Exosomes derived from plasma of septic patients inhibit apoptosis of T lymphocytes by down-regulating bad via hsa-miR-7-5p.

Immunosuppression is currently a vital pathophysiological characteristic and core problem of sepsis. Apoptosis of T lymphocyte contribute to immunosuppression by decreasing immune effector cells. A report has recently revealed the potential regulatory role of exosomal miRNAs derived from plasma of septic patients on immune system, but the underlying mechanism is unclear. We discovered the antiapoptotic effect of circulating exosomes derived from plasma of septic patients (Sepsis-Exos) on T lymphocytes and further investigated the molecular mechanism. Next-generation sequencing (NGS) indicated that sepsis induces prominent change of exosomal miRNA expression profile, including the overexpressed hsa-miR-7-5p. Gene Bad, which is in the cGMP-PKG signaling pathway, was negatively regulated by hsa-miR-7-5p by dual luciferase reporter assay. Sepsis-Exos were demonstrated to downregulate the mRNA and protein levels of proapoptotic gene Bad, active Caspase-3 and Bax, while upregulate that of antiapoptotic gene Bcl-2 via hsa-miR-7-5p, thus inhibited apoptosis of T lymphocytes induced by lipopolysaccharide (LPS) in vitro. Furthermore, Sepsis-Exos was verified to inhibit T lymphocytes apoptosis during sepsis in vivo, reducing mortality rate of septic model mice. In conclusion, we provide evidence that Sepsis-Exos participate in ameliorating apoptosis of T lymphocytes by directly suppressing Bad via hsa-miR-7-5p.

RISK FACTORS, TREATMENT STRATEGIES, AND OUTCOMES OF ENDOPHTHALMITIS ASSOCIATED WITH SEVERE FUNGAL KERATITIS.

PURPOSE: To investigate risk factors, treatment strategies, and outcomes of endophthalmitis associated with severe fungal keratitis. METHODS: Data from 392 patients diagnosed with fungal keratitis were retrospectively examined. Patients had severe disease that was refractory to topical or systemic antifungal therapy, and the infection involved the endothelium or perforated the cornea. The incidence and risk factors for endophthalmitis, and treatment outcomes were evaluated. RESULTS: Thirty-seven of 392 patients (9.4%) had endophthalmitis. Multivariate logistic regression revealed the following risk factors for endophthalmitis: topical steroid use (odds ratio [OR] = 6.35, 95% confidence interval [CI]: 2.01-20.08), previous corneal laceration suturing (OR = 5.05, 95% CI: 1.11-22.93), large corneal ulcer size (≥10-mm diameter; OR = 4.43, 95% CI: 1.71-11.50), hypopyon (OR = 11.05, 95% CI: 2.12-57.55), and aphakia (OR = 15.45, 95% CI: 1.59-149.82). Thirty of the 37 eyes (81.1%) with endophthalmitis were saved by penetrating keratoplasty, vitrectomy, or intravitreal antifungal injection; 7 eyes (18.9%) were eviscerated. CONCLUSION: Most patients with endophthalmitis secondary to corneal fungal infection were successfully managed by penetrating keratoplasty, vitrectomy, or intravitreal antifungal therapy. Multiple risk factors for endophthalmitis were identified. Timely diagnosis and risk factor assessment were essential for ensuring early surgical intervention for fungal keratitis-related endophthalmitis.

Prognostic value of procalcitonin in pneumonia: A systematic review and meta-analysis.

This meta-analysis was performed to determine the accuracy of procalcitonin (PCT) in predicting mortality in pneumonia patients with different pathogenic features and disease severities. A systematic search of English-language articles was performed using PubMed, Embase, Web of Knowledge and the Cochrane Library to identify studies. The diagnostic value of PCT in predicting prognosis was determined using a bivariate meta-analysis model. The Q-test and I(2) index were used to test heterogeneity. A total of 21 studies comprising 6007 patients were included. An elevated PCT level was a risk factor for death from community-acquired pneumonia (CAP) (risk ratio (RR) 4.38, 95% confidence interval (CI) 2.98-6.43), particularly in patients with a low CURB-65 score. The commonly used cut-off, 0.5 ng/mL, had low sensitivity (SEN) and was not able to identify patients at high risk of dying. Furthermore, the PCT assay with functional SEN <0.1 ng/mL was necessary to predict mortality in CAP in the clinic. For critically ill patients, an elevated PCT level was associated with an increased risk of mortality (RR 4.18, 95% CI: 3.19-5.48). The prognostic performance was nearly equal between patients with ventilator-associated pneumonia (VAP) and patients with CAP.

