[Research progress on AMPK activation in nonalcoholic fatty liver disease].

Nonalcoholic fatty liver disease (NAFLD) occurrence and progression are associated with lipid accumulation, insulin resistance, inflammation, liver damage, fibrosis, and other factors. AMP-dependent protein kinase (AMPK) is a key molecule that regulates bioenergy metabolism and participates in multiple biological processes, including lipid metabolism, autophagy, inflammation, and cell apoptosis. Promoting AMPK activation can reduce hepatic lipid accumulation and insulin resistance, alleviate the development of NAFLD, reduce liver inflammation and fibrosis, and inhibit the progression of NAFLD to nonalcoholic steatohepatitis.

Carbetocin vs. oxytocin at elective caesarean delivery: a double-blind, randomised, controlled, non-inferiority trial of low- and high-dose regimens.

Carbetocin or oxytocin are given routinely as first-line uterotonic drugs following delivery of the neonate during caesarean delivery to prevent postpartum haemorrhage. Low doses may be as effective as high doses with a potential reduction in adverse effects. In this double-blind, randomised, controlled, non-inferiority trial, we assigned low-risk patients undergoing elective caesarean delivery under spinal anaesthesia to one of four groups: carbetocin 20 µg; carbetocin 100 µg; oxytocin 0.5 IU bolus + infusion; and oxytocin 5 IU bolus + infusion. The study drug was given intravenously after delivery of the neonate. Uterine tone was assessed by the obstetrician 2, 5 and 10 minutes after study drug administration according to an 11-point verbal numerical rating scale (0 = atonic, 10 = excellent tone). The primary outcome measure was uterine tone 2 min after study drug administration. The pre-specified non-inferiority margin was 1.2 points on the 11-point scale. Secondary outcomes included uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects. Data were available for 277 patients. Carbetocin 20 µg resulting in uterine tone of (median (IQR [range])) 8 (7-8 [1-10]) was non-inferior to carbetocin 100 µg with tone 8 (7-9 [3-10]), median (95%CI) difference 0 (-0.44-0.44). Similarly, oxytocin 0.5 IU with tone 7 (6-8 [3-10]) was non-inferior to oxytocin 5 IU with tone 8 (6-8 [2-10]), median (95%CI) difference 1 (0.11-1.89). Carbetocin 20 µg was also non-inferior to oxytocin 5 IU, and oxytocin 0.5 IU was non-inferior to carbetocin 100 µg. Uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects were similar in all groups.

Short- and long-term outcome following thoracoamniotic shunting for fetal hydrothorax.

OBJECTIVES: To assess short- and long-term outcome in a cohort of fetuses diagnosed with hydrothorax (FHT) which underwent thoracoamniotic shunting in utero, and to examine the antenatal predictors of survival and of survival with normal neurodevelopmental outcome. METHODS: This was a retrospective analysis of 132 fetuses that underwent thoracoamniotic shunting at our center between 1991 and 2014. Data were extracted from hospital obstetric and relevant neonatal intensive care and neonatal developmental follow-up databases. Outcomes included survival to discharge and survival with normal neurodevelopmental outcome beyond 18 months. Information on malformations, syndromes and genetic abnormalities were obtained from antenatal, postnatal and pediatric hospital records or by parent report. We compared pregnancy characteristics among those who survived vs non-survivors and among those with normal neurodevelopmental outcome vs those who were abnormal or died. We explored whether there was a trend in survival over the study period. RESULTS: The mean gestational age at diagnosis of FHT was 25.6 weeks. The fetus was hydropic at diagnosis in 61% of cases, 69% had bilateral effusions and 55% had bilateral shunts inserted. Other diagnoses were present in 24% of cases, two-thirds of which were discovered only postnatally. There were 16 intrauterine and 30 neonatal deaths, with a 65% survival rate overall. The mean gestational age at delivery of liveborns was 35.4 (range, 26.9-41.6) weeks, and 88/116 (76%) were preterm (< 37 weeks). Of 87 liveborn at the treatment center, 75% experienced some respiratory and/or cardiovascular morbidity after birth, many with a lengthy hospital stay (mean, 36 (range, 1-249) days). Overall, 84% of survivors were developmentally normal beyond 18 months and outcomes were better when pleural effusions were isolated, 92% of these cases being neurodevelopmentally normal. There was no trend in survival or neurodevelopmental outcome over time. Despite the presence of FHT and neonatal respiratory issues, most (89%) of the 55 survivors with relevant follow-up had no long-term pulmonary complications. Gestational age at delivery was the only factor independently predictive of both survival and survival with normal neurodevelopmental outcome. CONCLUSIONS: FHT is associated with other pathologies in a quarter of cases and carries a significant risk of prematurity, mortality and neonatal morbidity. The outcome is good in survivors but is best in isolated cases. Predictors of outcome at diagnosis are poor. Future improvement in diagnostics at time of identification of FHT may help to identify those that would benefit most from thoracoamniotic shunting. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Oxytocin at elective caesarean delivery: a dose-finding study in women with obesity.

