Neurosyphilis complicated by anti-γ-aminobutyric acid-B receptor encephalitis: A case report

BACKGROUND Syphilis is an infectious disease caused by Treponema pallidum that can invade the central nervous system,causing encephalitis.Few cases of anti-N-methyl-Daspartate receptor autoimmune encephalitis(AE)secondary to neurosyphilis have been reported.We report a neurosyphilis patient with anti-γ-aminobutyric acid-B receptor(GABABR)AE.CASE SUMMARY A young man in his 30s who presented with acute epileptic status was admitted to a local hospital.He was diagnosed with neurosyphilis,according to serum and cerebrospinal fluid(CSF)tests for syphilis.After 14 d of antiepileptic treatment and anti-Treponema pallidum therapy with penicillin,epilepsy was controlled but serious cognitive impairment,behavioral,and serious psychiatric symptoms were observed.He was then transferred to our hospital.The Mini-Mental State Examination(MMSE)crude test results showed only 2 points.Cranial magnetic resonance imaging revealed significant cerebral atrophy and multiple fluidattenuated inversion recovery high signals in the white matter surrounding both lateral ventricles,left amygdala and bilateral thalami.Anti-GABABR antibodies were discovered in CSF(1:3.2)and serum(1:100).The patient was diagnosed with neurosyphilis complicated by anti-GABABR AE,and received methylprednisolone and penicillin.Following treatment,his mental symptoms were alleviated.Cognitive impairment was significantly improved,with a MMSE of 8 points.Serum anti-GABABR antibody titer decreased to 1:32.The patient received methylprednisolone and penicillin after discharge.Three months later,the patient’s condition was stable,but the serum anti-GABABR antibody titer was 1:100.CONCLUSION This patient with neurosyphilis combined with anti-GABABR encephalitis benefited from immunotherapy.

Effect of cooling rate during quenching on the microstructure and creep property of nickel-based superalloy FGH96

The effect of cooling rate during quenching on the microstructure and creep property of nickel-based superalloy FGH96 was investigated. Three groups of samples were quenched continuously with three fixed cooling rates, respectively, then subjected to a creep test under a constant load of 690 MPa at 700℃. Clear differences in size of secondary γ′ precipitates, creep properties and substructure of creep-tested samples were observed. The quantitative relationship among cooling rate, the size of secondary γ′ precipitates, and steady creep rate was constructed. It was found that with increasing cooling rate, the size of secondary γ′ precipitates decreases gradually, showing that the relationship between the size of secondary γ′ precipitates and the cooling rate obeys a power law, with an exponent of about –0.6, and the creep rate of steady state follows a good parabola relationship with cooling γ′ precipitate size. For 235℃/min, FGH96 alloy exhibited very small steady creep rate. The density of dislocation was low, and the isolated stacking fault was the dominant deformation mechanism. With decreasing cooling rates, the density of dislocation increased remarkably, and deformation microtwinning was the dominant deformation process. Detailed mechanisms for different cooling rate were discussed.

Mutations around interferon sensitivity-determining region:A pilot resistance report of hepatitis C virus 1b in a Hong Kong population

AIM: To explore mutations around the interferon sensitivity-determining region (ISDR) which are associated with the resistance of hepatitis C virus 1b (HCV-1b) to interferon-α treatment. METHODS: Thirty-seven HCV-1b samples were ob- tained from Hong Kong patients who had completed the combined interferon-α/ribavirin treatment for more than one year with available response data. Nineteen of them were sustained virological responders, while 18 were non-responders. The amino acid sequences of the extended ISDR (eISDR) covering 64 amino acids upstream and 67 amino acids downstream from the previously reported ISDR were analyzed. RESULTS: One amino acid variation (I2268V, P = 0.023) was significantly correlated with treatment outcomein this pilot study with a limited number of patients, while two amino acid variations (R2260H, P = 0.05 and S2278T, P = 0.05) were weakly associated with treatment outcome. The extent of amino acid variations within the ISDR or eISDR was not correlated with treatment outcome as previously reported. CONCLUSION: Three amino acid mutations near but outside of ISDR may associate with interferon treatment resistance of HCV-1b patients in Hong Kong.

