Objective:To explore the relationship between non-dipper heart rate (HR)and severity of cerebral em- bolism from atrial fibrillation in aged patients.Methods:A total of 95 aged patients with persistent atrial fibrillation complicated cerebral embolism received 24h Holter monitoring within 24h after hospitalization.According to 24h Holter monitoring results,patients were divided into dipper HR group (n=21),non-dipper HR group (n=56) and reverse dipper HR group (n=18).United States national institutes of health stroke score (NIHSS)was used to evaluate neurological deficit severity of three groups,and the relationship between HR and NIHSS score was retro- spectively analyzed.Results:Compared with dipper HR group,there were significant rise in mean HR [(83.09± 8.06)beats/min vs.(89.09±7.83)beats/min vs.(95.50±8.06)beats/min]and NIHSS score [(5.14±2.65) scores vs.(7.95±5.30)scores vs.(11.11±7.41)scores]in non-dipper HR group and reverse dipper HR group, and those of reverse dipper HR group were significantly higher than those of non-dipper HR group,P<0.05 or<0.01.Conclusion:Abnormal circadian changes of heart rate can aggravate patient's condition in aged patients with atrial fibrillation complicated cerebral embolism.So based on routine treatment,regulation of circadian rhythm of heart rate should also be noticed.

Objectives To explore the route of ESBL producing bacteria in neonatal faeces, and to investigate the gene and drug resistance of ESBL producing bacteria in intestinal tract of neonates. Methods Fecal samples of healthy newborns and their mothers were collected, and bacterial cultures were carried out using selective ESBL medium. The positive strains were identified by Time-of-flight mass spectrometry. ESBL genotyping and resistance gene detection were performed by whole genome sequencing technique. Results In 146 neonatal fecal specimens, the positive rate of ESBL producing bacteria was 8.90％,and the positive rate in the first time stool was 3.23％. Seventy-two hours after birth, the positive rate of fecal ESBL producing bacteria was 13.10％. Among the 13 ESBL producing strains, there were 9 strains of CTX type, 3 strains of TEM type and 1 strain of SHV type. Nine strains of CTX include five types such as CTX-M-24, CTX-M-18, CTX-M-27, CTX-M-42 and CTX-M-15. The positive rate of ESBL producing bacteria was 21.6％ in 167 mothers' fecal specimens. The ESBL genotype included 24 strains of CTX type, 6 strains of TEM type, 4 strains of SHV type and 2 strains of QnrS type. Twenty-four strains of CTX include CTX-M-24, CTX-M-14, CTX-M-18, CTX-M-27, CTX-M-42 and CTX-M-15. There were 2 or 3 ESBL genotypes in 12 maternal and neonatal specimens. It was detected to have 6 types of resistance gene such as aadA5, strA, strB, sul1, sul2 and dfrA17 in 49 strains of ESBL producing bacteria in maternal and neonatal strains. Resistance genes were exactly the same in the neonates as in mothers who were detected to have ESBL producing bacteria. A variety of resistance genes were detected in feces in 7 neonates and 23 mothers. Conclusions The neonates in hospital may be detected to have ESBL produing bacteria in the intestinal tract at the same time as their mothers or separately. However, there are many ways for neonates to have ESBL producing bacteria in intestinal tract. There are many genotypes and resistance genes of ESBL producing bacteria.

Objective　To investigate the association between gene polymorphism of the plasminogen activator inhibitor-1 (PAI-1) and myocardial infarction (MI) in Chinese. Methods　PAI-1 genotyping with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific polymerase chain reaction (ASPCR) was performed in 87 myocardial infarction patients and 92 unrelated healthy controls. All subjects'clinical features and PAI-1 activity were tested. Results　There were two polymorphisms within the promoter, a G/A single base substitution polymorphism upstream at -844*!bp, and a single guanosine deletion/insertion 4G/5G polymorphism -675*!bp upstream from the start of transcription. Significant differences between the patients and the controls were observed neither for the frequencies of the GG, GA and AA genotypes nor for the PAI-1 activities of these three types. But for the 4G/5G polymorphism, there were significant differences between patients and controls for the frequencies of the 4G/4G, 4G/5G and 5G/5G genotypes (P<0.05). In the MI group, the PAI-1 activity of the 4G/4G type was significantly higher than that of the 5G/5G type (P<0.05). Further more, a positive correlation between the glucose level and PAI-1 activity was found (r=0.34, P=0.02). Conclusion　This study indicates that the 4G/5G gene polymorphism of PAI-1 is associated with myocardial infarction, that 4G/4G type is probably an important hereditary risk factor, and that glucose has functional importance in regulating PAI-1 activity.

