OBJECTIVE: To investigate the antinociceptive effect of intrathecal administration of HSV-I amplicon vector-mediated HPPE. METHODS: Sprague Dawley rats (290+/-30) g were randomly divided into pHSVIRES-HPPE-LacZ (SHPZ) group, pHSVIRES-LacZ (SHZ) group, and saline group (NS), and 3 d, 1 week, 2 weeks, 3 weeks, 4 weeks, and 5 weeks group,which were anesthetized with 10% chlroral hydrate 300- 350 mg/kg. A microspinal catheter was inserted into the lumbar subarachnoid space. Rats were intrathecally delivered with recombinant HSV-I amplicon vector SHPZ, SHZ or NS. The HPPE expression was detected by reverse transcription-polymerase chain reaction (RT-PCR) and radioimmune assay. Formalin 50 microL (5%) was injected into the left hindpaw, pain intensity scoring (PIS) was used to assess the antinociceptive effect. RESULTS: After in vivo transferring,neurocyte demonstrated strong positive signals with X-gal immunohistochemical staining. RT-PCR and L-enkephalin radioimmune assay found that the neural cells transferred foreign gene (HPPE) had effective expression. Intrathecal delivery of SHPZ showed antinociceptive effects on formalin induced pain for 5 weeks compared with SHZ. CONCLUSION This amplicon virus can transfer HPPE into rat central nerve system neural cells and express efficiently, suggesting SHPZ is satisfactory treatment for gene therapy for chronic pain. Intrathecal delivery SHPZ demonstrated antinociceptive effects on formalin induced pain.
Animals ; Enkephalins ; genetics ; metabolism ; Formaldehyde ; Gene Transfer Techniques ; Genetic Therapy ; Genetic Vectors ; administration & dosage ; Herpesvirus 1, Human ; genetics ; Humans ; Injections, Spinal ; Male ; Nociceptors ; physiology ; Pain ; chemically induced ; Pain Management ; Protein Precursors ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To assess the impact of arterial stiffness on prognosis in patients with chronic kidney disease(CKD)stages 3-5(pre-dialysis).METHODS: 141 patients suffered from chronic kidney disease(CKD)stages 3-5 pre-dialysis were enrolled in this study between April 2006 and November 2010.Automatic pulse wave velocity(PWV)measuring system was used to examine carotid-femoral pulse wave velocity(CFPWV).According to CFPWV level,we divided the patients into elevated CFPWV group(CFPWV ≥12 m/s)and the normal group(CFPWV<12 m/s).Patients were followed up for the occurrence of cardiovascular event,cardiovascular death and all-cause death.Kaplan-Meier methods were used for survival analysis and Cox's proportional hazard regression model were used to analyze risk factors.RESULTS: Two groups were followed-up(93.72±47.93)months.The incidences of cardiac-cerebral vascular event,cardiac-cerebral vascular death and all-cause death were higher in high CFPWV level groups(62.2%vs.21.6%,56.7%vs.15.7%,64.4%vs.19.6%,P<0.05).The level of CFPWV was higher in patients with cardiac-cerebral vascular event,cardiac-cerebral vascular death and all-cause death than those without those events[(15.31±3.41)m/s vs.(12.08±2.94)m/s,(15.66±3.40)m/s vs.(12.14±2.88)m/s,(15.38±3.38)m/s vs.(11.97±2.87)m/s,P<0.01].Kaplan-Meier curve for overall survivals and cardiac-cerebral vascular event free survivals showed a significant distinct between high and normal CFPWV level groups,suggesting that the incidence of cardiac-cerebral vascular events,cardiac-cerebral vascular mortality and all-cause mortality were significantly higher in high CFPWV level group than in normal CFPWV group(P=0.000).Multivariate Cox regression analysis revealed that increased CFPWV and commencing dialysis were the independent risk factors for cardiac-cerebral vascular event,increased CFPWV and CRP and decreased ALB and commencing dialysis were the independent risk factors for cardiac-cerebral vascular mortality and all-cause mortality(P<0.05).CONCLUSION: The levels of CFPWV in pre-dialysis chronic kidney disease(CKD)stage 3-5 patients increases significantly.The incidence of cardiac-cerebral vascular events,cardiac-cerebral vascular mortality and all-cause mortality are significantly higher in elevated CFPWV group than those of normal group in patients with CKD G3-5.The elevated CFPWV is one of independent risk factors of cardiac-cerebral vascular event,cardiac-cerebral vascular mortality and all-cause mortality in patients with pre-dialysis chronic kidney disease.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases