Mutant p53 regulates Survivin to foster lung metastasis.

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers worldwide and evolves often to lung metastasis. P53R175H (homologous to Trp53R172H in mice) is a common hot spot mutation. How metastasis is regulated by p53R175H in ESCC remains to be investigated. To investigate p53R175H-mediated molecular mechanisms, we used a carcinogen-induced approach in Trp53R172H/- mice to model ESCC. In the primary Trp53R172H/- tumor cell lines, we depleted Trp53R172H (shTrp53) and observed a marked reduction in cell invasion in vitro and lung metastasis burden in a tail-vein injection model in comparing isogenic cells (shCtrl). Furthermore, we performed bulk RNA-seq to compare gene expression profiles of metastatic and primary shCtrl and shTrp53 cells. We identified the YAP-BIRC5 axis as a potential mediator of Trp53R172H -mediated metastasis. We demonstrate that expression of Survivin, an antiapoptotic protein encoded by BIRC5, increases in the presence of Trp53R172H Furthermore, depletion of Survivin specifically decreases Trp53R172H-driven lung metastasis. Mechanistically, Trp53R172H but not wild-type Trp53, binds with YAP in ESCC cells, suggesting their cooperation to induce Survivin expression. Furthermore, Survivin high expression level is associated with increased metastasis in several GI cancers. Taken together, this study unravels new insights into how mutant p53 mediates metastasis.

Molecular Mechanism of SOX18 in Lipopolysaccharide-Induced Injury of Human Umbilical Vein Endothelial Cells.

Endothelial dysfunction is associated with the progression of sepsis. This study sought to probe the molecular route of sex-determining region on the Y chromosome-box transcription factor 18 (SOX18) in sepsis-associated endothelial injury. Human umbilical vein endothelial cells (HUVECs) were treated with lipopolysaccharide (LPS) to establish the sepsis cell model. Cell viability, lactate dehydrogenase (LDH) release, oxidative stress (reactive oxygen species/malondialdehyde/superoxide dismutase), and inflammation (interleukin-1ß/tumor necrosis factor-α/interleukin-6) were evaluated by cell counting kit-8 assay and relevant assay kits. The expression levels of SOX18, microRNA (miR)-204-5p, and cadherin-2 (CDH2) in cells were determined by real-time quantitative polymerase chain reaction and Western blot assay. The interaction of SOX18, miR-204-5p, and CDH2 was analyzed by chromatin immunoprecipitation and dual-luciferase assay. LPS induced HUVECs injury and downregulation of SOX18. SOX18 overexpression increased cell viability, while decreased LDH activity, oxidative stress, and inflammation. SOX18 bound to the miR-204-5p promoter to promote miR-204-5p expression, and further repressed CDH2 expression. miR-204-5p knockdown and CDH2 overexpression abrogated the protective role of SOX18 in HUVECs injury. Overall, SOX18 alleviated LPS-induced injury of HUVECs by promoting miR-204-5p and repressing CDH2, suggesting it as a potential target for sepsis treatment.

Environmental drivers of the rising incidence of early-onset colorectal cancer in the United States.

Incidence of early-onset (diagnosed before age 50) colorectal cancer (EOCRC) has increased alarmingly since the 1990s in the United States. This study investigated what environmental exposures may have driven this increase. We obtained EOCRC incidence data from the Surveillance, Epidemiology, and End Results Program, and data for 11 exposures, for example, body mass index (BMI), from long-term national surveys. We aggregated these data for 30 to 49-year-olds during 1992 to 2016 by population subgroups defined by calendar period, age, race and sex, and used negative binomial regression models to identify and estimate associations of EOCRC with multiple exposures. Furthermore, we used counterfactual modeling to quantify contributions of identified risk factors to EOCRC incidence. The top models (with lowest Bayesian Information Criteria) consistently identified excess body weight, represented by overweight and obesity (BMI ≥25) or obesity alone (BMI ≥30), as the strongest risk factor. The best-performing model estimated increased EOCRC incidence due to overweight and obesity, with an incidence rate ratio (95% confidence interval) of 1.20 (1.17-1.22) for white men, 1.04 (1.00-1.08) for black men, 1.17 (1.15-1.21) for white women and 1.03 (0.97-1.08) for black women. Increases in overweight and obesity prevalence contributed to an estimated 30% (standard error: 1%) for men and 28% (standard error: 2%) for women of ECORC incidence during 1992 to 2016. These findings suggest excess body weight substantially contributed to and is likely a primary driver of the rising incidence of EOCRC in the United States. Prevention of excess weight gain may help lower colorectal cancer risk early in life.

