STAT3 ameliorates truncated tau-induced cognitive deficits

Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.

Respiratory Viruses and Mycoplasma Pneumoniae Surveillance Among Hospitalized Children with Acute Respiratory Infections—Wuhan City,Hubei Province,China,September-November 2023

Summary What is already known about this topic?Acute respiratory infections(ARIs)are a significant contributor to illness and death in children.There has been a notable rise in the occurrence of ARIs and the associated pathogens in China,which has garnered worldwide attention.What is added by this report?This study conducted a retrospective analysis of the clinical characteristics of children with ARIs in Wuhan City from September to November 2023.

Screening of SARS-CoV-2 in 299 Hospitalized Children with Hematooncological Diseases:A Multicenter Survey in Hubei,China

Summary:The SARS-CoV-2 infection status of hospitalized children was surveyed in the department of pediatric hematology and oncology in three different hospitals of epidemic areas in Hubei,China.A cross-sectional study was performed to investigate the clinical characteristics,lung CT scan,SARS CoV-2 nucleic acid test and serum antibodics of hospitalized children with hemato-oncological diseases from January 23 to April 24,2020.299 children were enrolled in this study,including 176 males(58.9%)and 123 females(41.1%),aged from 2 months to 16 years.255 cases(85.3%)received chemotherapy or other immunosuppressive therapies,and there were 44 cases(14.7%)of other benign diseases.Nucleic acid test was performed on 258 children(86.3%)and one case was positive.163 cases(54.5%)were tested for serum antibodies,and all of them were negative.Lung CT scan was performed on 247 children(82.6%),and 107 of them showed infectious changes.Only one case(0.33%)of COVID-19 was diagnosed in the group.The prevalence rate of COVID-19 in enrolled children with hemato-oncological diseases in Hubei was 0.33%.Immunosuppressed patients are not prone to produce related antibodies.Comprehensive protective measures and ward management can reduce the risk of SARS-CoV-2 infection in the group patients.

Tetrandrine Represses Inflammation and Attenuates Osteoarthritis by Selective Inhibition of COX-2

Objective There is a lack of effective and long-term safe drugs for the treatment of osteoarthritis(OA).Tetrandrine(Tet)has been approved and used to treat rheumatoid arthritis for several decades,but its effect on OA has not been investigated.Herein,we explored the effect of Tet on OA and its underlying mechanism.Methods OA was induced using destabilization of the medial meniscus(DMM)in C57BL/6J mice.The animals were randomly divided into sham,DMM,Tet,celecoxib(CXB),and indomethacin(INDO)groups.Each group was given solvent or corresponding drugs by gavage for 7 weeks after convalescence.Pathological staining,OARSI scores,micro-computed tomography and behavior tests were performed to evaluate the effects of Tet.Results Tet remarkably alleviated cartilage injury in the knee joint,limited bone remodeling in the subchondral bone,and delayed progression of OA.Tet also significantly relieved joint pain and maintained function.Further mechanistic studies revealed that Tet lowered inflammatory cytokine levels and selectively suppressed gene and protein expression of cyclooxygenase(COX)-2 but not COX-1(P<0.01).Tet also reduced the production of prostaglandin E2 without damaging the gastric mucosa.Conclusion We found that Tet could selectively inhibit COX-2 gene expression and decrease cytokine levels in mice,thus reducing inflammation and improving OA without obvious gastric adverse events.These results provide a scientific basis for the clinical application of Tet in the treatment of OA.

Erratum to:Tetrandrine Represses Inflammation and Attenuates Osteoarthritis by Selective Inhibition of COX-2

The authors examined the original data of their work and noticed misuse of images in fig.1 and fig.3(as shown below on the upper panels,red box).The correct images are shown on the lower panels(red box).The authors sincerely apologize for the mistake and confirm the change does not affect the scientific conclusion of the published work.

