重症急性胰腺炎患者医院感染危险因素分析

目的分析重症急性胰腺炎(SAP)患者医院感染的发生情况及相关危险因素,以制定预防措施,减少医院感染的发生。方法回顾性分析2011年1月-2017年12月东莞市人民医院收治的113例SAP患者的临床资料,分析医院感染发生情况及相关危险因素,采用SPSS 22.0统计软件进行分析。结果 113例SAP患者发生医院感染29例,医院感染发生率为25.66%,以下呼吸道感染为主(60.00%),检出病原菌35株,以革兰阴性杆菌为主(54.29%)。住院天数>14 d、采用机械通气、深静脉置管、留置导尿、入住重症监护病房(ICU)天数>6 d、改良CT严重指数(MCTSI)评分>6是SAP患者发生医院感染的危险因素。入住ICU天数>6 d、MCTSI评分>6是医院感染的独立危险因素。SAP患者发生医院感染的病死率高于未发生医院感染者(P <0.05)。结论 SAP患者的医院感染发生率较高,ICU入住时长和MCTSI评分与医院感染的发生密切相关,应尽量缩短ICU住院时间,对MCTSI评分高的患者应加强防治措施,避免医院感染发生。

Endoscopic extraction of a submucosal esophageal foreign body piercing into the thoracic aorta:A case report

BACKGROUND Aorto-esophageal injury is a rare but life-threatening complication of esophageal foreign bodies,which typically requires open surgery.The best way to treat patients with this condition remains unclear.To date,few reports have described an aortic wall directly penetrated by a sharp foreign body.Here,we present a rare case of a fishbone completely embedded in the esophageal muscularis propria and directly piercing the aorta,which was successfully treated by endoscopy and thoracic endovascular aortic repair(TEVAR).CASE SUMMARY We report the case of a 71-year-old man with a 1-d history of retrosternal pain after eating fish.No abnormal findings were observed by the emergency esophagoscopy.Computed tomography showed a fishbone that had completely pierced through the esophageal mucosa and into the aorta.The patient refused to undergo surgery for personal reasons and was discharged.Five days after the onset of illness,he was readmitted to our hospital.Endoscopy examination showed a nodule with a smooth surface in the middle of the esophagus.Endoscopic ultrasonography confirmed a fishbone under the nodule.After performing TEVAR,we incised the esophageal mucosa under an endoscope and successfully removed the fishbone.The patient has remained in good condition for 1 year.CONCLUSION Incising the esophageal wall under endoscope and extracting a foreign body after TEVAR may be a feasible option for cases such as ours.

Oncocytic adrenocortical tumor with uncertain malignant potential in pediatric population: A case report and review of literature

BACKGROUND Oncocytic adrenocortical tumor(OACT)is rare,with few cases reported in the literature.No more than 20 cases in children have been reported.The clinical characteristics,diagnosis,treatment and prognosis of children with OACT are summarized based on a literature review,in order to improve the understanding of OACT in children.CASE SUMMARY We report a case of a 17-mo-old patient who was admitted to our hospital due to symptoms of odynuria and fever,which are clinical features consistent with a functional adrenocortical tumor.The patient was diagnosed with OACT of uncertain malignant potential.Computed tomography indicated a soft tissue giant tumor in the right adrenal region,approximately 4.3 cm×5.5 cm in size.Multiple nodular and speckled calcifications were observed in the lesion.The patient received robot-assisted laparoscopic right adrenal tumor resection.Postoperative pathological results were consistent with OACT,and immunohistochemical results showed cytokeratin+/-,chromogranin A+,synaptophysin-,neuronspecific enolase-,S100-,Ki67 about 10%,CD34-and D2-40-.After surgery,urinary tract ultrasonography was reviewed monthly,catecholamine hormone and sex hormone levels were examined every 2 mo and computed tomography was performed every 6 mo.To date,no tumor metastasis or recurrence has been identified in this patient.The levels of sex hormones and catecholamine hormones decreased to normal 1 mo after surgery.CONCLUSION OACT is rare in the pediatric population,with few cases reported in the literature.Although most pediatric OACTs are benign,malignant cases have been reported.Surgical resection is the preferred option in most patients.

