Objective To explore the clinical significance of STING in peripheral blood in patients with primary biliary cirrho-sis.Methods Admitted 28 PBC patients hospitalized in Shanghai Changhai Hospital and Shanghai Changzheng Hospital from January 2014 to October 2015.Also enrolled 28 healthy controls.Baseline data and laboratory indicators were extrac-ted,and STING mRNA expression was determined using q-PCR.The correlation between STING and clinical parameters were analyzed.The changes of STING mRNA in 5 followed-up patients with PBC were analyzed.Results Compared with healthy controls,STING mRNA was significantly increased in PBC patients and was increased in patients with severer dis-ease stages (U=0.00,P<0.05).STING was positively correlated with Mayo risk and GGT (R=0.45,R=0.42,P<0.05),and not AST,ALT or ALP (R=0.33,0.21,0.27,P>0.05).After therapy,STING mRNA were significantly re-duced in 5 PBC patients (U=0.00,P<0.05).Conclusion STING may be involved in PBC pathogenesis.

Objective To test the predicative roles of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1( KIM-1 ) for acute kidney injury (AKI) in critically ill patients. Methods Children from pediatric intensive care unit, were randomly divided into four groups:critically ill patients with AKI (group 1 ), critically ill patients with non-AKI (group 2) , chronic kidney disease group (group 3), healthy control group (group 4). 1.5 ml venous blood and urine specimens were collected and kept under-70°C. Serum creatinine , urine NGAL and urine KIM-1 were analyzed. Results Compared with group 2, group 3 and group 4, the urine NGAL and urine KIM-1 increases obviously in group 1 (P<0.05). There is no signiifcance of urine NGAL and urine KIM-1 between group2, group3 and group 4 (P>0.05). The concentration of urine NGAL increased more than 10 times of base-line level 2 days before the diagnosis of AKI under the Acute Kidney Injury Network standard with area under curve (AUC) 0.955 (P<0.05) , and the concentration of urine KIM-1 increased more than 5 times of base-line level 1 day before AKI with AUC 0.878 (P<0.05). The AUC was 0.984 (P<0.01) when they were combined. There is negative correlation between the increased times of urinary KIM-1, urinary NGAL and vally value of creatin clearance rate. Conclusions The concentrations of urine NGAL and urine KIM-1 are useful early biomarkers for predicting AKI, especially when they were combined.

OBJECTIVETo explore the theory of "Fei and Dachang being interior-exteriorly related" and the pathogenesis of lung injury by observing changes of inflammatory cytokines and oxygen free radicals in ulcerative colitis (UC) rats.

METHODSTotally 50 healthy male Wistar rats were randomly divided into two groups, the normal control group and the model group, 25 rats in each group. The UC model was established by allergizing colon mucosa combined with TNBS-alcohol (50%) enema. Another 25 rats were recruited as the normal control group. At week 2 and 4 after modeling, the pathomorphological changes of the lung were observed. Furthermore, the contents of tumor necrosis factor alpha (TNF-alpha) and IL-1beta were determined by ELISA. The activities of superoxide dismutase (SOD) and malondialdehyde (MDA) were evaluated with colorimetry.

RESULTSCompared with the normal control group, the pathomorphology of the lung tissue in the model group appeared abnormal at week 2 and 4. Compared with the normal control group, levels of TNF-alpha, IL-1beta, and MDA in the lung tissue significantly increased in the model group (P < 0. 01) and the activities of SOD significantly decreased (P < 0.05, P < 0.01).

CONCLUSIONTNF-alpha, IL-1beta, SOD, and MDA might be common material bases for the large intestine involved in lung disease of UC patients, thus providing a modern scientific basis for the theory of Fei and Dachang being interior-exteriorly related.

Animals ; Colitis, Ulcerative ; diagnosis ; metabolism ; pathology ; Cytokines ; metabolism ; Interleukin-1beta ; metabolism ; Lung ; metabolism ; Male ; Malondialdehyde ; metabolism ; Medicine, Chinese Traditional ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism ; Superoxide Dismutase ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

In the past few decades, our understanding of platelets has made great progress. Platelets play an unexpected central role in cancer and greatly affect the behavior of cancer cells. At the same time, the physiology and phenotype of platelets are also affected by cancer cells. Therefore, platelet-based tumor targeted therapy strategies have attracted the attention of researchers, but the limitations of their application require more attention. In this paper, the strategies of platelet-based tumor targeted therapy are summarized, and the strategies of platelet mimicking nanocarrier delivery, platelet hitch riding, platelet membrane coating biomimetic and engineered platelet targeting are mainly introduced. The easy activation, hard storage and unknown functional and phenotypic changes of platelets were discussed. At the same time, the strategy of platelet-based targeted tumor therapy is reviewed from theoretical basis and practical application. The development potential of platelets in the field of tumor diagnosis and treatment is discussed, which will provide some theoretical reference for the study of platelet-related tumor diagnosis and targeted therapy.

