A knowledge-transfer-based approach for combining ordinal regression and medical scoring system in the early prediction of sepsis with electronic health records.

OBJECTIVE: The prediction of sepsis, especially early diagnosis, has received a significant attention in biomedical research. In order to improve current medical scoring system and overcome the limitations of class imbalance and sample size of local EHR (electronic health records), we propose a novel knowledge-transfer-based approach, which combines a medical scoring system and an ordinal logistic regression model. MATERIALS AND METHODS: Medical scoring systems (i.e. NEWS, SIRS and QSOFA) are generally robust and useful for sepsis diagnosis. With local EHR, machine-learning-based methods have been widely used for building prediction models/methods, but they are often impacted by class imbalance and sample size. Knowledge distillation and knowledge transfer have recently been proposed as a combination approach for improving the prediction performance and model generalization. In this study, we developed a novel knowledge-transfer-based method for combining a medical scoring system (after a proposed score transformation) and an ordinal logistic regression model. We mathematically confirmed that it was equivalent to a specific form of the weighted regression. Furthermore, we theoretically explored its effectiveness in the scenario of class imbalance. RESULTS: For the local dataset and the MIMIC-IV dataset, the VUS (the volume under the multi-dimensional ROC surface, a generalization measure of AUC-ROC for ordinal categories) of the knowledge-transfer-based model (ORNEWS) based on the NEWS scoring system were 0.384 and 0.339, respectively, while the VUS of the traditional ordinal regression model (OR) were 0.352 and 0.322, respectively. Consistent analysis results were also observed for the knowledge-transfer-based models based on the SIRS/QSOFA scoring systems in the ordinal scenarios. Additionally, the predicted probabilities and the binary classification ROC curves of the knowledge-transfer-based models indicated that this approach enhanced the predicted probabilities for the minority classes while reducing the predicted probabilities for the majority classes, which improved AUCs/VUSs on imbalanced data. DISCUSSION: Knowledge transfer, which combines a medical scoring system and a machine-learning-based model, improves the prediction performance for early diagnosis of sepsis, especially in the scenarios of class imbalance and limited sample size.

A novel approach to the analysis of Overall Survival (OS) as response with Progression-Free Interval (PFI) as condition based on the RNA-seq expression data in The Cancer Genome Atlas (TCGA).

BACKGROUND: Overall Survival (OS) and Progression-Free Interval (PFI) as survival times have been collected in The Cancer Genome Atlas (TCGA). It is of biomedical interest to consider their dependence in pathway detection and survival prediction. We intend to develop novel methods for integrating PFI as condition based on parametric survival models for identifying pathways associated with OS and predicting OS. RESULTS: Based on the framework of conditional probability, we developed a family of frailty-based parametric-models for this purpose, with exponential or Weibull distribution as baseline. We also considered two classes of existing methods with PFI as a covariate. We evaluated the performance of three approaches by analyzing RNA-seq expression data from TCGA for lung squamous cell carcinoma and lung adenocarcinoma (LUNG), brain lower grade glioma and glioblastoma multiforme (GBMLGG), as well as skin cutaneous melanoma (SKCM). Our focus was on fourteen general cancer-related pathways. The 10-fold cross-validation was employed for the evaluation of predictive accuracy. For LUNG, p53 signaling and cell cycle pathways were detected by all approaches. Furthermore, three approaches with the consideration of PFI demonstrated significantly better predictive performance compared to the approaches without the consideration of PFI. For GBMLGG, ten pathways (e.g., Wnt signaling, JAK-STAT signaling, ECM-receptor interaction, etc.) were detected by all approaches. Furthermore, three approaches with the consideration of PFI demonstrated better predictive performance compared to the approaches without the consideration of PFI. For SKCM, p53 signaling pathway was detected only by our Weibull-baseline-based model. And three approaches with the consideration of PFI demonstrated significantly better predictive performance compared to the approaches without the consideration of PFI. CONCLUSIONS: Based on our study, it is necessary to incorporate PFI into the survival analysis of OS. Furthermore, PFI is a survival-type time, and improved results can be achieved by our conditional-probability-based approach.

Luteolin regulating synthesis and catabolism of osteoarthritis chondrocytes via activating autophagy.