Hierarchical Polyimide Microparticles with Controllable Morphology.

Hierarchical polyimides (PIs) not only show outstanding thermal stability and high mechanical strength but also have great advantages in terms of microstructure and surface area, which makes them highly valuable in various fields such as aerospace, microelectronics, adsorption, catalysis, and energy storage. However, great challenges still remain in the synthesis of hierarchical PIs with well-defined microstructure. Herein, polyamide acid salts (PAAS) with tunable ionization degree are synthesized first via the polymerization of dianhydride and diamine monomers in deionized water with 1,2-dimethylimidazole (DMIZ). Then cationic cetyltrimethylammonium chloride (CTAC) is added to the PAAS aqueous solution to induce the formation of polyelectrolyte-surfactant complexes based on electrostatic interaction. After a typical hydrothermal reaction (HTR) procedure, hierarchical PIs with different microstructures such as urchin-like PI microparticles, flower-like PI microparticles, and lamellar PI petals can be fabricated simply by changing the additive amount of DMIZ and CTAC. The nanostructure self-assemblies of PAAS are dominated by the charges on macromolecular chains and the formation of hierarchical structures of polymers is ascribed to a geometrical selection process during crystal growth. This work provides valuable insights into the self-assembly behaviors of polyelectrolyte systems for synthesizing well-defined hierarchical polymers.

FEN1 inhibitor SC13 promotes CAR-T cells infiltration into solid tumours through cGAS-STING signalling pathway.

It is well known that chimeric antigen receptor T-cell immunotherapy (CAR-T-cell immunotherapy) has excellent therapeutic effect in haematological tumours, but it still faces great challenges in solid tumours, including inefficient T-cell tumour infiltration and poor functional persistence. Flap structure-specific endonuclease 1 (FEN1), highly expressed in a variety of cancer cells, plays an important role in both DNA replication and repair. Previous studies have reported that FEN1 inhibition is an effective strategy for cancer treatment. Therefore, we hypothesized whether FEN1 inhibitors combined with CAR-T-cell immunotherapy would have a stronger killing effect on solid tumours. The results showed that low dose of FEN1 inhibitors SC13 could induce an increase of double-stranded broken DNA (dsDNA) in the cytoplasm. Cytosolic dsDNA can activate the cyclic GMP-AMP synthase-stimulator of interferon gene signalling pathway and increase the secretion of chemokines. In vivo, under the action of FEN1 inhibitor SC13, more chemokines were produced at solid tumour sites, which promoted the infiltration of CAR-T cells and improved anti-tumour immunity. These findings suggest that FEN1 inhibitors could enable CAR-T cells to overcome poor T-cell infiltration and improve the treatment of solid tumours.

Anti-mesothelin CAR-T immunotherapy in patients with ovarian cancer.

Recently, chimeric antigen receptor T cell (CAR-T) therapy has received increasing attention as an adoptive cellular immunotherapy that targets tumors. However, numerous challenges remain for the effective use of CAR-T to treat solid tumors, including ovarian cancer, which is an aggressive and metastatic cancer with a poor therapeutic response. We screened for an effective anti-MSLN single-chain Fv antibody with comparable binding activity and non-off-target properties using human phage display library. A second-generation of anti-MSLN CAR was designed and generated. We demonstrated the efficacy of our anti-MSLN CAR-T cells for ovarian cancer treatment in an in vitro experiment to kill ovarian tumor cell lines. The anti-MSLN CAR-T cells impeded MSLN-positive tumor growth concomitant with a significant increase in cytokine levels compared with the control. Then, we demonstrated the efficacy of anti-MSLN CAR-T cells in an in vivo experiment against ovarian cancer cell-derived xenografts. Furthermore, we herein report three cases with ovarian cancer who were treated with autologous anti-MSLN CAR-T cells and evaluate the safety and effectiveness of adoptive cell therapy. In this investigator-initiated clinical trials, no patients experienced cytokine release syndrome or neurological symptoms over 2 grads. Disease stabilized in two patients, with progression-free survival times of 5.8 and 4.6 months. Transient CAR expression was detected in patient blood after infusion each time. The tumor partially subsided, and the patient's condition was relieved. In conclusion, this work proves the efficacy of the anti-MSLN CAR-T treatment strategy in ovarian cancer and provides preliminary data for the development of further clinical trials.