Mitochondrial DNA copy number, but not haplogroup is associated with keratoconus in Han Chinese population.

Oxidative stress may play a role in the pathogenesis of keratoconus (KC). Mitochondrial DNA (mtDNA) is closely related to mitochondrion function, and variations may affect the generation of reactive oxygen species (ROS) and be involved in the pathogenesis of KC. To test whether mtDNA background and copy number confer genetic susceptibility to KC in the Han Chinese population, we performed this association study. We analyzed mtDNA sequence variations in 210 KC patients and 309 matched individuals from China, and classified each subject by haplogroup. Mitochondrial DNA copy number was measured in a subset of these subjects (193 patients and 103 controls). Comparison of matrilineal components of the cases and control populations revealed no significant difference. However, measurement of mtDNA copy number showed that KC patients had significantly lower mtDNA copy numbers than controls (P = 0.0002), even when age, gender, and mtDNA background were considered. Our results suggest that mtDNA copy number, but not haplogroup, is associated with keratoconus, and may contribute to its pathogenesis.

The accuracy of presepsin (sCD14-ST) for the diagnosis of sepsis in adults: a meta-analysis.

INTRODUCTION: The early diagnosis of sepsis remains a challenge. Recently, soluble cluster of differentiation 14 subtype (sCD14-ST), also known as presepsin, has been identified as a potential biomarker of sepsis. We performed a meta-analysis to assess the diagnostic accuracy of presepsin for sepsis in patients with systemic inflammation. METHODS: We systematically searched the PubMed, Embase, Web of Knowledge and Cochrane databases. Studies were included if they assessed the diagnostic accuracy of presepsin for sepsis in adult patients with systemic inflammatory response syndrome (SIRS). Furthermore, a 2 × 2 contingency table was constructed based on these results. Two authors independently judged the studies and extracted the data. The diagnostic accuracy of presepsin in sepsis was calculated using a bivariate meta-analysis model. The Q-test and I (2) index were used to test the heterogeneity. RESULTS: Eight studies involving a total of 1,815 patients were included in the present study. The pooled sensitivity, specificity, diagnostic odds ratio, positive likelihood ratio and negative likelihood ratio were 0.86 (95% CI: 0.79-0.91), 0.78 (95% CI: 0.68-0.85), 22 (95% CI: 10-48), 3.8 (95% CI: 2.6-5.7), and 0.18 (95% CI: 0.11-0.28), respectively. The area under the summary receiver operator characteristic curve was 0.89 (95% CI: 0.86-0.92). Meta-regression analysis revealed that consecutive patient selection, sample size and setting significantly accounted for the heterogeneity of sensitivity. CONCLUSIONS: Our findings suggest that presepsin exhibits very good diagnostic accuracy (AUC=0.89) for the diagnosis for sepsis. Nevertheless, an overall assessment of all the clinical indexes for sepsis diagnosis and continual re-evaluation of presepsin during the course of the disease are needed.

Identification of four novel serum protein biomarkers in sepsis patients encoded by target genes of sepsis-related miRNAs.