Relationship of PDCD5 expression with apoptosis, inflammatory factors and MMPs/TIMPs expression in degenerated intervertebral disc tissue

Objective: To study the relationship of PDCD5 expression with apoptosis, inflammatory factors and MMPs/TIMPs expression in degenerated intervertebral disc tissue. Methods:Patients with lumbar disc herniation who were treated in the Seventh People's Hospital of Shanghai between March 2015 and February 2017 were selected as the LDH group and patients with violent thoracolumbar vertebral fracture were selected as the control group. The intervertebral disc tissue was collected to determine the mRNA expression of PDCD5 as well as the protein levels of apoptosis molecules, inflammatory factors and MMPs/TIMPs molecules. Results: PDCD5 mRNA expression in intervertebral disc tissue of LDH group was significantly higher than that of control group;Caspase-3, Caspase-8, Fas, Caspase-9, Bax, SDF-1, CXCR-4, TNF-α, PGE2, MMP1, MMP2, MMP8 and MMP9 protein levels in intervertebral disc tissue of LDH group were significantly higher than those of control group and positively correlated with PDCD5 mRNA expression while TIMP1 and TIMP2 protein levels were significantly lower than those of control group and negatively correlated with PDCD5 mRNA expression. Conclusion: The high expression of PDCD5 in degenerated intervertebral disc tissue can activate apoptosis and inflammatory response and cause MMPs/TIMPs imbalance.

Meplazumab in hospitalized adults with severe COVID-19(DEFLECT):a multicenter,seamless phase 2/3,randomized,third-party double-blind clinical trial

Meplazumab,a humanized CD147 antibody,has shown favourable safety and efficacy in our previous clinical studies.In DEFLECT(NCT04586153),167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo.Meplazumab at 0.12 mg/kg,compared to the placebo group,showed clinical benefits in significantly reducing mortality by 83.6%(2.4%vs.14.6%,p=0.0150),increasing the proportion of patients alive and discharged without supplemental oxygen(82.9%vs.70.7%,p=0.0337)and increasing the proportion of patients who achieved sustained clinical improvement(41.5%vs.31.7%).The response rate in the 0.2 mg/kg group was relatively increased by 16.0%compared with the placebo group(53.7%vs.46.3%).Meplazumab also reduced the viral loads and multiple cytokine levels.Compare with the placebo group,the 0.3 mg/kg significantly increased the virus negative rate by 40.6%(p=0.0363)and reduced IL-8 level(p=0.0460);the 0.2 mg/kg increased the negative conversion rate by 36.9%,and reduced IL-4(p=0.0365)and IL-8 levels(p=0.0484).In this study,the adverse events occurred at a comparable rate across the four groups,with no unexpected safety findings observed.In conclusion,meplazumab promoted COVID-19 convalescence and reduced mortality,viral load,and cytokine levels in severe COVID-19 population with good safety profile.

Tau-mediated Neurodegeneration and Potential Implications in Diagnosis and Treatment of Alzheimer＇s Disease

Objective：To review recent research advances on tau,a major player in Alzheimer＇s disease （AD） pathogenesis,a biomarker for AD onset,and potential target for AD therapy.Data Sources：This review was based on a comprehensive search using online literature databases,including PubMed,Web of Science,and Google Scholar.Study Selection：Literature search was based on the following keywords：Alzheimer＇s disease,tau protein,biomarker,cerebrospinal fluid （CSF）,therapeutics,plasma,imaging,propagation,spreading,seeding,prion,conformational templating,and posttranslational modification.Relevant articles were carefully reviewed,with no exclusions applied to study design and publication type.Results：Amyloid plaques enriched with extracellular amyloid beta （Aβ） and intracellular neurofibrillary tangles comprised of hyperphosphorylated tau proteins are the two main pathological hallmarks ofAD.Although the Aβ hypothesis has dominated AD research for many years,clinical Aβ-targeting strategies have consistently failed to effectively treat AD or prevent AD onset.The research focus in AD has recently shifted to the role oftau in AD.In addition to phosphorylation,tau is acetylated and proteolytically cleaved,which also contribute to its physiological and pathological functions.Emerging evidence characterizing pathological tau propagation and spreading provides new avenues for research into the molecular and cellular mechanisms underlying AD pathogenesis.Techniques to detect tau at minute levels in CSF and blood have been developed,and improved tracers have facilitated tau imaging in the brain.These advances have potential to accurately determine tau levels at early diagnostic stages in AD.Given that tau is a potential therapeutic target,anti-tau immunotherapy may potentially be a viable treatment strategy in AD intervention.Conclusion：Detecting changes in tau and targeting tau pathology represent a promising lead in the diagnosis and treatment of AD.