Hepatitis E virus superinfection impairs long-term outcome in hospitalized patients with hepatitis B virus-related decompensated liver cirrhosis.

INTRODUCTION AND OBJECTIVES: Hepatitis E virus (HEV) superinfection is a common excerbating event in patients with chronic hepatitis B, but the impact on the long-term prognosis is not clear. This study investigates the specific role of HEV superinfection in the long-term outcome of hepatitis B virus (HBV) patients with liver cirrhosis. PATIENTS AND METHODS: A retrospective, observational cohort study was conducted using clinical, laboratory, and survival data collected from patients suffering from hepatitis B cirrhosis with or without HEV superinfection. Disease progression and mortality rates were analyzed. RESULTS: After a two-year follow-up, HEV superinfection was identified in 27 of 811 patients. The transplantation-free mortality was significantly increased (51.9% vs. 14.3%, p< 0.001) in HEV superinfection compared to that in hepatitis B cirrhosis patients without HEV superinfection. Logistic regression analysis demonstrated that elderly people were independent host risk factors for hepatitis B cirrhosis patients with HEV superinfection before and after propensity score matching (PSM). Moreover, HEV superinfection was a risk factor for patients with hepatitis B cirrhosis with new acute decompensation (AD) and acute-on-chronic liver failure (ACLF) during hospitalization. A multivariate Cox proportional hazards regression model demonstrated that acute HEV co-infection is associated with two-year mortality (hazard ratio [HR]: 2.49; 95% CI: 1.40-4.43; p= 0.002; and HR: 5.79; 95% CI: 1.87-17.87; p= 0.002) in patients with hepatitis B cirrhosis before and after PSM. CONCLUSIONS: Elder patients with hepatitis B cirrhosis are susceptible to HEV superinfection, accelerating disease progression and increasing long-term mortality in hospitalized patients with HBV-related decompensated liver cirrhosis.

Identification and verification of characteristic differentially expressed ferroptosis-related genes in osteosarcoma using bioinformatics analysis.

BACKGROUND: This study identified and verified the characteristic differentially expressed ferroptosis-related genes (CDEFRGs) in osteosarcoma (OS). METHODS: We extracted ferroptosis-related genes (FRGs), identified differentially expressed FRGs (DEFRGs) in OS, and conducted correlation analysis between DEFRGs. Next, we conducted GO and KEGG analyses to explore the biological functions and pathways of DEFRGs. Furthermore, we used LASSO and SVM-RFE algorithms to screen CDEFRGs, and evaluated its accuracy in diagnosing OS through ROC curves. Then, we demonstrated the molecular function and pathway enrichment of CDEFRGs through GSEA analysis. In addition, we evaluated the differences in immune cell infiltration between OS and NC groups, as well as the correlation between CDEFRGs expressions and immune cell infiltrations. Finally, the expression of CDEFRGs was verified through qRT-PCR, western blotting, and immunohistochemistry experiments. RESULTS: We identified 51 DEFRGs and the expression relationship between them. GO and KEGG analysis revealed their key functions and important pathways. Based on four CDEFRGs (PEX3, CPEB1, NOX1, and ALOX5), we built the OS diagnostic model, and verified its accuracy. GSEA analysis further revealed the important functions and pathways of CDEFRGs. In addition, there were differences in immune cell infiltration between OS group and NC group, and CDEFRGs showed significant correlation with certain infiltrating immune cells. Finally, we validated the differential expression levels of four CDEFRGs through external experiments. CONCLUSIONS: This study has shed light on the molecular pathological mechanism of OS and has offered novel perspectives for the early diagnosis and immune-targeted therapy of OS patients.

Use of a convolutional neural network-based mammographic evaluation to predict breast cancer recurrence among women with hormone receptor-positive operable breast cancer.