The goal of the present study was to identify novel protein biomarkers from the target genes of six serum miRNAs that we identified previously in patients with sepsis. The target genes were predicted by bioinformatics analysis; the levels of the respective proteins in the sera of patients with sepsis were detected by ELISA. ACVR2A (activin A receptor, type IIA), FOXO1 (forkhead box O1), IHH (Indian hedgehog), STK4 (serine/threonine kinase 4) and DUSP3 (dual specificity phosphatase 3) were predicted to be the targets of the six miRNAs, and their encoded proteins were used for biomarker identification. Levels of ACVR2A (P<0.01) and FOXO1 (P<0.01) were significantly different among normal controls, patients with sepsis, patients with severe sepsis and patients with septic shock. Furthermore, levels of ACVR2A (P=0.025), FOXO1 (P<0.001), IHH (P=0.001) and STK4 (P=0.001) were differentially expressed in survivors and non-survivors. DUSP3 levels were not significantly different between any groups. Conjoin analysis of the four differentially expressed proteins showed that the area under the curve of the predictive probabilities was 0.875 [95% CI (confidence interval): 0.785-0.965], which was higher than the SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) scores. When the value of predictive probabilities was 0.449, the four proteins yielded a sensitivity of 68% and a specificity of 91%. Dynamic changes in ACVR2A, FOXO1 and IHH levels showed differential expression between survivors and non-survivors at all time points. On the basis of a combined analysis of the four identified proteins, their predictive value of 28-day mortality of patients with sepsis was better than the SOFA or APACHE II scores.

Serum miR-122 levels are related to coagulation disorders in sepsis patients.

BACKGROUND: Coagulation abnormalities may have a major impact on the outcome of sepsis in patients. This study aimed to explore the relationship between miRNA levels and coagulation disorders during sepsis. METHODS: Blood samples from 123 sepsis patients were collected on the day of admission and another 45 sepsis patients on days 1, 3, 5, 7, 10, and 14 following admission to the intensive care unit. miR-223, miR-15a, miR-16, miR-122, miR-193b*, and miR-483-5p levels were evaluated by quantitative reverse transcription polymerase chain reaction. Based on the International Society on Thrombosis and Haemostasis (ISTH) Disseminated Intravascular Coagulation (DIC) score, sepsis patients were divided into coagulation abnormal (CA) group and coagulation normal (CN) group. RESULTS: Only the levels of miR-122 were significantly higher in CA patients than in CN patients (p<0.001). Serum levels of miR-122 were correlated to the serum activated partial thromboplastin time (APTT) ratios (R=0.426, p=0.008) and the fibrinogen (FIB; R=0.398, p=0.008) and antithrombin III (R=0.913, p<0.001) levels. In addition, Pearson's correlation coefficients for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) with miR-122 were 0.663 (p<0.001) and 0.445 (p=0.001), respectively. In the 45 patients, the miR-122 levels were significantly higher on day 1, 3, 7, and 10 in the CA group than in the CN group, and no difference in the ISTH-DIC scores was evident. CONCLUSIONS: Serum levels of miR-122 were correlated to the coagulation disorder in sepsis patients.

Effects of vitamin b6 therapy for sepsis patients with linezolid-associated cytopenias: a retrospective study.

BACKGROUND: The common adverse effects of linezolid for treating septic patients with gram-positive cocci is anemia and thrombocytopenia, which limit its clinical application. OBJECTIVES: We determined the effects of vitamin B6 adjunctive therapy on linezolid-associated cytopenias, and retrospectively studied 75 septic patients who received at least 7 days of linezolid treatment. METHODS: Patients were divided into a linezolid treatment group (LTG; n = 41) that received linezolid only and a combination treatment group (CTG; n = 34) that received both linezolid and vitamin B6. Each group was further subdivided into those with sepsis and those with severe sepsis. Each patient had red blood cell (RBC), hemoglobin (Hb), hematocrit (Hct), and platelet (PLT) measurements at baseline (day 0) and every other day for 2 weeks during treatment; these parameters were compared between the groups and assessed for time-dependent trends. RESULTS: For patients in the LTG, RBC, Hb, and Hct values showed statistically significant reductions over time, and these values were lower compared with the values in the CTG. The CTG also showed downward trends, except on the first day of treatment. The PLT count also decreased in both groups. Patients with severe sepsis had lower PLT counts in both treatment groups compared with the septic patients. CONCLUSIONS: Septic patients who received a combination treatment of linezolid and vitamin B6 might show positive effects for linezolid-associated reductions in some hematologic parameters (RBC, Hb, and Hct). This combined treatment might also slow PLT reduction, which was more evident in patients with severe sepsis. ClinicalTrials.gov identifier: NCT01295801.

