Objective:To investigate effects of tumor specific TCR gene Vα12.2-Vβ7.1 modification on recognition of tumor antigen and activation of anti-tumor reactivity of T cells.Methods: T cells were transduced using recombinant Ad 5F35-TRAV-TRBV adenovirus ,and multiplicity of infection was optimized.Specific lysis of T cells was evaluated by calcein release assay.The frequency of apoptotic cells in target cells was detected by Annexin V /PI double-labeled FACS.The expression of FasL on T cells was analyzed by FACS.The secretion of cytokine IFN-γand IL-2 of T cells was determined by ELISA assays.Results: The highest tranduce efficiency was obtained at MOI 100 by recombinant Ad5F35-TRAV-TRBV adenovirus.The frequency of TCRVα12+Vβ7+cells reached above 25%3 days after transduction.TCR gene modification enhanced the ability of T cells to lyse HLA-A2+AFP+target cells(P<0.001), the ability of T cells to induce HepG-2 apoptosis(P<0.001),and expression of FasL on T cells(P<0.001).TCR gene modification also enhanced T cells to secret IFN-γafter coculture with antigen positive tumor cells ( P<0.001 ).Conclusion: Specific TCR gene modification by recombinant adeno virus effectively promotes T cells to recognize antigen positive tumor cell and exert anti -tumor reac-tivity.

Objective This study aims to investigate the effect of Lipoxin A4 receptor on acute lung injury (ALI) induced by intestine ischemia-reperfusion (IIR). Methods Thirty-two 8-week old SD rats were randomly divided into four groups: sham, intestine ischemia-reperfusion (IIR), IIR + BML111 (BML-111), Boc-2 + IIR +BML111 (Boc-2). BML-111 (1 mg/kg) was given intraperitoneally at the onset of reperfusion in the BML-111 and the Boc-2 group. Boc-2 (50 μg/kg) was given intraperitoneally after anesthesia in the Boc-2 group. Rats were subjected to superior mesenteric artery occlusion consisting of 45-min ischemia and 6-h reperfusion, and the sham laparotomy was served as controls. The lung pathology was assayed by the H&E staining. Lung water content was detected using dry/wet ratio. Concentrations of TNF-α, IL-1β, and IL-6 in lung tissue were determined by ELISA. The protein expression of p38 MAPK and NF-κB of lung was assayed by western blot. Results IIR induced serious ALI, with poor lung pathology and increased lung water content, elevation of TNF-α, IL-1β, and IL-6 levels in lung, accompanied with activation of p38 MAPK/NF-κB pathway. However, BML-111 could inhibit the activation of p38 MAPK/NF-κB pathway, leading to the reductions of TNF-α, IL-1β, and IL-6 in lung and attenuation of IIR-induced ALI. Conclusion BML-111 treatment could attenuate inflammation in lung after IIR injury via inactivating the p38 MAPK/NF-κB signaling pathway.

OBJECTIVETo compare the antioxidant active components from two species of chamomile-matricaria and Roman chamomile produced in Xinjiang.

METHODThe TLC-bioautography was used, with 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical as the experimental model. The peak areas of various antioxidant components were obtained by TLC-scanning for analyzing antioxidant active components contained in volatile oil extracts and flavone extracts from the two species of chamomiles. The total peak area was taken as the indicator for comparing the antioxidant capacities of the two types of extracts, and comparing them with the total antioxidant activity of flavone extracts of the two species of chamomiles.

RESULTSAccording to the result of TLC-bioautography in volatile oil extracts from the two species of chamomiles, volatile oil extracts from chamomile showed four white antioxidant spots, including en-yne-dicycloether, and volatile oil extracts from Roman chamomile showed only one white antioxidant spot. The TLC-scanning result showed that the peak area of antioxidant spots of volatile oil extracts from chamomile was significantly larger than that of volatile oil extracts from Roman chamomile. According to the test on the antioxidant activity of the two species of chamomiles with ultraviolet-visible spectrophotometry, the concentration of chamomile after scavenging 50% of DPPH radicals was 0.66 g x L(-1), whereas the figure for Roman chamomile was 0.33 g x L(-1). According to the result of TLC-bioautography in flavone extracts from the two species of chamomiles, flavone extracts from chamomile showed seven yellowish antioxidant spots, including apigenin and apigenin-7-glucoside, and flavone extracts of Roman chamomile showed eight yellowish antioxidant spots, including apigenin and apigenin-7-glucoside. The TLC-scanning results showed that the peak area of antioxidant spots of flavone extracts from Roman chamomile was significantly larger than that of flavone extracts from chamomile.

