Mendelian Randomization and Transcriptomic Analysis Reveal the Protective Role of NKT Cells in Sepsis.

Background: Sepsis is a life-threatening clinical syndrome caused by dysregulated host response to infection. The mechanism underlying sepsis-induced immune dysfunction remains poorly understood. Natural killer T (NKT) cells are cytotoxic lymphocytes that bridge the innate and adaptive immune systems, the role of NKT cells in sepsis is not entirely understood, and NKT cell cluster differences in sepsis remain unexplored. Methods: Mendelian randomization (MR) analyses were first conducted to investigate the causal relationship between side scatter area (SSC-A) on NKT cells and 28-day mortality of septic patients. A prospective and observational study was conducted to validate the relationship between the percentage of NKT cells and 28-day mortality of sepsis. Then, the single-cell RNA sequencing (scRNA-seq) data of peripheral blood mononuclear cells (PBMCs) from healthy controls and septic patients were profiled. Results: MR analyses first revealed the protective roles of NKT cells in the 28-day mortality of sepsis. Then, 115 septic patients were enrolled. NKT percentage was significantly higher in survivors (n = 84) compared to non-survivors (n = 31) (%, 5.00 ± 3.46 vs 2.18 ± 1.93, P < 0.0001). Patients with lower levels of NKT cells exhibited a significantly increased risk of 28-day mortality. According to scRNA-seq analysis, NKT cell clusters exhibited multiple distinctive characteristics, including a distinguishing cluster defined as FOS+NKT cells, which showed a significant decrease in sepsis. Pseudo-time analysis showed that FOS+NKT cells were characterized by upregulated expression of crucial functional genes such as GZMA and CCL4. CellChat revealed that interactions between FOS+NKT cells and adaptive immune cells including B cells and T cells were decreased in sepsis compared to healthy controls. Conclusion: Our findings indicate that NKT cells may protect against sepsis, and their percentage can predict 28-day mortality. Additionally, we discovered a unique FOS+NKT subtype crucial in sepsis immune response, offering novel insights into its immunopathogenesis.

Overactivated MX1 Positive Natural Killer Cells Promote the Progression of Sepsis-Induced Acute Respiratory Distress Syndrome.

Background: Natural killer (NK) cells are key regulators of immune defense in sepsis-induced acute respiratory distress syndrome (ARDS), yet the characteristics of NK cell clusters in ARDS remain poorly understood. Methods: A prospective and observational study enrolled septic patients with ARDS or not was conducted to determine the percentage of NK cells via flow cytometry. The transcriptomes of peripheral blood mononuclear cells (PBMCs) from healthy controls, patients with sepsis only, and patients with sepsis-induced ARDS were profiled. Vitro experiments were performed to confirm the mechanism mediating MX1+NK cell infiltration. Results: A total of 115 septic patients were analyzed, among whom 63 patients developed ARDS and 52 patients did not. Decreased NK percentages were found in sepsis with ARDS patients (%, 7.46±4.40 vs 11.65±6.88, P=0.0001) compared with sepsis-only patients. A lower percentage of NK cells showed a significant increase in 28-day mortality. Single-cell sequencing analysis revealed distinct characteristics of NK cells in sepsis-induced ARDS, notably the identification of a unique cluster defined as MX1+NK cells. Flow cytometry analysis showed an elevated percentage of MX1+NK cells specifically in individuals with sepsis-induced ARDS, compared with patients with sepsis only. Pseudo-time analysis showed that MX1+NK cells were characterized by upregulation of type I interferon-induced genes and other pro-inflammatory genes. MX1+NK cells can respond to type I interferons and secrete type I interferons themselves. Ligand-receptor interaction analysis also revealed extensive interaction between MX1+NK cells and T/B cells, leading to an uncontrolled inflammatory response in ARDS. Conclusion: MX1+NK cells can respond to type I interferons and secrete type I interferons themselves, promoting the development of sepsis-induced ARDS. Interfering with the infiltration of MX1+NK cells could be a therapeutic approach for this disease. Due to the limited sample size, a larger sample size was needed for further exploration.

Persistence of severe global inequalities in the burden of blindness and vision loss from 1990 to 2019: findings from the Global Burden of Disease Study 2019.