[Assessment of prognostic and influencing factors in elderly patients with multiple organ dysfunction syndrome].

OBJECTIVE: To preliminarily assess the prognosis of patients with multiple organ dysfunction syndrome (MODSE) and analyze their influencing factors. METHODS: The clinical data of 365 MODSE patients admitted into Chinese PLA General Hospital during January 2009 to June 2012 were analyzed retrospectively. According to 28-day outcomes, they were divided into 2 groups (28-day survival and non-survival) while 4 groups according to age. Then these prognosis were evaluated with the current scoring systems ((acute physiology and chronic health evaluation II (APACHEII and III), sample acute physiological score (SAPSII) and multiple organ dysfunction score (MODS)). The predictive powers were compared by receiver operating characteristic (ROC) curve. Finally a binary Logistic regression analysis was performed to evaluate the relevant influencing prognostic factors of MODSE. RESULTS: The mean age was (77.8 ± 9.1) years, mean number of failed organs (3.6 ± 1.2) and a 28-day mortality 45.8%. The ages of non-survival group were older than those of survival group ((78.1 ± 9.1) vs (76.7 ± 11.0) years). The number of organ failures ((4.3 ± 1.1) vs (3.1 ± 1.0)) and scores (APACHEII: (28 ± 7) vs (20 ± 8), APACHE III: (106 ± 27) vs (75 ± 31), SAPSII: (64 ± 16) vs (46 ± 18), MODS: (9 ± 3) vs (6 ± 3)) of non-survivals were significantly higher than that of survivals. The area under ROC curve of these four score systems were 0.790, 0.781, 0.780 and 0.780 respectively. Compared to the above systems, SAPSII had the best performance in sensitivity while APACHEII was more valuable in specificity. All clinical data underwent binary Logistic regression and the results showed that plasma concentration of albumin and mean arterial pressure (MAP) offered beneficial outcomes while age and number of organ failures had unfavorable prognosis. The greater patient age, the higher their mortality. CONCLUSIONS: All four scoring systems have accurate prognostic predictions of MODSE patients. And the predictive power of APACHEII is the best. Plasma concentration of albumin, MAP, age and organ failure number are independent prognostic factors in MODSE patients.

[Understanding the advantages and disadvantages of femtosecond laser comprehensive applications in ophthalmology].

The femtosecond (FS) laser is a novel laser technology, and is approved clinical application by FDA in 2000. FS laser initially mainly used in corneal refractive surgery to replace the mechanical microkeratome. Since the accuracy and controllability of the FS laser is very high, it shows superiority in the field of corneal refractive surgery. And with the development of the relative hard and software, FS laser is began to used in other fields of ophthalmology, such as corneal transplants, cataract surgery, as well as assisted diagnosis et al., although still have some limitations, the preliminary clinical results have been shown a very good prospects in the ophthalmology fields. Therefore, we reviewed the alternative applications, challenges and limitations, research direction in the future of FS laser, so that provide a reference and revelations for the peers.

[Clinical analysis of the occurrence of secondary glaucoma after pediatric congenital cataract surgery in the first 36 months of life].

