Hypoxia-inducible factor-1 (HIF-1) is an inportant regulatory factor in adapting to hypoxia in the hypoxic environment for cells.The changes of the numbers of HIF-1 in cells may regulate hypoxia-responsive gene transcription.HIF-1 may inhibit neuronal apoptosis and thus play a ncuroptotective role,and may also show a neurotoxic effect by inducing neuronal apoptosis.

Objective To establish a drug resistant human hepatoma cell line (QGY/DDP) induced by cisplatin (DDP) in vitro, and to investigate its biological features and mechanisms of resistance. Methods The drug resistant cell line (QGY/DDP) of hepatoma was established by intermittent administration of stepwise increas of the dosage of DDP. Drug sensitivity was evaluated by MTT assay. Cell counting was employed to graph the growth curve and to calculate the doubling time. Flow cytometry (FCM) was used to study the cell cycle distribution. In addition, the intracellular platinum accumulation was detected by atomic absorption spectrometry, and the expressions of P-glycoprotein (P-gp) and glutathione S-transferase-? (GST-?) were analyzed by FCM. Results QGY/DDP cell line was established successfully after 3 months with stable resistance to DDP, and the resistance index (RI) was 10.81. The established cell line exhibited obvious cross-resistance to 5-FU, VCR, MMC, EPI and HCPT. Compared with parental cell line, the QGY/DDP cell line grew slower and its doubling time became longer. The proportion of G0/G1 phase cells of the resistant cells was significantly higher than that of their parental cells, whereas the proportion of S and G2/M phase cells was decreased. The cellular platinum accumulation was obviously decreased in the QGY/DDP cell line, and the expression of GST-? in QGY/DDP cells was higher than that of their parental cells, but no over expression of P-gp was found in the resistant cell line. Conclusions QGY/DDP cell line shows the typical and stable resistant phenotype and possesses the basic biological features of resistant cells. The resistance of the cell line to DDP may be due to the reduction of intracellular platinum accumulation and the over expression of GST-?, but may not be related to the expression of P-gp.

Objective To investigate whether paclitaxel can efficiently induce the apoptosis of ovarian cell HO-8910,and to study the relationship between the apoptosis of cells and the cell cycle.Methods With the treatment of paclitaxel with different concentrations and different time,the morphologic change of HO-8910 ovarian cells was observed using fluorescence microscopy and transmission electron microscopy(TEM),and the apoptosis of cells and the changes of cell cycle were determined by flow cytometry(FCM). Results The typical changes of HO-8910 cell apoptosis were observed by TEM and Fluorescence microscopy.With the treatment of paclitaxel,the HO-8910 ovarian cells were firstly arrested in G_2/M phase,and the typical ultrastructural changes of apoptosis were appeared only after the cells were apparently arrested in G_2/M phase.Conclusion Paclitaxel can induce the apoptosis of HO-8910 cells and the apoptosis is associated with the blockage of G_2/M phase in cell cycle.

Objctive To study the effects of traditional Chinese medicine S Kangdu mixture on functions of immune system and bone marrow in mice. Methods Animal model, which marrow and immune system were inhibited, was established by 60 Co or cyclophosphamide injection. The mixture was administrated orally. The white blood cell counts, spleen colony formed unites (CFU S), and the index of carbon clean up were measured. Results The mixture obviously improved leukopenia in peripheral induced by cyclophosphamide administration, and facilitated marrow karyocyte proliferation and formation of CFU S in 60 Co treated mice and reinforced phagocytosis of mononuclear phagocytic system in cyclophosphamide treated mice. Conclusion Traditional Chinese medicine S Kangdu mixture can significantly ameliorate immunological function and stimulate hemopoietic function in mice.