To develop a recombinant lentivirus co-expressing structural protein of hepatitis C virus (HCV) and secreted Gaussia Luciferase (Gluc), we first constructed an expression vector that encoded HCV structural protein (C, E1, E2) and GLuc named pCSGluc2aCE1E2. The expression of HCV proteins and Gluc was confirmed by an immunofluorescence assay (IFA) and the detection of luciferase activity. Recombinant lentivirus (VSVpp-HCV) was developed by the co-transfection of pCSGluc2aCE1E2 into 293T cells with pHR'CMVA8.2 and pVSVG. The infectivity of VSVpp-HCV was confirmed by luciferase activity detection, IFA and western blotting. Virus-like particles were identified using electron microscopy after concentration. The results showed that the level of luciferase activity correlated with the expression of HCV protein after the infection of cells with lentivirus VSVpp-HCV. Therefore, the expression level of HCV proteins could be evaluated by detecting the luciferase activity of Gluc. In conclusion, this research pave a way for the development of transgenic mice that express HCV proteins and Gluc, which enable the evaluation of anti-HCV therapy and vaccine in vivo.
Animals ; Copepoda ; Genes, Reporter ; Genetic Vectors ; genetics ; metabolism ; Hepacivirus ; genetics ; metabolism ; Hepatitis C ; virology ; Humans ; Lentivirus ; genetics ; metabolism ; Luciferases ; genetics ; metabolism ; Recombinant Fusion Proteins ; genetics ; metabolism ; Viral Structural Proteins ; genetics ; metabolism

Objective To evaluate the efficacy and tolerance of antiretroviral therapy (ART)regimen containing lopinavir/ritonavir (LPV/r) as a second-line regimen.Methods Data of acquired immunodeficiency syndrome (AIDS) patients who have received the first-line therapy for over a year and changed to the second-line antiviral therapy regimen containing LPV/r for more than one year were collected retrospectively from the database of free antiviral therapy in Henan Province from January 1,2009 to December 31,2013.Based on the viral load inhibition status after the alteration of the regimen,the patients were assigned to virology failure with first-line therapy group,and successful viral inhibition but poor immunological reconstruction with first-line therapy group.The variation trend of CD4+ T lymphocyte counts of the two groups in 6,12,24 months after changed to the second-line regimen of LPV/r,the virology inhibition rates between 6 and 12 months,12 and 24 months,and occurrence of adverse events were analyzed.Quantitative data were analyzed by rank sum test,and qualitative data were analyzed by chi-square test.Results A total of 4 113 patients were divided into two groups,including the first-line therapy failure group (n=3 802) and poor immunological reconstruction group (n=311).At 6,12 and 24 months after the alteration of the regimen,the CD4+ T lymphocyte counts increased gradually (all P＜0.01).Between 6 and 12 months after the first-line therapy failure group changed to the secondline regimen,viral inhibition rate was 61.65％(1 408/2 284),while that 12 and 24 months was 68.91％(2 044/2 966).The incidences of adverse reaction of the two groups were 21.88％ (832/3 802) and 22.19％(69/311),respectively,which were not significantly different (x2 =0.015,P=0.901).Condusion The ART regimen containing LPV/r still has good viral inhibition effect and immunological reconstruction effect for AIDS patients who failed the initial therapy with poor immunological reconstruction.

OBJECTIVETo observe the clinical effect of Huikangling Tablet (HT, extracted from Scabrous Patrinia root) on peripheral blood micrometastasis of differentiated thyroid carcinoma (DTC) patients.

METHODSTotally 87 DTC patients with positive micrometastasis were randomly assigned to the treatment group (45 cases) and the control group (42 cases). DTC endocrine inhibition treatment standards were executed in all patients. They all took levothyroxine sodium (50 microg/tablet, from low dose, 25 microg each time, once per day, 0.5 h before breakfast), and its dosage was gradually added one week later. The dosage was adjusted according to tested results of TSH combined recurrence risk stratification and endocrine suppression induced adverse reactions risk stratification. Patients in the treatment group took HT (0.4 g per tablet, 3 tablets each time, three times per day for a total of 12 weeks) combined TSH suppression therapy, while those in the control group only received TSH suppression therapy. Peripheral micrometastatic cytokeratin 19 (CK19) and polymorphic epithelial mucin1 (MUC1) were detected by FCM at week 4 and 12. Meanwhile, distant metastasis and adverse reactions were observed.

RESULTSAfter 4-week treatment positive micrometastasis was shown in 18 cases (40%) of the treatment group and 29 cases (69%) in the control group with statistical difference (chi2 = 5.68, P < 0.05). After 12-week treatment positive micrometastasis was shown in 7 cases (15.6%) of the treatment group and 17 cases (44.7%) in the control group with statistical difference (chi2 = 8.49, P < 0.01). Pulmonary metastasis occurred in 2 cases and bone metastasis in 1 case of the control group at follow-ups. Cervical lymph node metastasis without accompanied recurrence of thyroid cancer occurred in one case of the treatment group. No obvious liver or renal abnormalities occurred.