Amyloid 13 Protein Aggravates Neuronal Senescence an, d Cognitive Deficits in 5XFAD Mouse Model of Alzheimer s Disease

Background： Amyloid β （Aβ） has been established as a key factor for the pathological changes in the brains of patients with Alzheimer＇s disease （AD）, and cellular senescence is closely associated with aging and cognitive impairment. However, it remains blurred whether, in theAD brains, Aβ accelerates the neuronal senescence and whether this senescence, in turn, impairs the cognitive function. This study aimed to explore the expression of senescence-associated genes in the hippocampal tissue from young to aged 5XFAD mice and their age-matched wild type （WT） mice to determine whether senescent neurons are present in the transgenic AD mouse model. Methods： The 5XFAD mice and age-matched wild type mice, both raised from 1 to 18 months, were enrolled in the study. The senescence-associated genes in the hippocampus were analyzed and differentially expressed genes （DEGs） were screened by quantitative real-time polymerase chain reaction. Cognitive perfom3ance of the mice was evaluated by Y-maze and Morris water maze tests. Oligomeric Aβ（oAβ） （1-42） was applied to culture primary neurons to simulate the in vivo manifestation. Aging-related proteins were detected by Western blotting analysis and immunofluorescence. Results： In 5XFAD mice, of all the DEGs, the senescence-associated marker p16 was most significantly increased, even at the early age. It was mainly localized in neurons, with a marginal expression in astrocytes （labeled as glutamine synthetase）, nil expression in activated microglia （labeled as lba1）, and negatively correlated with the spatial cognitive impairments of 5XFAD mice. oAβ （1-42） induced the production of senescence-related protein p1 6, but not p53 in vitro, which was in line with the in vivo manifestation. Conclusions： oAβ-accelerated neuronal senescence may be associated with the cognitive impairment in 5XFAD mice. Senescence-associated marker p16 can serve as an indicator to estimate the cognitive prognosis for A D population.

Prevalence of wearing-off and dyskinesia among the patients with Parkinson’s disease on levodopa therapy: a multi-center registry survey in China's Mainland

Objective:Chronic levodopa(L-dopa)treatment in Parkinson’s disease(PD)is often associated with the development of motor complications,but the corresponding epidemiological data is rare in Chinese PD patients.The present survey was to investigate the prevalence rate of wearing-off(WO)and dyskinesia among the patients with PD in China.Methods:From May 2012 to October 2012,a 3-step registry survey for wearing off(WO)and dyskinesia patients with PD receiving levodopa therapy was performed simultaneously at 28 movement disorders clinics in China.Results:There were 1,558 PD patients fulfilling the inclusion criteria.Among them,1,051 had at least one positive response of 9-item wearing off questionnaire(WOQ-9),724 and 160 patients were finally diagnosed with WO and dyskinesia by movement disorders specialists,respectively.The overall prevalence rates of WO and dyskinesia were 46.5%(95%CI 44.0%-48.9%)and 10.3%(95%CI 8.8%-11.8%),respectively.The mean score of WOQ-9 for those with WO was 3.8(SD=1.8),with movement slowness being the most common motor symptoms and pain/aching being the most common non-motor symptoms.Better improvement of motor symptoms(n=354,87.8%)and long-term disease control and drug selection(n=288,71.5%)were the two most frequently considered factors when movement disorders specialists adjusted therapeutic strategies for patients with WO.Conclusions:This survey provided the first multi-center epidemiological data of motor complications among PD patients on L-dopa therapy from China's Mainland.WO prevalence rate among Chinese PD patients was in line with,while dyskinesia prevalence rate was lower than previous reports from other Countries.