OBJECTIVE: To observe the rate of secondary glaucoma after pediatric congenital cataract surgery in the first 36 months of life. METHODS: Retrospective case series. The records of children who underwent surgery for congenital cataract within the first 36 months of life between July 1995 and July 2005 at Qingdao Eye Hospital were reviewed. Children with preoperative conditions associated with glaucoma were excluded. Age at surgery, unilateral or bilateral cataract, type of congenital cataract, primary intraocular lens (IOL) insertion, duration of follow-up, postoperative best corrected visual acuity, development of aphakic glaucoma, and development of glaucoma after secondary IOL implantation were evaluated. RESULTS: A total of 115 patients (204 eyes) with an average surgery age of (12.5 ± 9.2) months were included; the mean follow-up time was (83.7 ± 43.8) months. 15 eyes (11 patients) (7.4%) had subsequent development of glaucoma, 7 of which (4 patients) developed late-onset open-angle glaucoma. Of the 15 eyes, 13 eyes had surgery within 9 months, and 12 eyes developed nuclear or total cataract. None of the primarily pseudophakia eyes developed glaucoma in our study. Of 86 eyes that received implantation of secondary intraocular lens in the ciliary sulcus, 13 eyes (15.1%) developed pseudophakia glaucoma. CONCLUSIONS: Secondary glaucoma occurred after pediatric bilateral cataract surgery. As late-onset glaucoma usually occurred several years after primary surgery, long-time follow-up after pediatric cataract surgery needs to be emphasized.

[Pseudo-accommodation with accommodating intraocular lens in patients at different ages].

OBJECTIVE: To compare the clinical performances of patients in different ages with implantation of a accommodating IOLs. METHODS: It was a retrospective study. Forty-seven eyes (47 patients) were enrolled in 3 groups for phacoemulsification and a accommodating IOL implantation. According to their ages, they were divided into 3 groups: ≤ 45 years, 46 - 59 years, and ≥ 60 years. Parameters analyzed after more than 3 months postoperation were uncorrected distance, best-corrected distance, uncorrected near, and distance-corrected near visual acuities; changes of anterior chamber depth(ACD) during accommodative measured using the ultrasound biomicroscopy (UBM);changes of ACD by instilling 2% pilocarpine using the A-ultrasonic scan; and the amplitude of accommodation using the pushing-up test. RESULTS: No significant difference was observed between distance and near visual acuities of IOL groups. The mean changes of ACD measured with UBM in the group of ≤ 45 years [(0.16 ± 0.12) mm] was significantly higher than the other age groups [46 - 59 years, (0.06 ± 0.06) mm, P = 0.00; ≥ 60 years, (0.07 ± 0.05) mm, P = 0.008)]. The mean changes of ACD stimulated by pilocarpine measured with A-ultrasonic scan in the group of ≥ 60 years [(0.17 ± 0.14) mm] was significantly lower than the other age groups [≤ 45 years, (0.68 ± 0.44) mm, P = 0.00; 46 - 59 years, (0.43 ± 0.20) mm, P = 0.00]. The accommodative amplitude of the ≥ 60 years groups ((2.32 ± 0.88) D) was lower than the group of ≤ 45 years [(2.87 ± 0.52) D, P = 0.005]. CONCLUSIONS: The accommodative amplitude of patients implanted with accommodating IOLs stepped down following the increase of age. However, no statistical differences were found in distance and near visual acuities between the different age groups.

[Association between serum homocysteine and in-hospital death in patients with acute pulmonary embolism].

OBJECTIVE: To explore the association between serum homocysteine (Hcy) level and in-hospital death in patients with acute pulmonary embolism. METHODS: A total of 186 acute pulmonary embolism patients [ (66.8 ± 12.7) years, 89 male] hospitalized in our department between June 2008 and June 2011 were included in this prospective study. Patients were divided into high Hcy group (Hcy ≥ 15.2 µmol/L, n = 95) and low Hcy group (Hcy < 15.2 µmol/L, n = 91). Patients were followed-up for 1 year for the incidence rate of early death associated with acute pulmonary embolism. The Cox proportional hazard model was used to analyze the relationship between serum Hcy level and early death in acute pulmonary embolism patients. RESULTS: Patients were hospitalized for 1-37 days [(10 ± 6) days]. In-hospital death rate was 14.5% (27/186) and was significantly higher in high Hcy group than in low Hcy group [25.3% (24/95) vs. 3.3% (3/91) , P = 0.001]. Univariate Cox regression analysis indicated that admission heart rate, oxygen saturation, enlargement of right ventricle, Hcy ≥ 15.2 µmol/L, serum creatinine level, peak TnT level and deep venous thrombosis (P < 0.05) were independent risk factors for in-hospital death. Multivariate Cox regression analysis showed that Hcy ≥ 15.2 µmol/L (HR = 4.10, 95%CI:3.00-4.98, P = 0.017), admission heart rate (HR = 1.10, 95%CI:1.01-1.20, P = 0.031) , deep venous thrombosis (HR = 1.65, 95%CI:1.45-1.76, P = 0.034) and age (HR = 1.10, 95%CI:1.02-1.19, P = 0.010) were independent predictors of in-hospital death for acute pulmonary embolism patients. One-year follow up was finished in 142 patients (89.3%). There were 19 deaths ( 5 due to repeat pulmonary embolism, 4 due to decompensated respiratory and /or cardiac diseases, 6 due to malignant tumors, 2 due to fatal bleeding and 2 due to pneumonia) . Death rate was similar between the two groups during follow up. CONCLUSION: Higher serum homocysteine is an independent for in-hospital death for patients with acute pulmonary embolism.

