epithelial cells may become a specific and sensitive diagnostic method of clinical value. Furthermore, therapeutic strategies to alter these molecules in small intestine transplantation may improve the outcome of current antirejection therapy.

Field avian infectious bronchitis virus (IBV) designated as JS/9 5/03, which was isolated from Jiangsu province of china, was cultivated in chicken emb ryo. It's single strain RNA was extracted from purified virus and worked as temp late of reverse transcription polymerase chain reaction (RT-PCR), a pair of pri mer designed according to megalign results of published IBV sequences in Genbank was used to amplify the neucleocapsid gene, the RT-PCR product was sequenced d irectly. Sequence analysis revealed that the sequence of JS/95/03 is most homolo gized with that of M41 strain.

To evaluate lesion detection of MRI in knee joint osteoarthritis in patients with symptoms of pain, the correlation between MRI findings and varying degrees of reported pain was assessed. Twenty-eight patients (31 knees) with osteoarthritis were recruited for this study. The degree of knee pain was assessed by VRS scores. The knees were evaluated by plain film radiograph utilizing Kellgren-Lawrence scores. Multiple MR sequences were performed on a 1.5T MR-system, including sagittal and coronal dual fast spin echo (TR/TE 3660/11/120 ms, slice thickness 5 mm), coronal spin echo T1-weighted (TR/TE 360/9 ms, slice thickness 5 mm), sagittal fat saturated 3D-spoiled gradient-recalled echo (TR/TE 50/6 ms; slice thickness 1.5 mm; flip angle 40 degrees ), and 3D steady-state free precession (TR/TE 6/2.2 ms; slice thickness 1.6 mm; flip angle 30 degrees ) pulse sequences for the purpose of detecting abnormities of cartilage, menisci, the anterior cruciate ligaments, bone marrow edema-like lesions, osteophytes, synovitis, and joint effusions. MR findings were compared with the degree of pain using Fisher exact test with P values less than 0.05 indicating a statistically significant difference. The results showed that, of the 31 knees evaluated, mild pain was reported in 11 and severe pain in the remainder. Kellgren-Lawrence scores of all 31 evaluated OA knees were as follows: grade 1 lesions (n=6), grade 2 lesions (n=14), grade 3 lesions (n=8), and grade 4 lesions (n=3). Articular cartilaginous defects were found in 37.1% of knees. Abnormalities of the menisci and anterior cruciate ligaments, bone marrow edema-like lesions, osteophytes, synovitis, and joint effusions were detected in 32.3%, 38.7%, 45.2%, 100%, 15.1% and 67.7% of knees, respectively. Of these variables, only the differences in prevalence of joint effusions were significantly different in the mild and severe pain groups (P=0.004). It is concluded that MRI evaluates the entire joint structure of the osteoarthritic knee, demonstrating abnormalities of the cartilage, menisci, and anterior cruciate ligaments as well as bone marrow edema-like lesions, osteophytes, synovitis, and joint effusions. The difference in pain grading between OA patients reporting mild and severe degrees of pain is related to the presence of joint effusion.

OBJECTIVE： To provide reference for pharmaceutical manufacturers improving the quality system of GMP and drug regulatory departments improving their supervision level. METHODS： Through analyzing and summarizing the problems existing in the 28 pharmaceutical enterprises which had been published on the website in the National Medical Products Administration from February 6th， 2018 to January 25th， 2019， the common problems were found and their causes were analyzed， then the regulatory countermeasures were put forward. RESULTS & CONCLUSIONS： Pharmaceutical enterprises have some problems of inadequate implementation of GMP， such as the inadequate performance of personnel in key positions and the unsatisfactory training effect of relevant personnel， the inconsistency between actual production technology and approved legal technology， the non-standard management of enterprise materials， the incomplete batch production records and the inability to effectively monitor the production cycle. However， there are also some problems in the supervision department， such as the large difference in the scale of inspectors’ on-site inspection， the need to strengthen the inspectors’ inspection ability and level， and the lack of innovation in the means of supervision. It is suggested that pharmaceutical manufacturers should improve the construction of GMP quality management system and strengthen the training of relevant personnel； the regulatory authorities should continue to promote the reform of “release， control and service”， strictly enforce the access conditions of inspectors， strengthen the training of inspectors and ideological construction of the inspector team，further strengthen the construction of supervision system and enhance the innovation of supervision means， so as to jointly maintain the safety， effectiveness and quality controllability of medicines.

