Association between the ROX index and mortality in patients with acute hypoxemic respiratory failure: a retrospective cohort study.

BACKGROUND: Although ROX index is frequently used to assess the efficacy of high-flow nasal cannula treatment in acute hypoxemic respiratory failure (AHRF) patients, the relationship between the ROX index and the mortality remains unclear. Therefore, a retrospective cohort study was conducted to evaluate the ability of the ROX index to predict mortality risk in patients with AHRF. METHOD: Patients diagnosed with AHRF were extracted from the MIMIC-IV database and divided into four groups based on the ROX index quartiles. The primary outcome was 28-day mortality, while in-hospital mortality and follow-up mortality were secondary outcomes. To investigate the association between ROX index and mortality in AHRF patients, restricted cubic spline curve and COX proportional risk regression were utilized. RESULT: A non-linear association (L-shaped) has been observed between the ROX index and mortality rate. When the ROX index is below 8.28, there is a notable decline in the 28-day mortality risk of patients as the ROX index increases (HR per SD, 0.858 [95%CI 0.794-0.928] P < 0.001). When the ROX index is above 8.28, no significant association was found between the ROX index and 28-day mortality. In contrast to the Q1 group, the mortality rates in the Q2, Q3, and Q4 groups had a substantial reduction (Q1 vs. Q2: HR, 0.749 [0.590-0.950] P = 0.017; Q3: HR, 0.711 [0.558-0.906] P = 0.006; Q4: HR, 0.641 [0.495-0.830] P < 0.001). CONCLUSION: The ROX index serves as a valuable predictor of mortality risk in adult patients with AHRF, and that a lower ROX index is substantially associated with an increase in mortality.

Association between driving pressure-guided ventilation and postoperative pulmonary complications in surgical patients: a meta-analysis with trial sequential analysis.

BACKGROUND: Prior studies have reported inconsistent results regarding the association between driving pressure-guided ventilation and postoperative pulmonary complications (PPCs). We aimed to investigate whether driving pressure-guided ventilation is associated with a lower risk of PPCs. METHODS: We systematically searched electronic databases for RCTs comparing driving pressure-guided ventilation with conventional protective ventilation in adult surgical patients. The primary outcome was a composite of PPCs. Secondary outcomes were pneumonia, atelectasis, and acute respiratory distress syndrome (ARDS). Meta-analysis and subgroup analysis were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CI). Trial sequential analysis (TSA) was used to assess the conclusiveness of evidence. RESULTS: Thirteen RCTs with 3401 subjects were included. Driving pressure-guided ventilation was associated with a lower risk of PPCs (RR 0.70, 95% CI 0.56-0.87, P=0.001), as indicated by TSA. Subgroup analysis (P for interaction=0.04) found that the association was observed in non-cardiothoracic surgery (nine RCTs, 1038 subjects, RR 0.61, 95% CI 0.48-0.77, P< 0.0001), with TSA suggesting sufficient evidence and conclusive result; however, it did not reach significance in cardiothoracic surgery (four RCTs, 2363 subjects, RR 0.86, 95% CI 0.67-1.10, P=0.23), with TSA indicating insufficient evidence and inconclusive result. Similarly, a lower risk of pneumonia was found in non-cardiothoracic surgery but not in cardiothoracic surgery (P for interaction=0.046). No significant differences were found in atelectasis and ARDS between the two ventilation strategies. CONCLUSIONS: Driving pressure-guided ventilation was associated with a lower risk of postoperative pulmonary complications in non-cardiothoracic surgery but not in cardiothoracic surgery. SYSTEMATIC REVIEW PROTOCOL: INPLASY 202410068.

Burden and Trends of IBD in 5 Asian Countries From 1990 to 2019: A Comparison With the United States and the United Kingdom.

