CNS-LAND score: predicting early neurological deterioration after intravenous thrombolysis based on systemic responses and injury

ImportanceEarly neurological deterioration (END) is a critical complication in acute ischemic stroke (AIS) patients receiving intravenous thrombolysis (IVT), with a need for reliable prediction tools to guide clinical interventions.ObjectiveThis study aimed to develop and validate a rating scale, utilizing clinical variables and multisystem laboratory evaluation, to predict END after IVT.Design, setting, and participantsThe Clinical Trial of Revascularization Treatment for Acute Ischemic Stroke (TRAIS) cohort enrolled consecutive AIS patients from 14 stroke centers in China (Jan 2018 to Jun 2022).OutcomesEND defined as NIHSS score increase >4 points or death within 24 h of stroke onset.Results1,213 patients (751 in the derivation cohort, 462 in the validation cohort) were included. The CNS-LAND score, a 9-point scale comprising seven variables (CK-MB, NIHSS score, systolic blood pressure, LDH, ALT, neutrophil, and D-dimer), demonstrated excellent differentiation of END (derivation cohort C statistic: 0.862; 95% CI: 0.796–0.928) and successful external validation (validation cohort C statistic: 0.851; 95% CI: 0.814–0.882). Risk stratification showed END risks of 2.1% vs. 29.5% (derivation cohort) and 2.6% vs. 31.2% (validation cohort) for scores 0–3 and 4–9, respectively.ConclusionCNS-LAND score is a reliable predictor of END risk in AIS patients receiving IVT

Metatranscriptomic analysis revealed Prevotella as a potential biomarker of oropharyngeal microbiomes in SARS-CoV-2 infection

Background and objectivesDisease severity and prognosis of coronavirus disease 2019 (COVID-19) disease with other viral infections can be affected by the oropharyngeal microbiome. However, limited research had been carried out to uncover how these diseases are differentially affected by the oropharyngeal microbiome of the patient. Here, we aimed to explore the characteristics of the oropharyngeal microbiota of COVID-19 patients and compare them with those of patients with similar symptoms.MethodsCOVID-19 was diagnosed in patients through the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Characterization of the oropharyngeal microbiome was performed by metatranscriptomic sequencing analyses of oropharyngeal swab specimens from 144 COVID-19 patients, 100 patients infected with other viruses, and 40 healthy volunteers.ResultsThe oropharyngeal microbiome diversity in patients with SARS-CoV-2 infection was different from that of patients with other infections. Prevotella and Aspergillus could play a role in the differentiation between patients with SARS-CoV-2 infection and patients with other infections. Prevotella could also influence the prognosis of COVID-19 through a mechanism that potentially involved the sphingolipid metabolism regulation pathway.ConclusionThe oropharyngeal microbiome characterization was different between SARS-CoV-2 infection and infections caused by other viruses. Prevotella could act as a biomarker for COVID-19 diagnosis and of host immune response evaluation in SARS-CoV-2 infection. In addition, the cross-talk among Prevotella, SARS-CoV-2, and sphingolipid metabolism pathways could provide a basis for the precise diagnosis, prevention, control, and treatment of COVID-19

Integrative single-cell RNA sequencing and metabolomics decipher the imbalanced lipid-metabolism in maladaptive immune responses during sepsis

BackgroundTo identify differentially expressed lipid metabolism-related genes (DE-LMRGs) responsible for immune dysfunction in sepsis.MethodsThe lipid metabolism-related hub genes were screened using machine learning algorithms, and the immune cell infiltration of these hub genes were assessed by CIBERSORT and Single-sample GSEA. Next, the immune function of these hub genes at the single-cell level were validated by comparing multiregional immune landscapes between septic patients (SP) and healthy control (HC). Then, the support vector machine-recursive feature elimination (SVM-RFE) algorithm was conducted to compare the significantly altered metabolites critical to hub genes between SP and HC. Furthermore, the role of the key hub gene was verified in sepsis rats and LPS-induced cardiomyocytes, respectively.ResultsA total of 508 DE-LMRGs were identified between SP and HC, and 5 hub genes relevant to lipid metabolism (MAPK14, EPHX2, BMX, FCER1A, and PAFAH2) were screened. Then, we found an immunosuppressive microenvironment in sepsis. The role of hub genes in immune cells was further confirmed by the single-cell RNA landscape. Moreover, significantly altered metabolites were mainly enriched in lipid metabolism-related signaling pathways and were associated with MAPK14. Finally, inhibiting MAPK14 decreased the levels of inflammatory cytokines and improved the survival and myocardial injury of sepsis.ConclusionThe lipid metabolism-related hub genes may have great potential in prognosis prediction and precise treatment for sepsis patients

Short-term application of diquafosol ophthalmic solution benefits children with dry eye wearing orthokeratology lens