Objective To study the relationship between serum cystatin C(Cys C)level and the development of insulin resistance(IR)in elderly patients with type 2 diabetes mellitus (T2DM).Methods A cross-sectional survey research involving 757 elderly patients with T2DM was performed and patients were divided into groups according to Cys C and IR levels.Serum 1evels of fasting insulin (FBI),fasting blood glucose(FPG),fasting C-peptide (FCP),glycosylated hemoglobin A1 c (H bA1 c),homeostasis model assessment of insulin resistance (IR) (HOMA2 IR-C),homeostasis model assessment of insulin secretion,homeostasis model assessment of insulin sensitivity(HOMA2-％ S-C),micro-albuminuria(mALB)and serum lipid were measured and compared among the groups.Possible influence factors were adjusted,and the correlation between Cys C levels and IR was analyzed.The influencing factors on IR were also analyzed.Results There were statistically significant differences in ages,course of T2 DM,FBI,FCP,HbA1c,urinary mALB,IR,insulin secretion,insulin sensitivity,morbidity rate of coronary heart disease,hypertension and diabetic nephropathy among the three groups(allP＜0.05).Insulin sensitivity was decreased with the increase of Cys C level,while others were increased.Among 757 patients,the level of serum Cys C was positively correlated with FCP,HOMA2-IR C levels,and was negatively correlated with HOMA2-％ S-C levels(P＜0.05).Multiple logistic regression analysis showed that the higher level of Cys C was independent risk factors for IR in elderly T2DM patients(OR=3.41,95％CI:2.22-5.22,P＜0.05).Conclusions Serum Cys C level is closely related with IR in elderly T2DM,and the elevated level of serum Cys C is one of independent risk factors for elderly T2DM.

Objective: To explore the relationship between handgrip strength (HGS) and pulmonary function (PF) in college students with sedentary lifestyle, so as to provide a reference for taking HGS as an essential factor of PF. Methods: In March 1-5, 2023, a total of 44 college students were recruited and were divided into the sedentary group (22) and exercise group (22) according to the International Physical Activity Questionaire (IPAQ), with 22 students in each group. Independent sample t-test was used to compare the indexes between groups, pearson correlation coefficient was used to determine the correlation between HGS and PF. Multiple linear regression analysis was used to determine the predictive model of PF. Results: There were statistical significance of the correlations between HGS and FVC, MEP, PEF, FEV1, FIVC, MIP, and PIF ( r=0.79, 0.47, 0.44, 0.60, 0.72, 0.53 , 0.49, P <0.01). When gender, physical activity, age, height, weight, and HGS were included as predictors in the regression model, height and HGS had significant effects on FVC ( R 2=0.75, F= 60.55 , P <0.01), weight and HGS had a good predictive effect on FIVC ( R 2=0.67, F=41.77, P <0.01). Conclusion HGS is significantly associated with PF in college students with sedentary lifestyle. Therefore, HGS can be used as an important indicator to predict the PF status of habitual sedentary college students.

OBJECTIVE: To explore the genetic etiology of a child with Hypomagnesemia, epilepsy and mental retardation syndrome (HSMR). METHODS: A child who was admitted to the Children's Hospital of Shandong University on July 9, 2021 due to repeated convulsions for 2 months was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his pedigree members were collected for the extraction of genomic DNA. Whole exome sequencing was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 1-year-and-7-month-old male, had presented with epilepsy and global developmental delay. Serological testing revealed that he has low serum magnesium. Genetic testing showed that the child has harbored a heterozygous c.1448delT (p.Val483GlyfsTer29) variant of the CNNM2 gene, which was de novo in origin. The variant has caused substitution of the Valine at position 483 by Glycine and formation of a termination codon after 29 amino acids at downstream. As predicted by Swiss-Model online software, the variant may alter the protein structure, resulting in a truncation. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1448delT (p.Val483GlyfsTer29) was predicted as a pathogenic variant (PVS1+PS2+PM2_Supporting+PP4). CONCLUSION The heterozygous c.1448delT variant of the CNNM2 gene probably underlay the HSMR in this child. Above finding has enriched the phenotype-genotype spectrum of the CNNM2 gene.
Humans ; Male ; Cation Transport Proteins ; Computational Biology ; Ethnicity ; Intellectual Disability/genetics* ; Magnesium ; Mutation ; Seizures/genetics* ; Infant