BACKGROUND: IBD is becoming a global health challenge, with substantial variations in incidence and death rates between Eastern and Western countries. OBJECTIVE: This study aimed to investigate the burden and trends of IBD in 5 Asian countries, the United States, and the United Kingdom. DESIGN: This was a cross-sectional study. SETTING: Data were obtained from Global Burden of Disease 2019 Study. PATIENTS: Patients with IBD were included. MAIN OUTCOME MEASURES: Incidence, death, and age-standardized rates of IBD were measured. RESULTS: The age-standardized incidence and rates of death from IBD gradually decreased worldwide from 1990 to 2019. The age-standardized incidence rate in the United States decreased from 1990 to 2000 and then increased gradually from 2000 to 2019; the age-standardized incidence rates in the United Kingdom, Mongolia, and China increased gradually from 1990 to 2019, whereas in the Democratic People's Republic of Korea, it decreased from 1990 to 1995 and increased gradually from 1995 to 2019. The age-standardized death rate in the Republic of Korea exhibited a rising trend until 1995, fell significantly up to 2015, and then stabilized from 2015 to 2019. The age-standardized death rate in the United States showed a rising trend until 2007, and then decreased gradually from 2007 to 2019, whereas the rate in the United Kingdom showed a rising trend until 2010 and decreased from 2010 to 2019. The age-standardized death rates in China, Mongolia, the Democratic People's Republic of Korea, and Japan decreased gradually from 1990 to 2019. The age-standardized incidence and death rates in the United States and United Kingdom in recent decades were higher than those in the 5 Asian countries. The peak age-standardized incidence rates in the 7 countries were among people of 20 to 60 years of age. The age-standardized death rates in all 7 countries exhibited rising trends with increasing age, with older individuals, particularly those aged ≥70 years, accounting for the most deaths. LIMITATIONS: Limitations of this study include data from different countries with different quality and accuracy. CONCLUSIONS: There have been large variations in the burdens and trends of IBD between 5 Asian countries, the United States, and the United Kingdom during the past 3 decades. These findings may help policymakers to make better public decisions and allocate appropriate resources. See Video Abstract at http://links.lww.com/DCR/B996 . CARGA Y TENDENCIAS DE LA ENFERMEDAD INFLAMATORIA INTESTINAL EN CINCO PASES ASITICOS DESDE HASTA UNA COMPARACIN CON LOS ESTADOS UNIDOS Y EL REINO UNIDO: ANTECEDENTES:La enfermedad inflamatoria intestinal se está convirtiendo en un desafío en la salud mundial, con variaciones sustanciales en las tasas de incidencia y mortalidad entre los países orientales y occidentales.OBJETIVO:Investigar la carga y las tendencias de la enfermedad inflamatoria intestinal en cinco países asiáticos, EE. UU. y el Reino Unido.DISEÑO:Estudio transversal.ESCENARIO:Estudio de carga global de morbilidad 2019.PACIENTES:Enfermedad inflamatoria intestinal.PRINCIPALES MEDIDAS DE RESULTADO:Incidencia, muerte y tasas estandarizadas por edad de enfermedad inflamatoria intestinal.RESULTADOS:Las tasas de incidencia y muerte estandarizadas por edad de la enfermedad inflamatoria intestinal disminuyeron gradualmente en todo el mundo desde 1990 hasta 2019. La tasa de incidencia estandarizada por edad en los EE. UU. disminuyó de 1990 a 2000 y luego aumentó gradualmente de 2000 a 2019, las tasas en el Reino Unido, Mongolia y China aumentaron gradualmente de 1990 a 2019, mientras que la tasa en la República Popular Democrática de Corea disminuyó de 1990 a 1995 y aumentó gradualmente de 1990 a 2019. La tasa de mortalidad estandarizada por edad en la República de Corea exhibió un tendencia ascendente hasta 1995, cayó significativamente hasta 2015 y luego se estabilizó de 2015 a 2019. La tasa de mortalidad estandarizada por edad en los EE. UU. mostró una tendencia ascendente hasta 2007 y luego disminuyó gradualmente de 2007 a 2019, mientras que la tasa en el Reino Unido mostró una tendencia ascendente hasta 2010 y disminuyó de 2010 a 2019. Las tasas de mortalidad estandarizadas por edad en China, Mongolia, la República Popular Democrática de Corea y Japón disminuyeron gradualmente de 1990 a 2019. La tasa de incidencia estandarizada por edad y mortalidad en los EE. UU. y el Reino Unido en la última década fueron más altas que las de los cinco países asiáticos. Las tasas máximas de incidencia estandarizadas por edad en los siete países se dieron entre personas de 20 a 60 años. Las tasas de mortalidad estandarizadas por edad en los siete países exhibieron tendencias crecientes con el aumento de la edad, y las personas mayores, en particular las de ≥70 años, representaron la mayoría de las muertes.LIMITACIONES:Datos de diferentes países con diferente calidad y precisión.CONCLUSIONES:Ha habido grandes variaciones en las cargas y tendencias de la enfermedad inflamatoria intestinal entre cinco países asiáticos, EE. UU. y el Reino Unido durante las últimas tres décadas. Estos hallazgos pueden ayudar a los formuladores de políticas a tomar mejores decisiones públicas y asignar los recursos apropiados. Consulte Video Resumen en http://links.lww.com/DCR/B996 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

Norepinephrine combined with phenylephrine versus norepinephrine in patients with septic shock: a retrospective cohort study.