Metatranscriptome of human lung microbial communities in a cohort of mechanically ventilated COVID-19 Omicron patients.

The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infected a substantial proportion of Chinese population, and understanding the factors underlying the severity of the disease and fatality is valuable for future prevention and clinical treatment. We recruited 64 patients with invasive ventilation for COVID-19 and performed metatranscriptomic sequencing to profile host transcriptomic profiles, plus viral, bacterial, and fungal content, as well as virulence factors and examined their relationships to 28-day mortality were examined. In addition, the bronchoalveolar lavage fluid (BALF) samples from invasive ventilated hospital/community-acquired pneumonia patients (HAP/CAP) sampled in 2019 were included for comparison. Genomic analysis revealed that all Omicron strains belong to BA.5 and BF.7 sub-lineages, with no difference in 28-day mortality between them. Compared to HAP/CAP cohort, invasive ventilated COVID-19 patients have distinct host transcriptomic and microbial signatures in the lower respiratory tract; and in the COVID-19 non-survivors, we found significantly lower gene expressions in pathways related viral processes and positive regulation of protein localization to plasma membrane, higher abundance of opportunistic pathogens including bacterial Alloprevotella, Caulobacter, Escherichia-Shigella, Ralstonia and fungal Aspergillus sydowii and Penicillium rubens. Correlational analysis further revealed significant associations between host immune responses and microbial compositions, besides synergy within viral, bacterial, and fungal pathogens. Our study presents the relationships of lower respiratory tract microbiome and transcriptome in invasive ventilated COVID-19 patients, providing the basis for future clinical treatment and reduction of fatality.

Evidence for serum miR-15a and miR-16 levels as biomarkers that distinguish sepsis from systemic inflammatory response syndrome in human subjects.

BACKGROUND: Serum microRNAs may be useful biomarkers for diagnosing human diseases. We investigated serum levels of miR-15a and miR-16 in patients with sepsis and systemic inflammatory response syndrome (SIRS) without infection. METHODS: We enrolled 166 sepsis patients, 32 SIRS patients, and 24 normal controls. Serum miR-15a and miR-16 expression levels were determined by quantitative reverse transcriptase polymerase chain reaction assays (qRT-PCR). RESULTS: Serum miR-15a (p<0.001) and miR-16 (p<0.05) were both significantly higher in sepsis patients compared with normal controls, and miR-15a (p<0.001) and miR-16 (p<0.01) levels in SIRS patients were also significantly higher than those in normal controls. Serum miR-15a and miR-16 levels were not correlated with white blood cell counts. Receiver operating characteristic curves showed that miR-15a had the highest area under the curve of 0.858 [95% confidence interval (CI) 0.800-0.916] for the diagnosis of sepsis compared with C reactive protein and procalcitonin with areas under the curve of 0.572 (95% CI 0.479-0.665; p=0.198) and 0.605 (95% CI 0.443-0.767; p=0.168), respectively. When its cut-off point was set at 0.21, serum miR-15a had a sensitivity of 68.3% and a specificity of 94.4%. CONCLUSIONS: Serum miR-15a and miR-16 can both distinguish sepsis/SIRS from normal controls. miR-15a may be a biomarker that distinguishes between sepsis and SIRS.