Prophylactic oxytocin administration at the third stage of labour reduces blood loss and the need for additional uterotonic drugs. Obesity is known to be associated with an increased risk of uterine atony and postpartum haemorrhage. It is unknown whether women with obesity require higher doses of oxytocin in order to achieve adequate uterine tone after delivery. The purpose of this study was to establish the bolus dose of oxytocin required to initiate effective uterine contraction in 90% of women with obesity (the ED90 ) at elective caesarean delivery. We conducted a double-blind dose-finding study using the biased coin up-down design method. Term pregnant women with a BMI ≥ 40 kg.m-2 undergoing elective caesarean delivery under regional anaesthesia were included. Those with conditions predisposing to postpartum haemorrhage were not included. Oxytocin was administered as an intravenous bolus over 1 minute upon delivery of the fetus. With the first woman receiving 0.5 IU, oxytocin doses were administered according to a sequential allocation scheme. The primary outcome measure was satisfactory uterine tone, as assessed by the operating obstetrician 2 minutes after administration of the oxytocin bolus. Secondary outcomes included the need for rescue uterotonic drugs, adverse effects and estimated blood loss. We studied 30 women with a mean (SD) BMI of 52.3 (7.6) kg.m-2 . The ED90 for oxytocin was 0.75 IU (95%CI 0.5-0.93 IU) by isotonic regression and 0.78 IU (95%CI 0.68-0.88 IU) by the Dixon and Mood method. Our results suggest that women with a BMI ≥ 40 kg.m-2 require approximately twice as much oxytocin as those with a BMI < 40 kg.m-2 , in whom an ED90 of 0.35 IU (95%CI 0.15-0.52 IU) has previously been demonstrated.

Carbetocin at elective caesarean section: a sequential allocation trial to determine the minimum effective dose in obese women.

Postpartum haemorrhage is a leading cause of maternal death during childbirth. There is an increasing incidence of atonic postpartum haemorrhage in developed countries, and maternal obesity has been proposed as a contributing factor. The dose-response relationship of carbetocin in obese women has not yet been determined. We conducted a double-blind, dose-finding study of carbetocin using a biased coin up-and-down design in women with a body mass index ≥ 40 kg.m-2 undergoing elective caesarean section. The determinant for a successful response was satisfactory uterine tone, with no intra-operative need for additional uterotonic drugs. Secondary outcomes included the use of additional uterotonic drugs postoperatively, estimated blood loss and adverse effects of carbetocin administration. Thirty women were recruited to the study. The median (IQR [range]) body mass index was 44.93 (41.5-55.2 [40-66.5]) kg.m-2 . The ED90 of carbetocin was estimated as 62.9 (95%CI 57.0-68.7) µg using the truncated Dixon and Mood method, and 68 (95%CI 52-77) µg using the isotonic regression method. The estimated blood loss was 880 (621-1178 [75-2442]) ml. The overall rates of hypotension and hypertension after delivery were 40% and 6.7%, respectively, while nausea occurred in 26.7% of women. The ED90 for carbetocin in obese women at elective caesarean section is lower than the dose of 100 µg currently recommended by the Society of Obstetricians and Gynaecologists of Canada, but is approximately four times higher than the previously demonstrated ED90 of 14.8 µg in women with body mass index < 40 kg.m-2 .

