Objective To investigate the role of miR-27a-3p in sevoflurane-induced neurocognitive dysfunction.Methods Bioinformatics prediction and validation:Predicted the target genes of miR-27a-3p using bioinformatics databases,and verified the interaction between miR-27a-3p and target genes using dual-luciferase reporter gene assay and Western blot.Cell experiments:Cells were divided into two groups,the miR-27a-3p interference control(Sevo+NC)group was transfected with miR-27a-3p interference control plasmid,and the miR-27a-3p interference treatment(Sevo+anti-miR-27a-3p)group was transfected with miR-27a-3p interference plasmid.Before transfection,the plasmids were treated with 4％sevoflurane for 6 h.Western blot was used to detect the protein expression levels of tau and phosphorylaed tau(p-tau)in SY5Y cells of each group.Animal experiments:Mice were randomly divided into control group(no treatment),sevoflurane group(treated with 4％sevoflurane only),miR-27a-3p interference control group(Sevo+NC,injected with miR-27a-3p interference control plasmid after 4％sevoflurane treatment)and miR-27a-3p interference treatment group(Sevo+anti-miR-27-3p,injected with miR-27a-3p interference plasmid after 4％sevoflurane treatment).The neurocognitive abilities of mice were tested using the water maze experiment,and the level of tau phosphorylation in the hippocampal tissue of mice was detected by immunofluorescence.Results Bioinformatics prediction and validation:Bioinformatics prediction suggested that presenilin 1(PSEN1)might be a target gene of miR-27 a-3p.Dual-luciferase reporter gene assay and Western blot showed that miR-27 a-3p interacted with PSEN1.Cell experiments:The levels of p-tau in Sevo+NC group and Sevo+anti-miR27-3p group were 0.69±0.08 and 0.21±0.05,respectively.Animal experiments:The escape latency times of the control group,sevoflurane group,Sevo+NC group and Sevo+anti-miR-27-3p group were(27.54±3.67),(52.38±6.12),(55.16±5.79)and(38.46±4.78)s,respectively;the results of the novel object exploration index were 0.78±0.11,0.31±0.07,0.33±0.06,and 0.57±0.08,respectively.Immunofluorescence detection showed a significant decrease in p-tau levels in the hippocampal tissue of mice(P＜0.05).Conclusion miR-27 a-3p regulates the p-tau protein by targeting the PSEN1 gene,and interfering with miR-27 a-3p can alleviate sevoflurane-induced neurocognitive dysfunction in mice.

Objective To explore the clinical significance and antimicrobial resistance of group B Streptococcus(GBS)isolated from midstream urine culture,aiming to provide a basis for the diagnosis and treatment of clinical urinary tract infection(UTI).Methods Information about GBS strains isolated from midstream urine culture of in-patients and outpatient in a hospital in Nanjing from February 2020 to December 2022 were retrieved through labora-tory information system,strains with complete data were screened out.Case data,urine routine,and antimicrobial susceptibility testing results were reviewed.Results A total of 9 081 non-repetitive bacterial strains were detected from midstream urine culture,including 425 GBS strains,accounting for 4.7％,ranking sixth.Strains with incom-plete data were excluded,a total of 365 patients were included in the study.169(46.3％)were males and 196(53.7％)were females,with an average age of(55.4±15.2)years.365 patients who were detected GBS were from 17 de-partments,with the highest proportion being department of urology(n=237,64.9％).The underlying diseases of patients mainly included hypertension(n=136),diabetes(n=95),urolithiasis(n=120)and urinary tumors(n=98).211 patients underwent urological surgery,all were treated with antimicrobial agents before surgery,and 205 patients underwent indwelling urinary catheters after surgery;9 patients were detected GBS from urine during the middle and advanced stage of pregnancy.36.4％(n=133),38.9％(n=142)and 24.7％(n=90)patients had GBS colony count ≤104 CFU/mL,104-105 CFU/mL,and ≥105 CFU/mL,respectively.Patients with symptoms of UTI accounted for 24.9％(n=91),and asymptomatic bacteriuria accounted for 75.1％(n=274).The incidence of UTI symptoms in males was lower than that in females(19.5％vs 29.6％,P＜0.05).As the GBS colony count in urine culture increased,the proportion of patients with symptoms of UTI showed an upward trend(P＜0.05).On the day of urine culture,the positive rates of urine routine white blood cells,leukocyte esterase,and nitrite were 53.2％,50.1％,and 3.8％,respectively.The positive rates of urine occult blood,leukocyte esterase,white blood cells,and urine protein in patients with symptomatic UTI were all higher than those with asymptomatic bacteriuria patients(all P＜0.05).No GBS were found to be resistant to penicillin,ampicillin,vancomycin,linezolid,and tigecycline.The resistance rate to levofloxacin and moxifloxacin was about 40％,and resistance rate to tetracycline and clindamycin was over 60％.Conclusion GBS isolated from urine is more common in non-pregnant adults,and only a small percentage have symptoms of UTI.The results of urine culture and urine routine should be comprehen-sively judged based on patient's clinical symptoms and signs.GBS in urine is susceptible to multiple antimicrobial agents,and clinical medication should be adopted rationally based on antimicrobial susceptibility testing result.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Clinical data of 3 patients with linezolid-induced lactic acidosis treated in 2 hospitals in Beijing and Shandong were retrospectively analyzed,and relevant literatures at home and abroad were retrieved.The pathogene-sis,risk factors,clinical manifestations,and treatment scheme were valuated.Three patients received linezolid anti-infection treatment due to their disease condition.At different phases of treatment,they developed lactic acidosis that was difficult to be explained with septic shock.After discontinuing linezolid and receiving bedside continuous veno-venous hemofiltration(CVVH)treatment,patient's blood lactate levels decreased significantly.It is clinically diagnosed linezolid-induced lactic acidosis finally,but the initial diagnosis was septic shock by all doctors.After ac-tive treatment,2 patients recovered and 1 patient died.Linezolid-induced lactic acidosis is easily to be misdiagnosed as septic shock.Clinicians should enhance their understanding and recognition of the early diagnosis of the adverse reactions,take effective measures,so as to improve patient prognosis.

