Objective To investigate the association of proton pump inhibitors(PPIs)use with short-term and long-term mortality risk in patients with severe ischemic stroke.Methods This retrospective study based on the U.S.Medical Information Mark for Intensive Care Ⅲ(MIMIC-Ⅲ)database,ICU patients aged ≥18 years with the first ICU admission and a diagnosis of ischemic stroke were finally included in the study.All enrolled subjects were divided into PPIs group and non-PPIs group according to whether they had used PPIs(pantoprazole,lansoprazole and omeprazole)during hospitalization.Kaplan-Meier survival analyses and Cox regression models were used to analyze the association between the use of PPIs and the risk of ICU death,30 d risk of death,90 d risk of death in patients with severe ischemic stroke.Results A total of 1 015 patients were included,402 cases in the PPIs group and 613 in the non-PPIs group.The ICU-mortality,30 d and 90 d mortality were 15.37％,13.60％and 20.10％,respectively.Kaplan-Meier survival analyses illustrated that the PPIs group survived better than non-PPIs group in ICU mortality analysis(P=0.002).In Cox regression analysis,after adjustment for potential confounders,the hazard ratio(HR)for ICU mortality in the PPIs group relative to the non-PPIs group was 0.671 9(95％CI 0.478 8 to 0.942 8,P=0.021),but there was no significant difference between 30 d and 90 d mortality(P＞0.05).Conclusion In patients with severe ischemic stroke,the use of PPIs may be effective in reducing the risk of ICU death,but does not improve 30 d and 90 d risk of death in patients.

Objective:To explore the effect of NOD-like receptor thermal protein 3 ( NLRP3) knockout in γ-aminobutyric acid (GABA)-ergic neurons in the hippocampal CA1 area on improving cognitive dysfunction in mice after traumatic brain injury (TBI). Methods:Forty-eight healthy male NLRP3 flox/flox mice weighing 25-28 g were randomly divided into 4 groups ( n=12): sham-operated+control virus group (SV group), sham-operated+ NLRP3 specific knockout group (SG group), TBI+control virus group (TV group), TBI+ NLRP3 specific knockout group (TG group). TBI in the TV and TG groups was established by free-fall method, while surgical procedures such as scalp incision and cranial window opening without impact were given to the SV and SG groups. Adenovirus was injected into the hippocampal CA1 area of SG and TG groups 21 d before TBI to induce NLRP3 specific knockout in GABA-ergic neurons in the hippocampal CA1 area; empty virus was injected into the CA1 area of SV and TV groups. Cognitive function was evaluated using novel object recognition test 30 and 31 d after TBI, and learning and memory functions were assessed using Morris water maze test 32-36 d after TBI. Field potentials in the hippocampal CA1 area were recorded during novel object recognition 31 d after TBI. After behavioral tests, these mice were sacrificed. Immunofluorescent staining was used to detect the fluorescent intensity of microtubule-associated protein2 (MAP2), glutamic acid decarboxylase 67 (GAD67), and postsynaptic density protein 95 (PSD95) in the hippocampal CA1 area, as well as percentage of pyroptosis-associated inflammatory factor interleukin-18 (IL-18)/GAD67 double-positive neurons in total GAD67 positive neurons. Results:Compared with the SV and SG groups, the TV and TG groups had decreased novel object recognition index, decreased number of platform crossings during the experimental period, increased escape latency on day 3 and day 4 of the training period in Morris water maze test, decreased θ and γ oscillation power in the hippocampal CA1 area during novel object recognition, decreased fluorescent intensity of MAP2, GAD67, and PSD95 in the hippocampal CA1 area, increased percentage of IL-18/GAD67 double-positive neurons, with significant differences ( P<0.05). Compared with the TV group, the TG group had increased novel object recognition index, increased number of platform crossings in Morris water maze test, decreased escape latency during the training period, increased θ and γ oscillation power in the hippocampal CA1 area during novel object recognition, increased fluorescence intensity of MAP2, GAD67, and PSD95 in the hippocampal CA1 area, decreased percentage of IL-18/GAD67 double-positive neurons, with significant differences ( P<0.05). Conclusion:Specific inhibition of NLRP3 expression in GABA-ergic neurons in the hippocampal CA1 area can improve cognitive dysfunction in mice after TBI, whose mechanism may be related to inhibited GABA-ergic neuronal pyroptosis in the hippocampal CA1 area.