Determination of the optimal programmed intermittent epidural bolus volume of bupivacaine 0.0625% with fentanyl 2 µg.ml-1 at a fixed interval of forty minutes: a biased coin up-and-down sequential allocation trial.

The optimum time interval for 10 ml boluses of bupivacaine 0.0625% + fentanyl 2 µg.ml-1 as part of a programmed intermittent epidural bolus regimen has been found to be 40 min. This regimen was shown to be effective without the use of supplementary patient-controlled epidural analgesia boluses in 90% of women during the first stage of labour, although with a rate of sensory block to ice above T6 in 34% of women. We aimed to determine the optimum programmed intermittent epidural bolus volume at a 40 min interval to provide effective analgesia in 90% of women (EV90 ) during the first stage of labour, without the use of patient-controlled epidural analgesia. We performed a prospective double-blind dose-finding study using the biased coin up-and-down sequential allocation method in 40 women. The estimated EV90 was 11.0 (95%CI 10.0-11.7) ml with the isotonic regression method and 10.7 (95%CI 10.3-11.0) ml with the truncated Dixon and Mood method. Overall, 18 women had a sensory block above T6, and 37 women exhibited no motor block. No women required treatment for hypotension. In conclusion, it is not possible to reduce the programmed intermittent epidural bolus volume from 10 ml, used in our current regimen, without compromising the quality of analgesia. Using this regimen, a high proportion of women will develop a sensory block above T6.

Gastric ultrasound in the third trimester of pregnancy: a randomised controlled trial to develop a predictive model of volume assessment.

Bedside gastric ultrasonography can be performed reliably by anaesthetists to assess gastric content in the peri-operative period. We aimed to study the relationship between gastric cross-sectional area, assessed by ultrasound, and volumes of clear fluids ingested by pregnant women. We recruited 60 non-labouring third-trimester pregnant women in a randomised controlled and assessor-blinded study. A standardised scanning protocol of the gastric antrum was performed in the 45° semirecumbent and 45° semirecumbent-right lateral positions. Subjects were randomly allocated to drink one out of six predetermined volumes of apple juice (0 ml, 50 ml, 100 ml, 200 ml, 300 ml, 400 ml). Qualitative and quantitative assessments at a baseline period after an 8-h fast, and immediately after the drink, were used to establish the correlation between antral cross-sectional area and volume ingested. A predictive model to estimate gastric volume was developed. Antral cross-sectional area in the semirecumbent right lateral position significantly correlated with the ingested volume (Spearman rank correlation = 0.7; p < 0.0001). A cut-off value of 9.6 cm2 discriminated ingested volumes ≥ 1.5 ml.kg-1 with a sensitivity of 80%, a specificity of 66.7%, and an area under the curve of 0.82. A linear predictive model was developed for gastric volume based only on antral cross-sectional area (Volume (ml) = -327.1 + 215.2 × log (cross-sectional area) (cm2 )). We conclude that in pregnant women in the third trimester of gestation, the antral cross-sectional area correlates well with volumes ingested, and this cut-off value in the semirecumbent right lateral position discriminates high gastric volumes.

[Triptolide induces oxidative stress and apoptosis and activates PIK3/Akt signaling pathway in TM4 sertoli cells].