PurposeThis aim of this study was to evaluate the effect of 3% Diquafosol Ophthalmic Solution (DQS) on children with dry eye from wearing overnight orthokeratology (OrthoK) lenses.MethodsMyopic children aged 8–18 years with dry eye syndrome were enrolled in this prospective observational study, and they were grouped according to their OrthoK treatment history for at least 1 year. All participants received DQS 4 times per day for 1 month. The following indicators were measured at baseline 1 month after treatment: the Dry Eye Questionnaire-5 (DEQ-5), non-invasive tear meniscus height (TMH), non-invasive tear film break-up time (first and average, NIBUT-F and NIBUT-A), meibomian gland score (MG score), conjunctival hyperemia redness score (R-scan), and blink pattern analysis.ResultsA total of 104 participants (189 eyes) including 40 OrthoK wearers (72 eyes) and 64 Orthok candidates (117 eyes) completed the study. Of all, after DQS treatment for 1 month, DEQ-5 scores reduced from 5.54 ± 3.25 to 3.85 ± 2.98 (t = −3.36, p = 0.00). TMH increased from 0.20 ± 0.05 mm to 0.21 ± 0.05 mm (t = 2.59, p = 0.01), NIBUT-F and NIBUT-A were prolonged from 6.67 ± 4.71 s to 10.32 ± 6.19 s and from 8.86 ± 5.25 s to 13.30 ± 6.03 s (all p = 0.00), respectively. R-scan decreased from 0.69 ± 0.28 to 0.50 ± 0.25 (t = −9.01, p = 0.00). Upper MG scores decreased from 1.04 ± 0.32 to 0.97 ± 0.36 (t = −2.14, p = 0.03). Lower MG scores, partial blink rate, partial blinks, and total blinks did not change significantly. Both break-up time (BUT) and R-scan improved significantly after DQS treatment for 1 month (all p = 0.00) in OrthoK candidates and OrthoK wearers. Among the OrthoK wearers, TMH and dry eye symptoms increased significantly (all p = 0.00) but did not increase in OrthoK candidates (p > 0.05). There were no adverse events related to DQS.ConclusionDiquafosol Ophthalmic Solution was effective for children wearing overnight orthokeratology in relieving dry eye symptoms and improving ocular surface parameters, which may help improve children's OrthoK wearing tolerance and compliance

The DNA Methylome of Human Peripheral Blood Mononuclear Cells

Analysis across the genome of patterns of DNA methylation reveals a rich landscape of allele-specific epigenetic modification and consequent effects on allele-specific gene expression

Stochastic optimization of carbon mitigation path in Shenzhen based on uncertainty of power demand

The core elements of urban carbon emission mitigation optimization path include structural adjustment, low energy supply, technological innovation, and enhanced energy demand management and improvement. How to optimize the combination of these factors to achieve the city’s emission mitigation goals at the lowest cost is very important to study the path of urban low-carbon development. Due to many factors involved, it is difficult to solve this problem by building a mathematical optimization model that includes all the elements. This paper minimizes the total cost of emission mitigations in various departments in Shenzhen, combines the uncertainty of parameters and constraints, and uses mathematically standardized method to establish a stochastic optimization model for urban carbon emissions paths. Considering the uncertainty of energy demand, the optimal promotion rate of technical measures of the city’s various departments in the stochastic optimization model during the planning period can be obtained, and the optimal solution of the city’s low-carbon development optimization path can be formed

Characterization of oncogenic function of microRNA665 in esophageal squamous cell carcinoma

Background: Esophageal squamous cell carcinoma (ESCC) has been increasing in incidence, but knowledge of the genetic basis of this disease remains limited. In general, esophageal carcinoma can be divided into two main types: Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC). The pathogenesis of esophageal carcinoma still remains unclear, although some risk factors like chronic irritation, or chronic inflammation which may be caused by diseases such as gastroesophageal reflux disease (GERD) or unhealthy lifestyles like smoking have been proved to be related to the carcinogenic process. Diagnosis and treatment for this kind of cancer have continue to develop and evolve, but the 5-year overall survival rate is still relatively low. Therefore, it is clinically important to identify any potential genetic changes which may help us to discover some useful biomarker targets for the further development of more direct and harmless targeted therapy for our esophageal cancer patients. Objectives: In this study, I aimed to identify some potential oncogenic microRNA (miRNA) and to study their clinical meaning in ESCC patients. Methods: Microarray was applied to identify differentially expressed miRNAs in ESCC tumour tissue, compared with corresponding adjacent non-tumour esophageal tissue. One candidate oncogenic miRNA, miR-665, was investigated in the present study. After testing the expression level of miR-665 in ESCC cell lines and patients’ samples with RT-PCR, miR-665 stably expressing cells was established using two ESCC cell lines (KYSE30 and KYSE510). Functional characterization was then conducted using in vitro and in vivo assays to examine the effect of miR-665 towards the development of ESCC. Bioinformatic software such as Target Scan was used to generate a list of predicted target genes that may be modulated by miR-665. Results: The high expression of miR-665 has been confirmed in ESCC tissues and cell lines, showing the potential carcinogenic function of miR-665. Ectopic expression of miR-665 also demonstrates its ability to enhance tumour growth and invasion in vitro and in vivo. Bioinformatic analysis of miR-665 predicted targets showed putative binding sites for miR-665 within the 3’UTR region of NLK. Conclusions: This study has identified a novel miRNA and a related gene which might play an important role in the pathogenesis of ESCC, affecting the cancer process and tumour growth. This may help to find potential new biomarker for the future improvement and development of new treatment of ESCC patients.published_or_final_versionClinical OncologyMasterMaster of Philosoph