Objective:To evaluate the role of astrocytic NOD-like receptor protein 3 (NLRP3) in the lateral hypothalamus (LHA) in anxiety-like behaviors after hemorrhagic shock and resuscitation in mice.Methods:Forty-eight clean-grade male C57BL/6 mice, aged 10 weeks, weighing 25-30 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (group C), hemorrhagic shock and resuscitation group (group H), hemorrhagic shock and resuscitation + adeno-associated virus group (group HI), and hemorrhagic shock and resuscitation + control virus group (group HIV). The model of hemorrhagic shock and resuscitation was developed by bleeding and re-transfusion through the femoral vein in H, HI and HIV groups. At 21 days before developing the model, AAV-GfaABC1D-EGFP-Cre was injected into bilateral LHA in group HI, and AAV-GfaABC1D-EGFP was administered as a control in group HIV. Anxiety-like behaviors were evaluated by EPM-maze and bead-burying tests at 14 days after resuscitation. Mice were immediately sacrificed at the end of behavioral tests, and LHA-containing brain tissues were obtained for determination of co-localization of NLRP3 with glial fibrillary acidic protein (GFAP), the fluorescence intensity of Wisteria floribunda agglutinin was measured using immunofluorescent staining to reflect the expression of extracellular matrix in the LHA, and the percentage of cleaved caspase-1/GFAP and IL-18/GFAP positive cells in total cells was calculated. Results:Compared with group C, the number of buried beads and percentage of time of staying at the open arm were significantly decreased, the expression of extracellular matrix in the LHA was down-regulated, and the percentage of cleaved caspase-1/GFAP and IL-18/GFAP positive cells was increased in H, HI and HIV groups, and the co-localization coefficient of NLRP3 and GFAP was significantly decreased in group HI ( P<0.01). Compared with group H, the number of buried particles and percentage of time of staying at the open arm were significantly decreased, the expression of extracellular matrix in the LHA was up-regulated, the co-location coefficient of NLRP3 and GFAP was decreased, the percentage of cleaved caspase-1/GFAP and IL-18/GFAP positive cells was decreased ( P<0.01), and no significant change was found in the parameters mentioned above in group HIV ( P>0.05). Conclusions:Anxiety-like behaviors after hemorrhagic shock and resuscitation is associated with astrocytic NLRP3-induced pyroptosis in the LHA and reduction of extracellular matrix in mice.

Objective:To investigate the curative effect of the Pavlik harness and polyester material casting bandage for the early treatment of congenital knee dislocation (CDK).Methods:The clinical data of 12 patients (13 knees) with CDK treated in Provincial Hospital Affiliated to Shandong First Medical University from December 2011 and January 2019 were studied retrospectively.There were 3 males and 9 females.The median age at the initial visit was 3 days ( 1-29 days). Eleven patients had unilateral CDK, and 1 patient had bilateral CDK.There were 5 cases(5 knees) with dislocation and 7 cases(8 knees) with subluxation.Associated musculoskeletal anomalies were observed in 7 patients, which included developmental dysplasia of the hip (DDH) in 6 patients, bilateral DDH and right clubfoot in 1 patient.The Pavlik harness was applied to keep the knee in position for 1.5-2.0 months if passive flexion achieved 90°or more.If passive flexion was below 90°, the polyester material casting bandage was employed to increase knee flexion, and the bandage was changed once a week.After passive flexion reached 90°, the patient was treated with the Pavlik harness for 1.5-2.0 months.Cases with DDH who worn the Pavlik harness were evaluated by ultrasonography in the follow-up period, and cases with clubfoot were treated with Ponseti polyester material casting bandages.Results:Three children (4 knees) were directly fixed with Pavlik harness for 1.5-2.0 months, 9 children (9 knees) were fixed with Pavlik harness for 1.5-2.0 months after 1-8 times (average 2.9 times) of plaster fixation. No plaster and Pavlik harness complications were found during the treatment.Twelve patients were followed up for 29.8 months on average (12.0 to 65.0 months). Ten patients (11 knees) were rated excellent, and 2 patients (2 knees) were rated good.Conclusions:The Pavlik harness and polyester material casting bandage for early treatment of CDK is simple, effective and safe.Associated musculoskeletal anomalies can also be corrected in the treatment process.The knee joint dislocation should be treated at first.