BACKGROUND: Phenylephrine (PE) and norepinephrine (NE) may be used to maintain adequate blood pressure and tissue perfusion in patients with septic shock, but the effect of NE combined with PE (NE-PE) on mortality remains unclear. We hypothesized that NE-PE would not inferior to NE alone for all-cause hospital mortality in patients with septic shock. METHODS: This single-center, retrospective cohort study included adult patients with septic shock. According to the infusion type, patients were divided into the NE-PE or NE group. Multivariate logistic regression, propensity score matching and doubly robust estimation were used to analyze the differences between groups. The primary outcome was the all-cause hospital mortality rate after NE-PE or NE infusion. RESULTS: Among 1, 747 included patients, 1, 055 received NE and 692 received NE-PE. For the primary outcome, the hospital mortality rate was higher in patients who received NE-PE than in those who received NE (49.7% vs. 34.5%, p < 0.001), and NE-PE was independently associated with higher hospital mortality (odds ratio = 1.76, 95% confidence interval = 1.36-2.28, p < 0.001). Regarding secondary outcomes, patients in the NE-PE group had longer lengths of stay in ICU and hospitals. Patients in the NE-PE group also received mechanical ventilation for longer durations. CONCLUSIONS: NE combined with PE was inferior to NE alone in patients with septic shock, and it was associated with a higher hospital mortality rate.

Association of magnesium sulfate use with mortality in critically ill patients with sepsis: a retrospective propensity score-matched cohort study.

BACKGROUND: Trials have demonstrated lower rates of acute kidney injury in critically ill patients receiving magnesium supplementation, but they have yielded conflicting results regarding mortality. METHODS: This is a retrospective cohort study based on the MIMIC-IV (Medical Information Mart in Intensive Care-IV) database. Adult critically ill patients with sepsis were included in the analysis. The exposure was magnesium sulfate use during ICU stay. The primary outcome was 28-day all-cause mortality. Propensity score matching (PSM) was conducted at a 1:1 ratio. Multivariable analyses were used to adjust for confounders. RESULTS: The pre-matched and propensity score-matched cohorts included 10 999 and 6052 patients, respectively. In the PSM analysis, 28-day all-cause mortality rate was 20.2% (611/3026) in the magnesium sulfate use group and 25.0% (757/3026) in the no use group. Magnesium sulfate use was associated with lower 28-day all-cause mortality (hazard ratio [HR], 0.70; 95% CI, 0.61-0.79; P<0.001). Lower mortality was observed regardless of baseline serum magnesium status: for hypomagnesaemia, HR, 0.64; 95% confidence interval (CI), 0.45-0.93; P=0.020; for normomagnesaemia, HR, 0.70; 95% CI, 0.61-0.80; P<0.001. Magnesium sulfate use was also associated with lower ICU mortality (odds ratio [OR], 0.52; 95% CI, 0.42-0.64; P<0.001), lower in-hospital mortality (OR, 0.65; 95% CI, 0.55-0.77; P<0.001), and renal replacement therapy (OR, 0.67; 95% CI, 0.52-0.87; P=0.002). A sensitivity analysis using the entire cohort also demonstrated lower 28-day all-cause mortality (HR, 0.62; 95% CI, 0.56-0.69; P<0.001). CONCLUSIONS: Magnesium sulfate use was associated with lower mortality in critically ill patients with sepsis. Prospective studies are needed to verify this finding.

The Timing of Initiating Hydrocortisone and Long-term Mortality in Septic Shock.

