Objective:Continuous glucose monitoring (CGM) technology is used to compare the advantages of insulin degludec (IDeg) as a basal insulin regimen compared with insulin glargine (IGlar) in the treatment of adult type 1 diabetes mellitus.Methods:30 adult patients with T1DM admitted to Heji Hospital Affiliated to Changzhi Medical College from September 2019 to December 2020 were screened. According to the random number table method, the patients were randomly divided into two groups (insulin degludec group and insulin glargine group) at a ratio of 1∶1, respectively treated with IDeg, IGlar and aspartate insulin for 12 weeks. The main outcome measures were the coefficient of variation of blood glucose (CV), mean amplitude of glycemic excursions (MAGE), time in range (TIR), time above range (TAR) and time below range (TBR). The secondary outcome measures were mean blood glucose (MBG), standard deviation of blood glucose (SD), fasting blood glucose (FPG), 2 h postprandial blood glucose (2 h BG), hemoglobin A1c (HbA 1c), means of daily differences (MOOD), and the frequency of hypoglycemic events. Results:At 12 weeks of treatment, the HbA 1c, FPG, 2 h BG, MBG, SD, CV and MAGE of insulin degludec group were lower than those of insulin glargine group, with statistically significant difference (all P<0.05). The TIR in the insulin degludec group was significantly higher than that in the insulin glargine group [73(63, 75)% vs 43(28, 63)%, P<0.001], and the TAR was lower than that in the glycerine group [25(17, 23)% vs 35(33, 64)%, P=0.003]. From the curve spectrum of blood glucose level of the two groups, the stability of blood glucose in the insulin degludec group was better than that in the insulin glargine group. After 12 weeks of treatment, 8 cases (8/15) in insulin degludec group had HbA 1c<7.0%, and 4 cases (4/15) in insulin glargine group had HbA 1c<7.0%, without statistically significant difference ( P=0.264). There were 7 cases (7/15) in the insulin degludec group and 1 case (1/15) in the insulin glargine group who achieved high quality blood glucose control, with statistically significant difference ( P=0.035). At the 12th week of outpatient follow-up, the incidence of nocturnal hypoglycemic events in insulin degludec group was significantly lower than that in insulin glargine group (4/15 vs 11/15, P=0.027). Conclusions:Compared with insulin glargine, insulin degludec can achieve higher blood glucose compliance rate, lower blood glucose level and reduce blood glucose fluctuations in patients with type 1 diabetes.

Objective:To summarize the clinical features of developmental epileptic encephalopathy children with DNM1 gene variants. Methods:The genotypes and clinical features of 15 children with DNM1 variants related epilepsy in the Department of Pediatrics, Peking University First Hospital from June 2017 to October 2021 were retrospectively analyzed. Results:A total of 8 male and 7 female epilepsy patients with DNM1 gene variants with the age of seizure onset ranging from 15 days to 22 months were recruited, median age was 8 months.All cases belonged to de novo heterozygous variants of the DNM1 gene, including 13 cases of missense variants, 1 case of frame shift variant and 1 case of nonsense variant, 8 cases of ectopic sites have not been reported.Multiple seizure types were observed, including epileptic spasms in 15 patients, focal seizure in 9 patients, atypical absence seizure in 2 patients and tonic seizure in 2 patients.There were various types of seizures in 7 children.Nine cases occurred as infantile spasm for the first time.All 15 patients showed varied degrees of development delay, among them, 11 cases had developmental retardation before epilepsy.Three patients had slow rhythm of electroencephalogram background activity, the electroencephalography showed hypsarrhythmia in 13 patients; clinical seizures were detected in 8 cases, among them, epileptic spasms were captured in 7 patients, tonic seizure was captured in 1 patient.Widened frontotemporal subarachnoid space, cerebral atrophy, and corpus callosum dysplasia were examined in 6, 2 and 3 patients by cranial magnetic resonance imaging, respectively.All 15 cases were diagnosed as developmental epileptic encephalopathy, of which 13 cases were consistent with infantile spasms.The age of the last follow-up ranged from 1 year old to 7 years old.After multi-antiepileptic drug treatment, 2 patients were remission, 1 patient(small size of identical twins) died of severe pneumonia at the age of 2 years, and 12 patients still had intermittent seizures, of which 1 patient was transformed from infantile spasms to Lennox-Gastaut syndrome. Conclusions:The onset age of developmental epileptic encephalopathy caused by the DNM1 gene variant usually begins in the infantile period, the peak onset age was 8 months.The main types of seizures include epileptic spasms and focal seizures, developmental retardation can occur before seizures.The clinical manifestations are mostly infantile spasms syndrome, and some children can be transformed into Lennox-Gastaut syndrome.

