Objective　To evaluate the efficiency of low molecular weight heparin(LMWH, fraxiparine) given as a single predialysis bolus injection with reused dialyzers in comparison with standard heparin(SH) administered with a continuous infusion. Methods　30 hemodialysis patients were studied in a radomized crossover fashion. Dialyzers fibrer bundle volumes(FBV), predialysis hemocrit and 2 h clearance of urea, creatinine were observed in the first, the fourth dialysis. The plasma heparin activities(anti-Fxa levels) were measured by the chromogenic substrate assay in 0 h, 2 h, 4 h of dialysis. Results　Significant increase (P<0.05) was seen in the number of dialyzer reuse in LMWH group compared with SH group; there was not significant decrease in dialysis FBV as well as 2 h clearance of urea, creatinine (P>0.05); in addition, the plasma heparin activity(anti-Fxa levels) were comparable in both groups after 2 h of dialysis, however, they were significantly higher after 4 h in the LMWH than those in the SH group (P<0.05). Conclusion　LMWH as a single bolus dose can prevent decrease in dialyzer clearance. It is clinically worthy of further popularity.

Aim To explore the role of endoplasmic reticulum stress(ERS) in Astragaloside Ⅳ-induced cardioprotection in H9c2 cardiac cells, and to explore the potential mitochondrial mechanism.Methods Conventional culture was performed of rat heart tissue-derived H9c2 cells.Experiment was randomly divided into the control group, the ERS inducer 2-Deoxy-D-Glucose(2-DG) group, Astragaloside Ⅳ and 2-DG combination group, Astragaloside Ⅳ group.Confocal microscopy was used to observe the changes of TMRE fluorescence intensity so as to confirm the influence of ERS on the mitochondrial potential, and further speculate on the opening of the mitochondrial permeability transition pore(mPTP).Western blot analysis was applied to detect the expressions of ERS proteins GRP 78, GRP 94 and IRE1.Transmission electron microscopy was used to observe the ultrastructure of the cells.Results Different doses of 2-DG could mimic the mPTP opener atractyloside to induce the mPTP opening with the peak at 100 μmol·L-1;Astragaloside Ⅳ significantly reduced 2-DG-induced mPTP opening, the expression of GPR 78, GRP 94 and IRE1 and reduced injury of mitochondria and endoplasmic reticulum.Conclusions Endoplasmic reticulum stress could be induced by 2-DG.Astragaloside ⅳ-induced mitochondrial cardioprotection involves inhibition of the ERS through GRP 78, GRP 94 and IRE1 by prevention of the mPTP opening.

Objective To investigate the association of tumor necrosis factor-alpha (TNF-α) gene promoter region - 1031T/C and its combination with interleukin-6 (IL-6 ) gene promoter region -634C/G single nucleotide polymorphisms (SNP) with the genetic susceptibility to endometriosis.Methods Total of 432 endometriosis patients and 499 non-endometriosis women who had received an operation due to tubal ligation,tubal recanalization,laparoscopic hydrotubation,ovarian simple cyst and teratoma were collected and separated into endometriosis group and control group,that all cases were confirmed by operation and pathology.A case-control study was performed in endometriosis and control group to evaluate the association of these SNP with the susceptibility to endometriosis by using a fluorescent quantitative PCR-based high resolution melting ( HRM ) method.Results ( 1 ) TNF-α - 1031T/C genotype:the T and C of TNF-α - 1031T/C allele frequencies in the endometriosis group and control group were 79.2％ (684/864),20.8％ (180/864) and 81.8％ (816/998),18.2％ (182/998),respectively.The TT,TC and CC of TNF-α - 1031T/C genotype frequencies in the two groups were 63.7％ (275/432),31.0％ ( 134/432 ),5.3％ (23/432) and 66.5％ (332/499),30.5％ (152/499),3.0％ ( 15/499),respectively.There were no statistical significances in the TNF-α - 1031T/C alleles and genotypes distributions between the two groups ( P =0.158,P =0.186 ).( 2 ) TNF-α - 1031T/C and IL-6 - 634C/G conjoint genotypes:to research on the TNF-α - 1031T/C and IL-6 -634C/G genotypes for conjoint analysis,the TT + CC,TC + CC,CC +CC,TT + CG,TC + CG,CC + CG,TT + GG,TC + GG and CC + GG combination genotype frequencies in the two groups were 39.4％ ( 170/432 ),19.4％ ( 84/432 ),4.6％ ( 20/432 ),20.6％ ( 89/432 ),8.8％ (38/432),0.9％ (4/432),3.5％ (15/432),2.3％ (10/432),0.5％ (2/432) and 36.7％ ( 183/499),17.4％(87/499),1.4％ (7/499),26.1％ (130/499),10.4％ (52/499),1.2％ (6/499),3.8％ (19/499),2.6％ ( 13/499),0.4％ (2/499),respectively.There were no statistical significances in the combination genotypes distributions between the two groups ( P =0.107 ).As compared with carriers of TT + CC combination genotype,the endometriosis risk of carriers of CC + CC combination genotype enhanced 3.076 times ( 95％ CI:1.268 - 7.457,P =0.009 ),and the endometriosis risk of carriers of other combination genotypes were no statistical significances (all P ＞ 0.05 ).ConclusionsThe study demonstrates that there are no significant association between the SNP of TNF-α - 1031T/C and genetic susceptibility to endometriosis.However the results indicate that there are significant association betweengenetic susceptibility to endometriosis and the combination polymorphisms of TNF-α -1031T/C and IL-6- 634C/G.