Osteoarthritis (OA) is a prevalent bone and joint disease characterized by degeneration. The dysregulation between chondrocyte synthesis and breakdown is a key factor in OA development. Targeting the degenerative changes in cartilage tissue degradation could be a potential treatment approach for OA. Previous research has established a strong link between autophagy and the regulation of chondrocyte functions. Activating autophagy has shown promise in mitigating cartilage tissue degeneration. Currently, osteoarthritis treatment primarily focuses on symptom management, as there is no definitive medication to stop disease progression. Previous studies have demonstrated that luteolin, a flavonoid present in Chinese herbal medicine, can activate autophagy and reduce the expression of MMP1 and ADAMTS-5. This study utilized an in vitro osteoarthritis model with chondrocytes stimulated by IL-1ß, treated with varying concentrations of luteolin. Treatment with luteolin notably increased the levels of synthesis factors Aggrecan and Collagen II, while decreasing the levels of decomposition factors MMP-1 and ADAMTS-5. Moreover, inhibition of autophagy by Chloroquine reversed the imbalances in chondrocyte activities induced by IL-1ß. In an in vivo model of knee osteoarthritis induced by medial meniscal instability (DMM), luteolin was administered as a therapeutic regimen. After 12 weeks, knee cartilage tissues from mice were analyzed. Immunofluorescence and immunohistochemical staining revealed a decrease in P62 expression and an increase in Beclin-1 in the cartilage tissues. Additionally, cartilage wear in the knee joints of mice was alleviated by safranin O and fast green staining. Our study findings underscore the significant role of luteolin in effectively rebalancing chondrocyte activities disrupted by IL-1ß. Our results strongly indicate that luteolin has the potential to be developed as a novel therapeutic agent for the treatment of osteoarthritis, offering promising prospects for future drug development.

Cuproptosis-Related Gene FDX1 Suppresses the Growth and Progression of Colorectal Cancer by Retarding EMT Progress.

Colorectal cancer (CRC) is a usual cancer and a kind of lethiferous cancer. Cuproptosis-related gene ferredoxin 1 (FDX1) has been discovered to act as a suppressor, thereby suppressing some cancers' progression. But, the regulatory functions of FDX1 in CRC progression keep vague. In this work, at first, through TCGA database, it was revealed that FDX1 exhibited lower expression in COAD (colon adenocarcinoma) tissues, and CRC patients with lower FDX1 expression had worse prognosis. Furthermore, FDX1 expression was verified to be down-regulated in CRC tissues (n = 30) and cells. It was further uncovered that FDX1 expression was positively correlated with CDH1 and TJP1 (epithelial marker), and negatively correlated with CDH2, TWIST1, and FN1 (stromal marker), suggesting that FDX1 was closely associated with the epithelial-mesenchymal transition (EMT) progress. Next, it was demonstrated that overexpression of FDX1 suppressed cell viability, invasion, and migration in CRC. Furthermore, it was verified that FDX1 retarded the EMT progress in CRC. Lastly, through rescue assays, the inhibited CRC progression mediated by FDX1 overexpression was rescued by EGF (EMT inducer) treatment. At last, it was uncovered that the tumor growth and metastasis were relieved after FDX1 overexpression, but these changes were reversed after EGF treatment. In conclusion, FDX1 inhibited the growth and progression of CRC by inhibiting EMT progress. This discovery hinted that FDX1 may act as an effective candidate for CRC treatment.

Acute respiratory distress syndrome following multiple wasp stings treated with extracorporeal membrane oxygenation: A case report.

BACKGROUND: It is necessary for clinicians to be aware of a rare but possible acute respiratory distress syndrome (ARDS) complication caused by multiple wasp stings. Severe ARDS has a high mortality rate but no specific pharmacotherapies have been identified to date. This case study presents the first case of severe ARDS caused by multiple wasp stings, treated successfully with extracorporeal membrane oxygenation (ECMO). It also emphasizes the effectiveness of early ECMO treatment for severe ARDS with persistent hypoxemia. CASE SUMMARY: A 24-year-old woman was admitted to the emergency department after being stung by more than 10 wasps within a 30-min period, with clinical symptoms of multiple rashes, dizziness, chest tightness, nausea, and vomiting. On the 2nd day of admission, the patient developed progressive dyspnea. The patient was diagnosed with ARDS based on clinical manifestations and lung computed tomography (CT) scan. Because of the progressive dyspnea, the intensive care unit physician performed endotracheal intubation and continued to provide ventilator support, but the patient's respiratory distress worsened, as indicated by the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen. Veno-venous ECMO was initiated for 6 d. On day 7 of admission, ECMO was stopped. On the 11th day of admission, CT scan of the lungs revealed significant reduction of ground-glass opacities and consolidations. After about 2 wk, the patient recovered completely from ARDS and was discharged to home. At the 2-mo follow-up, the patient was in good health with no recurrence of dyspnea nor chest tightness. CONCLUSION: ARDS complication caused by multiple wasp stings may be fatal when mechanical ventilation becomes dangerous due to persistent hypoxemia and despite optimization of ARDS management. We propose that the early implementation of ECMO is a relatively effective treatment, although the evidence is relatively limited.