BACKGROUND: Previous studies on the association between the timing of corticosteroid administration and mortality in septic shock focused only on short-term mortality and produced conflicting results. We performed a retrospective review of a large administrative database of intensive care unit (ICU) patients to evaluate the association between the timing of hydrocortisone initiation and short- and long-term mortality in septic shock. We hypothesized that a longer duration between the first vasopressor use for sepsis and steroid initiation was associated with increased mortality. METHODS: Data were extracted from the Medical Information Mart in the Intensive Care-IV database. We included adults who met Sepsis-3 definition for septic shock and received hydrocortisone. The exposure of interest was the time in hours from vasopressor use to hydrocortisone initiation (>12 as late and ≤12 as early). The primary outcome was 1-year mortality. Secondary outcomes included 28-day mortality, 90-day mortality, in-hospital mortality, and length of hospital stay. Cox proportional hazard models were used to estimate the association between exposure and mortality. Competing risk regression models were used to evaluate the association between exposure and length of hospital stay. RESULTS: A total of 844 patients were included in this cohort: 553 in the early group and 291 in the late group. The median time to hydrocortisone initiation was 7 hours (interquartile range, 2.0-19.0 hours). After multivariable Cox proportional hazard analysis, we found that hydrocortisone initiation >12 hours after vasopressor use was associated with increased 1-year mortality when compared with initiation <12 hours (adjusted hazard ratio, 1.39; 95% confidence interval, 1.13-1.71; P = .002, E-value = 2.13). Hydrocortisone initiation >12 hours was also associated with increased 28-day, 90-day, and in-hospital mortality and prolonged length of hospital stay. CONCLUSIONS: In patients with septic shock, initiating hydrocortisone >12 hours after vasopressor use was associated with an increased risk of both short-term and long-term mortality, and a prolonged length of hospital stay.

Effect of early vasopressin combined with norepinephrine on short-term mortality in septic shock: A retrospective study based on the MIMIC-IV database.

BACKGROUND: Septic shock is a leading cause of death in intensive care units (ICUs), with short-term mortality rates of 35-40%. Vasopressin (AVP) is a second-line vasoactive agent for septic shock, and recent studies suggest that early AVP use can be beneficial. However, differences between early initiation of AVP combined with norepinephrine (NE) and nonearly AVP with NE are unclear. A retrospective cohort research was designed to explore the effects of early AVP initiation versus nonearly AVP initiation. METHODS: This retrospective single-center cohort study included adult patients with septic shock from the MIMIC (Medical Information Mart for Intensive Care)-IV database. According to whether AVP was used early in the ICU (intensive care unit), patients were assigned to the early- (within 6 h of septic shock onset) and non-early-AVP (at least 6 h after septic shock onset) groups. The primary outcome was 28-day mortality. The secondary outcomes were ICU and hospital mortality, the numbers of vasopressor-free and ventilation-free days at 28 days, ICU length of stay (LOS), hospital LOS, sequential organ failure assessment (SOFA) score on days 2 and 3, and renal replacement therapy (RRT) use on days 2 and 3. Univariate and multivariate cox proportional-hazards regression, propensity-score matching were used to analyze the differences between the groups. RESULTS: The study included 531 patients with septic shock: 331 (62.5%) in the early-AVP group and 200 (37.5%) in the non-early-AVP group. For 1:1 matching, 158 patients in the early-AVP group were matched with the same number of patients with nonearly AVP. Regarding the primary outcome, there was no significant difference between the early- and non-early-AVP groups in 28-day mortality (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.68-1.24). For the secondary outcomes, there were no differences between the early- and non-early-AVP groups in ICU mortality (HR = 0.95, 95% CI = 0.67-1.35), hospital mortality (HR = 0.95, 95% CI = 0.69-1.31), the numbers of vasopressor-free and ventilation-free days at 28 days, ICU LOS, hospital LOS, SOFA score on days 2 and 3, and RRT use on days 2 and 3. CONCLUSIONS: There was no difference in short-term mortality between early AVP combined with NE and nonearly AVP with NE in septic shock.

Incidence, risk factors, and consequences of emergence delirium after elective brain tumor resection.

BACKGROUND: Emergence delirium (ED) is a common phenomenon occurring in the recovery period. The aim of this study was to investigate the incidence, risk factors, and consequences of ED in adults after elective brain tumor resection. METHODS: We retrospectively analyzed the data of a prospective cohort performed in a tertiary university hospital. Adult patients admitted to the intensive care unit (ICU) immediately after elective brain tumor resection were consecutively enrolled. Level of consciousness was assessed using the Richmond Agitation-Sedation Scale and ED was assessed using the Confusion Assessment Method for the ICU. Risk factors for ED were determined by multivariable logistic regression. RESULTS: A total of 659 patients met the inclusion criteria, of which 41 patients with coma were excluded. Among the remaining 618 patients, 131 (21.2%) developed ED. Independent risk factors for ED were: age, education level, use of anticholinergic and mannitol, Glasgow Coma Score and arterial partial pressure of oxygen postoperatively, postoperative pain, malignant tumor, and frontal approach craniotomy. ED was associated with increased postoperative delirium, longer length of hospital stay, and higher hospitalization costs. There was no significant difference in the neurological function deficits (modified Rankin Scale score) between ED and non-ED groups. CONCLUSIONS: ED has a high incidence and is associated with poor outcomes in adults after elective brain tumor resection. Early screening and prevention for ED should be established in perioperative management of this population.