Eltrombopag-related renal vein thromboembolism in a patient with immune thrombocytopenia: A case report

BACKGROUND Eltrombopag is an orally administered thrombopoietin receptor agonist linked to a heightened risk of treatment-related thromboembolism.Both venous and arterial thromboses have been documented in the medical literature.CASE SUMMARY In the absence of nephropathy,a 48-year-old patient receiving eltrombopag for immune thrombocytopenia(ITP)developed renal vein thrombosis and pulmonary embolism.The renal vein thrombus spontaneously resolved during subsequent anticoagulant treatment,restoring venous circulation.CONCLUSION A rapid upsurge in platelets,rather than their absolute number,may trigger thrombotic events in this setting.For patients at high thrombotic risk,individualized eltrombopag dosing and vigilance in platelet monitoring are perhaps needed during treatment of ITP.

Outcomes of high-grade aneurysmal subarachnoid hemorrhage patients treated with coiling and ventricular intracranial pressure monitoring

BACKGROUND High-grade aneurysmal subarachnoid hemorrhage is a devastating disease with a low favorable outcome.Elevated intracranial pressure is a substantial feature of high-grade aneurysmal subarachnoid hemorrhage that can result to secondary brain injury.Early control of intracranial pressure including decompressive craniectomy and external ventricular drainage had been reported to be associated with improved outcomes.But in recent years,little is known whether external ventricular drainage and intracranial pressure monitoring after coiling could improve outcomes in high-grade aneurysmal subarachnoid hemorrhage.AIM To investigate the outcomes of high-grade aneurysmal subarachnoid hemorrhage patients with coiling and ventricular intracranial pressure monitoring.METHODS A retrospective analysis of a consecutive series of high-grade patients treated between Jan 2016 and Jun 2017 was performed.In our center,followed by continuous intracranial pressure monitoring,the use of ventricular pressure probe for endovascular coiling and invasive intracranial pressure monitoring in the acute phase is considered to be the first choice for the treatment of high-grade patients.We retrospectively analyzed patient characteristics,radiological features,intracranial pressure monitoring parameters,complications,mortality and outcome.RESULTS A total of 36 patients were included,and 32(88.89%)survived.The overall mortality rate was 11.11%.No patient suffered from aneurysm re-rupture.The intracranial pressure in 33 patients(91.67%)was maintained within the normal range by ventricular drainage during the treatment.A favorable outcome was achieved in 18 patients(50%)with 6 mo follow-up.Delayed cerebral ischemia and Glasgow coma scale were considered as significant predictors of outcome(2.066 and-0.296,respectively,P<0.05).CONCLUSION Ventricular intracranial pressure monitoring may effectively maintain the intracranial pressure within the normal range.Despite the small number of cases in the current work,high-grade patients may benefit from a combination therapy of early coiling and subsequent ventricular intracranial pressure monitoring.

Intravesically instilled gemcitabine-induced lung injury in a patient with invasive urothelial carcinoma: A case report

BACKGROUND Gemcitabine is a chemotherapy agent with relatively low toxicities,as a valid option for elderly patients with underlying diseases.Gemcitabine-induced pulmonary toxicities are rare and various,ranging from self-limited episodes of bronchospasm to fatal,progressive,severe,interstitial pneumonitis and respiratory failure.Intravesical gemcitabine instillations are commonly used to reduce recurrence or progression for non-muscle-invasive bladder cancer or urothelial cancer.Few severe toxicities have been reported for the intravesical instillation is assumed to be completely separated from the systemic circulation.CASE SUMMARY A 67-year-old patient received 30 cycles of intravesical gemcitabine instillation after transurethral resection and developed a 1-wk fever,cough,hemoptysis,and dyspnea.After a thorough checkup,bilateral consolidation and infiltration of the lungs were documented and a percutaneous lung biopsy confirmed organizing pneumonia after treatment with broad-spectrum empirical antibiotics failed.Tapered corticosteroids were administered,and pulmonary toxicity gradually resolved.CONCLUSION Gemcitabine-induced pulmonary toxicities present with various manifestations.In spite of the rare pulmonary involvement by the intravesical gemcitabine instillation,health care professionals who administer gemcitabine chemotherapy in this way should monitor for gemcitabine-induced pulmonary toxicities,particularly in patients with high-risk factors.

Advances in the therapeutic drugs of Coronavirus disease 2019 (COVID-19)

Since December 2019,the outbreak of a new coronavirus that named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and caused coronavirus disease 2019(COVID-19)has greatly threatened the public health and raised great concerns worldwide.In late December 2019,patients with COVID-19 were found in Wuhan,China.COVID-19 is an acute disease that causes the lesions in the lungs mainly,which develop into diffuse alveolar injury and pulmonary hyaline membrane formation to cause progressive respiratory failure in critically ill patients.Although specific drug therapies and vaccines have yet to be discovered,There're currently multiple medicines for the treatment of COVID-19 in the clinic.We have summarized the drugs widely used in the world,including remdesivir,chloroquine,favipiravir,lopinavir/ritonavir,ribavirin,some clinically adjuvant drugs and traditional Chinese medicines with great potential.In order to avoid the damage caused by immune disorders in COVID-19 patients,tocilizumab and dexamethasone plays an auxiliary role in fighting the epidemic.In this review,the potential effective drugs for COVID-19 will be summarized.