PURPOSE: We evaluated whether a novel, fully automated convolutional neural network (CNN)-based mammographic evaluation can predict breast cancer relapse among women with operable hormone receptor (HR)-positive breast cancer. METHODS: We conducted a retrospective cohort study among women with stage I-III, HR-positive unilateral breast cancer diagnosed at Columbia University Medical Center from 2007 to 2017, who received adjuvant endocrine therapy and had at least two mammograms (baseline, annual follow-up) of the contralateral unaffected breast for CNN analysis. We extracted demographics, clinicopathologic characteristics, breast cancer treatments, and relapse status from the electronic health record. Our primary endpoint was change in CNN risk score (range, 0-1). We used two-sample t-tests to assess for difference in mean CNN scores between patients who relapsed vs. remained in remission, and conducted Cox regression analyses to assess for association between change in CNN score and breast cancer-free interval (BCFI), adjusting for known prognostic factors. RESULTS: Among 848 women followed for a median of 59 months, there were 67 (7.9%) breast cancer relapses (36 distant, 25 local, 6 new primaries). There was a significant difference in mean absolute change in CNN risk score from baseline to 1-year follow-up between those who relapsed vs. remained in remission (0.001 vs. - 0.022, p = 0.030). After adjustment for prognostic factors, a 0.01 absolute increase in CNN score at 1-year was significantly associated with BCFI, hazard ratio = 1.05 (95% Confidence Interval 1.01-1.09, p = 0.011). CONCLUSION: Short-term change in the CNN-based breast cancer risk model on adjuvant endocrine therapy predicts breast cancer relapse, and warrants further evaluation in prospective studies.

Addressing patient heterogeneity in disease predictive model development.

This paper addresses patient heterogeneity associated with prediction problems in biomedical applications. We propose a systematic hypothesis testing approach to determine the existence of patient subgroup structure and the number of subgroups in patient population if subgroups exist. A mixture of generalized linear models is considered to model the relationship between the disease outcome and patient characteristics and clinical factors, including targeted biomarker profiles. We construct a test statistic based on expectation maximization (EM) algorithm and derive its asymptotic distribution under the null hypothesis. An important computational advantage of the test is that the involved parameter estimates under the complex alternative hypothesis can be obtained through a small number of EM iterations, rather than optimizing the objective function. We demonstrate the finite sample performance of the proposed test in terms of type-I error rate and power, using extensive simulation studies. The applicability of the proposed method is illustrated through an application to a multicenter prostate cancer study.

Diagnostic yield and clinical impact of exome sequencing in early-onset scoliosis (EOS).

BACKGROUND: Early-onset scoliosis (EOS), defined by an onset age of scoliosis less than 10 years, conveys significant health risk to affected children. Identification of the molecular aetiology underlying patients with EOS could provide valuable information for both clinical management and prenatal screening. METHODS: In this study, we consecutively recruited a cohort of 447 Chinese patients with operative EOS. We performed exome sequencing (ES) screening on these individuals and their available family members (totaling 670 subjects). Another cohort of 13 patients with idiopathic early-onset scoliosis (IEOS) from the USA who underwent ES was also recruited. RESULTS: After ES data processing and variant interpretation, we detected molecular diagnostic variants in 92 out of 447 (20.6%) Chinese patients with EOS, including 8 patients with molecular confirmation of their clinical diagnosis and 84 patients with molecular diagnoses of previously unrecognised diseases underlying scoliosis. One out of 13 patients with IEOS from the US cohort was molecularly diagnosed. The age at presentation, the number of organ systems involved and the Cobb angle were the three top features predictive of a molecular diagnosis. CONCLUSION: ES enabled the molecular diagnosis/classification of patients with EOS. Specific clinical features/feature pairs are able to indicate the likelihood of gaining a molecular diagnosis through ES.

Protective effect of γ-glutamylcysteine against UVB radiation in NIH-3T3 cells.