CONCLUSIONVolatile oil extracts from the two species of chamomiles have significant difference in the antioxidant activity in TLC-bioautography. Specifically, the antioxidant activity of volatile oil extracts from chamomile is stronger than volatile oil extracts from Roman chamomile; the known antioxidant active components in volatile oil extracts from chamomile is en-yne-dicycloether, while all of the other three antioxidant active components as well as antioxidant active components in volatile oil extracts from Roman chamomile are unknown components and remain to be further determined. Considering the significant difference in the number of antioxidant active spots in volatile oil extracts from the two species of chamomiles, the result can be applied to distinguish the two species of chamomiles. The antioxidant activity determination result for flavone extracts from two species of chamomiles was consistent with the result of TLC-bioautography, showing that flavone extracts from chamomile and Roman chamomile are more antioxidant active, while that of Roman chamomile is stronger than chamomile. Flavone extracts from both of the two species of chamomiles contain apigenin and pigenin-7-glucoside, which are known, while all of the other five antioxidant active components contained in flavone extracts from chamomile and the other six antioxidant active components contained in flavone extracts from Roman chamomile are unknown and remain to be further identified. The method lays a foundation for further identification of antioxidant active components contained in chamomile.

Antioxidants ; chemistry ; isolation & purification ; Apigenin ; chemistry ; isolation & purification ; Biphenyl Compounds ; metabolism ; Chamaemelum ; chemistry ; Chromatography, Thin Layer ; methods ; Flavones ; chemistry ; isolation & purification ; Free Radical Scavengers ; chemistry ; isolation & purification ; Glucosides ; chemistry ; isolation & purification ; Matricaria ; chemistry ; Oils, Volatile ; chemistry ; isolation & purification ; Picrates ; metabolism ; Plant Extracts ; chemistry ; isolation & purification ; Plant Oils ; chemistry ; isolation & purification

OBJECTIVETo evaluate the efficacy and safety of docetaxel (Taxotere) (DTX) and oxaliplatin (OXA) for treatment of recurrent epithelial ovarian cancer.

METHODSThirty-six patients with histologically confirmed recurrent epithelial ovarian cancer received chemotherapy with DTX and OXA. DTX at the dose of 75 mg/m(2) was administered on day 1 by intravenous infusion in 60 min, followed by OXA at 100 mg/m(2) given by a 2 h infusion. The chemotherapy cycles were repeated every 21 days, and the patients received at least 2 cycles.

RESULTSAll the patients were available for response evaluation, among whom 3 (8.3%) showed complete responses and 17 (47.2%) showed partial responses, with an overall response rate of 55.6%. The main adverse effects included hematological toxicities and peripheral neuropathy.

CONCLUSIONCombination of DTX and OXA produces good therapeutic effect with tolerable toxicity profile for treatment of recurrent epithelial ovarian cancer.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cystadenoma, Mucinous ; drug therapy ; Cystadenoma, Serous ; drug therapy ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; drug therapy ; Organoplatinum Compounds ; administration & dosage ; Ovarian Neoplasms ; drug therapy ; Taxoids ; administration & dosage

OBJECTIVETo evaluate the efficacy and adverse effects of irinotecan combined with cisplatin in the treatment of advanced non-small cell lung cancer (NSCLC).

METHODSFifteen patients (10 males and 5 females) aged from 32 to 58 years (median age of 47 years) with KPS>70 and the diagnosis of advanced NSCLC by pathology or cytology were treated with cisplatin 80 mg/m(2) plus irinotecan 60 mg/m(2) by intravenous infusion on 1, 8, 15 days, and the treatment was repeated every 4 weeks. After treatment for at least 2 cycles, the therapeutic effects and adverse drug reactions were evaluated.

RESULTSOf all the cases, PR was achieved in 4 (26.7%), SD in 9 (60%), and PD in 2 (13.3%), with an overall response rate of 26.7%. The median survival time was 11 months and 1-year survival rate was 46.7% (7/15). The main toxicities were delayed diarrhea and granulocytopenia.