Blast-Induced Traumatic Brain Injury Triggered by Moderate Intensity Shock Wave Using a Modified Experimental Model of Injury in Mice

Background： The increasing frequency of explosive injuries has increased interest in blast-induced traumatic brain injury （bTBI）. Various shock tube models have been used to study bTBI. Mild-to-moderate explosions are often overlooked because of the slow onset or mildness of the symptoms. However, heavy gas cylinders and large volume chambers in the model may increase the complexity and danger. This study sought to design a modified model to explore the effect of moderate explosion on brain injury in mice. Methods： Pathology scoring system （PSS） was used to distinguish the graded intensity by the modified model. A total of 160 mice were randomly divided into control, sham, and bTBI groups with different time points. The clinical features, imaging features, neurobehavior, and neuropathology were detected after moderate explosion. One-way analysis of variance followed by Fisher＇s least significant difference posttest or Dunnett＇s t 3-test was performed for data analyses. Results： PSS of mild, moderate, and severe explosion was 13.4 ± 2.2, 32.6 ± 2.7 （t = 13.92, P 〈 0.001; vs. mild group）, and 56.6 ± 2.8 （t = 31.37, P 〈 0.001; vs. mild group）, respectively. After moderate explosion, mice showed varied symptoms of malaise, anorexia, incontinence, apnea, or seizure. After bTBI, brain edema reached the highest peak at day 3 （82.5% ± 2.1% vs. 73.8% ± 0.6%. t - 7.76, P 〈 0.001）, while the most serious neurological outcomes occurred at day 1 （Y-maze： 8.25 ±2.36 vs. 20.00 ± 4.55, t = -4.59, P=0.048; 29.58% ± 2.84% vs. 49.09% ±11.63%, t = -3.08, P = 0.008; neurologic severity score： 2.50 ± 0.58 vs. 0.00±0.00, t = 8.65, P = 0.016）. We also found that apoptotic neurons （52.76% ± 1.99% vs. 1.30% ± 0.11%, t =57.20, P 〈 0.001 ） and gliosis （2.98 ± 0.24 vs. 1.00 ± 0.00, t = 14.42, P = 0.021） in the frontal were significantly higher at day 3 post-bTBI than sham bTB1. Conclusions： We provide a reliable, reproducible bTBI model in mice that can produce a graded explosive waveform similar to the free-field shock wave in a controlled laboratory environment. Moderate explosion can trigger mild-to-moderate blast damage of the brain.

Improved Strategies for CRISPR-Cas12-based Nucleic Acids Detection

The COVID-19 pandemic has brought great challenges to traditional nucleic acid detection technology.Thus,it is urgent to develop a more simple and efficient nucleic acid detection technology.CRISPR-Cas12 has signal amplification ability,high sensitivity and high nucleic acid recognition specificity,so it is considered as a nucleic acid detection tool with broad development prospects and high application value.This review paper discusses recent advances in CRISPR-Cas12-based nucleic acid detection,with an emphasis on the new research methods and means to improve the nucleic acid detection capability of CRISPR-Cas12.Strategies for improving sensitivity,optimization of integrated detection,development of sim-plified detection mode and improvement of quantitative detection capabilities are included.Finally,the future development of CRISPR-Cas12-based nucleic acids detection is prospected.

Small molecule proteomics quantifies differences between normal and fibrotic pulmonary extracellular matrices