Objective:To summarize the clinical characteristics and the features of electroencephalograph (EEG) of children with DEPDC5 gene variants related epilepsy.Methods:The clinical data, gene variation, EEG and head magnetic resonance image (MRI) of 20 epileptic children with DEPDC5 gene variants admitted to Department of Pediatrics, Peking University First Hospital from May 2017 to November 2020 were retrospectively analyzed.Results:Twenty patients with heterozygous DEPDC5 gene variants were enrolled, 8 of 20 patients were nonsense variants, 6 were missense variants, 3 were frame-shift variants, 2 were splicing variants, and 1 was large fragment deletion. Sixteen cases had hereditary variation and 4 had de novo variation. Fifteen of variations were novel. Nine were male, while 11 were female. Their latest follow-up age ranged from 10 months to 13 years and one month.The epilepsy onset age ranged from 3 hours to 11 years and 3 months, the median age was 10.5 months. Twelve (60%) patients had developmental delay. Nineteen patients had focal seizures, 7 had epileptic spasms, 1 had multiple seizure types including tonic, atypical absence, dystonic and myoclonic seizures. Epileptic form discharges were observed in 18 patients during the interictal phase, and 11 were focal discharges, 7 were multifocal discharges. Ten (50%) patients had abnormal brain MRI, including focal cortical dysplasia in 5 patients, undefined malformation of cortical development in 4 patients, hemimegalencephaly in 1 patient. Four patients were diagnosed as West syndrome and one patient was diagnosed as Lennox-Gastaut syndrome. Fourteen (70%) patients were diagnosed as drug-resistant epilepsy. Four patients became seizure-free by treatment with anti-epileptic drugs. Three children were treated with surgery, and 2 of them became seizure-free, 1 had more than 75% reduction in seizures.Conclusions:DEPDC5 gene variant epilepsy is inherited with incomplete penetrance and focal seizure is the major seizure type. However, epileptic spasms, generalized seizures can also be observed. Half of the patients brain malformations. Most of the patients are drug-resistant epilepsy. Patients with clear epileptogenic zones can be treated with surgery. Treatment-resistant patients are more likely to be complicated with developmental delay.

Objective:To investigate the relationship between YES-related protein 1(YAP1)and prostate-specific antigen(PSA)in human castration-resistant prostate cancer(CRPC), and explore the regulation mechanism of YAP1 on PSA.Methods:The luciferase reporter gene was used to detect the activity change of the PSA gene promoter region after the over expression of YAP1 in LNCaP and C4-2 cells.The effect of over expression of YAP1 gene on PSA protein in different prostate cancer cell lines was detected by Western blot(WB)method, and the effect of YAP1 silencing on PSA protein in C4-2 cells was observed.The Q-PCR method was used to further verify the expression change of PSA mRNA affected by YAP1 gene over expressed in C4-2 cells.Meanwhile, WB was used to explore the effect of YAP1 on androgen receptor(AR)in C4-2 cells.Results:After over expression YAP1 in CRPC, the luciferase experiment showed that the average C4-2 cell ratio of experimental group to control group was 3.17815892(>2 times, P<0.001). After Q-PCR detection of all over-expressed YAP1 gene fragments, the measured PSA mRNA values in the experimental groups were 2.306667, 1.553333333, 2.613333333, and 2.673333333, respectively, which were higher than those in the control group(1 time, P<0.001), indicating that the PSA expression was significantly increased.WB analysis showed that after C4-2 cells over expressed YAP1, the AR band was significantly enhanced in the experimental group compared with the control group, suggesting that the AR protein expression in the nucleus was significantly increased in the YAP1 over expression group. Conclusions:YAP1 might positively regulate the PSA expression in CRPC and have an ability to promote AR translocation into the nucleus.