Objective:To analyze the prevalence and genotypes of human pegivirus-1 (HPgV-1) among HIV-1-infected men who have sex with men (MSM) in Zhuhai, aiming to elucidate the impact of HPgV-1 on the progression of AIDS.Methods:This study collected 934 serum specimens positive for antibodies against HIV-1 for viral RNA extraction from MSM in Zhuhai from 2012 to 2020. HPgV-1 5′UTR was amplified by nested PCR and then E gene was amplified by nested PCR and sequenced in the 5′UTR-positive specimens. A phylogenetic tree was constructed to analyze genotype distribution. The influence of HPgV-1 infection on the progression of AIDS was evaluated through analyzing HIV-1 viral load and CD4 + cell counts in patients in the early stage of AIDS before antiviral treatment. Results:The positive rate of HPgV-1 in MSM with HIV-1 infection in Zhuhai was 31.05%. A total of 273 valid sequences were obtained after amplification. The main genotype of HPgV-1 was G3 (252, 92.31%), which was highly homologous to the epidemic strains in China and Japan in recent years, followed G2 (21, 7.69%), which was highly homologous to the epidemic strains in France and America. HPgV-1 strains of G1, G4, G5, G6 and G7 genotypes were not detected. There was no significant difference in HIV-1 virus load or CD4 + cell counts between patients with HIV-1 infection alone and those with HIV-1 and HPgV-1 (G3 or G2 genotype) co-infection. Conclusions:According to the data of this study, HPgV-1 infection could not delay the progression of AIDS in MSM in the early stage of AIDS before antiviral therapy. The widespread HPgV-1 of G3 genotype in China did not have a significant impact on the progression of AIDS. Therefore, a systematic in-depth research on various genotypes of HPgV-1 and further study on the pathogenic mechanism of HPgV-1, especially in patients with HPgV-1 and HIV co-infection, were needed to understanding the interaction mechanism between different genotypes of HPgV-1 and HIV-1.

Herpesvirus infections in Cervidae are a serious threat affecting some deer species worldwide. In our attempt to identify malignant catarrhal fever-associated herpesviruses in deer herds, ten gammaherpesviral DNA fragments were identified in five species of deer in herds in China by using a pan-herpesvirus polymerase chain reaction assay targeting viral DNA polymerase. Notably, in sambar (Rusa unicolor), a novel gamma-2 herpesvirus was identified that showed a close relationship with fallow deer lymphotropic herpesvirus (LHV), while the other fragments were phylogenetically grouped together with Elk-LHV. Determination of whether these viruses have any clinical implication in these deer species should be undertaken urgently.
Animals ; Cattle ; China ; Deer ; DNA ; DNA, Viral ; Herpesviridae Infections ; Herpesviridae ; Malignant Catarrh ; Polymerase Chain Reaction