Endoplasmic Reticulum Stress Induces the Early Appearance of Pro-apoptotic and Anti-apoptotic Proteins in Neurons of Five Familial Alzheimer＇s Disease Mice

Background： Amyloid β （Aβ） deposits and the endoplasmic reticulum stress （ERS） are both well established in the development and progression of Alzheimer＇s disease （AD）. However, the mechanism and role of Aβ-induced ERS in AD-associated pathological progression remain to be elucidated. Methods： The five familial AD （5×FAD） mice and wild-type （WT） mice aged 2, 7, and 12 months were used in the present study. Monis water maze test was used to evaluate their cognitive performance, lmmunofluorescence and Western blot analyses were used to examine the dynamic changes of pro-apoptotic （CCAAT/enhancer-binding protein homologous protein [CHOP] and cleaved caspase-12） and anti-apoptotic factors （chaperone glucose-regulated protein [GRP] 78 and endoplasmic reticulum-associated protein degradation-associated ubiquitin ligase synovial apoptosis inhibitor 1 [SYVN 1]） in the ERS-associated unfolded protein response （UPR） pathway. Results： Compared with age-matched WT mice, 5 xFAD mice showed higher cleaved caspase-3, lower neuron-positive staining at the age of 12 months, but earlier cognitive deficit at the age of 7 months （all P 〈 0.05）. Interestingly, for 2-month-old 5×FAD mice, the related proteins involved in the ERS-associated UPR pathway, including CHOP, cleaved caspase-12, GRP 78, and SYVN 1, were significantly increased when compared with those in age-matched WT mice （all P 〈 0.05）. Moreover, ERS occurred mainly in neurons, not in astrocytes. Conclusions： These findings suggest that compared with those of age-matched WT mice, ERS-associated pro-apoptotic and anti-apoptotic proteins are upregulated in 2-month-old 5×FAD mice, consistent with intracellular Aβ aggregation in neurons.

Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication.Meplazumab is a humanized anti-CD147 IgG_(2) monoclonal antibody,which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019(COVID-19)patients.Here,we conducted a randomized,double-blinded,placebo-controlled phase 1 trial to evaluate the safety,tolerability,and pharmacokinetics of meplazumab in healthy subjects,and an open-labeled,concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients.In phase 1 study,59 subjects were enrolled and assigned to eight cohorts,and no serious treatment-emergent adverse event(TEAE)or TEAE grade≥3 was observed.The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics.No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort.The biodistribution study indicated that meplazumab reached lung tissue and maintained>14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32.In the exploratory phase 2 study,17 COVID-19 patients were enrolled,and 11 hospitalized patients were involved as concurrent control.The meplazumab treatment significantly improved the discharged(P=0.005)and case severity(P=0.021),and reduced the time to virus negative(P=0.045)in comparison to the control group.These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

Reduction of Glucose Metabolism in Olfactory Bulb is an Earlier Alzheimer＇s Disease-related Biomarker in 5XFAD Mice

Background：Early diagnosis assumes a vital role in an effective treatment of Alzheimer＇s disease （AD）.Most of the current studies can only make anAD diagnosis after the manifestation of typical clinical symptoms.The present study aimed to investigate typical and other biomarkers of AD to find a possible early biomarker.Methods：A total of 14 5XFAD mice （at 3 and 6 months old）,with 14 age-matched wild-type （WT） mice as control,were enrolled in this case-control study.Morris water maze test was performed to evaluate the cognitive function;buried food pellet test and olfactory maze test were employed to investigate the olfactory function;immunofluorescence to detect amyloid deposition and positron emission tomography to examine 2-deoxy-2-（18F） fluoro-D-glucose （[18F]-FDG） uptake in the hippocampus and cerebral cortex.Results：With the increasing age,cognitive performance （P =0.0262） and olfactory function were significantly deteriorated （day 1 P =0.0012,day 2 P =0.0031,day 3 P =0.0160,respectively） and the （18F）-FDG uptake was markedly decreased in multi-cerebral regions including the olfactory bulb （P 〈 0.0001）,hippocampus （P =0.0121）,and cerebral cortex （P 〈 0.0001）.Of note,in 3-month-old 5XFAD mice,a significant decline of （18F）-FDG uptake in the olfactory bulb was found when compared with that of age-matched WT mice （P =0.023） while no significant difference was present when the uptakes in other cerebral regions were compared.Conclusions：The decline of （18F）-FDG uptake in the olfactory bulb occurs earlier than other incidents,serving as an earlier in vivo biological marker of AD in 5XFAD mice and making early diagnosis of AD possibly.