AIMS: To assess the global burden and economic inequalities in the distribution of blindness and vision loss between 1990 and 2019. METHODS: A secondary analysis of the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019. Data for disability-adjusted life-years (DALYs) due to blindness and vision loss were extracted from the GBD 2019. Data for gross domestic product per capita were extracted from the World Bank database. Slope index of inequality (SII) and concentration index were computed to assess absolute and relative cross-national health inequality, respectively. RESULTS: Countries with high, high-middle, middle, low-middle and low Socio-demographic Index (SDI) had decline of age-standardised DALY rate of 4.3%, 5.2%, 16.0%, 21.4% and 11.30% from 1990 to 2019, respectively. The poorest 50% of world citizens bore 59.0% and 66.2% of the burden of blindness and vision loss in 1990 and 2019, respectively. The absolute cross-national inequality (SII) fell from -303.5 (95% CI -370.8 to -236.2) in 1990 to -256.0 (95% CI -288.1 to -223.8) in 2019. The relative inequality (concentration index) for global blindness and vision loss remained essentially constant between 1991 (-0.197, 95% CI -0.234 to -0.160) and 2019 (-0.193, 95% CI -0.216 to -0.169). CONCLUSION: Though countries with middle and low-middle SDI were the most successful in decreasing burden of blindness and vision loss, a high level of cross-national health inequality persisted over the past three decades. More attention must be paid to the elimination of avoidable blindness and vision loss in low-income and middle-income countries.

Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Vaccination for Negative Conversion Time of Nucleic Acid in Nonsevere COVID-19 Patients Infected by SARS-CoV-2 Omicron Variant.

SARS-CoV-2 Omicron variant is significantly different from all the previous variants and has rapidly replaced other variants as the dominant variant across the globe. An easily obtained, inexpensive, and rapid marker is needed to predict the negative conversion time (NCT) of nucleic acid in nonsevere COVID-19 patients infected by the Omicron variant. This retrospective study enrolled 226 patients infected by the Omicron variant between April 23, 2022, and May 16, 2022. The median age of the patients was 61 (interquartile range (IQR), 48-70) years, and 56.2% were male. 84 patients (37.2%) had at least one comorbidity, and 49 patients (21.7%) were classified into the moderate illness group. 145 patients (64.2%) received at least one dose of vaccine, in which 67 patients (29.6%) received a booster dose of vaccine. The median duration of NCT was 8 (IQR, 7-11) days. Univariate Cox analyses found that high NLR (>2.22), aged ≥65 years, vaccination, and moderate illness were significantly related to the NCT of nucleic acid. Multivariate Cox regression analysis showed that high NLR (NLR > 2.22, hazard ratio (HR):0.718, 95% CI: 0.534-0.964, p = 0.028) and vaccination (vaccinated ≥1 dose, HR: 1.536, 95% CI: 1.147-2.058, p = 0.004) were independently associated with NCT of nucleic acid. NLR is a rapid, simple, and useful prognostic factor for predicting NCT of nucleic acid in nonsevere COVID-19 patients with the Omicron variant. In addition, vaccination may also play a valuable role in predicting the NCT of nucleic acid.

Impact of Different Traditional Chinese Medicine Constitutions on the Clinical Outcomes of COVID-19 Patients Infected with SARS-CoV-2 Omicron Variant: A Retrospective Observational Study.

Purpose: Traditional Chinese Medicine (TCM) constitution and disease occurrence, development, and prognosis are interrelated. This study aimed to investigate the association between TCM constitution and the time to negative nucleic acid test results in patients with coronavirus disease 2019 (COVID-19) infected with the SARS-CoV-2 Omicron variant. Patients and Methods: We identified COVID-19 patients (≥18 years) infected with the SARS-CoV-2 Omicron variant and collected clinical data, including clinical symptoms, time to negative nucleic acid test results, and TCM constitution. Linear and logistic regression analyses explored the relationship between TCM constitution and the time to negative nucleic acid test results in patients with the COVID-19 Omicron variant. Results: We included 486 patients with COVID-19, with a mean age of 40.2 years; 321 (66.0%) men and 165 (34.0%) women. Balanced constitution accounted for 43.8%, and unbalanced constitution accounted for 56.2%. Chi-square test showed that different TCM constitutions had significant differences in the influence of clinical symptoms of COVID-19 patients (P < 0.01). After controlling for various factors, multiple linear regression analysis revealed that an unbalanced constitution was significantly positively correlated with time to negative nucleic acid test results (P < 0.05). After controlling for various factors, logistic regression analysis revealed that an unbalanced constitution was closely related to the 7-day nucleic acid test conversion rate (odds ratio (OR): 0.53, 95% confidence interval (CI): 0.36-0.80, P < 0.05). After dividing the unbalanced constitution into deficiency constitution and non-deficiency constitution, the non-deficiency constitution was closely associated with the 7-day nucleic acid test conversion rate (OR = 0.45, 95% CI: 0.28-0.74, P < 0.05). Further analysis revealed that damp-heat constitution in the non-deficiency constitution was associated with the 7-day nucleic acid test conversion rate (OR = 0.33, 95% CI: 0.18-0.60, P < 0.05). Conclusion: In patients with COVID-19, an unbalanced constitution is associated with a longer time to negative nucleic acid test results and lower 7-day nucleic acid test conversion rates.