Objective:To observe the genetic variation of SH2B3 in patients with myeloid neoplasms.Methods:The results of targeted DNA sequencing associated with myeloid neoplasms in the Department of Hematology,Xuanwu Hospital,Capital Medical University from November 2017 to November 2022 were retrospectively analyzed,and the patients with SH2B3 gene mutations were identified.The demographic and clinical data of these patients were collected,and characteristics of SH2B3 gene mutation,co-mutated genes and their correlations with diseases were analyzed.Results:The sequencing results were obtained from 1 005 patients,in which 19 patients were detected with SH2B3 gene mutation,including 18 missense mutations(94.74％),1 nonsense mutation(5.26％),and 10 patients with co-mutated genes(52.63％).Variant allele frequency(VAF)ranged from 0.03 to 0.66.The highest frequency mutation was p.Ile568Thr(5/19,26.32％),with an average VAF of 0.49,involving 1 case of MDS/MPN-RS(with SF3B1 mutation),1 case of MDS-U(with SF3B1 mutation),1 case of aplastic anemia with PNH clone(with PIGA and KMT2A mutations),2 cases of MDS-MLD(1 case with SETBP1 mutation).The other mutations included p.Ala567Thr in 2 cases(10.53％),p.Arg566Trp,p.Glu533Lys,p.Met437Arg,p.Arg425Cys,p.Glu314Lys,p.Arg308*,p.Gln294Glu,p.Arg282Gln,p.Arg175Gln,p.Gly86Cys,p.His55Asn and p.Gln54Pro in 1 case each.Conclusion:A wide distribution of genetic mutation sites and low recurrence of SH2B3 is observed in myeloid neoplasms,among of them,p.Ile568Thr mutation is detected with a higher incidence and often coexists with characteristic mutations of other diseases.