High flow nasal oxygen versus conventional oxygen therapy in gastrointestinal endoscopy with conscious sedation: Systematic review and meta-analysis with trial sequential analysis.

OBJECTIVES: Although conventional oxygen therapy (COT) is widely used, hypoxemia frequently occurs in gastrointestinal endoscopy with conscious sedation and can lead to life-threatening consequences. High flow nasal oxygen (HFNO) has been applied to improve oxygenation in clinical entities. However, its efficacy to prevent hypoxemia in gastrointestinal endoscopy with conscious sedation has not been evaluated. METHODS: We searched databases to identify randomized controlled trials that compared the efficacy of HFNO with COT in gastrointestinal endoscopy with conscious sedation. The primary outcome was hypoxemia. Meta-analyses with trial sequential analysis were performed using a random-effects model. RESULTS: Eight trials with 3212 patients were included. Compared with COT, HFNO significantly reduced the risk of hypoxemia (eight trials; 3212 patients; risk ratio 0.30; 95% confidence interval [CI] 0.13-0.70). Trial sequential analysis showed that the cumulative Z curve did not cross the monitoring or futility boundaries, nor reach the required information size line, indicating that more trials are needed to reach a definitive conclusion. Subgroup analyses indicated the superiority of HFNO over COT with respect to hypoxemia in patients at low risk and high risk. HFNO further improved the lowest oxygen saturation (four trials; 459 patients; mean difference 2.30, 95% CI 0.84-3.77). CONCLUSIONS: Compared with COT, HFNO can reduce the risk of hypoxemia and improve the lowest oxygen saturation in gastrointestinal endoscopy with conscious sedation. However, the results should be interpreted with caution due to substantial heterogeneity and limited evidence. Further studies are needed to verify the preliminary findings.

Elevated central venous pressure is associated with increased mortality and acute kidney injury in critically ill patients: a meta-analysis.

BACKGROUND: The association of central venous pressure (CVP) and mortality and acute kidney injury (AKI) in critically ill adult patients remains unclear. We performed a meta-analysis to determine whether elevated CVP is associated with increased mortality and AKI in critically ill adult patients. METHODS: We searched PubMed and Embase through June 2019 to identify studies that investigated the association between CVP and mortality and/or AKI in critically ill adult patients admitted into the intensive care unit. We calculated the summary odds ratio (OR) and 95% CI using a random-effects model. RESULTS: Fifteen cohort studies with a broad spectrum of critically ill patients (mainly sepsis) were included. On a dichotomous scale, elevated CVP was associated with an increased risk of mortality (3 studies; 969 participants; OR, 1.65; 95% CI, 1.19-2.29) and AKI (2 studies; 689 participants; OR, 2.09; 95% CI, 1.39-3.14). On a continuous scale, higher CVP was associated with greater risk of mortality (5 studies; 7837 participants; OR, 1.10; 95% CI, 1.03-1.17) and AKI (6 studies; 5446 participants; OR, 1.14; 95% CI, 1.06-1.23). Furthermore, per 1 mmHg increase in CVP increased the odds of AKI by 6% (4 studies; 5150 participants; OR, 1.06; 95% CI, 1.01-1.12). Further analyses restricted to patients with sepsis showed consistent results. CONCLUSIONS: Elevated CVP is associated with an increased risk of mortality and AKI in critically ill adult patients admitted into the intensive care unit. TRIAL REGISTRATION: PROSPERO, CRD42019126381.

[The miR-184 level in the seminal plasma exosome of male infertility patients and its clinical significance].