Clinic, neuropathology and molecular genetics of frontotemporal dementia: a mini-review

Frontotemporal lobar degeneration(FTLD)represents a group of clinically,neuropathologically and genetically heterogeneous disorders with plenty of overlaps between the neurodegenerative mechanism and the clinical phenotype.FTLD is pathologically characterized by the frontal and temporal lobar atrophy.Frontotemporal dementia(FTD)clinically presents with abnormalities of behavior and personality and language impairments variants.The clinical spectrum of FTD encompasses distinct canonical syndromes:behavioural variant of FTD(bvFTD)and primary progressive aphasia.The later includes nonfluent/agrammatic variant PPA(nfvPPA or PNFA),semantic variant PPA(svPPA or SD)and logopenic variant PPA(lvPPA).In addition,there is also overlap of FTD with motor neuron disease(FTD-MND or FTD-ALS),as well as the parkinsonian syndromes,progressive supranuclear palsy(PSP)and corticobasal syndrome(CBS).The FTLD spectrum disorders are based upon the predominant neuropathological proteins(containing inclusions of hyperphosphorylated tau or ubiquitin protein,e.g transactive response(TAR)DNA-binding protein 43 kDa(TDP-43)and fusedin-sarcoma protein in neurons and glial cells)into three main categories:(1)microtubule-associated protein tau(FTLD-Tau);(2)TAR DNA-binding protein-43(FTLD-TDP);and(3)fused in sarcoma protein(FTLD-FUS).There are five main genes mutations leading clinical and pathological variants in FTLD that identified by molecular genetic studies,which are chromosome 9 open reading frame 72(C9ORF72)gene,granulin(GRN)gene,microtubule associated protein tau gene(MAPT),the gene encoding valosin-containing protein(VCP)and the charged multivesicular body protein 2B(CHMP2B).In this review,recent advances on the different clinic variants,neuroimaging,genetics,pathological subtypes and clinicopathological associations of FTD will be discussed.

A Remark on the Beale-Kato-Majda Criterion for the 3D MHD Equations with Zero Kinematic Viscosity

In this paper, we study the blow-up criterion of smooth solutions to the 3D magneto-hydrodynamic system in B^0∞,∞. We show that a smooth solution of the 3D MHD equations with zero kinematic viscosity in the whole space R3 breaks down if and only if certain norm of the vorticity blows up at the same time.

Surrogate markers and predictors of endogenous insulin secretion in children and adolescents with type 1 diabetes

Background No studies have examined endogenous insulin secretion in pediatric patients with type 1 diabetes in China using the gold-standard mixed-meal tolerance test.Because the latter is labor-intensive,we examined simpler surrogate markers of endogenous insulin secretion in Chinese youth,as previously reported for a European population.Methods Participants were 57 children and adolescents with type 1 diabetes aged 4.4-16.8 years(56% females).We per-formed 120-minute mixed-meal tolerance tests with serum C-peptide(CP)measurements every 30 minutes.Severe insulin deficiency(SID)was defined as CP peak<0.2 nmol/L.Urine CP and creatinine levels were measured at 0 and 120 minutes.Results Twenty-five(44%)patients had SID.Fasting CP levels missed one case(96% sensitivity)with no false posi-tives(100% specificity).While the 120-minute urine CP/creatinine had 100% sensitivity,it yielded markedly lower speci-ficity(63%).Every 1-year increase in diabetes duration and 1-year decrease in age at diagnosis were associated with 37%(P<0.001)and 20%(P=0.005)reductions in serum CP area-under-the-curve,respectively.Thus,86% of children aged<5 years had SID compared to none among patients aged ≥11 years.Conclusions Simple fasting CP measurements could be used to detect most SID cases in Chinese youth with type 1 diabe-tes.Fasting CP is a far more reliable measure of endogenous insulin secretion than the more commonly used insulin dose.Therefore,it could more precisely determine insulin secretory capacity to target those who could benefit,if treatments to preserve residual insulin secretion are developed.