BACKGROUND: Ultraviolet (UV) radiation-induced oxidative stress is the main cause of photodamage to the skin. Glutathione (GSH) serves important physiological functions, including scavenging oxygen-free radicals and maintaining intracellular redox balance. γ-glutamylcysteine (γ-GC), as an immediate precursor of GSH and harboring antioxidant and anti-inflammatory properties, represents an unexplored option for skin photodamage treatment. PURPOSE: The purpose of this study was to investigate whether γ-GC can reduce UVB-induced NIH-3T3 cell damage. METHODS: The experimental groups were as follows: control, UVB radiation, UVB radiation after pretreatment with γ-GC. Cell counting kit-8 (CCK-8) assays were used to measure cell proliferation, flow cytometry, and immunoblotting to detect the apoptosis rate and apoptosis-associated proteins. The levels of Reactive Oxygen Species (ROS), Superoxide Dismutase (SOD), and GSH/GSSG (oxidized GSH) were measured to assess oxidative stress. Immunoblotting and immunofluorescence were used to detect DNA damage. The members of the MAPK signaling pathways were detected by immunoblotting. RESULTS: UVB irradiation significantly reduced cell viability and destroyed the oxidative defense system. Pretreatment with γ-GC reduced UVB-induced cytotoxicity, restored the oxidation defense system, and inhibited activation of the MAPK pathway. It also reduced the apoptosis rate, downregulated the levels of cleaved caspase 3 and cleaved PARP. Furthermore, pretreatment with γ-GC reduced the accumulation of γH2AX after UVB radiation exposure, indicating that γ-GC could protect cells from DNA damage. CONCLUSION: γ-GC protected NIH-3T3 from damage caused by UVB irradiation. The photoprotective effect of γ-GC is mediated via strengthening the endogenous antioxidant defense system, which prevents DNA damage and inhibits the activation of the MAPK pathway.

Serum Interleukins as Potential Prognostic Biomarkers in HBV-Related Acute-on-Chronic Liver Failure.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is relatively common in China and has complex pathogenesis, difficult clinical treatment, and poor prognosis. Immune status is an important factor affecting ACLF prognosis. Interleukins are a family of secreted lymphocyte factors that interact with a host of cell types including immune cells. These signaling molecules play important roles in transmitting information; regulating immune cells; mediating the activation, proliferation, and differentiation of T and B cells; and modulating inflammatory responses. Many studies have investigated the correlation between interleukin expression and the prognosis of HBV-ACLF. This review focuses on the potential use of interleukins as prognostic biomarkers in HBV-ACLF. References were mainly identified through PubMed and CNKI search, including relevant studies published until December 2021. We have summarized reports of several promising diagnostic interleukin biomarkers that predict susceptibility to HBV-ACLF. The use of biomarkers to understand early prognosis can help devise different therapeutic measures and improve patient survival. Ongoing research on prognostic biomarkers of HBV-ACLF is promising, and future preclinical and clinical studies are warranted.

All-Graphitic Multilaminate Mesoporous Membranes by Interlayer-Confined Molecular Assembly.

Layered mesostructured graphene, which combines the intrinsic advantages of planar graphene and mesoporous materials, has become interestingly important for energy storage and conversion applications. Here, an interlayer-confined molecular assembly method is presented for constructing all-graphitic multilaminate membranes (MMG⊂rGO), which are composed of monolayer mesoporous graphene (MMG) sandwiched between reduced graphene oxide (rGO) sheets. Hybrid assembly of iron-oleate complexes and organically modified GO sheets enables the preferential assembly of iron-oleate precursors at the interlayer space of densely stacked GO, driven by the like-pair molecular van der Waals interactions. Confined pyrolysis of iron-oleate complexes at GO interlayers leads to close-packed, carbon-coated Fe3 O4 nanocrystal arrays, which serve as intermediates to template the subsequent formation of MMG⊂rGO membranes. To demonstrate their application potentials, MMG⊂rGO membranes are exploited as dual-functional interlayers to boost the performance of Li-S batteries by concurrently suppressing the shuttle of polysulfides and the growth of Li dendrites. This work showcases the capability of molecular-based hybrid assembly for synthesizing multilayer mesostructured graphene with high packing density and its use in electrochemical energy applications.

Regularized matrix data clustering and its application to image analysis.

We propose a novel regularized mixture model for clustering matrix-valued data. The proposed method assumes a separable covariance structure for each cluster and imposes a sparsity structure (eg, low rankness, spatial sparsity) for the mean signal of each cluster. We formulate the problem as a finite mixture model of matrix-normal distributions with regularization terms, and then develop an expectation maximization type of algorithm for efficient computation. In theory, we show that the proposed estimators are strongly consistent for various choices of penalty functions. Simulation and two applications on brain signal studies confirm the excellent performance of the proposed method including a better prediction accuracy than the competitors and the scientific interpretability of the solution.

Development and application of a novel triplex protein microarray method for rapid detection of antibodies against avian influenza virus, Newcastle disease virus, and avian infectious bronchitis virus.