PURPOSE: Breast cancer is the most frequently diagnosed malignancy in women worldwide. MicroRNAs (miRNAs) are thought to serve as potential biomarkers in various cancers, including breast cancer. METHODS: We evaluated the miRNA expression profiles in 1,083 breast cancer samples and 104 normal breast tissues from The Cancer Genome Atlas database. We used the edgeR package of R software to analyze the differentially expressed miRNAs in normal and cancer tissues, and screened survival-related miRNAs by Kaplan-Meier analysis. A receiver operating characteristic curve was generated to evaluate the accuracy of these miRNAs as molecular markers for breast cancer diagnosis. Furthermore, the functional role of these miRNAs was verified using cell experiments. Targets of candidate miRNAs were predicted using 9 online databases, and Gene Ontology (GO) functional annotation and pathway analyses were conducted using Database for Annotation, Visualization and Integrated Discovery online tool. RESULTS: A total of 68 miRNAs showed significantly different expression patterns between the groups (p < 0.001), and 13 of these miRNAs were significantly associated with poor survival (p < 0.05). Three miRNAs with high specificity and sensitivity, namely, miR-148b-3p, miR-190b, and miR-429, were selected. In vitro experiments showed that the overexpression of these 3 miRNAs significantly promoted the proliferation and migration of MDA-MB-468 and T47D cells and reduced the apoptosis of T47D cells. GO and pathway enrichment analyses revealed that the targets of these dysregulated miRNAs were involved in many critical cancer-related biological processes and pathways. CONCLUSION: The miR-148b-3p, miR-190b, and miR-429 may serve as potential diagnostic and prognostic markers for breast cancer. This study demonstrated the roles of these 3 miRNAs in the initiation and progression of breast cancer.
Apoptosis ; Biological Phenomena ; Biological Processes ; Biomarkers ; Breast Neoplasms ; Breast ; Diagnosis ; Female ; Gene Ontology ; Genome ; Humans ; In Vitro Techniques ; Kaplan-Meier Estimate ; MicroRNAs ; ROC Curve ; Sensitivity and Specificity

Objective To determine levels of nuclear factor (NF)-κB, interleukin (IL)-10, and visfatin in adipocytes treated by different degrees of intermittent hypoxia (IH), and to investigate the mechanism of IH leading to insulin resistance (IR). Methods The cell model of intermittent hypoxia/re-oxygenation (IH/ROX) in obstructive sleep apnea (OSA) was established. Differentiation mature 3T3-L1 adipocytes, were randomly divided into 10 groups including four different-frequency intermittent hypoxia groups(IH1-4, fixed intermittent hypoxia scheme for 1.5%O2 45 s and then re-oxygen 21%O2 for 2 min 15 s, 4 min 15 s, 5 min 45 s and 8 min 45 s, 60 times circulation), and their normal oxygen control groups (SC1-4, instead each IH group 1.5%O2 to 21%O2, the rest groups were treated as same as IH group), continuous hypoxia group (CH, 10%O2 for 6 h) and normal oxygen control group (CC, 21%O2 for 6 h). ELISA method was used to determine the levels of IL-10 and visfatin in the supematant of adipocytes. Western blot method was used to determine the protein levels of NF-κB p65 and visfatin. Real-time PCR method was used to determine the mRNA levels of IL-10 and visfatin. Results The protein and mRNA expressions of IL-10 were significantly lower in IH group and CH group than those of control groups (P<0.01). The levels of NF-κB p65 protein were significantly increased in IH group and CH group than those of control group. The protein and mRNA expressions of visfatin were significantly higher in IH1, IH2 and CH groups than those of control group (P<0.01). Conclusion As a prominent feature of OSA pathophysiology, IH may take part in insulin resistance of OSA patients by abnormally secreting NF-κB, IL-10 and visfatin in adipocytes.

BACKGROUNDSince 2009, health reform had launched in China and essential public health services were provided for all residents to ensure service equity and accessibility, and to achieve sustained population-wide health improvement. This study aimed to investigate the differences and determinants among populations with different characteristics access to essential public health services in China, especially hypertension people and children aged 0-6 years.

METHODSA cross-sectional study with socio-demographic data analysis was undertaken to estimate distribution characteristics of receiving essential public health services of hypertension patients and children. Regular follow-ups and effective blood pressure control reflected the effective management for hypertension patients, and for children, public services provided were vaccination on schedule and regular physical check-up. Logistic regression was used to determine the predictors for effective management.