CONCLUSIONHT inhibited peripheral blood micrometastasis of DTC patients and its mechanism needed to be further studied.

Antineoplastic Agents ; pharmacology ; therapeutic use ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Neoplasm Micrometastasis ; drug therapy ; Neoplasm Recurrence, Local ; Tablets ; Thyroid Neoplasms ; drug therapy

Objective To explore the clinical significance of neutrophils/lymphocyte(NLR)and platelet/lymphocyte ratioof (PLR)peripheral blood in patients with primary biliary cirrhosis.Methods Retrospectively analyzed 62 patients with PBC and three subgroup patients according to Child-pugh,who were hospitalized in Shanghai Changhai Hospital and Shanghai Changzheng Hospital from January 2010 to July 2015.Enrolled 59 healthy controls.Baseline data and laboratory indicators were extracted,and the correlation between PLR and NLR and disease activity were analyzed.The changes of NLR in 3 pa-tients with PBC were analyzed.3 patients were followed up and their NLRs were recorded before and after therapy.Results Compared with healthy controls,NLR was significantly increased in PBC patients (P<0.05),and not PLR (P>0.05). NLR was positively correlated with TBIL and Mayo risk (R=0.35,0.30,P<0.05),and not ALT,AST or ALP (P>0.05).After therapy,NLRs were significantly reduced in three PBC patients (P<0.05).Conclusion NLR may be a useful biomarker for assessing clinical therapy in PBC patients.

Objective To assess efficacy, infection rate and recurrence rate of tacrolimus prescribed in infants with steroid-resistant nephrotic syndrome (SRNS). Method From August 2011 to August 2014, 22 cases of SRNS infants (treatment group) received oral tacrolinms treatment, 0.1 to 0.15 mg/ kg per day and once every 12 hours were enrolled in this retrospective longitudinal study and were compared with 23 cases infant SRNS (control group) treated with high-dose methylprednisolone pulse therapy. Followed up for 1 year we analysed the data of proteinuria, lymphocyte count, proteinuria relapse and complication (infection, hyperglycemia) of the two groups’ patients at every point time. Results The pathology of the patients maintains of MCD, MsPGN, FSGS and IgM nephropathy so on. Follow-up to 6 months, the total remission rate 95.45% of treatment group was significantly higher than that in control group (60.87%). Follow-up to 6 months , 24 h urinary protein of the treatment group were respectively 67.88 mg/(kg·d) which were remarkably lower than base line [657.5 mg/(kg·d)], meanwhile which were obviously lower than the 6th month point of control group [305.55 mg/(kg·d)]. Lymphocyte counts had been done during the initial and the destination in the treatment group. Follow-up to 12 months, the CD4+ 795.16/uL, CD8+ 496.85/uL, CD19+ 358.23/uL had decreased observably than when at origin what was 2697.45/uL, 2265.63/uL, 1579.34/uL. Followed-up 1 year, the person-time of infection of treatment group existed superior to the control groups; The recurrence rate was 71.43% in treatment group, which compared with control groups (60.87%) without no significant difference. The treatment group with BG and CCr maintained stably. Conclusion Tacrolimus show its own advantages of reliable effect and less side-effect on the infant with steroid-resistant nephrotic symdrome associated with genes , but it could not lessen the relapse of the disease, and it′s long-term prognosis is still not very clear.

Objective To develop a gene microarray system for detection of clinical common pathogenic fungi.MethodsThere were 8 clinical common fungi chosen as the subjects including Candida albicans,Candida glabrata,Candida tropicalis,Candida parapsilokis,Candida pseudotropicalis,Aspergillus terreus,Aspergillus flavus,Aspergillus oryzae,Aspergillus fumigatus.Universal primers,probes and specific probes for the PCR amplification and microarray preparation were designed in ITS region of the fungi genomic DNA.The PCR products amplified from those fungi's genome DNA were denatured and hybridized with the probes in gene microarray.The rapid detection of fungi was based on the investigation on the fluorescent signal intensity in the chip.The detection results of gene microarray system were verified by true positive and negative clinical samples.Results There were totally 25 positive samples identified by clinical routine microbiological methods.The 10 samples identified as bacteria positive were determined as negative without fluorescent signal by the fungi gene microarray,while the 12 samples identified as fungi positive were determined as positive with certain fungus by the fungi gene microarray.And 3 artificial Candida krusei samples were detected as fungi positive,while they were failure to be identified as certain fungus.There was no fluorescent signal in positions of the 8 fungi specific probes,but there was fluorescent signal in the position of fungi universal probe.It indicated that there were fungi in the samples but it couldn't identify the species of the fungi,because the Candida krusei wasn't included in the detection fungi list of the fungi gene microarray.ConclusionsThe fungi gene microarray established by the study could detect the common fungi in clinic rapidly and accurately.This study lays technology foundation for clinical application of gene chip.