AIM: To evaluate the efficacy and safety of foveal-sparing internal limiting membrane peeling(FSIP)or complete internal limiting membrane peeling(CMIP)for the treatment of myopic traction maculopathy(MTM)during vitrectomy.METHODS: CNKI, Wanfang, VIP, PubMed, Embase, Cochrane Library, and Web of Science were searched from January 1th 2000 to July 1th 2022, and studies that compared FSIP and CMIP for MTM were collected. The change and recovery rate of best corrected visual acuity(BCVA), incidence of full-thickness macular hole(FTMH), change of central foveal thickness(CFT)and the rate of complete reattachment.RESULTS: A total of 484 eyes from 12 literatures were included, with 203 eyes in the FSIP group and 281 eyes in the CMIP group. The results of Meta-analysis showed that FSIP group were superior to the CMIP group in the mean change of BCVA(SMD=0.52, 95%CI: 0.20～0.85, P=0.002), the improvement rate of BCVA(RR=1.50, 95%CI: 1.22～1.85, P=0.0002)and the incidence of postoperative FTMH(RR=0.23, 95%CI: 0.10～0.54, P=0.0008). There was no statistical difference between the two surgical methods in terms of mean change in CFT(SMD=0.04, 95%CI: -0.19～0.26, P=0.75)and the rate of complete reattachment(RR=1.12, 95%CI: 0.94～1.32, P=0.20).CONCLUSION: FSIP have similar anatomical outcomes compared to CMIP, but FSIP resulted in better visual acuity and lower incidence of postoperative FTMH.

Abstract：Objective To improve the replication level of varicella⁃zoster virus（VZV）in human diploid cell line MRC⁃5 and increase the yield of VZV vaccine by reducing the expression of interferon（IFN）related genes via optimizing the cell line MRC⁃5. Methods Interferon receptor 1（IFNAR1）silenced MRC⁃5 cell line（MRC⁃5IFNAR1⁃）was constructed by CRISPR／Cas9 gene editing technology，which was determined for the relative expression of IFNAR1 mRNA，and for those of mRNA of IFN related genes IFNβ and OAS1 after VZV infection by qRT⁃PCR to evaluate the effect of gene silencing. Gene mutation sequences were further identified by sequencing of the silenced sites. The replication of VZV in MRC⁃5 and MRC⁃5IFNAR1⁃ cell lines was compared 168 h after VZV infection by using qRT⁃PCR and plaque formation unit（PFU）assay， to evaluate the effect of MRC⁃5IFNAR1⁃cell line on VZV replication. Results The growth status of MRC⁃5IFNAR1⁃ cell line wasconsistent with that of MRC ⁃ 5 cells，and the relative expression of IFNAR1 mRNA decreased by 73%；The relative expressions of IFNβ and OAS1 mRNA in MRC⁃5IFNAR1⁃ cell line were 61% and 90% lower than those in MRC⁃ 5 cells respectively after VZV infection；In addition，168 h after VZV infection，the level of DNA replication and the titer of VZV increased by 5. 7 folds and 4 folds respectively. Conclusion The successful establishment of MRC⁃5IFNAR1⁃ cell line may be a potential scheme to increase the yield of vaccines based on human diploid cells，and provided a reference for expanding production of VZV vaccine.

BACKGROUND: Growth differentiation factor 15 (GDF-15) has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events. This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality, considering traditional risk factors and other biomarkers. METHODS: A prospective study was conducted and 3699 patients with stable coronary artery disease (CAD) were enrolled into the research. Baseline GDF-15 levels were measured. Median follow-up was 3.1 years during the study. We analyzed clinical variables and several biomarkers. Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction (MI), heart failure, stroke, cardiovascular death, and non-cardiovascular death. RESULTS: Baseline GDF-15 levels for 3699 patients were grouped by quartile (≤ 1153, 1153-1888, 1888-3043, > 3043 ng/L). Higher GDF-15 levels were associated with older age, male gender, history of hypertension, and elevated levels of N-terminal pro B-type natriuretic peptide (NT-pro BNP), soluble suppression of tumorigenesis-2 (sST2), and creatine (each with P < 0.001). Adjusting for established risk factors and biomarkers in Cox proportional hazards models, a 1 standard deviation (SD) increase in GDF-15 was associated with elevated risk of clinical events [hazard ratio (HR) = 2.18, 95% confidence interval (CI): (1.52-3.11)], including: MI [HR = 2.83 95% CI: (1.03-7.74)], heart failure [HR = 2.71 95% CI: (1.18-6.23)], cardiovascular and non-cardiovascular death [HR = 2.48, 95% CI (1.49-4.11)] during the median follow up of 3.1 years. CONCLUSIONS Higher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death, independent of clinical risk factors and other biomarkers. GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.

OBJECTIVE: To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD). METHODS: Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice. RESULTS: The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05). CONCLUSIONS YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.
Mice ; Male ; Animals ; Lactic Acid/pharmacology* ; Intestinal Mucosa ; Colon/pathology* ; Dexamethasone/pharmacology* ; Diet, High-Protein ; Pneumonia/pathology*