RESULTSA total of 1 505 hypertension patients and 749 children were involved; 39.14% of hypertension participants could control their blood pressure in the normal range, and the rate in urban areas (43.61%) was higher than that in rural (31.88%). And 34.68% of them could receive more than 4 times follow-ups by the medical technician. Of 754 children, 79.84% could receive the periodic physical examination and 98.40% had vaccinated regularly. Children living in rural areas were more likely to have regular check-ups (83.96%) and regular vaccination (nearly 99%). Overall, geographic location and education level were the determinants of people access to essential public health services.

CONCLUSIONSImplementation of the health reform since 2009 has headed China's public health system in the right direction and promoted the improvement of public health system development. Our study highlights the growing needs for more public health services in China, and China's public health system needs to be greatly improved in terms of its quality and accessibility.

Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; Health Care Reform ; Health Services Needs and Demand ; statistics & numerical data ; Humans ; Hypertension ; Infant, Newborn ; Male ; Middle Aged ; Public Health ; statistics & numerical data ; Young Adult

HOX gene belongs to a highly conserved subgroup of the homeobox superfamily .The HOX genes constitute a family of transcription factors that play key roles in embryonic development , regulating numerous processes , such us cellular growth, differentiation, apoptosis, motility and angiogenesis.The present review shows that there is a close relationship between aberrant expression of HOX genes and malignancy .This article summarizes briofly the advances in the research on HOX genes and their roles in tumor genesis .

Objective To study the relationship of the levels of serum interleukin-6 (IL-6) and C-reactive protein (CRP) with insulin resistance in normal glucose tolerant first-degree relatives (NGT) of type 2 diabetics.Methods A total of 218 normal glucose tolerance subjects , including 136 NGT of type 2 diabetes , and 82 normal control ( NC) without type 2 diabetes family history were enrolled.The levels of blood glucose, hemoglobin A1c (HbA1c), lipid, insulin, IL-6, and high-sensitivity C-reactive protein (hs-CRP) were measured.Results ⑴Compared with NC, the levels of homeostasis model assessment of insulin resistance (HOMA-IR), hs-CRP , and IL-6 in NGT were significantly increased [1.03~1.94 vs 0.42~0.95 , P <0.01;0.46~2.78 mg/L vs 0.39~1.56 mg/L, P <0.01;(13.6 ±8.99) pg/ml vs (8.08 ±3.67) pg/ml, P <0.01];⑵In NGT, hs-CRP was positively correlated with HOMA-IR and IL-6 ( r =0.326 , P <0.01;r =0.258 , P <0.05 );IL-6 was positively correlated with HOMA-IR ( r =0.350 , P <0.01).Conclusions IL-6 and CRP may correlate with the degree of insulin resistance in NGT of type 2 diabetics.

Objective To study the role of ganoderma lucidum spore oil and ganoderma lucidum extraction spore oil in neovascularization of human high malignant breast cancer .Methods Human high malignant breast cancer cell MDA-MB-231 and tumor-bearing nude mice established with MDA-MB-231 were treated with different doses of ganoderma lucidum spore oil and ganoderma lucidum extraction spore oil .Epidermal growth factor receptor ( EGFR) expression level was examined by Western blotting and the RNA expression levels of neovascularization related molecules such as EGFR , vascular endothelial growth factor (VEGF), metalloproteinases(MMPs), thrombospondin(TSP-1), platelet derived growth factor( PDGF) , fibroblast growth factor ( FGF) were detected by Real-time PCR.Results Both ganoderma lucidum spore oil and ganoderma lucidum extraction spore oil inhibited the expression of EGFR in vitro and in vivo in a dose-dependent way.Both compounds induced down-regulation of VEGF and up-regulation of TSP-1 at RNA level.The effect of Ganoderma lucidum extraction spore oil was more significant than that of ganoderma lucidum spore oil .Conclusion Both ganoderma lucidum spore oil and ganoderma lucidum extraction spore oil inhibite the expression of neovascularization related molecules and increase the expression of molecules inhibiting neovascularization , whereas the effect of ganoderma lucidum extraction spore oil is more obvious .