OBJECTIVE: To explore the changes of mTOR signal pathway in HeLa cells under different nutritional conditions infected with Coxsackie virus B3 (CVB3). METHODS: The HeLa cells were cultured with two methods: the conventional culture method cultured HeLa cells with medium with 10% fetal bovine serum for 24 h and changed the medium next day, and then infected with CVB3; the serum starvation method cultured HeLa cells with medium without fetal bovine serum for 24 h, and then infected with CVB3. The expression of the coat protein of CVB3, mTOR, p70S6K mRNA was detected with RT-PCR at different time points. RESULTS: The virus group showed the expressions of mTOR and p70S6K mRNA were significantly higher than those in the control group at 12 h and 24 h (P<0.05) in the conventional culture. The virus group showed the expressions of mTOR and p70S6K mRNA were lower than those in the control group (all P<0.05) in the starvation serum. The expression of mTOR mRNA in the starvation serum virus group was higher than that in the conventional culture virus group (all P<0.05) and the control group. The expression of p70S6K mRNA was not significantly different in the two groups (P>0.05). CONCLUSION CVB3 can down-regulate the expressions of mTOR and p70S6K mRNA. The mTOR expression in the starvation serum is higher than that in the conventional culture.
Cell Culture Techniques ; Down-Regulation ; Enterovirus B, Human ; pathogenicity ; HeLa Cells ; Humans ; RNA, Messenger ; genetics ; metabolism ; Signal Transduction ; physiology ; TOR Serine-Threonine Kinases ; genetics ; metabolism

Objective To investigate the iodine nutritional and thyroid stimulating hormone level of patients with thyroid nodules in different regions of Qinghai Province and analyze the characteristics of changes in different regions.Methods In 2014-2016,thyroid nodules in 9 regions of Qinghai Province (Tibetan areas:Xiewu,Nangqian,Jiegu,Guoluo;non-Tibetan areas:Xining,Huzhu,Menyuan,Minhe,and Ledu) were selected and serum thyroid stimulating hormone (TSH) and urine iodine were measured.Results A total of 553 thyroid nodules,the median urinary iodine (MUIC) was 160.8 μg/L and the median TSH was 2.97 mU/L.The iodine nutritional status was at an appropriate level.Among them,MUIC (206.8 μg/L) in thyroid nodules in the Menyuan area was slightly higher than the appropriate amount,there was a significant difference in MUIC among different region (x2 =47.747,P ＜ 0.05);of TSH in thyroid nudules in the 9 regions,the differences were statistically significant (x2 =34.832,P ＜ 0.05).Non-Tibetan areas were compared with Tibetan areas,there was a significant difference in MUIC (155.6,185.6 μg/L),TSH (2.68,3.45 mU/L,Z =-3.677,-5.410,P ＜ 0.05);Among them,the differences was statistically significant between MUIC (152.8,187.7 μg/L) of women with thyroid nodules (Z =-3.504,P ＜ 0.05);there was a statistically significant difference in TSH levels among men (2.58,3.46 mU/L) and women (2.80,3.44 mU/L) with thyroid nodules (Z =-3.613,-4.040,P ＜ 0.05);there were no significant differences in MUIC levels among thyroid nodules of each age groups (P ＞ 0.05);of the TSH level in 30-and 50-＜ 65 years groups (2.63,3.17;2.25,3.58 mU/L),the differences were statistically significant (Z =-2.892,-3.233,P ＜ 0.05),and other groups were no significant differences (P ＞ 0.05).Conclusion The iodine nutrition of patients with thyroid nodules in these regions of Qinghai Province is generally at an appropriate level,the MUIC and TSH levels in Tibetan areas were lower than those in non-Tibetan areas,and iodine nutrition status and TSH levels should be monitored for key populations.