CONCLUSIONIrinotecan plus cisplatin is an effective and tolerable treatment for advanced NSCLC with low incidence of adverse effects.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cisplatin ; administration & dosage ; adverse effects ; Female ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged

Objective:To study the relationship between fasting glucose (FPG) and gene polymorphisms of adiponectin (ADIPOQ), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in early pregnancy and insulin resistance in patients with gestational diabetes mellitus (GDM).Methods:Sixty patients diagnosed with GDM within 24 -28 weeks from January 2022 to August 2022 in the Affiliated Hospital of Jining Medical University were selected as the GDM group, and another 60 healthy pregnant women were taken as the normal control group. The fasting insulin (FINS), FPG levels and the homeostatic model assessment insulin resistance index (HOMA-IR) and other clinical data were detected at 8 -12 weeks of pregnancy. Meanwhile, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the polymorphisms of ADIPOQ gene at S0100622 locus, IL-6 gene at S01006318 locus, TNF- α gene at S01009718. Receiver operating characteristics(ROC) curve was used to evaluate the diagnostic performance of FPG combined with polymorphisms of ADIPOQ, IL6 and TNF-α in predicting GDM in early pregnancy.Results:The body mass index (BMI), early pregnancy FPG, mid pregnancy FPG, 75 g oral glucose tolerance test (OGTT) 1 h blood glucose, OGTT 2 h blood glucose, glycosylated hemoglobin (HbA 1c), FINS and HOMA-IR in the GDM group were higher than those in the normal control group: (27.1 ± 2.6) kg/m 2 vs. (25.6 ± 2.5) kg/m 2, (4.7 ± 1.3) mmol/L vs. (4.1 ± 1.5) mmol/L, (5.5 ± 1.3) mmol/L vs. (4.2 ± 1.2) mmol/L, (6.3 ± 1.5) mmol/L vs. (5.5 ± 1.7) mmol/L, (6.0 ± 1.5) mmol/L vs. (5.2 ± 1.4) mmol/L, (5.8 ± 0.7)% vs. (5.2 ± 0.6)%, (6.4 ± 1.1) mU/L vs. (5.2 ± 1.2) mU/L, 1.5 ± 0.6 vs. 1.0 ± 0.7, there were statistical differences ( P<0.05). According to the risk assessment of genotype, the high-risk rate in the GDM group was 88.33% (53/60), while the normal control group was 56.67% (34/60), there was statistical difference ( χ2 = 17.67, P<0.05). In GDM group, the HOMA-IR with ADIPOQ gene S0100622 locus TG genotype was higher than that with TT genotype: 6.58 ± 0.89 vs. 4.98 ± 0.58; the HOMA-IR with IL-6 gene S01006318 locus CG genotype was higher than CC and GG genotype: 8.13 ± 1.31 vs. 6.53 ± 0.81, 4.85 ± 0.54, the HOMA-IR with TNF-αgene S01009718 locus AG genotype was higher than GG genotype: 6.31 ± 1.04 vs. 5.16 ± 0.82, there were statistical differences ( P<0.05). Logistic regression analysis showed that age>35 years, previous diabetes history, BMI, TG genotype at S0100622 locus of ADIPOQ gene, CG genotype at S01006318 locus of IL-6 gene, AG genotype at S01009718 locus TNF- α gene were risk factors for the onset of GDM ( P<0.05). The results of ROC curve analysis showed that the area under the curve (AUC) of FPG for predicting GDM onset was 0.737, with a specificity of 83.50%; FPG combined with ADIPOQ, IL-6, TNF- α genetic risk assessment predicted with AUC of 0.921 and a specificity of 86.80%. Conclusions:ADIPOQ gene TG genotype at S0100622 locus, IL-6 gene CG genotype at S01006318 locus, TNF- α gene AG genotype at the S01009718 locus has a certain correlation with the onset of GDM, which can predict the onset of GDM and is associated with perioperative insulin resistance in patients. Early FPG testing combined with genetic screening has practical clinical guiding significance in reducing adverse pregnancy outcomes for mothers and infants.

Objective A stable model of acute obstructive suppurative cholangitis was established in rats to detect pathophysiological indexes and provide a reliable standardized animal model for the study of acute cholangitis and cholestasis.Methods SPF-grade male SD rats were selected,and the model was constructed via the injection of toxoid into the lower bile duct,followed by ligation of the common bile duct.Changes in body weight,mortality,major indexes of liver function,and histopathological changes in the liver were evaluated before and after modeling.Results After modeling,the body weight of rats in the model group decreased significantly.There were no deaths and no abnormalities of liver function in the sham-operation group.Three rats died in the model group,and the mortality rate of the model group was 12％.The main indexes of liver function and liver pathology showed obvious cholestasis and injurious changes to hepatic function in the model.Conclusions In this study,an acute obstructive suppurative cholangitis model rat was successfully established.The model has the advantages of ease of operation,minimal injury,low mortality,and a highly successful modeling rate,and it can provide a standardized experimental animal model for studying the mechanisms of and developing drugs for these common diseases.