Age-related Changes in Humanin Expression in the Ovarian Tissue of Rat

Objective This study examined humanin expression in rat ovarian tissue,its cellular localization,and its correlation with rat age under physiological conditions.Methods A total of 40 Sprague-Dawley rats of various ages(2,12,30,and 60 days old and 1 year old)were grouped by age.Immunofluorescence and immunohistochemical techniques were used to observe humanin expression and cellular location in the ovarian tissues of rats from each age group.In addition,Western blotting and Real-time quantitative reverse transcription PCR(qRT-PCR)techniques were used to measure humanin expression level in the ovarian tissues of rats from each age group.Results The immunofluorescence and immunohistochemical results confirmed that humanin was expressed in rat ovarian tissues.In addition,cellular localization analysis showed that humanin was expressed in the cytoplasm of oocytes,interstitial cells,granulosa cells and theca cells in all levels of follicles after the primary follicles,and in the corpus luteum.The qRT-PCR results revealed that the level of humanin expression in the ovarian tissues of 12-day-old rats was non-significantly higher than that in the ovarian tissues of 2-day-old rats(P>0.05),whereas the levels of humanin expression in the ovarian tissues of 30-day-old,60-day-old,and 1-year-old rats were significantly lower than that in the ovarian tissues of 2-day-old rats(P<0.05).The Western blotting results demonstrated that the levels of humanin protein expression in the ovarian tissues of 60-day-old and 1-year-old rats were significantly lower than those of 2-day-old rats(P<0.01),whereas there was no significant difference in the level of humanin protein expression between the ovarian tissues of 12-day-old and 30-day-old rats.Conclusion This study confirmed that humanin is expressed in the cytoplasm of various cells in rat ovarian tissues.Moreover,the level of humanin expression was highest in the ovarian tissues of 12-day-old rats,and it subsequently decreased with age.The changes in the expression of humanin in the ovary of rats at different ages will lay the foundation for the role of humanin in ovarian aging.The effect of humanin on ovarian function is worthy of further study in the future.

Expression of MMIF, HIF-1α and VEGF in Serum and Endometrial Tissues of Patients with Endometriosis

The aim of this study was to investigate the expression of macrophage migration inhibitory factor （MMIF）, hypoxia-inducible factor- 1 α（HIF- 1α ）and vascular endothelial growth factor （VEGF） in the serum and endometrial tissues of patients with endometriosis （EM） and the clinical significance. Eighty EM patients [American Reproductive Association stage Ⅰ （n=20）, stage Ⅱ （n=22）, stage Ⅲ （n=21） and stage Ⅳ （n=17）] were enrolled and divided into mild （10- 14 points, n=28）, moderate （16-24 points, n=27） and severe （26-30 points, n=25） dysmenorrhea groups. The control group included 40 healthy women of childbearing age who underwent routine healthcare examinations in the enrolment period. The expression of MMIF, HIF- 1α and VEGF in the serum and endometrial tissues was measured by enzyme-linked immunosorbent assay and Western blotting, respectively. Meanwhile, the sensitivity and specificity of serum MMIF, HIF-1α, and VEGF when separately used as single indexes or jointly used as one index were examined as well. The results showed that serum concentrations of MMIF, HIF-1α, and VEGF were significantly higher in EM patients than in controls （P〈0.05）. The expression of all three proteins in both serum and endometrial tissues increased significantly with the R-AFS stage （P〈0.05） and with dysmenorrheal severity （P〈0.05）. The sensitivity and specificity of the combined detection of serum MMIF, HIF-1α, and VEGF levels were significantly higher than those of single index detection （P〈0.05）. In conclusion, the expression of MMIF, HIF-1α, and VEGF in the serum and endometrial tissues may be used to assess the stage of EM and the severity of dysmenorrhea. Combined evaluation of MMIF, HIF-1α, and VEGF significantly improves the diagnostic sensitivity and specificity.

Alterations of biliary biochemical constituents and cytokines in infantile hepatitis syndrome