OBJECTIVE: To investigate the effect of triptolide (TP) on oxidative stress and apoptosis in TM4 sertoli cells and related molecular mechanism. METHODS: TM4 cells were incubated with different concentrations of triptolide for 24 h, then collected for further experiments. Cell proliferation analysis was used to measure the inhibitive effect of triptolide on proliferation of TM4 cells; DCFH-DA (6-carboxy-2',7'-dichlorofluorescein diacetate) probe was used to stain the TM4 cells, the level change of intracellular ROS was discovered through flow cytometry; the TM4 cells were stained by Annexin V-FITC/PI to detect whether triptolide induced apoptosis in the TM4 cells; Protein was extracted from the TM4 cells in control and triptolide group. Western blot was performed to determine the expression of apoptosis marker protein cleaved-PARP and PI3K/Akt signaling pathway-related proteins [p-Akt (Ser473), Akt, p-mTOR (Ser2448), mTOR, p-p70S6K (Thr389), p70S6K]. RESULTS: Cell proliferation analysis revealed that triptolide reduced the TM4 cells viability significantly compared with control group in a dosage-dependent manner [10 nmol/L: (73.77±20.95)%, 100 nmol/L: (51.60±10.43)%, 500 nmol/L: (44.34±5.78)%]; The level of intracellular ROS in the TM4 cells was significantly induced in a dosage-dependent manner (P<0.01); triptolide remarkably induced early-stage and late-stage apoptosis in the TM4 cells [control: (3.84±1.50)%, 100 nmol/L: (13.04±2.03)%, 200 nmol/L: (16.24±1.34)%, 400 nmol/L: (18.76±3.45)%]; The expression of cleaved-PARP was significantly upregulated in the TM4 cells after incubation with triptolide (P<0.01); The expression levels of p-Akt/Akt and p-p70S6K/p70s6k were significantly increased compared with control group (P<0.01). No significant change was observed among the expression levels of p-mTOR/mTOR (P>0.05). CONCLUSION: In vitro studies showed that triptolide could effectively suppress the proliferation and induce apoptosis of TM4 sertoli cells. The oxidative stress was upregulated after incubation with triptolide, which may be one of the mechanisms of cytotoxicity in TM4 cells. Treatment of triptolide led to activation of Akt and p70S6K, indicating that the PI3K/Akt signaling pathway may be involved in response to oxidative stress in TM4 cells. The activation of PI3K/Akt signaling pathway was one of the molecular mechanisms involved in triptolide-mediated oxidative stress in TM4 cells. Our study provides insight into alleviating reproductive toxicity of triptolide in clinical and developing male contraceptive.

Genotype and genetic variation of HCV infections with low-risk factors in Putian coastal regions, China.

Hepatitis C virus (HCV) infection is one of the leading causes of death and morbidity associated with liver disease. Risk factors identified for the transmission of HCV include contaminated blood products, intravenous drug use, body piercing, an infected mother at birth, sexual activity, and dental therapy, among others. However, the exact diversity of the HCV genotype and genetic variation among patients with low-risk factors is still unknown. In this study, we briefly described and analysed the genotype distribution and genetic variation of HCV infections with low-risk factors using molecular biology techniques. The results suggested that genotype 1b was predominant, followed by genotypes 2a and 1a. Genetic variations in the 5' UTR sequences of HCV were identified, including point mutations, deletions, and insertions. The frequency of genetic variations in 1b was higher than in 2a. This study provides considerable value for the prevention and treatment of liver disease caused by HCV among patients with low-risk factors and for the development of HCV diagnostic reagents and vaccines.

[Clinic analysis of femtosecond laser-assisted cataract surgery].

OBJECTIVE: To evaluate the safety and effectiveness of femtosecond laser-assisted cataract surgery. METHODS: The interventional case series enrolled 314 eyes undergoing cataract surgery in Xiamen Ophthalmic Center between April and December 2013, patients were randomized to femtosecond laser-assisted cataract surgery(153 eyes) and conventional phacoemulsification cataract surgery(161 eyes). The clincic parameters of preoperation, during operation and postoperation were compared and statistically studied. Quantitative data were analyzed using the analysis of variance, independent t tests. Qualitative datawere analyzed using the crosstabs analysis chi-square test or the Fisher's exact test. RESULTS: The patient's demographics parameters(age, gender, IOP, axial length, mean keratometry, AC depth, Cataract grade) did not differ significantly between groups (P>0.05) . The CDE showing 4.78% (3.18%-8.88%) and EPT showing 14.05 s (10.07-20.85 s) in the laser group were significantly lower than the CDE showing 8.82% (6.01%-19.16%) and EPT showing 23.65 s (18.36-46.96 s) in the conventional group (z=2.30, 2.91; P<0.05) . The relative diameter and circularity in laser-assisted capusulotomies were significantly more accurate (t=2.58, 3.92; P<0.05). The corneal endothelial cell loss showing 73.50 (-69.51-111.03)/mm(2) was significantly lower in the laser group than the loss of 118.06 (53.55-299.03)/mm(2) in the conventional group 1 month postoperatively (z=2.44; P<0.05). Postoperative anterial chamber flare was significantly greater in the conventional group at 1 day of 18.81 (13.32-20.23) ph/ms in laser group, 24.51(16.38-32.18)ph/m in conventional group and at 1 month of 13.01(9.23-16.28) ph/ms in laser group, 18.05(12.37-24.97) ph/ms in conventional group than the laser group (z=2.40, 2.31; P<0.05). There were no severe surgical complications for both groups. CONCLUSIONS: The femtosecond laser-assisted cataract surgery was effective and safe. It reduced EPT and CDE during operation, therefore decreased endothelial damage and postoperative anterior chamber inflammation. It also provided more precise and reproducible capsulotomies.