OBJECTIVE: To study the miR-184 level in the seminal plasma exosome of male infertility patients and its clinical significance. METHODS: Between 2015 and 2019, we collected 285 seminal plasma samples from 97 azoospermia (AS) and 96 asthenospermia (AZS) patients and 92 age-matched normal fertile controls in Jiangsu Provincial Hospital of Traditional Chinese Medicine, General Hospital of Eastern Theater Command and the First Hospital Affiliated to Wenzhou Medical University, identified the isolated seminal plasma exosomes by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western blot, and detected the miR-184 level in the seminal plasma exosomes by quantitative real-time PCR (qRT-PCR). We determined the clinical value of the miR-184 level and its correlation with semen parameters by multiple statistics, predicted the target genes and involved pathways of miR-184 by bioinformatic algorithms, and analyzed their relationship with male infertility. RESULTS: NTA, TEM and Western blot exhibited plenty of exosomes in the seminal plasma of the patients. The results of qRT-PCR showed that the miR-184 level in the seminal plasma exosome was dramatically decreased in the AS patients compared with that in the normal fertile controls (0.227 ［0.092, 0.790］ vs 0.650 ［0.408, 1.061］, P < 0.01), but increased in AZS males in comparison with that in the control group (1.176 ［0.661, 1.946］ vs 0.650 ［0.408, 1.061］, P < 0.01). The areas under the ROC curve (AUC) for differentiating the AS and AZS patients from the controls were 0.866 (95% CI: 0.815－0.916) and 0.724 (95% CI: 0.653－0.795), respectively, and that for differentiating the AS from the AZS group was 0.964 (95% CI: 0.943－0.985). The miR-184 level in the seminal plasma exosome of the AZS patients was correlated positively with the sperm count (r = 0.243, P = 0.017) but negatively with the percentage of progressively motile sperm (r = －0.407, P = 0.006). Bioinformatics analysis indicated that the downstream target genes of miR-184 were significantly enriched in the protein regulatory pathways closely related to male reproduction and spermatogenesis. CONCLUSIONS: The miR-184 level in the seminal plasma exosome of infertility patients is significantly different from that of normal fertile males, which may serve as a potential auxiliary marker for the diagnosis of and participate in the development and progression of male infertility.

Artesunate Decreases ß-Catenin Expression, Cell Proliferation and Apoptosis Resistance in the MG-63 Human Osteosarcoma Cell Line.

BACKGROUND: This study aims to determine the effects of artesunate on proliferation, apoptosis and ß-catenin expression in the human osteosarcoma cell line MG-63. METHODS: MG-63 cells in the logarithmic growth phase were collected and cultured with different concentrations of artesunate (12.5 µg/mL, 25 µg/mL and 50 µg/mL) for 24 h, 48 h and 72 h. The total number of MG-63 cells and the morphological changes were observed under an inverted microscope. The MTT assay was adopted to test the inhibition rate (IR) of cell growth. The apoptosis rate was detected using annexin V/propidium iodide (PI) staining. Cell cycle distribution was identified by flow cytometry (FCM), and the expression levels of ß-catenin, cyclins and cyclin dependent kinases (CDKs) were measured using Western blotting. RESULTS: The results of the MTT assay indicated that artesunate could remarkably inhibit MG-63 cell proliferation compared with the rates in the untreated control group (0 µg/mL artesunate), and the inhibitory effect was dose-dependent. The apoptosis rate of MG-63 cells was elevated as the concentration of artesunate increased, and all the rates were significantly higher than that in the control group. Additionally, as the artesunate concentration increased, the proportion of MG-63 cells in G0/G1 phase gradually declined whereas that of cells in the G2/M and S phases increased. Western blotting confirmed that a higher concentration of artesunate reduced the expression levels of ß-catenin, cyclin A, cyclin D1 and CDK1 and increased the expression levels of cyclin B1; however, artesunate had no impact on CDK2 expression in MG-63 cells. CONCLUSION: These results demonstrated that artesunate can inhibit ß-catenin expression and cell proliferation as well as promote cell apoptosis in MG-63 cells, which indicates that artesunate may serve as a promising drug in the clinical treatment of osteosarcoma.

GIT1 gene deletion delays chondrocyte differentiation and healing of tibial plateau fracture through suppressing proliferation and apoptosis of chondrocyte.