Factors associated with COVID-19 vaccination coverage in hypertensive patients with Omicron infection in Shanghai, China.

The potential future burden of COVID-19 is determined by the level of susceptibility of the population to infection. The protective effect provided by those previously infected diminishes over several months, while individuals with mixed immunity have the highest degree and persistence of protection. This study aimed to clarify the vaccination status of COVID-19 patients with hypertension and to analyze the characteristics and risk factors of non-vaccinated patients to protect this vulnerable population in the future. The study ultimately enrolled 4576 hypertensive patients with Omicron infection from April 6, 2022, to May 15, 2022. Among them, 3556 patients (77.7%) had received at least one dose of vaccine, and 2058 patients (45.0%) received a booster dose. In the multivariate logistic analysis, male (OR 1.328, 95% CI 1.138-1.550, p < .001), age (60-69 years vs.18-49 years) (OR 0.348, 95% CI 0.270-0.448, p < .001), age (≥70 years vs.18-49 years) (OR 0.130, 95% CI 0.100-0.169, p < .001), diabetes mellitus (OR 0.553, 95% CI 0.463-0.661, p < .001), chronic pulmonary diseases (OR 0.474, 95% CI 0.260-0.863, p = .015), chronic kidney disease (OR 0.177, 95% CI 0.076-0.410, p < .001), and cancer (OR 0.225, 95% CI 0.094-0.535, p = .001) were associated with vaccinated status. The vaccine coverage rate, especially the booster vaccine, was low for hypertensive patients with Omicron infection. Females, increasing age, and coexisting chronic diseases were associated with more inadequate vaccine coverage in hypertensive COVID-19 patients. Targeted interventions are required to address the under-vaccination of diverse hypertensive populations.

CRISPR-Hybrid: A CRISPR-Mediated Intracellular Directed Evolution Platform for RNA Aptamers.

Recent advances in gene editing and precise regulation of gene expression based on CRISPR technologies have provided powerful tools for the understanding and manipulation of gene functions. Fusing RNA aptamers to the sgRNA of CRISPR can recruit cognate RNA-binding protein (RBP) effectors to target genomic sites, and the expression of sgRNA containing different RNA aptamers permit simultaneous multiplexed and multifunctional gene regulations. Here, we report an intracellular directed evolution platform for RNA aptamers against intracellularly expressed RBPs. We optimized a bacterial CRISPR-hybrid system coupled with FACS, and identified novel high affinity RNA aptamers orthogonal to existing aptamer-RBP pairs. Application of orthogonal aptamer-RBP pairs in multiplexed CRISPR allowed effective simultaneous transcriptional activation and repression of endogenous genes in mammalian cells.

Identification of indications for albumin administration in septic patients with liver cirrhosis.

BACKGROUND: Albumin infusion is the primary therapeutic strategy for septic patients with liver cirrhosis. Although recent studies have investigated the efficacy of albumin in the resuscitation stage of septic patients with liver cirrhosis, it remains unclear whether daily albumin administration can improve outcomes. Furthermore, the indications for initiating albumin therapy are not well defined. METHODS: Septic patients with liver cirrhosis were obtained from the Medical Information Mart for Intensive Care (MIMIC-IV 2.0) database. Marginal structural Cox models were employed to investigate the association between daily albumin infusion and 28-day mortality. We also aimed to explore under what circumstances enrolled patients could benefit most from albumin administration, based on the clinical parameters collected on the day of albumin infusion, including serum albumin concentration, serum lactate concentration, mean arterial pressure (MAP), and vasopressor dosage. RESULTS: A total of 2265 patients were included in the final analysis, of whom 1093 (48.3%) had received albumin treatment at least once. The overall 28-day mortality was 29.6%. After marginal structural modeling, daily albumin infusion was associated with a reduced risk of 28-day death (hazard ratio, 0.76; 95% CI 0.61-0.94). We found that patients benefit most from albumin infusion when initiated on the day of serum albumin concentration between 2.5 and 3.0 g/dL, serum lactate concentration greater than or equal to 2 mmol/L, MAP less than 60 mmHg, or vasopressor dosage between 0.2 and 0.3 mcg/kg/min (norepinephrine equivalent, NEE). CONCLUSIONS: Albumin infusion is associated with a reduction in mortality in septic patients with liver cirrhosis under specific circumstances. Serum albumin concentration, serum lactate, MAP, and vasopressor dosage were found to be modifiers of treatment effectiveness and should be considered when deciding to initial albumin infusion.