Objective To investigate the effects of MCSO on physiological behavior and antioxidant index in D.melanogaster.Methods One-day-old wild type D.melanogaster was divided into control group,0.25％,0.5％,1％,2％and 4％dose groups,as well as male and female groups.The control group was exposed to the base medium,and each dose group was exposed to the MCSO medium added with 0.25％,0.5％,1％,2％and 4％concentrations,respectively.The optimal dosage concentration and time of administration were investigated by climbing experiment.Then the flies were divided into control group,model group and MCSO group.The model group was established by depriving the flies of sleep through repeated nocturnal light stimulation.Period of drug treatment,appetite test,negative geotaxis ability test,stress test,olfactory memory test,and sleep-wake rhythm detection were used to explore the effects of MCSO on their physiological behavior.The activities of super oxidase dismutase(SOD),catalase(CAT),and malondialdehyde(MDA)were detected by enzyme-linked immunosorbent assay.Results MCSO enhanced the locomotory ability of 30-day-old D.melanogaster(P＜0.01),increased the activity of SOD and CAT(P＜0.01),and decreased the concentration of MDA(P＜0.01).Improve olfactory memory of senile fruit flies.After sleep deprivation,the night sleep time of female Drosophila model group was reduced(P＜0.05),and that of male Drosophila model group was reduced(P＜0.01).After feeding MCSO,the night sleep time of female drosophila model group was extended(P＜0.05),and that of male drosophila model group was extended(P＜0.01).Conclusions MCSO had a certain antioxidant effect,prolonging the sleep time and improving the olfactory memory of sleep-deprived Drosophila.

Objective To investigate the epidemiological status of toxic diffuse goiter hyperthyroidism (abbreviated as hyperthyroidism) in Xining area and analyze its influencing factors. Methods Patients with toxic diffuse goiter and hyperthyroidism who were hospitalized in Class ⅲ Grade A hospitals in Xining from January 2020 to January 2023 were collected as the experimental group by random cluster sampling method. During the same period, 500 healthy people in each hospital were selected as the control group. The general data of the patients were collected and the levels of thyroid function indexes of the two groups were detected. Multivariate logistic regression was used to analyze the influencing factors of diffuse goiter with hyperthyroidism. Results A total of 718 questionnaires were collected in this study, and 705 questionnaires were collected after excluding invalid questionnaires. There were 234 males and 471 females in 705 patients with diffuse goiter and hyperthyroidism. The most common age was 41-50 years, followed by 51-60 years and 31-40 years. The serum TSH level of the experimental group was lower than that of the control group, and the levels of FT3 and FT4 were higher than those of the control group ( P < 0.05 ) . There was no significant difference in family history, thyroid texture and thyroid imaging between the two groups ( P > 0.05 ). There were significant differences in exophthalmos and thyroid weight between the two groups (P<0.05). Multivariate Logistic regression analysis showed that exophthalmos, thyroid weight ≥30g , TSH , FT3 and FT4 were independent risk factors for the experimental group ( P < 0.05) . Conclusion Gender, age, exophthalmos, thyroid weight and thyroid related hormone levels are the influencing factors of diffuse goiter and hyperthyroidism in Xining area . Thyroid function should be monitored for early prevention and treatment of the disease.

Insomnia has become a common central nervous system disease. At present, the pathogenesis of insomnia is not clear. Animal models can help us understand the pathogenesis of the disease and can be used in transformational medicine. Therefore, it is very necessary to establish an appropriate model of insomnia. Clinical data show that insomnia patients with high levels of thyroxine and often accompanied by cardiovascular problems, a common mechanism underlying all of these physiological disruptions is the sympathetic nervous system. Combined with the characteristics of chronic onset of clinical insomnia, an insomnia model induced by long-term intraperitoneal injection of thyroid hormone has been created in our laboratory. In this paper, the insomnia-like state of the model was evaluated based on three validity criteria. Face validity has been demonstrated in metabolism, the Morris water maze, electrocardiogram (ECG) and electroencephalogram (EEG). Structure validity has been proved by the results of targeted metabolomics. After treatment with diazepam, a commonly used clinical anti-insomnia drug, the above physiological and pathological disorders were reversed. The results of comprehensive analysis show that the established thyrotoxicosis-associated insomnia model meets the validity requirement to establish an appropriate animal model of insomnia. The model presented in this article might help to study pathogenetic mechanisms of clinical insomnia, as well as to test promising methods of insomnia treatment.