BACKGROUNDMicroRNAs (miRNAs) are highly conserved small non-coding RNAs of 18 - 25 nucleotides (nt) that mediate post-transcriptional gene regulation. Hepatitis B virus (HBV) can cause either acute or chronic hepatitis B, and is a high risk factor for liver cirrhosis and hepatocellular carcinoma. Some mammalian viruses have been shown to modulate the expression of host cellular miRNAs. However, interactions between the HBV and the host cellular miRNAs are largely unknown.

METHODSmiRNA microarray and Northern blotting analysis were used to compare the expression profile of cellular miRNAs of a stable HBV-expressing cell line HepG2.2.15 and its parent cell line HepG2. mRNA microarray assay and the miRanda program were used to predict the miRNA targets. A flow cytometric assay was further used to investigate the expression of human leukocyte antigen (HLA)-A.

RESULTSEighteen miRNAs were differentially expressed between the two cell lines. Among them, eleven were up-regulated and seven were down-regulated in HepG2.2.15 cells. Northern blotting analysis confirmed that the expression of miR-181a, miR-181b, miR-200b and miR-146a were up-regulated and the expression of miR-15a was down-regulated, which was in consistent with the results of the microarray analysis. Furthermore, some putative miRNA targets were predicted and verified to be linked with mRNA expression. The 3'-UTR of HLA-A gene had one partially complementary site for miR-181a and miR-181a might down-regulate the expression of HLA-A.

CONCLUSIONHBV replication modulates the expression of host cellular miRNAs, which may play a role in the pathogenesis of HBV-related liver diseases.

Blotting, Northern ; Cell Line, Tumor ; metabolism ; virology ; Flow Cytometry ; Gene Expression Profiling ; Gene Expression Regulation ; HLA-A Antigens ; metabolism ; Hepatitis B virus ; growth & development ; physiology ; Humans ; MicroRNAs ; genetics ; Oligonucleotide Array Sequence Analysis

Objective:To investigate the clinical features and influencing factors of early-onset gout.Methods:Male patients with gout admitted to Department of Endocrinology and Metabolism were recruited from 2015 to 2018. Patients with gout onset before age 30 were defined as the " early-onset" group, and those with onset at 30~60 years were defined as the "late-onset" group. Clinical characteristics were compared between two groups. Factors associated with early-onset gout were analyzed.Results:A total of 1 243 male patients were enrolled in this study; 480 individuals were in the early-onset, and 763 in the late-onset groups. Compared with the late-onset group, patients with early-onset gout had higher consumption rates of sugar-sweetened beverage(28.0% vs 15.0%, P=0.001), a higher homeostasis model assessment for insulin resistance level(3.78±2.93 vs 3.10±2.39, P<0.01), and larger proportions of family histories of diabetes(30.8% vs 20.4%, P<0.01)and hypertension(51.2% vs 42.6%, P=0.003). Logistic regression analysis showed that factors associated with early-onset gout were drinking sugar-sweetened beverage( P=0.012), family history of diabetes( P=0.037). Conclusion:Early-onset gout was associated with a family history of diabetes. Patients with family histories of diabetes are more likely to have early-onset gout, which may be associated with a common genetic basis.

Aim To determine the effect of cornel iri-doid glycoside ( CIG ) on human hepatocyte cell line (L-02) injured by D-galactosamine (GalN) and tumor necrosis factor-α( TNF-α) .Methods Firstly, CIG was extracted , separated and purified . Cell lesion model injured by D-GalN/TNF-αwas tested by MTT method.T-AOC, SOD, MDA and calcium ion concen-tration were taken as indicators to study the effects of CIG on L-02 cell injured by D-GalN/TNF-α.The ex-pression of p-PERK, p-eIF-2α, caspase-3 protein were detected by Western blot .Results 44 mg · L-1 D-GalN and 100 μg · L-1 TNF-αwere suitable for L-02 cell lesion model.CIG high, middle, low concentra-tion group could significantly increase the L-02 cell ac-tivity by 21％, 13％, 8％, respectively and SOD activity and T-AOC ability as well compared with model group.At the same time, they markedly reduced the MDA activity except the low concentration .Three con-centrations of CIG could reduce the expression of endo-plasmic reticulum stress related protein PERK , eIF-2αand apoptosis-associated protein caspase-3. Conclu-sions CIG could protect L-02 cells injured by D-GalN/TNF-α.Increasing the cellular antioxidant abili-ty, reducing the damage of endoplasmic reticulum stress and the expression of apoptosis-associated protein may be the possible mechanism .