Objective To investigate the influence and significance of methylprednisolone(MP) on the genetic expression and distribution of peripheral blood mononuclear cells (PBMCs) IL-23 and IL-17 as well as Th17 and Treg in patients with ankylosing spondylitis (AS). Methods 30 patients in the active period of ASwere selected as study group and treated with short-term and high-dose MP. The treatment regimen was 2. 5-4 mg/kg, Qd, 3-4 d/course, 3-4 d interval and 2-3 courses. 30 healthy persons were selected as control group and given isometric normal saline by the same administration time and method. RT-PCRtest was used to assess the expression of PBMCs IL-23 P19 mRNAand IL17AmRNA, and FCMwas used to assess the cell distributions of PBMCs Th17 and Treg in control group and study group before and after treatment. Associations of them with clinical symptoms and indicators of disease activity were analyzed. Results 1. Cell distribution of Th17 and genetic expression of IL-23 and IL-17 in study group were higher than those in control group, and positively associated with BASDAI, hypnalgia, erythrocyte sedimentation rate(ESR) and CRP. Cell distribution of Treg in study group was lower than that in control group, and negatively associated with indicators mentioned above. 2. In study group, cell distribution of Th17, genetic expression of IL-23 and genetic expression of IL-17 were positively associated with each other, and the genetic expression of IL-23 and the cell distribution of Th17 were negatively associated with the cell distribution of Treg respectively. 3. In study group, BASDAI, BASFI, hypnalgia, ESRand CRPafter treatment were lower than those before treatment while cell distribution of Treg after treatment was higher than that before treatment. All the differences above were statistically significant. Conclusion The axis of IL-23/IL-17 and the unbalance of Th17/Treg could be involved in the attack and disease activity of AS. MPcould improve the clinical symptoms of ASand reduce the disease activity by inhibiting the secretion of proinflammatory factors IL-23 and IL-17, and correcting the unbalance of Th17/Treg.

OBJECTIVES: Insulin signaling pathway plays an important role in metabolic associated fatty liver disease (MAFLD), however, the association between polymorphisms of genes related to insulin signaling pathway and MAFLD remains unclear. This study aims to investigate the association between insulin signaling pathway-related gene polymorphisms and gene-gene interactions with MAFLD susceptibility in obese children so as to provide scientific basis for further study of genetic mechanism. METHODS: A total of 502 obese children with MAFLD who admitted to Hunan Provincial Children's Hospital from September 2019 to October 2021, were recruited as a case group, and 421 obese children with non-MAFLD admitted during the same period were recruited as a control group. Socio-demographic information, preterm birth history, eating habits, and exercise status of the subjects were collected by inquiry survey, and anthropometric information was collected by physical measurement. At the same time, 2 mL of venous blood was collected to extract DNA, and the polymorphism of insulin signaling pathway-related genes (5 representative candidate genes, 12 variants) was detected. Multivariate Logistic regression analysis was used to investigate the association between insulin signaling pathway-related gene polymorphisms and MAFLD in obese children. RESULTS: After adjusting for confounder factors, INS rs3842748 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 1.749 (1.053 to 2.905), 1.909 (1.115 to 3.267), 1.862 (1.098 to 3.157), all P<0.05]; INS rs3842752 was significantly associated with the risk of MAFLD in obese children in heterozygous and dominant models [OR and 95% CI 1.736 (1.028 to 2.932), 1.700 (1.015 to 2.846), all P<0.05]. NR1H3 rs3758674 was significantly correlated with the risk of MAFLD in obese children in allele model [OR and 95% CI 0.716 (0.514 to 0.997), P<0.05]. SREBP-1c rs2297508 was significantly associated with the risk of MAFLD in obese children in allele and dominant models [OR and 95% CI 0.772 (0.602 to 0.991) and 0.743 (0.557 to 0.991), all P<0.05]. SREBP-1c rs8066560 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 0.759 (0.589 to 0.980), 0.733 (0.541 to 0.992), 0.727 (0.543 to 0.974), all P<0.05]. NR1H3 rs3758674 mutant C and SREBP-1c rs2297508 mutant G had interaction in the development of MAFLD in obese children [OR and 95% CI 0.407 (0.173 to 0.954), P<0.05]. CONCLUSIONS The INS, NR1H3, and SREBP-1c gene polymorphisms in the insulin signaling pathway are associated with the susceptibility of MAFLD in obese children, but the functions and mechanisms of these genes need to be further studied.
Child ; Infant, Newborn ; Humans ; Female ; Pediatric Obesity/genetics* ; Sterol Regulatory Element Binding Protein 1 ; Premature Birth ; Non-alcoholic Fatty Liver Disease ; Signal Transduction/genetics* ; Insulins