Background:Pulmonary fibrosis is a respiratory disease caused by the proliferation of fibroblasts and accumulation of the extracellular matrix(ECM).It is known that the lung ECM is mainly composed of a three-dimensional fiber mesh filled with various high-molecular-weight proteins.However,the small-molecular-weight proteins in the lung ECM and their differences between normal and fibrotic lung ECM are largely unknown.Methods::Healthy adult male Sprague-Dawley rats(Rattus norvegicus)weighing about 150 to 200 g were randomly divided into three groups using random number table:A,B,and C and each group contained five rats.The rats in Group A were administered a single intragastric(i.g.)dose of 500μL of saline as control,and those in Groups B and C were administered a single i.g.dose of paraquat(PQ)dissolved in 500μL of saline(20 mg/kg).After 2 weeks,the lungs of rats in Group B were harvested for histological observation,preparation of de-cellularized lung scaffolds,and proteomic analysis for small-molecular-weight proteins,and similar procedures were performed on Group C and A after 4 weeks.The differentially expressed small-molecular-weight proteins(DESMPs)between different groups and the subcellular locations were analyzed.Results::Of the 1626 small-molecular-weight proteins identified,1047 were quantifiable.There were 97 up-regulated and 45 downregulated proteins in B vs.A,274 up-regulated and 31 down-regulated proteins in C vs.A,and 237 up-regulated and 28 downregulated proteins identified in C vs.B.Both the up-regulated and down-regulated proteins in the three comparisons were mainly distributed in single-organism processes and cellular processes within biological process,cell and organelle within cellular component,and binding within molecular function.Further,more up-regulated than down-regulated proteins were identified in most sub-cellular locations.The interactions of DESMPs identified in extracellular location in all comparisons showed that serum albumin(Alb)harbored the highest degree of node(25),followed by prolyl 4-hydroxylase beta polypeptide(12),integrinβ1(10),apolipoprotein A1(9),and fibrinogen gamma chain(9).Conclusions::Numerous PQ-induced DESMPs were identified in de-cellularized lungs of rats by high throughput proteomics analysis.The DESMPs between the control and treatment groups showed diversity in molecular functions,biological processes,and pathways.In addition,the interactions of extracellular DESMPs suggested that the extracellular proteins Alb,Itgb1,Apoa1,P4hb,and Fgg in ECM could be potentially used as biomarker candidates for pulmonary fibrosis.These results provided useful information and new insights regarding pulmonary fibrosis.

Development of a Handheld Nano-centrifugal Device for Visual Virus Detection

Gold nanoparticles(AuNPs)colorimetric assays based on distance-dependent optical characteristics have been widely employed for bioanalysis.However,this assay is not effective for visually detecting low-concentration targets due to the faint color change.Here,we developed a handheld nano-centrifugal device which could separate the crosslinked and non-crosslinked AuNPs.Results showed that the handheld nano-centrifugal device could easily reach more than 6000 r/min within 10 s simply by stretching and tightening the coiled rope in an appropriate rhythm.Further,combined with the CRISPR/Cas12a nucleic acids recognition system,a field-deployable colorimetric platform termed handheld nano-centrifugal device assisted CRISPR/Cas12a(Hand-CRISPR)has been validated.Moreover,clinical diagnostics applications for Epstein-Barr virus(EBV)and severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)detection with high sensitivity and accuracy(100%consistency with reverse transcription quantitative real-time polymerase chain reaction(RT-qPCR)test results)have been demonstrated.Overall,the Hand-CRISPR platform showed great promise in point-of-care-test(POCT)application,expected to become a powerful supplement to the standard nucleic acid testing method in remote or poverty-stricken areas.

NfvInsight:A Framework for Automatically Deploying and Benchmarking VNF Chains

With the advent of virtualization techniques and software-defined networking(SDN),network function virtualization(NFV)shifts network functions(NFs)from hardware implementations to software appliances,between which exists a performance gap.How to narrow the gap is an essential issue of current NFV research.However,the cumbersomeness of deployment,the water pipe effect of virtual network function(VNF)chains,and the complexity of the system software stack together make it tough to figure out the cause of low performance in the NFV system.To pinpoint the NFV system performance,we propose NfvInsight,a framework for automatic deployment and benchmarking VNF chains.Our framework tackles the challenges in NFV performance analysis.The framework components include chain graph generation,automatic deployment,and fine granularity measurement.The design and implementation of each component have their advantages.To the best of our knowledge,we make the first attempt to collect rules forming a knowledge base for generating reasonable chain graphs.NfvInsight deploys the generated chain graphs automatically,which frees the network operators from executing at least 391 lines of bash commands for a single test.To diagnose the performance bottleneck,NfvInsight collects metrics from multiple layers of the software stack.Specifically,we collect the network stack latency distribution ingeniously,introducing only less than 2.2%overhead.We showcase the convenience and usability of NfvInsight in finding bottlenecks for both VNF chains and the underlying system.Leveraging our framework,we find several design flaws of the network stack,which are unsuitable for packet forwarding inside one single server under the NFV circumstance.Our optimization for these flaws gains at most 3x performance improvement.