OBJECTIVE：To optimize the extraction technology of Senecio scandens ，and to provide reference for the further development and utilization of the medicinal material. METHODS ：The method of reflux extraction with 80 ℃ water bath was used to extract S. scandens . HPLC method was adopted to determine the contents of chlorogenic acid and hyperoside. The determination was performed on Diamonsil C 18 with mobile phase consisted of 0.2％ glacial acetic acid water solution-methanol （82∶18，V/V）at the flow rate of 1.0 mL/min；the column temperature was set at 35 ℃；the detection wavelength was 327 nm，and the sample size was 5 μL. UV-Vis spectrophotometry was used to determine the contents of total flavonoids（by rutin ）and total alkaloids （by matrine）and the detection wavelengths were set at 509 nm and 208 nm，respectively. Based on single factor tests ，using ethanol volume fraction （A，％），solvent folds （B，mL/g），extraction time （C，h），extraction times （D，times）as factors ，using the contents of chlorogenic acid ，hyperoside，total flavonoids and total alkaloids as indexes ，and t he weight coefficients of above indicator components were calculated based on information entropy weighting method so as to calculate their comprehensive scores ， then L 9（34）orthogonal design was used to further optimize the extraction technology. The validation tests were also performed. RESULTS：The optimal extraction technology of S. scandens included that 8-fold 50％ ethanol，extracting for 3 times，lasting for 1.5 h each time. Results of 3 times of validation tests showed that RSDs of the contents of chlorogenic acid ，hyperoside，total flavonoids and total alkaloids were all lower than 1.5％（n＝3）. CONCLUSIONS ：The optimized technology is reproducible ， stable and feasible ，and can be used for the extraction of S. scandens .

ObjectiveTo investigate the relationship between hyponatremia and degree of liver injury, complications and survival time, and the prognostic value of hyponatremia in patients with decompensated liver cirrhosis. MethodsA total of 218 patients who were diagnosed with decompensated liver cirrhosis for the first time in The First Affiliated Hospital of Dalian Medical University from January 2000 to March 2005 were enrolled in this study, and according to the serum sodium concentration, these patients were divided into group Ⅰ with a serum sodium concentration of ≥130 mmol/L (n=51), group Ⅱ with a serum sodium concentration of ≥120 and ＜130 mmol/L (n=97), group Ⅲ with a serum sodium concentration of ＜120 mmol/L (n=70). The patients′sex, age, serum sodium concentration, Child-Pugh class, and complications were analyzed, and the survival time was calculated. The one-way analysis of variance was applied for comparison of continuous data between groups, and the least significant difference t-test was applied for comparison between any two patients; the chi-square test was applied for comparison of categorical data between groups; the Kaplan-Meier method was applied for survival analysis, and the Cox regression model was applied for regression analysis. ResultsCompared with groups Ⅰ and Ⅱ, group Ⅲ had the highest proportion of patients with Child-Pugh C cirrhosis. With the increasing Child-Pugh score, the serum sodium concentration decreased; the serum sodium concentration showed significant differences across the patients with Child-Pugh A, B, and C cirrhosis (F=17.336, P＜0001), and differed significantly between any two groups of these patients (all P ＜0.05). Compared with groups Ⅰ and Ⅱ, group Ⅲ had the highest incidence rate of complications, and the incidence rates of hepatic encephalopathy and hepatorenal syndrome showed significant differences across the three groups (χ2=17.718 and 6.277, both P＜0.05). Group Ⅲ had a significantly shorter survival time than groups Ⅰ and Ⅱ (both P＜0.05). ConclusionIn patients with decompensated liver cirrhosis, the severity and incidence rate of hyponatremia increase significantly as liver injury becomes more severe, which suggests that hyponatremia can be used as a prognostic indicator in patients with decompensated liver cirrhosis.

Objective: To elucidate the effects of chlorogenic acid (CGA), a bioactive polyphenol compound prevalent in traditional Chinese medicine and various foods, including Lonicera japonica Thunb. (Jin Yin Hua), Eucommia ulmoides Oliv. (Du Zhong Ye), tea, and coffee, on cardiomyocyte ferroptosis and heart failure. Methods: We assessed the effect of CGA on cardiac function using a mouse model of heart failure induced by transverse aortic constriction (TAC). These indicators included the left ventricular ejection fraction (LVEF), fractional shortening (LVFS), end-systolic volume (LVESV), end-diastolic volume (LVEDV), end-systolic diameter (LVESD), and end-diastolic diameter (LVEDD). An isoprenaline hydrochloride (ISO)-induced H9c2 cardiomyocyte cell model was also established, and the cells were treated with various concentrations of CGA. To assess the effect of CGA on ferroptosis in cardiomyocytes, we measured cell viability and evaluated the levels of intracellular reactive oxygen species (ROS), ferrous ions (Fe2+), and lipid peroxidation using fluorescent staining. To clarify the ferroptosis signaling pathway regulated by CGA, western blotting was used to examine the expression of ferroptosis biomarkers, specifically solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), in H9c2 cardiomyocytes and mouse myocardial tissues. Results: CGA significantly enhanced cardiac performance indices such as LVEF, LVFS, LVESV, LVEDV, LVESD, and LVEDD. H9c2 cardiomyocytes exposed to ISO showed decreased cell viability and increased ROS levels, Fe2+ content, and lipid peroxidation levels. However, CGA treatment significantly ameliorated these changes. Additionally, in both H9c2 cardiomyocytes and myocardial tissue obtained from mice with TAC, CGA increased the expression of ferroptosis-related proteins, including SLC7A11 and GPX4. Conclusion CGA has the potential to enhance cardiac function and diminish lipid peroxidation and ROS levels in cardiomyocytes via the SLC7A11/GPX4 signaling pathway. This process alleviates ferroptosis in cardiomyocytes. These results provide new insights into the clinical use of CGA and the management of heart failure.