Objective To investigate the preventive and adverse effects of postnatal inhalation of Budesonide in early stage on bronchopulmonary dysplasia (BPD) in very low birth weight infants.Methods A total of 105 cases of high risk premature infants with BPD,who were born in the Neonatal Intensive Care Unit (NICU) from Shenzhen Maternity and Child Healthcare Hospital from July 15,2015 to December 25,2016,and their gestational age ≥ 27 weeks and ＜ 32 weeks or birth weight ≥ 1 000 g and ＜ 1 500 g were collected for a prospective randomized controlled trial,and were randomly divided into 3 groups:early inhalation group(34 cases),late inhalation group(34 cases) and non-inhalation group(37 cases).The oxygen time,and the incidence of BPD,periventricular-intraventricular hemorrhage (IVH),retinopathy of prematurity (ROP),necrotizing enterocolitis of the newborns (NEC),patent ductus arteriosus in preterm infants (PDA),sepsis and hyperglycemia of infants in 3 groups were compared.Results The average oxygen time in early inhalation group was 9 days,while in late inhalation group and the non-inhalation group was 15 days and 18 days,respectively.The average oxygen time in early inhalation group was significantly lower than that in the late inhalation group and the non-inhalation group,with the difference being statistically significant (H =6.09,P ＜ 0.05).The noninvasive ventilation time in early inhalation group was 3 days,while both the late inhalation group and non-inhalation group were 6 days.The noninvasive ventilation time in early inhalation group was significantly lower than that in the late inhalation group and non-inhalation group,with the difference being statistically significant (H =6.17,P ＜0.05).The incidence of BPD in the early inhalation group,late inhalation group and non-inhalation group were 14.7％ (5/34 cases),20.6％ (7/34 cases) and 37.8％ (14/37 cases),respectively.The incidence of BPD in non-inhalation group was significantly higher than that in the early inhalation group and late inhalation group,with the difference being statistically significant (x2 =12.017,P ＜ 0.05).There were no significant differences in IVH,ROP,NEC,PDA,sepsis and hyperglycemia among the 3 groups (all P ＞ 0.05).Conclusions Postnatal inhalation of Budesonide in early stage in high risk very low birth weight infants can reduce the incidence of BPD and the oxygen time,and the adverse reactions are not obvious.

Objective: To describe the molecular epidemiological characteristics of norovirus gastroenteritis outbreaks in Zhuhai from 2011 to 2016. Methods: Anal swab specimens were collected from 576 cases with 56 outbreaks of acute norovirus gastroenteritis from 2011 to 2016. Specimens were tested by real-time RT-PCR. Three to four of norovirus positive specimens were selected from every outbreak to amplify the VP1 gene by RT-PCR and one strain was chosen randomly from every outbreaks to determine the genotype by phylogenetic tree analysis. Results: Eight genotypes were identified from 56 outbreaks and all of them belonged to GⅡ genogroup. The genotype of norovirus strain changed with prevalence time. The GⅡ.4/2006b was dominant from 2011 to 2012, and replaced by GⅡ.4/Sydney _2012 during the 2012—2013 norovirus season, and both of them never appeared after Feb. 2013. GⅡ.17 was the only genotype during the 2014—2015 norovirus season. All the 7 outbreaks occurred from 2015 to 2016 were caused by GⅡ.3 norovirus. The GⅡ.17and GⅡ.3 were identified from Apr. to Sep. 2016; GⅡ.p16-GⅡ.2 were the only genotype in 12 outbreaks from Nov. to Dec. 2016. The GⅠ genogrope was never identified from 2011 to 2016 in Zhuhai. Conclusions The Norovirus GⅡ was the only pathogeny which caused the outbreaks of norovirus gastroenteritis. The recombinant norovirus strain GⅡ.p16-GⅡ.2 emerged and caused large outbreaks in the last two months of 2016 in Zhuhai; several recombinant strains of the GⅡ.p16 RdRp gene were found now, which suggests that attention should be focused on the prevalence and evolution of the recombinant norovirus.