Risk Factors and Disease Profile Associated with the Nucleic Acid Conversion Time of COVID-19 Patients Infected with the SARS-CoV-2 Omicron Variant in Fangcang Shelter Hospitals.

Purpose: This study aimed to determine the clinical profile connected to the nucleic acid conversion time of COVID-19 patients harboring the SARS-CoV-2 Omicron variant at the hospitals at the Fangcang shelter. Methods: We reported 39,584 COVID-19 patients who were hospitalized in Shanghai, China, between April 5 and May 5, 2022, and who had contracted the Omicron strain of SARS-CoV-2. Demographic data, medical and vaccination history, clinical symptoms, and NCT were reported for the patient. Results: The median age of the patients with COVID-19 included in this study was 45 (interquartile range [IQR]: 33-54), and 64.2% of them were male. The two most prevalent comorbidities among the patients were hypertension and diabetes. Additionally, we discovered that the percentage of unimmunized patients was negligible (13.2%). We found that male sex, age under 60, and other comorbidities including hypertension and diabetes are significant risk factors for extending NCT when we analyzed the risk variables for NCT. We discovered that vaccination with two or more doses can significantly reduce NCT. The analysis of the young (18-59 years) and older (60 years) populations produced the same outcomes. Conclusion: Our findings confirm that a full COVID-19 vaccine series or booster doses are highly recommended to significantly reduce NCT. In order to reduce NCT, it is also advised that elderly people who have no clear contraindications take vaccination shots.

Association of Perceived Stress With Depression Among Vaccinated Healthcare Workers During the SARS-CoV-2 Variant Outbreak: The Mediating Role of Compassion Fatigue.

OBJECTIVE: Depression was common during coronavirus disease-2019 (COVID-19) pandemic, while the association of perceived stress with depression among vaccinated healthcare workers has not been investigated. This study aimed to address this issue. METHODS: We included a total of 898 fully vaccinated healthcare workers during the outbreak of severe acute respiratory syndrome coronavirus 2 Delta variant in Nanjing, 2021. Depression was ascertained by Patient Health Questionnaire-9, with a cut-off score of ≥5 indicative of mild-to-severe depression. Perceived stress, resilience, and compassion fatigue were assessed by Perceived Stress Scale-10, Resilience Scale-25, and Professional Quality of Life Scale version-5, respectively. Logistic regression analyses were used to estimate the odds ratio (OR) and 95% confidence interval (CI), along with subgroup and mediation analyses. RESULTS: The prevalence of mild-to-severe depression was 41.1% in vaccinated healthcare workers. The odd of mild-to-severe depression was increased with higher perceived stress. Compared with vaccinated healthcare workers with the lowest tertile of perceived stress, those with the highest tertile had increased odds of mild-to-severe depression by 120% (OR 2.20, 95% CI 1.46 to 3.31) after multivariable-adjustment. However, perceived stress was not associated with mild-to-severe depression in vaccinated healthcare workers with strong resilience, but was in those with weak resilience (pinteraction=0.004). Further analysis showed that compassion fatigue mediated the relationship between perceived stress and mild-to-severe depression, with a mediating effect of 49.7%. CONCLUSION: Perceived stress was related to an increased odd of mild-to-severe depression in vaccinated healthcare workers during COVID-19 pandemic, and this relationship might be explained by compassion fatigue.

Value of Laboratory Indicators in Predicting Pneumonia in Symptomatic COVID-19 Patients Infected with the SARS-CoV-2 Omicron Variant.