The diagnostic value of next-generation sequencing technology in sepsis.

Objective: This study aims to assess the clinical utility of next-generation sequencing (NGS) in sepsis diagnosis. Methods: A prospective study was conducted on patients with a high suspicion of sepsis by unknown pathogens from January 2017 to December 2021. Blood samples were taken from patients to perform NGS, blood culture (BC), leucocyte (WBC), procalcitonin (PCT), creatinine (CREA), Albumin (ALB) and C-reactive protein (CRP) tests. Results: The feedback time for BC was 3~5 days for bacteria and 5~7 days for fungi, while the turnover time for NGS was only 24 h. The clinical diagnosis was considered the "gold standard". 83 patients passed our inclusion criteria and were separated into two groups by clinical diagnosis. 62 met the clinical diagnosis criteria for sepsis and 21 were non-sepsis. The data from the two groups were retrospectively compared and analyzed. Of 62 sepsis in 83 patients, 8(9.64%) were diagnosed by both BC and NGS, 51 (61.45%) by NGS only, 1(1.20%) by BC and 2 (2.41%) by conventional testing only; PCT, CREA, CRP levels and the detection rate of NGS and BC were higher in the sepsis group than in the non-sepsis group, while ALB levels were lower (p<0.05). The logistic regression results in our study revealed that NGS and ALB were independent prediction factors for sepsis (p<0.05), the area under the receiver operating characteristic curve (AUC), sensitivity and specificity of NGS for diagnosing sepsis was 0.857, 95.16% and 76.19%, while ALB was 0.728, 58.06%, 80.95%, respectively. The combination's sensitivity, specificity and AUC of NGS and ALB were 93.55%, 85.71% and 0.935, greater than that of Albumin or NGS only (both p<0.05). Conclusion: NGS can effectively and quickly identify pathogens, thereby emerges as a promising technology for sepsis diagnosis. Combination of NGS and ALB can be used for early screening and is more powerful than NGS or ALB only.

Study of a High-Temperature and High-Density Water-Based Drilling Fluid System Based on Non-sulfonated Plant Polymers.

The environment-friendly water-based drilling fluid system developed for the petroleum development industry cannot successfully withstand temperatures up to 180 °C, and most high temperature-resistant additives with sulfonic acid groups that have been successfully applied to water-based drilling fluid are not good for environmental protection. In order to solve the above technical problems, a non-sulfonated filtrate reducer and viscosity reducer with resistance to high temperature were prepared by using humic acid, lignin and a multifunctional monomer as raw materials. In laboratory experiments, the molecular weights of the FLO-H filtrate reducer and the VR-H viscosity reducer were 5.45 × 105 g/mol and 8.51 × 103 g/mol, respectively, and all of them showed good high-temperature resistance. The API filtration loss of the bentonite-base slurry with 3.0 wt% FLO-H was only 6.2 mL, which indicated that FLO-H had a prominent reduction in filtration loss after aging at high temperature. When the dosage of VR-H was 1.0 wt%, the plastic viscosity of the water-based drilling fluid after aging at 200 °C decreased from 71 mPa·s to 55 mPa·s, which provided excellent dispersion and dilution. The high-temperature and high-density water-based drilling fluid containing the FLO-H filtrate reducer and the VR-H viscosity reducer had good suspension stability and low filtration performance at the high temperature of 200 °C, which can meet the requirements of high-temperature deep well drilling.

Poldip2 knockdown protects against lipopolysaccharide-induced acute lung injury via Nox4/Nrf2/NF-κB signaling pathway.

Polymerase δ-interacting protein 2 (Poldip2) has been reported to mediate acute lung injury (ALI); however, the underlying mechanism is not fully explored. Male C57BL/6 mice and A549 cells were used to establish the lipopolysaccharide (LPS)-induced ALI model, then the expression of Poldip2 and its effect on oxidative stress and the resulting inflammation were detected. Adeno-associated virus serotype 6 (AAV6) mediated Poldip2 knockdown was transfected into mice via intratracheal atomization. And A549 cells stimulated with LPS was used to further confirm our hypothesis in vitro. ML385, specifically inhibited the activation of the Nrf2 signaling pathway. Our data suggested that LPS stimulation remarkably increased protein levels of Nox4 and p-P65, activities of NADPH and MPO, and generation of ROS, TNF-α, and IL-1ß while decreased protein levels of Nrf2 and HO-1 compared with those in NC shRNA + Saline group, which were obviously reversed by Poldip2 knockdown. Concomitantly, Poldip2 knockdown dramatically reduced contents of MDA and enhanced activities of SOD and GSH-Px compared to NC shRNA + LPS group. In vitro, we found that knockdown of Poldip2 significantly reversed LPS-induced increase protein levels of Nox4 and p-P65, activity of NADPH, and generation of ROS, TNF-α, and IL-1ß, and decrease protein levels of Nrf2 and HO-1, ML385 pretreatment reversed the effects of Poldip2 knockdown mentioned above. Our study indicated that Poldip2 knockdown alleviates LPS-induced ALI via inhibiting Nox4/Nrf2/NF-κB signaling pathway.