Objective To evaluate the value of monitoring non-invasive cardiac output parameters in medical treatment of patent ductus arteriosus (PDA) in premature infants.Method Premature infants with PDA diagnosed three days after birth (gestational age:28 ～ 31 weeks or birth weight of 1 000 ～ 1 799 g) admitted to the neonatal intensive care unit (NICU) of our Hospital from February 2016 to August 2016 were enrolled in the study.These premature infants were assigned into treated PDA group (the treatment group) and untreated PDA group (the observation group) based on results of non-invasive cardiac output parameters CI and MD,with aorta CI ≥2.95 L/(min · m2),MD ≥21.50 m/min and pulmonary artery CI ≥4.55 L/(min · m2),MD ≥26.50 m/min as cut-off values.Statistical analysis was carried out using t test,x2 test.The closure rate of arterial duct of two groups and changes in non-invasive cardiac output parameters before and after the closure of arterial duct in the treatment group were compared.Result The overall closure rate of arterial duct was 85.1％ (57/67).The closure rate of arterial duct of the treatment group was 70.8％ (17/24),that of the observation group was 93.0％ (40/43),and the difference had statistical significance (P ＜ 0.05);Comparing the following parameters before and after ductal closure in the treatment group,the difference of pulmonary artery flow time (FT),aorta stroke volume index (SVI) and the integral of the flow profile (Vti) had statistical significance (P ＜ 0.05) [(217.6±19.3) ms vs.(235.8 ±21.4) ms,(22.4±6.0)ml/m2 vs.(25.2 ±7.7)ml/m2,(15.1 ± 4.1) cm vs.(17.2 ±5.3) cm].In the treatment group,after arterial duct was closed,aorta and pulmonary artery CI,MD decreased to some degree,but the difference had no statistical significance (P ＞ 0.05).Conclusion Non-invasive cardiac output parameters including aorta and pulmonary artery CI,MD have certain guiding significance for PDA drug treatment among premature infants;after PDA drug treatment,arterial duct closure condition cannot be judged simply by the changes of aorta and pulmonary artery CI,MD,ultrasonic cardiogram examination results should also be considered.

Objective To investigate the molecular mechanism of bone marrow mesenchymal stem cells (BM-MSCs) in repairing cisplatin-induced acute renal injury.Methods The rats were injected 6 mg/kg of cisplatin intraperitoneally,and bone marrow mesenchymal stem cells (BM-MSCs group) or PBS (PBS group) were injected respectively via tail vein after 24 hours.The rats without injecting cisplatin were selected as a normal control group.The repair effect of BM-MSCs on renal injury was observed by HE staining and immunohistochemistry.In addition,NRK-52E cells were cultured in vitro and treated with cisplatin for 6 hours.Then,NRK-52E cells were continued to culture for 48 hours or co-cultured with BM-MSCs for 48 hours,and NRK-52E cells untreated with cisplatin were used as a control.The expression levels of miR-92b and its target gene PTEN were detected by qRT-PCR,and the expression level of p-Akt by western blot.Results HE staining showed that the tubular protein casts in BM-MSCs group were significantly less than that in PBS group,and that the renal tubular structure was significantly improved in BM-MSCs group.Immunohistochemical staining indicated that the number of cells expressing proliferating cell nuclear antigen (PCNA) in BM-MSCs group (131.0 ± 14.4) was significantly higher than that in PBS group (42.2 ±6.1,t =11.28,P ＜0.01).qRT-PCR results showed that in the vivo experiment,compared with the expression level of miR-92b and PTEN in the normal control group (1.11 ± 0.78,1.01 ± 0.21),PBS group were (4.64 ± 1.06) and (0.61 ± 0.2),respectively (all P ＜ 0.05);BM-MSCs group were (2.27 ± 0.81) and (1.1 ± 0.1),respectively (all P ＜ 0.05).In vitro experiment,compared with the expression level of miR-92b and PTEN in the negative control group (1.12 ± 0.77,1.02 ± 0.13),cisplatin group were (7.64 ± 0.72) and (0.58 ± 0.2),respectively (all P ＜ 0.05),cell group were (4.38 ± 0.50) and (1.15 ± 0.23),respectively (all P ＜ 0.05).Western blot results showed that compared with the expression level of p-Akt in cisplatin group (0.96 ± 0.18),p-Akt expression in cell group was (2.11 ± 0.11,P ＜ 0.01).Conclusion BM-MSCs may repair the cisplatin-induced acute renal injury via down-regulating the expression level of miR-92b.