[The diagnostic and prognostic values of serum total RNA concentration in patients with sepsis].

OBJECTIVE: To explore the diagnostic and prognostic roles of serum total RNA in patients with sepsis. METHODS: Seventy-six patients with sepsis admitted to intensive care unit (ICU) of Chinese PLA General Hospital from October 2009 to November 2010 were enrolled. Blood samples were drawn from these patients and total RNAs of these blood samples were isolated. The concentration of total RNA in the samples was detected. C-reactive protein (CRP) was determined by scattering turbidimetry, and procalcitonin (PCT) was determined using enzyme-linked fluorescence analysis (ELFA). Acute physiology and chronic health evaluation II (APACHE II ) score and sequential organ failure assessment (SOFA) score were recorded. Twenty-four healthy individuals with matched age and sex were enrolled as normal controls. Receiver operating characteristic curve (ROC curve) was used to determine the optimal concentration of serum total RNA for the diagnosis of sepsis. Binary logistic regression analysis was used to analyze the risk factors of sepsis patients. RESULTS: The concentration of serum total RNA (ng/µl) in sepsis group was significantly higher than healthy controls [4.233 (0.204, 37.733) vs. 1.593 (0.319, 5.913), P<0.01]. The area under curve (AUC) of the diagnosis of sepsis was 0.820. When the cut-off point was set at 2.027 ng/µl, the concentration of serum total RNA yielded a sensitivity of 95.9% and a specificity of 65.2%. Total RNA concentration in the healthy controls, the survival group (n=42) and non-survival group (n=34) were step wisely increased [1.593 (0.319, 5.913), 4.178 (0.204, 10.776), 5.006 (0.997, 37.733), respectively, F=8.061, P=0.001]. Binary multivariate logistic regression analysis showed that APACHE II score and SOFA score were independent risk factors of septic patients [APACHE II score: odds ratio (OR)=1.265, 95% confidence interval (95%CI) 1.031 to 1.553, P=0.025; SOFA score: OR=1.151, 95%CI 1.031 to 2.284, P=0.012]. But PCT was not independent risk factor of sepsis patients (OR=1.075, 95%CI 0.974 to 1.187, P=0.151). In the binary univariate logistic regression analysis model, the OR of total RNAs was 1.149, but P value was 0.061, because of the small sample size. CONCLUSIONS: The concentration of total RNA in sepsis patients' serum was significantly increased and correlated to the severity of sepsis, which can be used as biomarkers for sepsis patients.

[Signal transduction pathways mediated by Toll-like receptors and their relations with fungal keratitis].

Toll-like receptors (TLRs) were identified as transmembrane signal transduction proteins in recent years. As a group of pattern recognition receptors (PRRs), TLRs play important roles in the innate immunity by recognizing pathogen-associated molecular patterns (PAMPs). Activated innate immunity subsequently leads to effective adaptive immunity. It, thereby, activities not only innate but ultimately also adaptive immunity. It has been reported that some kinds of TLRs expressed in corneal epithelial cells, stroma cells and endothelial cells. In addition to their recognition function, TLR activation triggers a complex signal transduction cascade that induces the production of inflammatory cytokines and co-stimulatory molecules, thus initiating innate and adaptive immunity. And TLRs play an important role in innate and adaptive immunity of fungal keratitis. In summary, further studies on the regulation of intracellular signaling transduction will contribute significantly to our understanding of immunoregulation of fungal keratitis, eventually provide some way to cure the fungal infection.

[Scientific and rational performance of corneal refractive surgery].

Domestic corneal refractive surgery is embarking on a steady development stage, and following the introduction of femto-second laser, which will open up a new era of corneal surgery. Facing new historical opportunity and challenge, it is vital for scientifically and healthy performance of the surgery both concerning on the improvement of visual quality and preventing the occurrence of complications. Only under a harmony and healthy environment, we will achieve the win-win situation between doctors and patients and sustainable development of corneal refractive surgery in the future.