AIM: To investigate the biliary biochemical constituents and cytokines in infantile hepatitis syndrome (IHS). METHODS: From 42 IHS subjects and 21 controls, serum and biliary biochemical constituents, including total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GT), total bile acid (TBA), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) both in bile and serum, were assayed. The subjects with IHS were divided into a cholestasis group (n = 21) and a hepatitis group (n = 21). RESULTS: In the cholestasis group, serum TBIL, DBIL, ALT, γ-GT, TBA, IL-6 and TNF-α levels were higher than those in the control (P < 0.01); and also the biliary TBIL, DBIL, γ-GT and TBA levels were lower than those in the control, whereas biliary IL-6 and TNF-α levels were higher than those in the control (P < 0.01). In the cholestasis group, serum IL-6 and TNF-α levels were lower than those in bile (P < 0.01). In the hepatitis group, serum DBIL, ALT, γ-GT, TBA, IL-6 and TNF-α levels were higher than those in the control (P < 0.01 or 140.57 ± 70.32 vs 79.06 ± 35.25, P < 0.05), while biliary TBIL, DBIL, γ-GT and TBA levels were lower than those in the control (P < 0.01), and biliary IL-6 and TNF-α levels were higher than those in the control (P < 0.01). In the hepatitis group, serum IL-6 and TNF-α levels were also lower than those in bile (P < 0.01). Serum TBIL, DBIL, γ-GT, IL-6 and TNF-α levels in the cholestasis group were higher than those in the hepatitis group, while biliary IL-6 and TNF-α levels in the cholestasis group were higher than those in the hepatitisgroup. Biliary IL-6 and TNF-α were found to be more significantly increased than serum IL-6 and TNF-α in IHS (P < 0.01). The biliary IL-6 and TNF-α levels were positively correlated with serum DBIL, TBA and γ-GT levels in IHS subjects. CONCLUSION: Biliary biochemical constituents alter in coincidence with pathological changes in hepatocellular injury. Cholestasis is more serious in IHS patients of cholestasis subtype. Assay of biliary IL-6 and TNF-α levels can be specific and sensitive to determine the inflammatory status of impaired liver in IHS.

Cognitive deficits and Alzheimer-like neuropathological impairments during adolescence in a rat model of type 2 diabetes mellitus

Numerous studies have shown that many patients who suffer from type 2 diabetes mellitus exhibit cognitive dysfunction and neuronal synaptic impairments. Therefore, growing evidence suggests that type 2 diabetes mellitus has a close relationship with occurrence and progression of neurodegeneration and neural impairment in Alzheimer＇s disease. However, the relationship between metabolic disorders caused by type 2 diabetes mellitus and neurodegeneration and neural impairments in Alzheimer＇s disease is still not fully determined. Thus, in this study, we replicated a type 2 diabetic animal model by subcutaneous injection of newborn Sprague-Dawley rats with monosodium glutamate during the neonatal period. At 3 months old, the Barnes maze assay was performed to evaluate spatial memory function. Microelectrodes were used to measure electrophysiological function in the hippocampal CA1 region. Western blot assay was used to determine expression levels of glutamate ionotropic receptor NMDA type subunit 2 A（GluN2A） and GluN2B in the hippocampus. Enzyme-linked immunosorbent assay was used to determine levels of interleukin-1β, tumor necrosis factor α, and interleukin-6 in the hippocampus and cerebral cortex, as well as hippocampal amyloid beta（Aβ）1-40 and Aβ_（1-42） levels. Our results showed that in the rat model of type 2 diabetes mellitus caused by monosodium glutamate exposure during the neonatal period, latency was prolonged and the number of errors increased in the Barnes maze. Further, latency was increased and time in the escape platform quadrant shortened. Number of times crossing the platform was also reduced in the Morris water maze. After high frequency stimulation of the hippocampus, synaptic transmission was inhibited, expression of GluN2A and GluN2B were decreased in the hippocampus, expression of interleukin 1β, interleukin 6, and tumor necrosis factor α was increased in the hippocampus and cortex, and levels of Aβ_（1-40） and Aβ_（1-42） were increased in the hippocampus. These findings confirm that type 2 diabetes mellitus induced by neonatal monosodium glutamate exposure results in Alzheimer-like neuropathological changes and further causes cognitive deficits and neurodegeneration in young adulthood.

Association of Serotonin Receptors with Attention Deficit Hyperactivity Disorder： A Systematic Review and Meta-analysis