Background: The pathogenicity of Omicron is different from that of the previous strains. The value of hematological indicators in patients at high risk of Omicron infection remains unclear. We need rapid, inexpensive and widely available biomarkers to guide the early detection of people at risk of pneumonia and to provide early intervention. We aimed to assess the value of hematological indicators as risk factors for pneumonia in symptomatic COVID-19 patients infected with the SARS-CoV-2 Omicron variant. Patients and Methods: The study enrolled 144 symptomatic COVID-19 patients with Omicron infection. We collected available clinical details, including laboratory tests and CT examinations. Univariate and multivariate logistic analyses and receiver operating characteristic (ROC) curve analyses were used to assess the value of laboratory markers in predicting the development of pneumonia. Results: Among the 144 patients, 50 (34.7%) had pneumonia. The ROC analysis revealed that the areas under the ROC curve (AUC) for leukocytes, lymphocytes, neutrophils, and fibrinogen were 0.603 (95% confidence interval (CI): 0.501-0.704, P=0.043), 0.615 (95% CI: 0.517-0.712, P=0.024), 0.632 (95% CI: 0.534-0.730, P=0.009) and 0.635 (95% CI: 0.539-0.730, P=0.008), respectively. The AUC for neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), fibrinogen to lymphocyte ratio (FLR), and fibrinogen to D-dimer ratio (FDR) were 0.670 (95% CI: 0.580-0.760, P=0.001), 0.632 (95% CI: 0.535-0.728, P=0.009), 0.669 (95% CI: 0.575-0.763, P=0.001) and 0.615 (95% CI: 0.510-0.721, P=0.023), respectively. Univariate analysis showed that elevated levels of NLR (odds ratio (OR): 1.219, 95% CI: 1.046-1.421, P=0.011), FLR (OR: 1.170, 95% CI: 1.014-1.349, P=0.031) and FDR (OR: 1.131, 95% CI: 1.039-1.231, P=0.005) were significantly correlated with the presence of pneumonia. Multivariate analysis indicated elevated NLR (OR: 1.248, 95% CI: 1.068-1.459, P=0.005) and FDR (OR: 1.160, 95% CI: 1.054-1.276, P=0.002) levels were associated with the existence of pneumonia. The AUC for the combination of NLR and FDR was 0.701 (95% CI: 0.606-0.796, P<0.001, sensitivity 56.0%, specificity 83.0%). Conclusion: NLR and FDR can predict the presence of pneumonia in symptomatic COVID-19 patients infected with the SARS-CoV-2 Omicron variant.

Effects of hydrocortisone combined with vitamin C and vitamin B1 versus hydrocortisone alone on microcirculation in septic shock patients: A pilot study.

OBJECTIVE: To investigate the effects of hydrocortisone combined with vitamin C and vitamin B1 versus hydrocortisone on sublingual microcirculation in septic shock patients. METHODS: This pilot study enrolled septic shock patients admitted to the ICU of a tertiary teaching hospital from February 2019 to January 2020. We randomly assigned the enrolled patients to the treatment group (hydrocortisone combined with vitamin C and vitamin B1 added to standard care) and the control group (hydrocortisone alone added to standard care) in a 1 : 1 ratio. The primary outcome was perfused small vascular density (sPVD) monitored by a sublingual microcirculation imaging system at 24 hours after treatment. RESULTS: Twelve patients in the treatment group and ten in the control group completed the study. The baseline characteristics were comparable between the groups. No statistically significant difference was found in the sPVD between the groups at baseline. The sPVD in the treatment group was significantly higher than that in the control group at 4 hours after treatment (mean difference, 7.042; 95% CI, 2.227-11.857; P = 0.009) and 24 hours after treatment (mean difference, 7.075; 95% CI, 2.390-11.759; P = 0.008). CONCLUSIONS: Compared with hydrocortisone, hydrocortisone combined with vitamin C and vitamin B1 significantly improves microcirculation in septic shock patients.

Identifying high-risk phenotypes and associated harms of delayed time-to-antibiotics in patients with ICU onset sepsis: A retrospective cohort study.

PURPOSE: To identify phenotypes of Intensive Care Unit (ICU) onset sepsis and its associated harms of delayed time-to-antibiotics. MATERIALS AND METHODS: The Medical Information Mart for Intensive Care IV (MIMIC-IV) database was employed to identify patients with ICU onset sepsis. The primary exposure was time-to-antibiotics, as measured from sepsis recognition to first antibiotic administered. Latent profile analysis (LPA) was used to identify phenotypes of sepsis based on individual organ failure score derived from Sequential Organ Failure Assessment (SOFA). Interactions between phenotypes and time-to-antibiotics on 28-day mortality were explored. RESULTS: 6246 patients were enrolled in final analysis. The overall 28-day mortality was 12.7%. Delayed time-to-antibiotics was associated with increased 28-day mortality in patients with ICU onset sepsis (HR 1.12, 95% CI 1.08-1.18). Four phenotypes of sepsis were identified: phenotype 1 was characterized by respiratory dysfunction, phenotype 2 was characterized by cardiovascular dysfunction, phenotype 3 was characterized by multiple organ dysfunction, and phenotype 4 was characterized by neurological dysfunction. The adjusted HR of 28-day mortality was 1.16 (95% CI 1.08-1.25) in phenotype 1, and 1.06 (95% CI 1.00-1.13) in phenotype 2, while no significant interaction was observed. CONCLUSIONS: Septic patients with respiratory or cardiovascular dysfunction were associated with harms of delayed time-to-antibiotics.