BACKGROUND: Although tibial plateau fracture is an uncommon injury, its regulation is challenging and there are some influencing factors, including the effects of severe bone displacement, depression and cancellous bone cartilage, and inevitable cartilage damage. And GIT1 plays an important role in bone mass and 78 osteoblast cell migration. METHODS: The study used 72 C57/BL6 mice. A tibial plateau fracture model was established by using mice with the same number of GIT1 gene deletions (the experimental group) and their wild-type littermates (the control group). Joint and bone callus recovery were evaluated by X-ray and CT thin layer scans. Micro CT assay and histomorphometry were conducted in order to evaluate the volume of newly formed blood vessels. Type II collagen expression in tibial tissues after tibial plateau fracture were detected by immunohistochemistry after 7, 14 and 21 days. The number of proliferating cell nuclear antigen (PCNA) positive cells after tibial plateau fracture was tested by immunohistochemistry after 14 and 21 days. The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining was conducted after 14 and 21 days in order to test chondrocyte apoptosis in tibial tissues after tibial plateau fracture. RESULTS: The GIT1 gene deletion group mice spent less time on the rotating rod than the control group mice (P < 0.05). Compared with the control group, postoperative recovery was retarded, because GIT1 gene deletion slowed down neovascularization after tibial plateau fracture (P < 0.05). Compared with the control group, mouse type II collagen expression significantly decreased in the GIT1 gene deletion group, and the proportion of PCNA positive cells significantly decreased (P < 0.05). The TUNEL results indicate that GIT1 gene deletion led to reduced chondrocyte apoptosis. CONCLUSION: GIT1 gene deletion can inhibit chondrocyte proliferation and apoptosis during the recovery of tibial plateau fracture, so as to delay chondrocyte differentiation and tibial plateau fracture healing.

Relationship between Annualized Case Volume and Mortality in Sepsis: A Dose-Response Meta-analysis.

BACKGROUND: The relationship between annualized case volume and mortality in patients with sepsis is not fully understood. The authors performed a dose-response meta-analysis to assess the effect of annualized case volume on mortality among patients with sepsis in the intensive care unit, emergency department, or hospital, hypothesizing that higher annualized case volume may lead to lower mortality. METHODS: The authors searched PubMed and Embase through July 2015 to identify observational studies that examined the relationship between annualized case volume and mortality in sepsis. The predefined outcome was mortality. Odds ratios with 95% CIs were pooled using a random-effects model. RESULTS: Ten studies involving 3,495,921 participants and 834,009 deaths were included. The pooled estimate suggested that annualized case volume was inversely associated with mortality (odds ratio, 0.76; 95% CI, 0.65 to 0.89; P = 0.001), with high heterogeneity (I = 96.6%). The relationship was consistent in most subgroup analyses and robust in sensitivity analysis. Dose-response analysis identified a nonlinear relationship between annualized case volume and mortality (P for nonlinearity less than 0.001). CONCLUSIONS: This meta-analysis confirmed the study hypothesis and provided strong evidence for an inverse and a nonlinear dose-response relationship between annualized case volume and mortality in patients with sepsis. Variations in cutoff values of category for annualized case volume across studies may mainly result in the overall heterogeneity. Future studies should uncover the mechanism of volume-mortality relationship and standardize the cutoff values of category for annualized case volume in patients with sepsis.

Bridging external fixation versus non-bridging external fixation for unstable distal radius fractures: A systematic review and meta-analysis.

OBJECTIVE: A systematic review and meta-analysis was conducted to compare the relative effectiveness of bridging external fixation and non-bridging external fixation for distal radius fractures treatment. METHOD: Relevant literature were comprehensively searched using the PubMed, Springer Link, Karger Medical and Scientific Publishers, Chinese Biomedical Database (CBM) and Chinese National Knowledge Infrastructure (CNKI) databases without any language restrictions. STATA Version 12.0 software and Comprehensive Meta-analysis 2.0 were applied. RESULTS: A total of 905 patients with distal radius fracture from six eligible cohort studies were selected for statistical analysis. Our meta-analysis results indicate that the non-bridging cases had a higher risk of pin track infection, rupture of the extensor pollicis longus and nerve injury than the bridging cases. Subgroup analysis stratified by country indicated non-bridging patients showed evidence of an increased risk of pin track infection and higher risk of rupture of the extensor pollicis longus compared with the patients treated with bridging external fixation in the UK population. The follow-up results showed flexion degree of patients treated with non-bridging external fixation was slightly better than that of patients treated with bridging external fixation (P < 0.05). CONCLUSION: There is evidence in our systematic review and meta-analysis to support that bridging external fixation can reduce the incidence of pin tract infections and nerve injury compared to non-bridging external fixation, but have no significant difference in other complications and the recovery of wrist joint function. Bridging external fixation could therefore be a better choice in patients with distal radius fractures.