GPCR proteins represent the largest family of signaling membrane proteins in eukaryotic cells. Their importance to basic cell biology, human diseases, and pharmaceutical interventions is well established. Many crystal structures of GPCR proteins have been reported in both active and inactive conformations. These data indicate that agonist binding alone is not sufficient to trigger the conformational change of GPCRs necessary for binding of downstream G-proteins, yet other essential factors remain elusive. Based on analysis of available GPCR crystal structures, we identified a potential conformational switch around the conserved Asp2.50, which consistently shows distinct conformations between inactive and active states. Combining the structural information with the current literature, we propose an energy-coupling mechanism, in which the interaction between a charge change of the GPCR protein and the membrane potential of the living cell plays a key role for GPCR activation.
Binding Sites ; GTP-Binding Proteins ; chemistry ; genetics ; metabolism ; Humans ; Hydrogen Bonding ; Membrane Potentials ; Models, Molecular ; Protein Conformation ; Receptors, G-Protein-Coupled ; chemistry ; genetics ; metabolism ; Signal Transduction

Objective:To analyze the survival status and death factors of confirmed HIV-infected patients in Hangzhou to provide a basis for the formulation of AIDS prevention and treatment strategies.Methods:A retrospective cohort study was conducted. The data were from the HIV/AIDS Comprehensive Response Information Management System of the Chinese Disease Control and Prevention Information System.Epidemiological characteristics of HIV-infected patients were comparied in Hangzhou City from 2004 to 2023 by using chi-square Test. The survival rate of HIV-infected patients in Hangzhou was calculated by the life table method, the survival curves of different subgroups were described by the Kaplan-Meier method, and the Cox proportional hazard regression model was used to analyze the influencing factors of death risk. The SPSS 26.0 software was used for statistical analysis.Results:Among the 9 457 subjects, the total follow-up time was 58 004.18 person-years, 494 patients died, fatality rate of all-cause cases was 0.85 per 100 person-years.The average survival time was 18.59 (95% CI:18.40-18.78) years. Malignant neoplasms and pneumocystis pneumonia were the first (14.37%,71/494) and second (10.73%, 53/494) causes of death, respectively. Death within 6 months after diagnosis accounted for 42.51% (210/494), and suicide accounted for 4.25% (21/494). Multivariate Cox regression analysis showed that compared with those who received antiviral treatment (ART) within 3 months of diagnosis, those who received ART outside 3 months and those who did not receive ART had a 1.65 (95% CI:1.25-2.19) and 20.68 (95% CI:15.80-27.06) times risk of death, respectively. The HIV-infected patients with high CD4 +T lymphocytes (CD4) counts for the first time had a lower risk of death. The risk of death of patients with baseline CD4 counts of 200-349 cells/μl, 350-499 cells/μl, and ≥500 cells/μl was 0.38 (95% CI:0.29-0.49), 0.26 (95% CI:0.19-0.36), 0.21 (95% CI:0.14-0.31) times higher than that of baseline CD4 counts <200 cells/μl, respectively. Conclusions:The overall survival of the HIV-infected patients was good in Hangzhou from 2004 to 2023. Early detection of HIV infection and timely mobilization to participate in ART was the key to improving the survival rate of patients. At the same time, given the suicide problem of HIV-infected patients, suicide surveillance and depression and anxiety screening of HIV-infected patients should be further strengthened, and targeted psychological intervention policies should be implemented.

【Objective】 To investigate the molecular mechanism of long non-coding RNA (lncRNA) TDRG1 in facilitating the malignant progression and poor prognosis of patients with cervical cancer. 【Methods】 Cervical cancer cell lines and normal cervical cell Ect1/E6E7 were collected. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of TDRG1. Cervical cancer cell lines were transfected with TDRG1-siRNA, and the proliferation of cancer cells was detected by CCK-8 method and cell plate cloning experiment. The invasion and migration of cancer cells were measured by Transwell experiment. The apoptosis of cancer cells was examined by flow cytometry, and the expressions of relevant proteins were tested by Western blot. 【Results】 Compared with Ect1/E6E7, cervical cancer cell lines showed relatively increased expression of TDRG1. Downregulation of TDRG1 expression inhibited the proliferation and colony formation (162±21 vs. 411±33, P<0.05), as well as the invasion and migration (invasion: 86±13 vs. 315±38, P<0.01; migration: 177±22 vs. 406±41, P<0.01) of Hela cells. Meanwhile, the apoptosis of Hela cells increased [(28±1.5)% vs. (16±1.2)%, P<0.05] and the expression of Bcl-2 protein reduced. In addition, TDRG1 knockdown also decreased the activity of autophagy in Hela cells. 【Conclusion】 TDRG1 facilitates the malignant biological progression of cervical cancer by inhibiting the apoptosis and providing a protective autophagy in cervical cells.