Clinical outcome and risk factors for acute fulminant myocarditis supported by venoarterial extracorporeal membrane oxygenation: An analysis of nationwide CSECLS database in China.

BACKGROUND: To assess the outcomes and risk factors for adult patients with acute fulminant myocarditis (AFM) supported with venoarterial extracorporeal membrane oxygenation (VA ECMO) in China mainland. METHODS: Data were extracted from Chinese Society of ExtraCorporeal Life Support (CSECLS) Registry database. Data from adult patients who were diagnosed with AFM and needed VA ECMO in the database were retrospectively analyzed. The primary outcome was 90-day mortality after ECMO initiation in patients with AFM supported with VA ECMO. Cox proportional hazard regression model was used to examine the risk factors associated with 90-day mortality. RESULTS: Among 221 patients enrolled and followed up to 90 days, 186 (84.2%) patients weaned from ECMO and 159 (71.9%) patients survived and discharged home. The median age was 38 years (IQR 29-49) and males (n = 115) represented 52.0% of the total accounted patients. The median ECMO duration was 134 h (IQR 96-177 h). The main adverse event during ECMO course was bleeding (16.3%), followed by infection (15.4%). In the multivariate Cox model analysis, cardiac arrest prior to ECMO initiation (adjusted HR 2.529; 95%CI: 1.341-4.767, p = 0.004), lower pH value (adjusted HR 0.016; 95%CI: 0.010-0.059, p < 0.001) and higher lactate concentration at 24 h after ECMO initiation (adjusted HR 1.146; 95%CI: 1.075-1.221, p < 0.001) were associated with 90-day mortality. CONCLUSIONS: 71.9% patients with AFM (clinical diagnosed) supported with VA ECMO survived. Cardiac arrest prior to ECMO, lower pH and higher lactate concentration at 24 h after ECMO initiation were correlated with 90-day mortality of AFM patients supported with VA ECMO.

Prevalence of myopia and uncorrected myopia among 721 032 schoolchildren in a city-wide vision screening in southern China: the Shantou Myopia Study.

AIMS: To explore the prevalence and risk factors for myopia and uncorrected myopia in schoolchildren in southern China. METHODS: The government-led Shantou Myopia Study was conducted from September 2020 to June 2021. Non-cycloplegic refraction was performed. Uncorrected visual acuity (UCVA) was measured along with presenting visual acuity if participants wore spectacles. Spherical equivalent refraction (SER) is defined as the spherical dioptres added to half of the cylindrical dioptres. Myopia is defined as SER <-0.50 dioptre with UCVA of <20/20 in at least one eye. RESULTS: This study enrolled 724 828 schoolchildren (77.8% of all schoolchildren in Shantou) from 901 schools. Data from 721 032 schoolchildren (99.5%) were analysed (mean age 11.53±3.13 years, 6-20 years, 373 230 boys and 347 802 girls). Among them, 373 459 (51.8%) had myopia: 37.1% of 465 696 children in primary schools, 75.4% of 170 164 children in junior high schools and 84.8% of 85 172 children in senior high schools. The prevalence of myopia increases non-linearly with age. Older age, female and urban living environment were independently associated with myopia prevalence and myopic SER. Among the 373 459 children with myopia, 60.0% had no refractive correction: 74.9%, 53.9% and 35.5% in primary, junior high and senior high schools, respectively. CONCLUSION: The overall prevalence of myopia among schoolchildren in Shantou was 51.8%, higher than the national average in China. The proportion of uncorrected myopia is high, especially in primary schools. Our results indicate the need for public education on eye care among schoolchildren even in a municipal city.

Mental health symptoms and sleep quality of asymptomatic/mild SARS-CoV-2 infected individuals during the Omicron wave of the COVID-19 pandemic in Shanghai China.

OBJECTIVE: To investigate mental health symptoms (anxiety, depression, and sleep status) and their associated factors among people infected with the SARS-CoV-2 omicron variant during the quarantine period in Shanghai. METHODS: To investigate the mental health symptoms among participants with SARS-CoV-2 omicron infection, an anonymous online survey questionnaire was used. The survey panel included the 9-item Patient Health Questionnaire-9 (PHQ-9), 7-item Generalized Anxiety Disorder Scale (GAD-7), Pittsburgh Sleep Quality Index (PSQI), and 22-item Ruminative Responses Scale (RRS). Group comparisons and correlation analyses were employed to explore the epidemiological characteristics of patients and factors related to depression and anxiety symptoms. RESULTS: A total of 960 participants completed the survey. Of the total respondents, 583 participants (60.7%) were male, and the mean (SD) age was 34.33 (9.21) years (95% CI: 33.74-34.91). The prevalence of depressive and anxiety symptoms among the participants was 13.7% (n = 151, 95% CI: 11.6%-15.7%) and 8.6% (n = 90, 95% CI: 6.9%-10.3%), respectively. Age-stratified analysis showed that the prevalence of anxiety among the 36- to 45-year-old group (12.9%; n = 35, 8.9%-16.9%) was significantly higher than that of the 18- to 15-year-old group (7.4%; n = 42, 5.3%-9.6%, p = .011). Spearman's correlation analyses showed that rumination (assessed by the RRS) was significantly and positively correlated with depression (rho = .706, p < .001) and anxiety symptoms (rho = .758, p < .001). CONCLUSION: The results suggest that female and middle-aged populations manifest higher susceptibility to mental health distress during the current Omicron wave of the COVID-19 pandemic. Population-specific psychological crisis intervention is warranted to improve the quality of epidemic prevention methods and to promote the mental well-being of the public.