Induction chemotherapy increases efficacy and survival rate of patients with locally advanced esophageal squamous cell carcinoma.

Objective: The efficacy of concurrent chemoradiotherapy (CRT) after induction chemotherapy (IC) in the treatment of esophageal squamous cell carcinoma (ESCC) remains unclear. The purpose of this study was to explore the efficacy of IC in patients with ESCC. Methods: 124 patients with ESCC receiving CRT were included. Patients were divided into IC+CRT group and CRT group. Short-term and long-term efficacy as well as survival time of the two groups were compared, influencing factors of IC efficacy were investigated, and overall survival (OS) and progression-free survival (PFS) between the two groups were compared in different subgroups. Results: There was no significant difference in the objective response rate (ORR) between the two groups. After IC, the ORR was higher in patients with single-drug concurrent chemotherapy weekly and patients with effective IC. In the long-term efficacy, advanced clinical stage patients had a shorter PFS compared to early-stage patients, and chemoradiotherapy mode ameliorates patients' PFS. OS and PFS of IC+CRT group were longer than that of CRT group in both tumor diameter <5cm and single-drug chemotherapy weekly subgroups. In addition, OS of IC+CRT group was longer than that of CRT group in pathological grade G1-2 subgroup. Conclusions: IC improve the efficacy and survival rate of patients with locally advanced ESCC, and the benefits are more advantageous in subgroups of effective IC, pathological grade G1-2, tumor diameter < 5cm, single-drug concurrent chemotherapy weekly.

Case Report: A Candida Meningitis in an Immunocompetent Patient Detected Through the Next-Generation Sequencing.

Background: Fungal infections of the central nervous system (CNS) are not commonly seen clinically. Clinical diagnosis of fungal infections often depend on the pathogen culture and the clinical features. This method is time-consuming and insensitive, which can lead to misdiagnosis. The authors introduce an adult patient with fungal infections diagnosed by next-generation sequencing (NGS). Case: The patient was a 60-year-old male Chinese who had both hypermyotonia of the lower extremities and fever. The auxiliary examinations such as MRI, CT, and cerebrospinal fluid (CSF) analysis showed obvious abnormalities. Because of the difficulties in diagnosis, it was hard to determine the treatment plan. The NGS detected specific sequences of Candida albicans in 3 days. The patient was then treated with liposomal amphotericin B and fluconazole. About 3 weeks later, the symptoms of the patient improved significantly and he was discharged from the hospital. Conclusion: Compared with the routine cultural method, NGS has made a huge advancement in infection diagnosis and targeting antimicrobial therapy for CNS infection.

Knowledge, attitudes, and practices related to augmented renal clearance among pediatricians in China: A cross-sectional study.

ABSTRACT: Our purpose was to assess pediatricians' knowledge of augmented renal clearance (ARC).We conducted cross-sectional analyses of 500 pediatricians from 16 tertiary hospitals in Anhui Province, China. Pediatricians provided demographic information and were asked questions about their knowledge of ARC, including risk factors, evaluation tools, and the impact on patient prognosis, with a focus on the attitude and practice of pediatricians related to adjusting vancomycin regimens when ARC occurs.A total of 491 valid questionnaires were finally included, only 276 pediatricians stated that they "know about ARC." Compared with the "do not know about ARC" group, the "know about ARC" group was younger (43.7 ±â€Š8.0 vs 48.0 ±â€Š7.9, P < .001), and their main source of ARC knowledge was from social networking platforms. A total of 193 (70%) chose at least 4 of the following factors as risk factors for children with ARC: severe trauma, sepsis, burns, major surgery, lower disease severity, and hematological malignancies. A total of 110 (40%) and 105 (38%) pediatricians chose the Schwartz formula and cystatin C, respectively, as the indicators to evaluate the renal function of ARC children. Concerning the estimated glomerular filtration rate threshold to identify ARC children, 201 (73%) pediatricians chose 130 mL/min/1.73 m2, while 55 (20%) chose "age-dependent ARC thresholds." Overall, 220 (80%) respondents indicated that ARC would impact the treatment effect of vancomycin, but 149/220 (68%) were willing to adjust the vancomycin regimen; only 22/149 (8%) considered that the dose should be increased, but no one knew how to increase. Regarding the prognosis of ARC children, all respondents chose "unclear."ARC is relatively common in critically ill children, but pediatricians do not know much about it, as most of the current knowledge is based on adult studies. Furthermore, ARC is often confused with acute kidney injury, which would lead to very serious treatment errors. Therefore, more pediatric studies about ARC are needed, and ARC should be written into official pediatric guidelines as soon as possible to provide reference for pediatricians.