Attention deficit hyperactivity disorder （ADHD） is one of the most common mental disorders in childhood, with a high heritability about 60% to 90%. Serotonin is a monoamine neurotransmitter. Numerous studies have reported the association between the serotonin receptor family （5-HTR） gene polymorphisms and ADHD, but the results are still controversial. In this study, we conducted a meta-analysis of the association between 5-HTRIB, 5-HTR2A, and 5-HTR2C genetic variants and ADHD. The results showed that the 861G allele of 5-HTRIB SNP rs6296 could significantly increase the risk of ADHD （OR= 1.09, 95% CI： 1.01-1.18）; the 5-HTR2C gene rs518147 （OR=1.69, 95% CI： 1.38-2.07） and rs3813929 （OR = 1.57, 95% CI： 1.25-1.97） were all associated with the risk of ADHD. In addition, we also carried on a case- control study to explore the relevance between potential candidate genes 5-HTR1A, 5-HTRIE, 5-HTR3A and ADHD. The results indicated that 5-HTRIA rs6295 genotype （CC＋CG vs. GG OR=Z00, 95% CI： 1.23-3.27） and allele （OR=1.77, 95% CI： 1.16-2.72） models were statistically significantly different between case group and control group. This study is the first comprehensive exploration and summary of the association between serotonin receptor family genetic variations and ADHD, and it also provides more evidence for the etiology of ADHD.

SOD2 Alleviates Hearing Loss Induced by Noise and Kanamycin in Mitochondrial DNA4834-deficient Rats by Regulating PI3K/MAPK Signaling

Superoxide dismutase 2(SOD2)-mediated gene therapy has significant protective effects against kanamycin-induced hearing loss and hair cell loss in the inner ear,but the underlying mechanisms are still unclear.Herein,an in vivo aging model of mitochondrial DNA(mtDNA)4834 deletion mutation was established using D-galactose,and the effects of noise or kanamycin on inner ear injury was investigated.Rats subjected to mtDNA4834 mutation via D-galactose administration showed hearing loss characterized by the disruption of inner ear structure(abnormal cell morphology,hair cell lysis,and the absence of the organ of Corti),increased SOD2 promoter methylation,and an increase in the degree of apoptosis.Exposure to noise or kanamycin further contributed to the effects of D-galactose.SOD2 overexpression induced by viral injection accordingly counteracted the effects of noise and kanamycin and ameliorated the symptoms of hearing loss,suggesting the critical involvement of SOD2 in preventing deafness and hearing-related conditions.The PI3K and MAPK signaling pathways were also regulated by noise/kanamycin exposure and/or SOD2 overexpression,indicating that they may be involved in the therapeutic effect of SOD2 against age-related hearing loss.

Adverse Effects of Exposure to Fine Particulate Matters and Ozone on Gestational Hypertension

Gestational hypertension(GH)is a common complication during pregnancy.GH is regarded as a potential public health challenge for pregnant women and infants.Limited evidence has linked ambient air pollution to an increased GH risk.However,most of the studies were conducted in developed countries,with inconsistent results obtained.The present study was performed to explore whether exposure to particulate matters with an aerodynamic diameter≤2.5(PM2.5)and ozone(O3)was related to elevated odds of GH in a Chinese population.This population-based cohort study involved 38115 pregnant women in Wuhan,China.All information was collected from the Wuhan Maternal and Child Health Management Information System,using standardized quality control.The daily air pollutant data for PM2.5 and O3 were obtained from the 20 monitoring stations of the Wuhan Environmental Monitoring Center during 2014.The nearest monitor approach was applied to individual exposure assessment of PM2.5 and O3 for each participant.After adjusting for major confounders and other air pollutants,a 10μg/m^3 increase in PM25 and O3 concentrations was found to correlate to a 1.14-fold[95%confidence interval(95%CI):1.09,1.20]and a 1.05-fold(95%CI:1.02,1.07)increase in GH risk,respectively.Additionally,stronger relationships between GH risk and PM25 and O3 exposure were observed in women who conceived in winter and summer,respectively.These findings suggest that air pollutants may contribute to the development of GH.

Risk Factors for Strangulated Ovarian Hernia in Female Infants:the Role of Ovarian Volume

The risk factors associated with strangulated ovarian hernia (SOH)in female patients (<1 year old)were identified.A retrospective analysis was conducted regarding the data from 2006 to 2017.The patients were divided into 2groups:SOH group (n=9)and non-SOH group (n=23). Patient demographics,clinical signs,preoperative examinations and intraoperative findings were compared between the two groups,and risk factors for SOH were tested using a binary logistic regression model.To explore whether greater ovary was more likely to be twisted,leading to SOH, all the patients were divided into ovary volume <5cm^3 and ≥5cm^3 groups and the association between ovarian volume and ovary torsion was assessed.Among a total of 32 female patients (<1year old)with incarcerated ovarian herniation,9 patients developed SOH.The single variate analysis revealed that times of manual reduction,ovarian volume,ovary with or without multiple cysts,ovary torsion or not and angle of ovary torsion were found to be significant factors associated with SOH.The multivariate analysis showed ovarian volume was evidenced as an independent risk factor for SOH.Furthermore,the incidence of ovary torsion was significantly higher in ovarian volume ≥5cm^3 group than in ovarian volume <5cm^3 group,indicating that larger ovary was more likely to result in ovary torsion,leading to SOH.Our study demonstrated that the odds of SOH increased with increasing ovarian volume in female patients (<1 year old)because the relatively greater ovary at this age was more likely to be incarcerated and twisted,leading to SOH.