Avian influenza virus (AIV), Newcastle disease virus (NDV), and avian infectious bronchitis virus (IBV) inflict immense damage on the global poultry industry annually. Serological diagnostic methods are fundamental for the effective control and prevention of outbreaks caused by these viruses. In this study, a novel triplex protein microarray assay was developed and validated for the rapid and simultaneous visualized detection of antibodies against AIV, NDV, and IBV in chicken sera. The AIV nuclear protein (NP), NDV phosphoprotein (P), and IBV nonstructural protein 5 (nsp5) were produced in a prokaryotic expression system, purified, and immobilized onto an initiator integrated poly(dimethylsiloxane) (iPDMS) film as probes to detect antibodies against these viruses in chicken sera. After optimization of the reaction conditions, no cross-reactivity was detected with infectious bursal disease virus, avian leukosis virus subgroup J and chicken anemia virus antisera. The lowest detectable antibody titers in this assay corresponded to hemagglutination inhibition (HI) titers of 24 and 21 for AIV and NDV, respectively, and to an IDEXX antibody titer of 103 for IBV, using the HI assay and IDEXX commercial ELISA kit as the reference methods. When156 serum samples were tested using the new assay, the HI test and the IBV IDEXX ELISA kit, the assay showed 96.8% (151/156), 97.4% (152/156) and 99.4% (155/156) diagnostic accuracy for detection of AIV, NDV and IBV antibody, respectively. The current study suggests that the newly developed triplex microarray is rapid, sensitive, and specific, providing a viable alternative assay for AIV, NDV, and IBV antibody screening in epidemiological investigations and vaccination evaluations.

High body mass index is a significant risk factor for the progression and prognosis of imported COVID-19: a multicenter, retrospective cohort study.

BACKGROUND: Coronavirus disease 2019(COVID-19) has spread worldwide. The present study aimed to characterize the clinical features and outcomes of imported COVID-19 patients with high body mass index (BMI) and the independent association of BMI with disease severity. METHODS: In this retrospective cohort study, 455 imported COVID-19 patients were admitted and discharged in Zhejiang province by February 28, 2020. Epidemiological, demographic, clinical, laboratory, radiological, treatment, and outcome data were collected, analyzed and compared between patients with BMI ≥ 24and < 24. RESULTS: A total of 268 patients had BMI < 24, and 187 patients had BMI ≥ 24. Those with high BMI were mostly men, had a smoking history, fever, cough, and sputum than those with BMI < 24. A large number of patients with BMI ≥ 24 were diagnosed as severe/critical types. Some biochemical indicators were significantly elevated in patients with BMI ≥ 24. Also, acute liver injury was the most common complication in these patients. The median days from illness onset to severe acute respiratory syndrome coronavirus 2 detection, duration of hospitalization, and days from illness onset to discharge were significantly longer in patients with BMI ≥ 24 than those with BMI < 24. High BMI, exposure to Wuhan, any coexisting medical condition, high temperature, C-reactive protein (CRP), and increased lactate dehydrogenase (LDH) were independent risk factors for severe/critical COVID-19. After adjusting for age, sex and above factors, BMI was still independently associated with progression to severe/critical illness (P = 0.0040). Hemoglobin, alanine aminotransferase (ALT), CRP, and serum creatinine (Scr) were independent risk factors associated with high BMI. CONCLUSIONS: Contrasted with the imported COVID-19 patients with BMI < 24, high proportion of COVID-19 patients with BMI ≥ 24 in our study, especially those with elevated CRP and LDH, developed to severe type, with longer hospitalization duration and anti-virus course. Thus, high BMI is a risk factor for the progression and prognosis of imported COVID-19.

The Clinical Characteristics and Risk Factors of Severe COVID-19.