A pivotal role for the IL-1ß and the inflammasome in preterm labor.

During labor, monocytes infiltrate massively the myometrium and differentiate into macrophages secreting high levels of reactive oxygen species and of pro-inflammatory cytokines (i.e. IL-1ß), leading to myometrial contraction. Although IL-1ß is clearly implicated in labor, its function and that of the inflammasome complex that cleaves the cytokine in its active form, has never been studied on steps preceding contraction. In this work, we used our model of lipopolysaccharide-induced preterm labor to highlight their role. We demonstrated that IL-1ß was secreted by the human myometrium during labor or in presence of infection and was essential for myometrial efficient contractions as its blockage with an IL-1 receptor antagonist (Anakinra) or a neutralizing antibody completely inhibited the induced contractions. We evaluated the implication of the inflammasome on myometrial contractions and differentiation stages of labor onset. We showed that the effects of macrophage-released IL-1ß in myometrial cell transactivation were blocked by inhibition of the inflammasome, suggesting that the inflammasome by producing IL-1ß was essential in macrophage/myocyte crosstalk during labor. These findings provide novel innovative approaches in the management of preterm labor, specifically the use of an inflammasome inhibitor to block the precursor stages of labor before the acquisition of the contractile phenotype.

Trends in overweight and obesity among rural preschool children in southeast China from 1998 to 2005.

OBJECTIVE: To examine the trends in prevalence of overweight and obesity, as well as the impact of stunting on overweight/obesity, among rural children aged <60 months in southeast China between 1998 and 2005. STUDY DESIGN: Data from the population-based Child Health Care Surveillance System (CHCSS) from eight counties in southeast China were used. Overweight and obesity were defined as weight-for-height/length z score >2 and >3 standard deviations (SDs), respectively, and stunting was defined as height/length-for-age z score <-2 SD, in accordance with the 2006 World Health Organization growth standard. METHODS: A total of 550,693 clinic visit records of 280,931 children from the CHCSS, collected between 1998 and 2005, were included in the analysis. The age- and sex-adjusted prevalence rates of overweight, obesity and stunting were estimated for each year, and the trends over time were examined. The impact of stunting on overweight/obesity was determined using multiple logistic regression analysis. RESULTS: The prevalence of overweight increased from 3.7% in 1998 to 3.9% in 2005 (P < 0.001), but no increase in the prevalence of obesity was observed (0.5% in 1998 and 0.6% in 2005; P > 0.05). The prevalence of obesity increased significantly in 2005 compared with 1998 among boys aged ≥24 months, but was similar between 1998 and 2005 for girls aged ≥12 months. The prevalence of stunting decreased from 3.9% in 1998 to 1.6% in 2005 (P < 0.001). There was a positive association between stunting and overweight/obesity in both 1998 and 2005, although the association was attenuated in 2005. CONCLUSION: There was a small increase in the prevalence of overweight among rural preschool children in southeast China from 1998 to 2005. The prevalence of obesity remained stable. However, the prevalence of stunting decreased and its positive influence on overweight/obesity was weaker in 2005.

[Research advances on the mechanism of non-coding RNA regulated diabetic wound healing].

Diabetic wounds are a common complication of diabetic patients, and the incidence has been increasing in recent years. In addition, its poor clinical prognosis seriously affects the quality of life of patients, which has become the focus and difficulty of diabetes treatment. As the RNA regulating gene expression, non-coding RNA can regulate the pathophysiological process of diseases, and play an important role in the healing process of diabetic wounds. In this paper, we reviewed the regulatory role, diagnostic value, and therapeutic potential of three common non-coding RNA in diabetic wounds, in order to provide a new solution for the diagnosis and treatment of diabetic wounds at the genetic and molecular level.