Effect of lung-protective ventilation with lower tidal volumes on clinical outcomes among patients undergoing surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: In anesthetized patients undergoing surgery, the role of lung-protective ventilation with lower tidal volumes is unclear. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of this ventilation strategy on postoperative outcomes. METHODS: We searched electronic databases from inception through September 2014. We included RCTs that compared protective ventilation with lower tidal volumes and conventional ventilation with higher tidal volumes in anesthetized adults undergoing surgery. We pooled outcomes using a random-effects model. The primary outcome measures were lung injury and pulmonary infection. RESULTS: We included 19 trials (n=1348). Compared with patients in the control group, those who received lung-protective ventilation had a decreased risk of lung injury (risk ratio [RR] 0.36, 95% confidence interval [CI] 0.17 to 0.78; I2=0%) and pulmonary infection (RR 0.46, 95% CI 0.26 to 0.83; I2=8%), and higher levels of arterial partial pressure of carbon dioxide (standardized mean difference 0.47, 95% CI 0.18 to 0.75; I2=65%). No significant differences were observed between the patient groups in atelectasis, mortality, length of hospital stay, length of stay in the intensive care unit or the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen. INTERPRETATION: Anesthetized patients who received ventilation with lower tidal volumes during surgery had a lower risk of lung injury and pulmonary infection than those given conventional ventilation with higher tidal volumes. Implementation of a lung-protective ventilation strategy with lower tidal volumes may lower the incidence of these outcomes.

Rapid identification of new minor chemical constituents from Smilacis Glabrae Rhizoma by combined use of UHPLC-Q-TOF-MS, preparative HPLC and UHPLC-SPE-NMR-MS techniques.

INTRODUCTION: Herbs are an important resource for new drug development. However, the conventional approach for the discovery of new compounds from herbs was time-consuming, tedious, and inefficient. OBJECTIVES: Establish a quick approach to identify new minor constituents in herbs. METHODS: The constituents in herbs were firstly analysed using ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). Based on the accurate masses, isotopic ions, and the characteristic fragmentation ions in the mass spectra, the molecular compositions and possible structures of compounds were first deduced. After being enriched by a preparative HPLC method, the potential new minor structures were definitely identified by an on-line UHPLC-solid phase extraction-nuclear magnetic resonance-mass spectrometry (UHPLC-SPE-NMR-MS) approach. RESULTS: By combined the use of UHPLC-Q-TOF-MS, preparative HPLC and UHPLC-SPE-NMR, three new minor compounds were definitely identified as bis-3,4-dihydroxyphenylpropanoid-substituted catechins (A2 and A3) and 4″-formyl-astilbin (B5). In addition, five isomers of bis-dihydroxyphenylpropanoid-substituted catechin (A1, A4-A7), four isomers of 4″-formyl-astilbin (B1-B4), engeletin formates and isomers (C1-C5), formyl-cinchonains (D1-D4), formyl-caffeoylshikimic acid (E1-E4) were also tentatively determined by MS and MS/MS characterisation. CONCLUSION: The combination of UHPLC-Q-TOF-MS, preparative HPLC and UHPLC-SPE-NMR-MS techniques is a quick and effective approach for finding new minor constitutes from herbs.

Metabolites software-assisted flavonoid hunting in plants using ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry.

Plant secondary metabolism drives the generation of metabolites used for host plant resistance, as biopesticides and botanicals, even for the discovery of new therapeutics for human diseases. Flavonoids are one of the largest and most studied classes of specialized plant metabolites. To quickly identify the potential bioactive flavonoids in herbs, a metabolites software-assisted flavonoid hunting approach was developed, which mainly included three steps: firstly, utilizing commercial metabolite software, a flavonoids database was established based on the biosynthetic pathways; secondly, mass spectral data of components in herbs were acquired by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF-MS); and finally, the acquired LC-MS data were imported into the database and the compounds in the herbs were automatically identified by comparison of their mass spectra with the theoretical values. As a case study, the flavonoids in Smilax glabra were profiled using this approach. As a result, 104 flavonoids including 27 potential new compounds were identified. To our knowledge, this is the first report on profiling the components in the plants utilizing the plant metabolic principles with the assistance of metabolites software. This approach can be extended to the analysis of flavonoids in other plants.