OBJECTIVE: We aim to investigate the clinical characteristics and risk factors for the severe cases of coronavirus disease 2019 (COVID-19) in comparison with the non-severe patients. METHODS: We searched PubMed, EMBASE, Web of Science, and CNKI to collect all relevant studies published before July 26, 2020, and a total of 30 papers were included in this meta-analysis. RESULTS: In the severe COVID-19 patients, 60% (95% CI = 56-64%) were male, 25% (95% CI = 21-29%) were over 65 years old, 34% (95% CI = 24-44%) were obese, and 55% (95% CI = 41-70%) had comorbidities. The most prevalent comorbidities were hypertension (34%, 95% CI = 25-44%), diabetes (20%, 95% CI = 15-25%), and cardiovascular disease (CVD; 12%, 95% CI = 9-16%). The most common blood test abnormalities were elevated C-reactive protein (CRP; 87%, 82-92%), decreased lymphocyte count (68%, 58-77%), and increased lactate dehydrogenase (69%, 95% CI = 57-81%). In addition, abnormal laboratory findings revealing organ dysfunctions were frequently observed in the severe cases, including decrease in albumin (43%, 95% CI = 24-63%) and increase in aspartate aminotransferase (47%, 95% CI = 38-56%), alanine aminotransferase (28%, 95% CI = 16-39%), troponin I/troponin T (TnI/TnT; 29%, 95% CI = 13-45%), and serum Cr (SCr; 10%, 95% CI = 5-15%). CONCLUSION: The male, elderly and obese patients and those with any comorbidities, especially with hypertension, diabetes, and CVD, were more likely to develop into severe cases. But the association between hypertension, diabetes, CVD, and severity of COVID-19 was declined by the increase of age. A significant elevation in cardiac TnI/TnT, the hepatic enzymes, and SCr and the reduction in lymphocytes with elevated CRPs are important markers for the severity. Specific attention should be given to the elderly male and obese patients and those with indications of severe immune injury in combination with bacterial infection and indication of multi-organ dysfunction or damages.

A fatal case of Exophiala dermatitidis meningoencephalitis in an immunocompetent host: A case report and literature review.

BACKGROUND: Central nervous system (CNS) infection due to Exophiala dermatitidis is rare and fatal, and primarily reported in immunocompromised patients or those with caspase recruitment domain-containing protein 9 deficiency. Herein, we describe a case of an otherwise healthy person (without underlying disease or gene deficiency) diagnosed with Exophiala dermatitidis meningoencephalitis. The patient achieved clinical remission under high-dose antifungal therapy in the first 14 months but died after 2 years of the therapy. CASE PRESENTATION: A 15-year-old student with headache and fever was admitted to our department. Lumbar puncture showed increased cerebrospinal fluid (CSF) pressure, moderately high CSF protein levels and cell counts, and a remarkable decrease in CSF glucose and chloride. Magnetic resonance imaging of the brain revealed multiple lesions and cerebral pia mater enhancement. CSF culture confirmed E. dermatitidis infection. We administered 4-week antifungal therapy of amphotericin B, but his CSF culture remained positive. After receiving the 12-week standard dose of voriconazole (200 mg q12h), the patient's CSF culture became negative, but his condition deteriorated with intracranial lesion enlargement. We administered a high-dose voriconazole therapy (600-800 mg per day) for 12 months, which led to clinical remission. The voriconazole dose was reduced due to adverse effects including hepatic dysfunction and hypokalemia, and the disease progressed with high intracranial pressure and epileptic seizures. CONCLUSIONS: CNS infection caused by E. dermatitidis is fatal and the most serious form of fungal infection. Initially, high-dose and long-term antifungal therapy could be effective. Gene defect and related antifungal immunodeficiency may be the most important pathogenic and lethal factor.

Posterior fossa decompression with or without duraplasty for patients with chiari type I malformation and basilar impression: a meta-analysis.

BACKGROUND: To compare clinical effect and safety between posterior fossa decompression with duraplasty (PFDD) and posterior fossa decompression without duraplasty (PFD) in treatment of Chiari type I malformation and basilar impression. METHODS: A comprehensive computer search was conducted from 2000 to 2019. The quality assessment was performed by the QUADAS-2 tool. The clinical value of comparison between PFDD and PFD was evaluated by using the pooled estimate of sensitivity and specificity. In addition, sensitivity analysis and bias analysis were applied to ensure the accuracy of the results. RESULTS: Finally, 468 patients were enrolled in 6 studies and ultimately met the eligibility criteria. The PFDD and PFD groups were 282 and 186, respectively. The meta-analysis showed no significant difference in the Chicago Chiari Outcome Scale (COSS score) (MD = 0.14, 95% CI [-0.23, 0.50], P = 0.47; P = heterogeneity = 0.86, I2 = 0%). Meanwhile, Significant difference existed in length of stay (MD = -1.08, 95% CI [-1.32, -0.84], P = 0.001; heterogeneity P < 0.000001, I2 = 85%) and complications (OR = 0.35, 95%CI [0.20, 0.62], P = 0.0003; P for Heterogeneity = 0.04, I2 = 56%). CONCLUSION: PFD is a more efficient and safer therapy than PFDD in the treatment of Chiari type I malformation with basilar impression.