[Analysis of clinical characteristics and risk factors of death in critical burn patients complicated with invasive fungal infection].

Objective: To investigate the clinical characteristics and risk factors of critical burn patients complicated with invasive fungal infection. Methods: A retrospective case series study was conducted. From January 2017 to December 2022, 88 critical burn patients combined with invasive fungal infection who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, including 61 males and 27 females, aged 26-74 years. Data on invasive fungal infection sites and the detection of pathogens in patients were recorded. According to the survival outcome within 28 days after admission, the patients were divided into survival group (63 cases) and death group (25 cases). The following data of patients were compared between the two groups, including the basic data and injuries of patients at admission such as age, sex, body weight, total burn area, combination of inhalation injury, combination of hypertension and diabetes, acute physiology and chronic health status evaluation Ⅱ (APACHE Ⅱ) score, and admission time after burns, the levels of blood biochemical indexes within 24 h after admission such as white blood cell count, platelet count, red blood cell count, monocyte count, neutrophil count, lymphocyte count, alanine transaminase, aspartate transaminase, glucose, creatinine, urea nitrogen, D-dimer, galactomannan (GM), 1,3-ß-D glucan, and creatine kinase, the application of invasive procedures and vasoactive drugs during the treatment such as continuous renal replacement therapy, ventilator-assisted breathing, tracheotomy, deep vein catheterization, skin grafting >2 times, the levels of infection indicators on post admission day (PAD) 1, 3, 7, and 14 including C-reactive protein (CRP), procalcitonin, lactic acid, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the detection of pathogens in the process of treatment. Data were statistically analyzed with independent sample t test, analysis of variance for repeated measurement, chi-square test, Mann-Whitney U test, and Bonferroni correction. Multivariate logistic regression analysis was performed to screen the independent risk factors that affected death of critical burn patients complicated with invasive fungal infection. Results: The main sites of invasive fungal infection were the wounds (67 cases) and blood stream (46 cases), with Candida fungi (58 strains) as the main strain for fungi infection, and there were a total of 30 cases of infection with mixed pathogenic bacteria. Compared with those in survival group, the APACHE Ⅱ score, proportions of combination with inhalation injury and hypertension of patients in death group were significantly increased (t=2.11, with χ2 values of 6.26 and 9.48, respectively, P<0.05), while the other basic data and injury condition had no significant changes (P>0.05). Compared with those in survival group, the levels of D-dimer, GM, and 1,3-ß-D glucan of patients in death group were significantly increased within 24 h after admission (with t values of 2.42, 2.05, and 2.21, respectively, P<0.05), while the other blood biochemical indexes within 24 h after admission, as well as the proportions of applying invasive procedures and application of vasoactive drugs during the treatment process were not significantly changed (P>0.05). The levels of infection indicators of patients on PAD 1 and 3 were similar between the two groups (P>0.05). The procalcitonin level on PAD 7 and the levels of CRP, procalcitonin, lactic acid, IL-6, and TNF-α on PAD 14, as well as the proportion of infection with mixed pathogenic bacteria of patients in death group were significantly higher than those in survival group (with t values of 4.69, 3.89, 6.70, 6.14, 4.65, and 3.26, respectively, χ2=12.67, P<0.05). Multivariate logistic regression analysis showed that combination with inhalation injury, combination with hypertension, and infection with mixed pathogenic bacteria were independent risk factors for death of critical burn patients complicated with invasive fungal infection (with odds ratios of 5.98, 4.67, and 6.19, respectively, 95% confidence intervals of 1.42-15.39, 1.41-25.28, and 1.86-20.58, respectively, P<0.05). Conclusions: The main sites of infection in critical burn patients complicated with invasive fungal infection are the wounds and blood stream, with Candida fungi as the main strain for fungi infection, and a large proportion of infection with mixed pathogenic bacteria. The combined inhalation injury, combined hypertension, and infection with mixed pathogenic bacteria are the independent risk factors for the death of those patients.