Longitudinal phenotypes in patients with acute respiratory distress syndrome: a multi-database study.

BACKGROUND: Previously identified phenotypes of acute respiratory distress syndrome (ARDS) have been limited by a disregard for temporal dynamics. We aimed to identify longitudinal phenotypes in ARDS to test the prognostic and predictive enrichment of longitudinal phenotypes, and to develop simplified models for phenotype identification. METHODS: We conducted a multi-database study based on the Chinese Database in Intensive Care (CDIC) and four ARDS randomized clinical trials (RCTs). We employed latent class analysis (LCA) to identify longitudinal phenotypes using 24-hourly data from the first four days of invasive ventilation. We used the Cox regression model to explore the association between time-varying respiratory parameters and 28-day mortality across phenotypes. Phenotypes were validated in four RCTs, and the heterogeneity of treatment effect (HTE) was investigated. We also constructed two multinomial logistical regression analyses to develop the probabilistic models. FINDINGS: A total of 605 ARDS patients in CDIC were enrolled. The three-class LCA model was identified and had the optimal fit, as follows: Class 1 (n = 400, 66.1% of the cohort) was the largest phenotype over all study days, and had fewer abnormal values, less organ dysfunction and the lowest 28-day mortality rate (30.5%). Class 2 (n = 102, 16.9% of the cohort) was characterized by pulmonary mechanical dysfunction and had the highest proportion of poorly aerated lung volume, the 28-day mortality rate was 47.1%. Class 3 (n = 103, 17% of the cohort) was correlated with extra-pulmonary dysfunction and had the highest 28-day mortality rate (56.3%). Time-varying mechanical power was more significantly associated with 28-day mortality in Class 2 patients compared to other phenotypes. Similar phenotypes were identified in four RCTs. A significant HTE between phenotypes and treatment strategies was observed in the ALVEOLI (high PEEP vs. low PEEP) and the FACTT trials (conservative vs. liberal fluid management). Two parsimonious probabilistic models were constructed to identify longitudinal phenotypes. INTERPRETATION: We identified and validated three novel longitudinal phenotypes for ARDS patients, with both prognostic and predictive enrichment. The phenotypes of ARDS can be accurately identified with simple classifier models, except for Class 3.

Addition of terlipressin to norepinephrine in septic shock and effect of renal perfusion: a pilot study.

PURPOSE: Terlipressin improves renal function in patients with septic shock. However, the mechanism remains unclear. Here, we aimed to evaluate the effects of terlipressin on renal perfusion in patients with septic shock. MATERIALS AND METHODS: This pilot study enrolled patients with septic shock in the intensive care unit of the tertiary hospital from September 2019 to May 2020. We randomly assigned patients to terlipressin and usual care groups using a 1:1 ratio. Terlipressin was intravenously pumped at a rate of 1.3 µg/kg/hour for 24 h. We monitored renal perfusion using renal contrast-enhanced ultrasound (CEUS). The primary outcome was peak sonographic signal intensity (a renal perfusion parameter monitored by CEUS) at 24 h after enrollment. RESULTS: 22 patients were enrolled in this study with 10 in the terlipressin group and 12 in the usual care group. The baseline characteristics of patients between the two groups were comparable. The peak sonographic signal intensity at 24 h after enrollment in the terlipressin group (60.5 ± 8.6 dB) was significantly higher than that in the usual care group (52.4 ± 7.0 dB; mean difference, 7.1 dB; 95% CI, 0.4-13.9; adjusted p = .04). Patients in the terlipressin group had a lower time to peak, heart rates, norepinephrine dose, and a higher stroke volume at 24 h after enrollment. No significant difference in the urine output within 24 h and incidence of acute kidney injury within 28 days was found between the two groups. CONCLUSIONS: Terlipressin improves renal perfusion, increases stroke volume, and decreases norepinephrine dose and heart rates in patients with septic shock.