Initial clinical features of suspected coronavirus disease 2019 in two emergency departments outside of Hubei, China.

With an increasing number of Coronavirus Disease 2019 (COVID-19) cases outside of Hubei, emergency departments (EDs) and fever clinics are facing challenges posed by the large number of admissions of patients suspected to have COVID-19. Therefore, it is of crucial importance to study the initial clinical features of patients, to better differentiate between infected and uninfected patients outside Hubei. A total of 116 patients suspected of having COVID-19 who presented to two emergency departments in Anhui for the first time between 24 January 2020 and 20 February 2020 were enrolled in the study. The initial clinical data of these patients, such as epidemiological features, symptoms, laboratory results, and chest computed tomography (CT) findings were collected using a standard case report form on admission. Thirty-two patients were diagnosed with COVID-19; the remaining 84 patients were referred to as negative cases. The median age of the diagnosed patients was 46 years, but only 35 years for negative cases. History of exposure to Wuhan or COVID-19 patients in the previous 2 weeks was observed in 63% of the diagnosed and 44% of negative cases. Median time from illness onset to ED admission was 5 days for all patients, diagnosed patients, and negative cases, respectively. Fever was observed in 27 (84%) and 57 (68%) diagnosed and negative cases, respectively. Nineteen (59%) diagnosed and 24 (29%) negative cases had lymphopenia on admission in ED. A chest CT scan on admission revealed the presence of pneumonia in the majority of the diagnosed patients (30 out of 32, 94%) and in 56 (67%) negative cases. Bilateral involvement and ground-glass opacity (GGO) were present in 91% and 47% of the diagnosed patients. Thirty-two patients were diagnosed with COVID-19; the remaining 84 patients were referred to as negative cases. The median age of the diagnosed patients was 46 years, but only 35 years for negative cases. History of exposure to Wuhan or COVID-19 patients in the previous 2 weeks was observed in 63% of the diagnosed and 44% of negative cases. Median time from illness onset to ED admission was 5 days for all patients, diagnosed patients, and negative cases, respectively. Fever was observed in 27 (84%) and 57 (68%) diagnosed and negative cases, respectively. Nineteen (59%) diagnosed and 24 (29%) negative cases had lymphopenia on admission in ED. A chest CT scan on admission revealed the presence of pneumonia in the majority of the diagnosed patients (30 out of 32, 94%) and in 56 (67%) negative cases. Bilateral involvement and GGO were present in 91% and 47% of the diagnosed patients.

A modified PLASMIC score including the lactate dehydrogenase/the upper limit of normal ratio more accurately identifies Chinese thrombotic thrombocytopenic purpura patients than the original PLASMIC score.

BACKGROUND: The PLASMIC score was recently published to aid in the early identification of thrombotic thrombocytopenic purpura (TTP) patients. This study aims to evaluate whether this score is suitable for Chinese suspected TTP patients and find the utility of patients' other characteristics in predicting severe ADAMTS13 deficiency. METHODS: We retrospectively studied a Chinese cohort of 38 consecutive hospitalized patients with suspected TTP, ADAMTS13 test results, and other clinical data from September 2016 to May 2018. The predictive power of PLASMIC score in our cohort was evaluated, and patients' other characteristics, especially the high lactate dehydrogenase/the upper limit of normal (LDH/ULN), were studied to determine their distinguishing ability for TTP patients. RESULTS: In this Chinese cohort, 17 patients were diagnosed with TTP according to ADAMTS13 activity results. When dichotomized at intermediate-high risk (scores 5-7) vs low risk (scores 0-4), the PLASMIC score predicted TTP with a sensitivity of 100%, a specificity of 9.52%, and a misdiagnosis rate of 90.48%. And the LDH/ULN alone, or plus platelet count, reticulocyte percentage and indirect bilirubin (IBIL) both had excellent predictive power (area under the curve [AUC] 0.937, 95% confidence interval [CI] 0.863-1.000, P = .000, and AUC 0.994, 95% CI 0.980-1.000, P = .000, respectively). The model including platelet count, reticulocyte percentage, IBIL, and LDH/ULN ratio had a sensitivity of 100%, a specificity of 95.2%, and a misdiagnosis rate of 4.8%. CONCLUSIONS: A modified PLASMIC score plus LDH/ULN ratio might be more suitable for identifying ADAMTS13 deficiency patients, especially for making an earlier diagnosis, guiding the immediate and reasonable plasma exchange, and also avoiding unnecessary allocation of plasma.