Objective: To investigate the clinical features of children with infectious mononucleosis (IM), to compare the difference of therapeutic effects between general treatment to antiviral therapy for IM. Methods: This prospective study analyzed the clinical data and laboratory test results of 201 cases with IM in our hospital from January 1, 2016 to December 31, 2016. The follow-up period was 6-12 months. The patients were divided into two groups according to the order of admission. The clinical symptoms and laboratory test results of the two groups were observed after hospitalization. Results: Of the total of 201 patients, male to female is 1.72∶1; Age: 8 months to 13 years 6 months (average 4.8±2.8 years), The disease frequently occurred in summer and autumn, accounted for 64.18%.The major clinical manifestations was fever (97.51%), angina (79.10%), enlarged of lymph node(68.66%), eyelid swelling (67.16%), hepatomegaly (53.73%) and splenomegaly (46.77%). There was no statistical difference in duration of fever, improved angina time, lymph nodes(liver, spleen) enlargement recovery time, heterotypic lymphocytes normalization time, lymphocyte function normalization time.There was significant difference in reducing the serum/plasma or total blood EBV-DNA in the short term between antiviral group and general treatment group (P<0.01), but for the long-term reduction of EBV-DNA, there was no significant difference (P>0.05). The low affinity EBV-CA-IgG was converted to high affinity EBV-CA-IgG in 89.41% of patients after 3 months and in 98.68% of patients after 6 months. With the recovery of the disease, the positive rate of EBV-CA-IgM and EBV-EA-IgG decreased. But the positive rate of EBV-NA-IgG increased. Serum/plasma EBV-DNA was completely overcast after 3 months, but after 12 months, the patient’s total blood EBV-DNA positive rate was still 71.11%. Conclusions In general IM patients, there was no significant difference between antiviral therapy and general treatment, so antiviral therapy is not generally recommended. EBV DNA in the whole blood of patients with IM will continue to be positive more than 6-12 months, indicating that to observe changes of IM should not use whole blood samples for EBV DNA testing.

ObjectiveTo explore the compatibility advantage of Scutellariae Radix-Coptidis Rhizoma in the prevention and treatment of neuroinflammation， and to elucidate the action characteristics and mechanism of the compatibility advantage based on Toll like receptor （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappaB （NF-κB） pathway. MethodRepresentative mouse microglia cells （BV2） in vitro were selected and divided into 8 groups： control group， model group， Scutellariae Radix-Coptidis Rhizoma group， Piracetam group， Scutellariae Radix group and Coptidis Rhizoma group. The BV2 cell inflammatory model was established by lipopolysaccharide （LPS）， and the cell activity was detected by cell counting kit-8 （CCK-8）. Cell morphology was observed under bright field. The production and release of pro-inflammatory factors in BV2 cells were determined by enzyme-linked immunosorbent assay （ELISA） and immunofluorescence assay， and the mRNA expressions of TLR4， MyD88 and NF-κB were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The nuclear translocation of NF-κB p65 was detected by immunofluorescence， and TLR4 signal transduction inhibitor （CLI-095） and NF-κB inhibitor （PDTC） were used to confirm the anti-neuroinflammation targets of Scutellariae Radix-Coptidis Rhizoma. ResultCompared with the conditions in the control group， most cells in LPS-induced model group were activated， and the contents of IL-6， TNF-α and IL-1β in culture medium and cells and the mRNA expressions of TLR4， MyD88， NF-κB p50 and NF-κB p65 were increased （P<0.01）， with obvious nuclear entry of NF-κB p65. Compared with the conditions in the model group， BV2 cell morphology was mostly recovered after pretreatment in Scutellariae Radix-Coptidis Rhizoma and Piracetam groups， and the levels of IL-6， TNF-α and IL-1β and the mRNA expressions of TLR4， MyD88， NF-κB p50 and NF-κB p65 were decreased （P<0.05， P<0.01）， with NF-κB p65 mostly observed in cytoplasm. Compared with the conditions in the model group， cell morphology was slightly recovered in Scutellariae Radix group and Coptidis Rhizoma group， and the levels of pro-inflammatory factors and mRNA expressions of TLR4， MyD88， NF-κB p50 and NF-κB p65 were reduced. In terms of inhibitory effect on pro-inflammatory factors， Scutellariae Radix group and Coptidis Rhizoma group were lower than Scutellariae Radix-Coptidis Rhizoma group （P<0.05）. Compared with the model group， the "Scutellariae Radix-Coptidis Rhizoma+CLI-095" group and "Scutellariae Radix-Coptidis Rhizoma+PDTC" group had lowered mRNA expressions of TLR4， MyD88， NF-κB p50 and NF-κB p65 （P<0.05， P<0.01）， and the transfer of NF-κB p65 into nucleus was obviously inhibited. ConclusionThe anti-neuroinflammation effect of Scutellariae Radix-Coptidis Rhizoma was significantly better than Scutellariae Radix or Coptidis Rhizom alone， and the anti-neuroinflammation advantage was closely related to the inhibition of activation of TLR4/MyD88/NF-κB signaling pathway in microglial cells. It was confirmed that TLR4， MyD88 and NF-κB were potential targets for Scutellariae Radix-Coptidis Rhizoma to exert the compatibility advantage.