Mild Encephalopathy/Encephalitis with a Reversible Splenial Lesion(MERS):A Report of Five Neonatal Cases

Mild encephalopathy/encephalitis with a reversible splenial(MERS) lesion is a clinic-radiological entity. The clinical features of MERS in neonates are still not systemically reported. This paper presents five cases of MERS, and the up-to-date reviews of previously reported cases were collected and analyzed in the literature. Here we describe five cases clinically diagnosed with MERS. All of them were neonates and the average age was about 4 days. They were admitted for the common neurological symptoms such as hyperspasmia, poor reactivity and delirium. Auxiliary examinations during hospitalization also exhibited features in common. In this report, we reached following conclusions. Firstly, magnetic resonance imaging revealed solitary or comprehensive lesions in the splenium of corpus callosum, some of them extending to almost the whole corpus callosum. The lesions showed low intensity signal on T1-weighted images, homogeneously hyperintense signal on T2-weighted images, fluid-attenuated inversion recovery and diffusion-weighted images, and exhibited an obvious reduced diffusion on apparent diffusion coefficient map. Moreover, the lesions in the magnetic resonance imaging disappeared very quickly even prior to the clinical recovery. Secondly, all the cases depicted here suffered electrolyte disturbances especially hyponatremia which could be easily corrected. Lastly, all of the cases recovered quickly over one week to one month and majority of them exhibited signs of infections and normal electroencephalography.

Coxsackievirus A6 was the most common enterovirus serotype causing hand,foot,and mouth disease in Shiyan City,central China

BACKGROUND Hand,foot,and mouth disease(HFMD)has become one of the most common infectious diseases in China.Before 2016,the primary causal serotypes were enterovirus A71(EV-A71)and coxsackievirus A16(CV-A16).Following the introduction of EV-A71 vaccines in China since 2016,the situation could change.CV-A6 has recently replaced EV-A71 and CV-A16 in some areas of China.However,the epidemiological characteristics of central China remain unknown.AIM To investigate the clinical symptoms and pathogen spectrum of HFMD in Shiyan City,central China,in recent years.METHODS The epidemiological,clinical,and laboratory data from HFMD cases reported to the Shiyan Center for Disease Control and Prevention between January 2016 and December 2020 were analyzed.196 throat swab specimens were collected from hospitalized HFMD patients between January 2018 and December 2020.To detect and genotype enteroviruses,real-time reverse transcription-polymerase chain reaction and sequencing of the 5'-untranslated region were used.In Shiyan,168 laboratory-confirmed HFMD cases were studied using a logistic regression model to determine the effect of predominant enterovirus serotypes.Based on the logistic regression model,the least absolute shrinkage and selection operator model was used to analyze the correlation between CV-A6 infection and various clinical characteristics in HFMD patients in Shiyan.RESULTS From 2016 to 2020,35840 HFMD cases were reported in Shiyan.The number of cases decreased by 48.4%from 2016 to 2017.Approximately 1.58-fold increases were found in 2018 and 2019 when compared to the previous year,respectively.In 2020,a decrease of about 85.5%was reported when compared to 2019.The most common serotypes shifted from EV-A71 and CV-A16(about 60%-80%in 2016 and 2018)to others(more than 80.0%in 2017,2019,and 2020).EV-A71 lost its dominance in 2017 in Shiyan.Among 196 confirmed HFMD cases,85.7%tested positive for enterovirus,with CV-A6 being the most common serotype(121/168,72.0%).The positive rates for CV-A16 and CVA10 were 4.8%and 3.0%,respectively.There was no EV-A71 discovered.Infection with CV-A6 was linked to fever,myocardial damage,increased creatine kinase MB isoenzyme,and lactate dehydrogenase levels.CONCLUSION CV-A6 was the most common enterovirus serotype in Shiyan City,replacing EV-A71 and CV-A16 as the HFMD pathogen.Developing vaccines against CV-A6 or multiple pathogens,as well as rising CV-A6 surveillance,will help prevent HFMD in central China.

Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China

Since December 2019,COVID-19 has occurred unexpectedly and emerged as a health problem worldw ide.Despite the rapidly increasing number of cases in subsequent weeks,the clinical characteristics of pediatric cases are rarely described.A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province.A total of 25 confirmed pediatric cases of COVID-19 were collected.The demographic data,epidemiological history,underlying discascs,clinical mani festations,laboratory and radiological data,treatments,and outcomes were analyzcd.Of 25 hospitalized patients with COVID-19,the boy to girl ratio was 1.27:1.The median age was 3 years.COVID-19 cases in children aged<3 years,3-6 years,and≥6-years patients were 10(40%),6(24%),and 9(36%),respectively.The most common symptoms at onset of ilness were fever(13[52%]),and dry cough(11[44%]).Chest CT images showed essential normal in 8 cases(33.3%),unilateral involvement of lungs in 5 cases(20.8%),and bilateral involvement in 11 cases(45.8%).Clinical diagnoses included upper respiratory tract infection(n=8),mild pneumonia(n=15),and critical cases(n=2).Two critical cases(8%)were given invasive mechanical ventilation,corticosteroids,and immunoglobulin.The symptoms in 24(96%)of 25 patients were alleviated and one patient had been discharged.It was concluded that children were susceptible to COVID-19 like adults,while the clinical presentations and outcomes were more favorable in children.However,children less than 3 years old accounted for majority cases and critical cases lied in this age group,which demanded extra attentions during home caring and hospitalization treatment.

Role of GSK-3β in Isoflurane-induced Neuroinflammation and Cognitive Dysfunction in Aged Rats

Summary： This study investigated the role of glycogen synthase kinase-3D （GSK-3β） in isoflu- rane-induced neuroinflammation and cognitive dysfunction in aged rats. The hippocampi were dissected from aged rats which had been intraperitoneally administered lithium chloride （LiC1, 100 mg/kg） and then exposed to 1.4% isoflurane for 6 h. The expression of GSK-313 was detected by Western blotting. The mRNA and protein expression levels of tumor necrosis factor （TNF）-a, interleukin （IL）-lβ and IL-6 were measured by real-time PCR and enzyme-linked immunosorbent assay （ELISA）, respectively. Mor- ris water maze was employed to detect spatial memory ability of rats. The results revealed that the level of GSK-3β was upregulated after isofurane exposure. Real-time PCR analysis demonstrated that isoflu- rane anesthesia increased mRNA levels of TNF-a IL-Iβ and IL-6, which was consistent with the ELISA results. However, these changes were reversed by prophylactic LiC1, a non-selective inhibitor of GSK-3β. Additionally, we discovered that LiC1 alleviated isoflurane-induced cognitive impairment in aged rats. Furthermore, the role of GSK-313 in isoflurae-induced neuroinflammation and cognitive dysfunction was associated with acetylation of NF-r,B p65 （Lys310）. In conclusion, these results suggested that GSK-3β is associated with isoflurane-induced upregulation of proinflammatory cytokines and cognitive disorder in aged rats.

Risk factors and antibiotic resistance of pneumonia caused by multidrug resistant Acinetobacter baumannii in pediatric intensive care unit