Therapeutic role of melatonin in migraine prophylaxis: A systematic review.

BACKGROUND: Melatonin is the "clock factor" generated from pineal gland dominating regular circadian rhythm in humans. Migraine is one of the most severe and debilitating primary headache disorders. Thus far, many diseases have been found to associate with melatonin, including the migraine. Therefore, melatonin's therapeutic potential for migraine is drawing attention. OBJECTIVES: The aim of this study is to offer a systematic review of extant data of melatonin in migraine prophylaxis and to provide clinical implications and specific recommendations for future studies. DATA SOURCES AND STUDY METHODS: A systematic research was conducted in September 2018 by using PubMed and Google Scholar databases to search for science literature published after 1988. RESULTS: In all, 7 eligible articles were identified, including 4 randomized controlled studies and 3 observational studies. Due to high heterogeneities and limited number of studies, meta-analysis was not feasible, and only systematic review was performed. The results show that present evidence cannot claim melatonin's effectiveness according to the conflicting outcomes; however, the two negative outcomes of melatonin not different from placebo and melatonin inferior to amitriptyline are possible under-powering because of methodological, pharmacological, and therapeutic shortcomings. Observational studies also support melatonin's efficacy in migraine. As a result, melatonin is very likely to benefit migraine in prophylaxis and may have a similar effectiveness to other main preventive medications. Immediate-release melatonin 3 mg was established as effective, melatonin receptor agonist (Agomelatine) 25 mg and prolonged-release melatonin 4 mg were observed efficacious in observational studies. Melatonin displayed ineffective in the 2-month trial; thus, 3 months or more may be an enough duration for migraine therapy. Despite melatonin being generally safe, emerging literature is illustrating that a few severe adverse effects can be caused by melatonin, for example, liver injuries, reproductive system dysfunctions, and detrimental immunostimulation. CONCLUSIONS: Melatonin is very likely to be a promising alternative for migraine prophylaxis. Current literature examining melatonin's efficacy in migraine prevention is growing, but still limited. Future studies of perfect design in methodology, pharmacology, and therapeutics are needed to achieve a deeper awareness of melatonin's role in migraine as well as more studies to explore the safety issues of melatonin medicine.

[Risk factors and etiological analysis of ventilator-associated pneumonia: three year's cases analysis of intensive care unit in county hospital].

OBJECTIVE: To investigate the risk factors of ventilator-associated pneumonia (VAP) and the distribution and drug resistance of pathogens in intensive care unit (ICU) of county hospital. METHODS: 234 patients on mechanical ventilation for more than 48 hours admitted to ICU of Shexian People's Hospital of Huangshan City from January 2016 to June 2018 were enrolled. The clinical data of all patients including gender, age, past medical history, exposure to antibiotics, medication, the duration of mechanical ventilation, the length of ICU stay, serum albumin, tracheotomy, re-intubation, prognosis, and pathogenic bacteria and drug sensitivity test of VAP patients were collected. The patients were divided into VAP group and non-VAP group according to the occurrence of VAP. The differences of each index between the two groups were compared. The risk factors of VAP were analyzed by multivariate Logistic regression. The distribution and drug resistance of pathogenic bacteria in sputum culture of lower respiratory tract of VAP patients were analyzed. RESULTS: Among the 234 patients on mechanical ventilation, 95 patients had VAP, and the incidence of VAP was 40.60%. (1) Risk factors of VAP: it was shown by univariate analysis that there were significant differences between VAP patients and non-VAP patients in past history, the duration of mechanical ventilation, the length of ICU stay, albumin < 28 g/L, antibiotic exposure and tracheotomy, but there were no significant differences in gender, age, glucocorticoid, sedative, gastric motility and coma between the two groups. It was shown by multivariate Logistic regression analysis that brain injury and cerebrovascular accident, the duration of mechanical ventilation > 7 days, albumin < 28 g/L and tracheotomy were independent risk factors for VAP occurrence [brain injury: odds ratio (OR) = 41.40, 95% confidence interval (95%CI) = 2.14-799.60, P = 0.014; cerebrovascular accident: OR = 36.07, 95%CI = 1.86-699.64, P = 0.018; the duration of mechanical ventilation > 7 days: OR = 1.23, 95%CI = 1.11-1.36, P < 0.001; albumin < 28 g/L: OR = 2.27, 95%CI = 1.03-5.01, P = 0.042; tracheotomy: OR = 3.33, 95%CI = 1.30-8.56, P = 0.012]. (2) Distribution and drug resistance of VAP pathogens: a total of 108 strains of pathogens were isolated from sputum samples of 95 patients with VAP. Gram-negative (G-) bacteria accounted for 86.11% (93/108). The isolation rate of Klebsiella pneumoniae was the highest, reaching 31.48% (34/108); the isolation rates of Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii were 22.22% (24/108), 8.33% (9/108) and 9.26% (10/108), respectively. Gram-positive (G+) bacteria accounted for 6.48% (7/108), of which Staphylococcus aureus was 4.63% (5/108); and fungi was 7.41% (8/108). Drug resistance analysis showed that Klebsiella pneumoniae was 100% sensitive to amikacin (AMK), meropenem (MEM) and polymyxin (POL), and were suggested as the preferred drug. Pseudomonas aeruginosa was 100% sensitive to AMK, tobramycin (TOB) and POL, but 100% resistant to compound trimethoprim (PCST). Stenotrophomonas maltophilia was 100% sensitive to PCST and 100% resistant to AMK, piperacillin (PIP), piperacillin tazobactam (TZP) and TOB. Acinetobacter baumannii was 100% sensitive to cefoxitin (FOX), cefuroxime (CXM) and POT. Staphylococcus aureus was 100% sensitive to gentamicin (GEN), furantoin (NIT), rifampicin (RIF), vancomycin (VAN) and teicoplanin (TEC), while the drug resistance to clindamycin (CLI) and penicillin (PEN) was high (both 80.00%). Most pathogens were multidrug-resistant. The mortality of patients with multidrug resistant bacteria infection was significantly higher than that of non-multidrug resistant bacteria infection [51.85% (28/52) vs. 30.56% (11/36), χ 2 = 4.240, P = 0.046]. CONCLUSIONS: VAP was associated with brain injury and cerebrovascular accident, duration of mechanical ventilation < 7 days, albumin > 28 g/L and tracheotomy. VAP patients were infected mainly with G- bacteria and showed multiple drug resistance.