Adenovirus mediated knockdown of bone morphogenetic protein 2 inhibits human lung cancer growth and invasion in vitro and in vivo.

Bone morphogenetic protein 2 (BMP-2) is a member of the TGF-beta superfamily of signaling molecules, and has been shown to function as a tumor suppressor involved in development and progression of many malignancies. BMP-2 has previously been reported to be closely correlated with lung cancer. But, the role and molecular mechanisms of BMP-2 in lung cancer have not yet been comprehensively explained. The present study aims to elucidate the role of BMP-2 in growth and invasion of human lung adenocarcinoma (LAC) in vitro and in vivo. Adenovirus vector-mediated BMP-2 small hairpin RNA (shBMP-2) was used to transfect into A549 LAC cells to determine the functional relevance of BMP-2 and tumor growth and invasion in vitro and in vivo, and further investigate the expression levels of BMP-2, vascular endothelial growth factor (VEGF), matrix metallopeptidase-9 (MMP-9), phosphatidylinositol 3-kinase p85alpha (PI3Kp85alpha) and phosphorylated AKT (p-AKT). As a result, LAC cell proliferation and invasion were significantly diminished by knockdown of BMP-2 indicated by MTT and Transwell assays, and cell apoptosis and cycle arrest were markedly induced indicated by flow cytometry. When BMP-2 expression was knocked down, the expression of PI3Kp85alpha, p-AKT, VEGF and MMP-9 was also down-regulated in LAC cells. In addition, the tumor volumes in LAC subcutaneous nude mouse model treated with shBMP-2 were significantly smaller than those in control and ad-GFP groups. Taken together, our findings indicate that knockdown of BMP-2 inhibits growth and invasion of LAC cells possibly via blockade of the PI3K/AKT signaling pathway, and BMP-2 may be a potential therapeutic target for lung cancer.

Factors associated with antibiotic administration delay among preterm infants with late-onset bloodstream infection.

Early antibiotic administration is an important modifiable factor in reducing mortality from late-onset bloodstream infections in preterm infants. In a cohort study including 142 infants with non-coagulase negative staphylococcus bloodstream infection at two tertiary neonatal intensive care units, we identified typical practice-related factors that may be targeted to prevent delays in antibiotic administration. Collection of cerebrospinal fluid or urine sample before administering antibiotics, a longer time taken to site a peripheral intravenous catheter among those without pre-existing access, and a longer time taken to administer fluid boluses were associated with a longer than median time to antibiotic administration.

[Value of cerebral hypoxic-ischemic injury markers in the early diagnosis of sepsis associated encephalopathy in burn patients with sepsis].