The Efficiency of Convalescent Plasma Therapy in the Management of Critically Ill Patients Infected With COVID-19: A Matched Cohort Study.

Background: The convalescent plasma of patients who recover from coronavirus disease 2019 (COVID-19) contains high titers of neutralizing antibodies, which has potential effects on the viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and improving the prognosis of patients with COVID-19. The goal of this study was to clarify the effects of convalescent plasma therapy on the 60-day mortality and negative conversion rate of SARS-CoV-2 during the hospitalization of patients with severe and life-threatening COVID-19 infection. Methods: This was a retrospective, case-matched cohort study that involved patients with severe COVID-19 infections. The patients who received convalescent plasma therapy were matched by age, sex, diabetes, hypertension, heart failure, the onset of symptoms to hospital admission, respiratory support pattern, lymphocyte count, troponin, Sequential organ failure assessment (SOFA), glucocorticoid, and antiviral agents to no more than three patients with COVID-19 who did not receive convalescent plasma therapy. A Cox regression model and competing risk analysis were used to evaluate the effects of convalescent plasma therapy on these patients. Results: Twenty-six patients were in the convalescent plasma therapy group, and 78 patients were in the control group. Demographic characteristics were similar in both groups, except for the SOFA score. Convalescent plasma therapy did not improve 60-day mortality [hazard ratio (HR) 1.44, 95% CI 0.82-2.51, p = 0.20], but the SARS-CoV-2 negative conversion rate for 60 days after admission was higher in the convalescent plasma group (26.9 vs. 65.4%, p = 0.002) than in the control. Then, a competing risk analysis was performed, which considered events of interest (the negative conversion rate of SARS-CoV-2) and competing events (death) in the same model. Convalescent plasma therapy improved events of interest (p = 0.0002). Conclusion: Convalescent plasma therapy could improve the SARS-CoV-2 negative conversion rate but could not improve 60-day mortality in patients with severe and life-threatening COVID-19 infection. Clinical Trial Number: The study was registered at ClinicalTrials.gov (NCT04616976).

Hepatocyte growth factor protects pulmonary endothelial barrier against oxidative stress and mitochondria-dependent apoptosis.

BACKGROUND: Pulmonary microvascular endothelial cells (PMVECs) were not complex, and the endothelial barrier was destroyed in the pathogenesis progress of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Previous studies have demonstrated that hepatocyte growth factor (HGF), which was secreted by bone marrow mesenchymal stem cells, could decrease endothelial apoptosis. We investigated whether mTOR/STAT3 signaling acted in HGF protective effects against oxidative stress and mitochondria-dependent apoptosis in lipopolysaccharide (LPS)-induced endothelial barrier dysfunction and ALI mice. METHODS: In our current study, we introduced LPS-induced PMEVCs with HGF treatment. To investigate the effects of mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) pathway in endothelial oxidative stress and mitochondria-dependent apoptosis, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 were, respectively, used to inhibit mTOR/STAT3 signaling. Moreover, lentivirus vector-mediated mTORC1 (Raptor) and mTORC2 (Rictor) gene knockdown modifications were introduced to evaluate mTORC1 and mTORC1 pathways. Calcium measurement, reactive oxygen species (ROS) production, mitochondrial membrane potential and protein, cell proliferation, apoptosis, and endothelial junction protein were detected to evaluate HGF effects. Moreover, we used the ALI mouse model to observe the mitochondria pathological changes with an electron microscope in vivo. RESULTS: Our study demonstrated that HGF protected the endothelium via the suppression of ROS production and intracellular calcium uptake, which lead to increased mitochondrial membrane potential (JC-1 and mitochondria tracker green detection) and specific proteins (complex I), raised anti-apoptosis Messenger Ribonucleic Acid level (B-cell lymphoma 2 and Bcl-xL), and increased endothelial junction proteins (VE-cadherin and occludin). Reversely, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 could raise oxidative stress and mitochondria-dependent apoptosis even with HGF treatment in LPS-induced endothelial cells. Similarly, mTORC1 as well as mTORC2 have the same protective effects in mitochondria damage and apoptosis. In in vivo experiments of ALI mouse, HGF also increased mitochondria structural integrity via the mTOR/STAT3 pathway. CONCLUSION: In all, these reveal that mTOR/STAT3 signaling mediates the HGF suppression effects to oxidative level, mitochondria-dependent apoptosis, and endothelial junction protein in ARDS, contributing to the pulmonary endothelial survival and barrier integrity.