Draft genome sequence of an NDM-1-, OXA-421- and AmpC-producing Acinetobacter pittii ST220 in Anhui Province, China.

OBJECTIVES: Acinetobacter pittii carrying the blaNDM-1 gene is frequently reported in the world recently, however most of the blaNDM-1 genes are located on plasmids. Here we report a multidrug-resistant (MDR) A. pittii isolated in China co-harbouring blaNDM-1, blaOXA-421 and blaAmpC in the genome. METHODS: Bacterial genomic DNA was extracted using the cetyl trimethylammonium bromide (CTAB) method. Whole-genome sequencing of A. pittii was performed using an Illumina MiSeq system (2×251bp) in combination with PacBio single-molecule real-time (SMRT) sequencing. De novo genome assembly was performed using SPAdes v.3.9.0, A5-miseq v.20150522 and Canu v.1.4, respectively. The genome sequence was analysed by bioinformatics methods. RESULTS: The 4211131-bp genome with 38.99% G+C content displayed several resistance genes, including blaNDM-1, blaOXA-421 and blaAmpC. Meanwhile, 4426 protein-coding sequences were predicted within the genome. CONCLUSION: The genome sequence reported here can be compared with the already published genomes of NDM-1-producing isolates. These data might facilitate further understanding of the specific genomic feature of MDR A. pittii in China.

[Diagnostic value of dynamic-extended focused assessment with sonography for trauma in patients with multiple trauma].