BACKGROUND:With beta-lactam drugs and immunosuppressants widely used,the infection caused by Acinetobacter baumannii(Ab) has become more and more serious with multidrug resistant Acinetobacter baumannii(MDRAb) emerging and worsening rapidly.Compared with other patients,the incidence and multidrug resistance of MDRAb are higher in children in pediatric intensive care unit(PICU) because of immune deficiency,severe basic diseases,prolonged hospitalization and invasive operations.Hence it is significant to study the epidemiology and changes of antibacterial susceptibility in order to reduce the incidence of MDRAb in children.METHODS:A total 115 patients with MDRAb pneumonia and 45 patients with negative MDRAb(NMDRAb) pneumonia who had been treated from January 2009 to August 2011 were studied retrospectively at the PICU of Wuhan Children's Hospital.Clinical data were analyzed with univariate and multivariate Logistic regression.RESULTS:In 176 clinical strains of Acinetobacter baumannii isolated,there were 128 strains of MDRAb,accounting for 72.73%.Drug susceptibility tests showed that the resistance rates of β-lactam antibiotics were more than 70%except for cefoperazone sulbactam.The rates to carbapenems were higher than 90%.They were significantly higher than those of NMDRAb.Amikacin,levofloxacin,ciprofloxacin and minocycline had the lowest drug-resistance rates(<20%).Multivariate Logistic regression revealed that ICU stay,the time of mechanical ventilation,anemia,hypoproteinemia and the use of carbapenems were independent risk factors for MDRAb pneumonia.CONCLUSIONS:MDRAb is an important opportunistic pathogen to pneumonia in PICU,and its drug-resistance is severe.It increases significantly the mortality of patients.It is important to take the effective prevention measures for controlling it.

Correlations of Serological Markers with Development of Systemic Involvement in Adult Immunoglobulin A Vasculitis:A Retrospective Study of 259 Patients in Central China

Objective:Although relatively rare,adult immunoglobulin A vasculitis(IgAV)can lead to severe complications and longer hospitalization,and result in poor prognosis,when compared to childhood IgAV.Hence,early identification and prevention for patients prone to develop systemic involvement are essential.The purpose of this study was to explore the correlations of common serological markers with the development of systemic involvement in adult IgAV.Methods:A retrospective analysis was performed for adult IgAV patients,who were hospitalized in Wuhan Union Hospital between January 2016 and December 2019.A total of 259 patients were enrolled,and the pre-treatment serological markers were comprehensively assessed.Results:In the present study,49.0% and 33.2% of patients developed renal and gastrointestinal(GI)involvement,respectively.Furthermore,the elevated levels of white blood cells count,D-Dimer(D-D),C-reactive protein(CRP)and neutrophil granulocyte ratio(NE%)>60% were significantly associated with GI involvement in the univariate analysis,while the decrease in high density lipoprotein level,and the elevated D-D and CRP levels were significantly associated with renal involvement(P<0.05).Moreover,a prediction model that combined multiple markers was established by performing a logistic regression analysis,and this presented a more favorable value of prediction than the individual serological markers.Conclusion:The present study suggests that common serological markers have close correlations with systemic involvement in adult IgAV,and that the establishment of a prediction model for systemic involvement may be helpful in facilitating personalized therapeutic strategies and clinical management for IgAV patients.

Prenatal Diagnosis of Sirenomelia by Two-Dimensional and Three-Dimensional Skeletal Imaging Ultrasound

Summary： This study sought to evaluate the contribution of two-dimensional ultrasound （2D-US） and three-dimensional skeletal imaging ultrasound （3D-SUIS） in the prenatal diagnosis of sirenomelia. Be- tween September 2010 and April 2014, a prospective study was conducted in a single referral center using 3D-SU1S performed after 2D-US in 10 cases of sirenomelia. Diagnostic accuracy and detailed findings were compared with postnatal three-dimensional helical computed tomography （3D-HCT）, radiological findings and autopsy. Pregnancy was terminated in all 10 sirenomelia cases, including 9 singletons and I conjoined twin pregnancy, for a total of 5 males and 5 females. These cases of sirenomelia were deter- mined by autopsy and/or chromosomal examination. Initial 2D-US showed that there were 10 cases of oligohydranmios, bilateral renal agenesis, bladder agenesis, single umbilical artery, fusion of the lower limbs and spinal abnormalities; 8 cases of dipus or monopus; 2 cases of apus; and 8 cases of cardiac abnormalities. Subsequent 3D-SUIS showed that there were 9 cases of scoliosis, l0 cases of sacrococ- cygeal vertebra dysplasia, 3 cases of hemivertebra, 1 case of vertebral fusion, 3 cases of spina bifida, and 5 cases of rib abnormalities. 3D-SUIS identified significantly more skeletal abnormalities than did 2D-US, and its accuracy was 79.5% （70/88） compared with 3D-HCT and radiography. 3D-SUIS seems to be a useful complementary method to 2D-US and may improve the accuracy of identifying prenatal skeletal abnormalities related to sirenomelia.