[Comparison of Pentacam and OrbscanII systems for the diagnosis of keratoconus suspects].

OBJECTIVE: To compare the sensitivity of Pentacam and OrbscanII and to analyze the morphology characteristic of topography in normal eyes and different stages of keratoconus, to provide the basis for early screening of keratoconus suspects. METHODS: One hundred and ninety six normal eyes, 50 eyes with keratoconus suspect and 73 eyes with clinical keratoconus were enrolled. The changes of corneal anterior/posterior curvature, best fitting sphere (BFS). Inferior-Superior value (I-S) (3 mm and 5 mm), classification of elevation maps and corneal thickness were measured. RESULTS: There were significant differences including posterior curvature, anterior/posterior BFS, elevation value and corneal thickness in normal eyes between the data measured by these two different instruments, values obtained by Pentacam were less than those by Orbscan. Concerning the elevation maps pattern, the progressively decreasing pattern was dominant in Pentacam with normal eyes and keratoconus suspects, with the progressively increasing pattern accounting for 14.4% (28/196) and 20.0% (10/50) respectively in anterior surface, and 2.0% (41/96) and 26.0% (13/50) in posterior surface. The progressively increasing pattern was in dominant with clinical keratoconus, accounting for 91.7% (67/73) and 94.5% (69/73) respectively in anterior and posterior surface. Progressively increasing pattern in Orbscan was presented in 80.4% (165/196) normal eyes and suspected or clinical stage keratoconus. As to the receiver-operating-characteristic (ROC) curves and cutoff value, Orbscan I-S value (3 mm and 5 mm) of anterior and posterior surface was sensitive for the diagnosis of keratoconus suspects, with the cutoff value of anterior and posterior 5 mm I-S at 1.15 D and 0.65 D, respectively. In addition to the sensitivity of I-S values in Pentacam, the elevation value of anterior and posterior surface also displayed important diagnostic meaning. The cutoff of anterior, posterior elevation values was 4.5 µm and 7.5 µm, respectively. CONCLUSIONS: Numerous measured indicators revealed obviously difference between the two instruments in normal eyes, with slightly smaller values in Pentacam. In addition to I-S values, pattern changes and elevation values in elevation map of Pentacam represent remarkable advantages for the screening of keratoconus suspects. There is an incremental risk of corneal ectasia in the increasing pattern of elevation map.

Analysis of risk factors of rapid attenuation of graft endothelium in the early stage after penetrating keratoplasty.

This study aimed to analyze the factors of rapid attenuation of graft endothelium in the early stage after penetrating keratoplasty (PKP), with a view to guiding patients with PKP to better long-term outcomes. This study included 226 patients who underwent PKP with follow-up time >1 year at the Qingdao Eye Hospital of Shandong First Medical University from January 2018 to June 2020. Medical records were retrospectively studied, and donor factors, patient factors, and surgical factors were comparatively analyzed to clarify those affecting the rapid decay of graft endothelium after PKP. The median time between excision and death >60 min and patient age >60 years were risk factors for endothelial cell loss (ECL) rate >30% at 1 month postoperatively. However, a higher percentage of patients with donor age ≤60 years and Optisol preservation solution had endothelial cell density (ECD) >2000 cells/mm2 in the graft at postoperative 1 year. A year after the surgery, patients with corneal endothelial decompensation and immune rejection were at risk for ECD < 1000 cells/mm2. The combined operations had a significant effect on the ECL in the early postoperative period. Patients who underwent combined extracapsular cataract extraction or intraocular lens implantation had a significantly higher rate of ECL at postoperative 1 month than other patients, and no significant effect at postoperative 1 year. However, patients without combined operations have a higher probability of maintaining a high level of graft ECD. The graft diameter also affected postoperative ECL. In patients with a larger graft diameter, attenuation of ECD was slower. The ultimate goal of PKP is to maintain graft transparency for extended periods. The use of younger donors, minimizing unnecessary operation in the anterior chamber, and minimizing immune rejection may maintain a greater donor corneal endothelium in the long term.