Objective: To understand prevalence and transmission of transmitted drug resistance (TDR) among HIV infected men who have sex with men (MSM) in Tianjin from 2014 to 2017. Methods: A total of 225 blood samples were collected from HIV infected MSM in Tianjin from 2014 to 2017. Pol gene fragments were obtained by viral RNA extraction and nested PCR amplification. Phylogenetic and drug resistance analyses were conducted. Results: A total of 205 samples were successfully sequenced and analyzed. Based on pol sequences, 53.2% (109/205), 28.8% (59/205), 10.2% (21/205), 4.9% (10/205) and 2.9% (6/205) of the samples were positive for HIV subtypes CRF01_AE, CRF07_BC, B, CRF55_01B and unique recombinant forms (URFs). Twenty transmission clusters, including 75 sequences, were identified and 62.5% (10/16) of sequences with TDR were in 5 clusters. The prevalence of TDR was 7.8% between 2014 and 2017. The annual prevalence rate increased from 3.9% (2/51) in 2014, 5.7% (3/53) in 2015, 9.6% (5/52) in 2016 to 12.2%(6/49) in 2017, the difference was not significant (χ(2)=2.504, P=0.127). CRF01_AE and B strains had high TDR prevalence (3.4%, 7/205) and (2.9%, 6/205), respectively. The TDR mutation was mainly NNRTIs, the TDR prevalence was 6.3% (13/205). In contract, the TDR prevalence of NRTIs and PIs were 1.5% (3/205) and 1.0% (2/205) respectively. Conclusion: Results from this study suggested that the prevalence of HIV-1 TDR strains in MSM was serious in Tianjin. It is necessary to take effective prevention and control measures.
China ; Drug Resistance, Viral/genetics* ; Genes, pol ; Genotype ; HIV Infections/transmission* ; HIV Reverse Transcriptase/genetics* ; HIV Seropositivity/genetics* ; HIV-1/isolation & purification* ; Homosexuality, Male/statistics & numerical data* ; Humans ; Male ; Mutation ; Phylogeny ; Polymerase Chain Reaction ; Prevalence ; RNA, Viral/genetics* ; pol Gene Products, Human Immunodeficiency Virus/genetics*

OBJECTIVE： To predict the anti-inflammatory active components and mechanism of couplet medicine of Notopterygium incisum-Angelica pubescens. METHODS： According to the principle of oral bioavailability≥30％ and drug- likeness≥0.18， active components of N. incisum and A. pubescens were screened； TCMSP was used to predict and screen the potential target of them. Using “Anti-inflammatory” as keyword， inflammatory related target genes were retrieved from human gene database Genecards. Common target was screened by mapping the target genes of active ingredients from couplet medicine of N. incisum-A. pubescens. The active ingredient-target network was established by using Cytoscape 3.5.1 software. The screened targets were used to construct the target protein interaction （PPI） network on the STRING V 10.5 platform. Its anti-inflammatory mechanism was studied by KEGG signaling pathway and GO biological enrichment analysis. RESULTS： Totally 15 active components such as coumarin， beta-sitosterol， ammidin， nodakenin were selected from couplet medicine of N. incisum-A. pubescens. Acting on 49 targets such as transcription factor AP-1， PI3-kinase subunit gamma， estrogen receptor， they mainly involved 19 signaling pathways such as hepatitis B and cell apoptosis， and were involved in 47 biological processes such as regulating inflammatory response and prostaglandin biosynthesis. CONCLUSIONS： The anti-inflammatory mechanism of active components of couplet medicine of N. incisum-A. pubescens on multi-target， multi-channel and multi-biological processes is predicted， and it points out the direction for further anti-inflammatory mechanism study.