OBJECTIVE: To investigate the diagnostic value of dynamic-extended focused assessment with sonography for trauma (D-EFAST) in patients with multiple trauma in intensive care unit (ICU). METHODS: A prospective clinical study was conducted. Eighty patients with multiple trauma admitted to ICU of Anhui Provincial Hospital from September 1st, 2014 to December 31st, 2016 were enrolled. Extended focused assessment with sonography for trauma (E-FAST) check was conducted at first, for those who had positive findings diagnosis was confirmed by immediately CT examination or surgical exploration. If it was negative, the patients received E-FAST every morning for 7 days (defined as D-EFAST), for those with positive findings, immediately CT or surgery was performed to clarify the diagnosis. The final clinical diagnosis was used as the "gold standard" to calculate the diagnostic accordance rate of EFAST and D-EFAST examination technique for pneumothorax, pleural effusion, spleen injury, kidney damage, liver damage, gastrointestinal injury, pericardial effusion, bladder rupture, and pancreatic injury, as well as their sensitivity, specificity, positive predictive value, negative predictive value, accuracy rate, and missed diagnosis rate, and the difference between EFAST and D-EFAST was compared. RESULTS: There were 4 patients excluded because of death and abandoning treatment, and finally 76 patients were included in the study. The total sensitivity of E-FAST examination technique for pneumothorax, pleural effusion, spleen injury, liver damage, gastrointestinal injury, pericardial effusion, and bladder rupture was 75.9% (66/87), and the specificity was 98.3% (587/597), the positive predictive value was 86.8% (66/76), and the negative predictive value was 96.5% (587/608), the accuracy rate was 95.5% (653/684), and the rate of missed diagnosis was 24.1% (21/87). The most of the delayed injury in patients with multiple trauma occurred at 2-7 days after injury with incidence of 4.8% (33/684). The diagnostic sensitivity of D-EFAST for delayed injury was 98.3% (118/120), the specificity was 99.8% (563/564), the positive predictive value was 99.2% (118/119), the negative predictive value was 99.6% (563/565), the diagnostic accuracy rate was 99.6% (681/684), and rate of missed diagnosis was 1.7% (2/120). When the final clinical diagnosis was set as the "gold standard", D-EFAST technology for the detection rate was 98.3% (118/120) for patients with multiple trauma on organ injury while the detection rate of E-FAST was 75.9% (66/87), with statistical significant difference (P < 0.01), indicating that D-EFAST was better than E-FAST in check of multiple trauma patients with organ injury. CONCLUSIONS: Although the E-FAST technology can quickly diagnose the multiple trauma patients and win the rescue time for critical patients, multiple trauma patients injured after 2-7 days prone to delayed damage and are difficult to detect, and D-EFAST can be used to find delayed damage earlier, and reduce the misdiagnosis rate of multiple trauma patients.

Inflammatory responses and histopathological changes in a mouse model of Staphylococcus aureus-induced bloodstream infections.

INTRODUCTION: Staphylococcus aureus-induced bloodstream infections (BSIs) remain a prevalent clinical challenge and the underlying pathogenesis is still poorly understood. The aim of this study was to investigate the inflammatory responses and histopathological changes in BSIs in mice. METHODOLOGY: Male C57BL/6 mice were inoculated with S. aureus intravenously to induce BSIs. The survival rate, weight loss, and murine sepsis scores (MSS) were monitored in BSI and phosphate-buffered saline (PBS) control mice. Blood samples and tissue homogenates were plated on agar plates to determine the bacterial burden. Inflammatory proteins and cytokines were determined by enzyme-linked immunosorbent assay (ELISA) kits. Histopathologic changes were assessed by pathological inflammation score (PIS) and macroscopic and microscopic examinations. RESULTS: BSI mice induced by 4.5 × 108 CFU/mL S. aureus showed ~70% survival rate, higher sepsis scores, significantly decreased body weight, elevated levels of white blood cell (WBC) counts, C-reactive protein (CRP), procalcitonin (PCT), interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α. Prominent correlations were found between elevated CRP and PCT levels as well as among IL-1ß, IL-6, and TNF-α. Pathological changes and higher PIS were also observed in BSI mice. CONCLUSIONS: Our results demonstrate that inflammatory proteins (PCT and CRP) and cytokines (IL-6, IL-1ß and TNF-α) play an important role in the inflammatory responses and histopathological changes in S. aureus-induced BSIs.

VraR Binding to the Promoter Region of agr Inhibits Its Function in Vancomycin-Intermediate Staphylococcus aureus (VISA) and Heterogeneous VISA.

Acquisition of vancomycin resistance in Staphylococcus aureus is often accompanied by a reduction in virulence, but the mechanisms underlying this change remain unclear. The present study was undertaken to investigate this process in a clinical heterogeneous vancomycin-intermediate S. aureus (hVISA) strain, 10827; an hVISA reference strain, Mu3; and a VISA reference strain, Mu50, along with their respective series of vancomycin-induced resistant strains. In these strains, increasing MICs of vancomycin were associated with increased expression of the vancomycin resistance-associated regulator gene (vraR) and decreased expression of virulence genes (hla, hlb, and coa) and virulence-regulated genes (RNAIII, agrA, and saeR). These results suggested that VraR might have a direct or indirect effect on virulence in S. aureus In electrophoretic mobility shift assays, VraR did not bind to promoter sequences of hla, hlb, and coa genes, but it did bind to the agr promoter region. In DNase I footprinting assays, VraR protected a 15-nucleotide (nt) sequence in the intergenic region between the agr P2 and P3 promoters. These results indicated that when S. aureus is subject to induction by vancomycin, expression of vraR is upregulated, and VraR binding inhibits the function of the Agr quorum-sensing system, causing reductions in the virulence of VISA/hVISA strains. Our results suggested that VraR in S. aureus is involved not only in the regulation of vancomycin resistance but also in the regulation of virulence.