Objective: To explore the value of cerebral hypoxic-ischemic injury markers in the early diagnosis of sepsis associated encephalopathy (SAE) in burn patients with sepsis. Methods: A retrospective case series study was conducted. From October 2018 to May 2021, 41 burn patients with sepsis who were admitted to Zhengzhou First People's Hospital met the inclusion criteria, including 23 males and 18 females, aged 18-65 (35±3) years. According to whether SAE occurred during hospitalization, the patients were divided into SAE group (21 cases) and non-SAE group (20 cases). The gender, age, deep partial-thickness burn area, full-thickness burn area, and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) scores of patients were compared between the two groups. The serum levels of central nervous system specific protein S100ß and neuron specific enolase (NSE) at 12, 24, and 48 h after sepsis diagnosis (hereinafter referred to as after diagnosis), the serum levels of interleukin-6 (IL-6), IL-10, tumor necrosis factor α (TNF-α), Tau protein, adrenocorticotropic hormone (ACTH), and cortisol at 12, 24, 48, 72, 120, and 168 h after diagnosis, and the mean blood flow velocity of middle cerebral artery (VmMCA), pulsatility index, and cerebral blood flow index (CBFi) on 1, 3, and 7 d after diagnosis of patients in the two groups were counted. Data were statistically analyzed with chi-square test, analysis of variance for repeated measurement, independent sample t test, and Bonferroni correction. The independent variables to predict the occurrence of SAE was screened by multi-factor logistic regression analysis. The receiver operating characteristic (ROC) curve was drawn for predicting the occurrence of SAE in burn patients with sepsis, and the area under the curve (AUC), the best threshold, and the sensitivity and specificity under the best threshold were calculated. Results: The gender, age, deep partial-thickness burn area, full-thickness burn area, and APACHE Ⅱ score of patients in the two groups were all similar (χ2=0.02, with t values of 0.71, 1.59, 0.91, and 1.07, respectively, P>0.05). At 12, 24, and 48 h after diagnosis, the serum levels of S100ß and NSE of patients in SAE group were all significantly higher than those in non-SAE group (with t values of 37.74, 77.84, 44.16, 22.51, 38.76, and 29.31, respectively, P<0.01). At 12, 24, 48, 72, 120, and 168 h after diagnosis, the serum levels of IL-10, Tau protein, and ACTH of patients in SAE group were all significantly higher than those in non-SAE group (with t values of 10.68, 13.50, 10.59, 8.09, 7.17, 4.71, 5.51, 3.20, 3.61, 3.58, 3.28, 4.21, 5.91, 5.66, 4.98, 4.69, 4.78, and 2.97, respectively, P<0.01). At 12, 24, 48, 72, and 120 h after diagnosis, the serum levels of IL-6 and TNF-α of patients in SAE group were all significantly higher than those in non-SAE group (with t values of 8.56, 7.32, 2.08, 2.53, 3.37, 4.44, 5.36, 5.35, 6.85, and 5.15, respectively, P<0.05 or P<0.01). At 12, 24, and 48 h after diagnosis, the serum level of cortisol of patients in SAE group was significantly higher than that in non-SAE group (with t values of 5.44, 5.46, and 3.55, respectively, P<0.01). On 1 d after diagnosis, the VmMCA and CBFi of patients in SAE group were significantly lower than those in non-SAE group (with t values of 2.94 and 2.67, respectively, P<0.05). On 1, 3, and 7 d after diagnosis, the pulsatile index of patients in SAE group was significantly higher than that in non-SAE group (with t values of 2.56, 3.20, and 3.12, respectively, P<0.05 or P<0.01). Serum IL-6 at 12 h after diagnosis, serum Tau protein at 24 h after diagnosis, serum ACTH at 24 h after diagnosis, and serum cortisol at 24 h after diagnosis were the independent risk factors for SAE complicated in burn patients with sepsis (with odds ratios of 2.42, 1.38, 4.29, and 4.19, 95% confidence interval of 1.76-3.82, 1.06-2.45, 1.37-6.68, and 3.32-8.79, respectively, P<0.01). For 41 burn patients with sepsis, the AUC of ROC of serum IL-6 at 12 h after diagnosis for predicting SAE was 0.92 (95% confidence interval was 0.84-1.00), the best threshold was 157 pg/mL, the sensitivity was 81%, and the specificity was 89%. The AUC of ROC of serum Tau protein at 24 h after diagnosis for predicting SAE was 0.92 (95% confidence interval was 0.82-1.00), the best threshold was 6.4 pg/mL, the sensitivity was 97%, and the specificity was 99%. The AUC of ROC of serum ACTH at 24 h after diagnosis for predicting SAE was 0.96 (95% confidence interval was 0.89-1.00), the best threshold was 14.7 pg/mL, the sensitivity was 90%, and the specificity was 94%. The AUC of ROC of serum cortisol at 24 h after diagnosis for predicting SAE was 0.93 (95% confidence interval was 0.86-1.00), the best threshold was 89 nmol/L, the sensitivity was 94%, and the specificity was 97%. Conclusions: Serum Tau protein, ACTH, and cortisol have high clinical diagnostic value for SAE complicated in burn patients with sepsis.

[Clinical effects of medical ozone autologous blood transfusion combined with Xingnaojing in the treatment of septic encephalopathy in burns].

Objective: To investigate the clinical effects of medical ozone autologous blood transfusion combined with Xingnaojing in the treatment of septic encephalopathy in burns. Methods: The retrospective cohort study was conducted. From August 2015 to May 2019, 90 patients with burn septic encephalopathy and conforming to the inclusion criteria were admitted to Zhengzhou First People's Hospital. Forty-six patients (25 males and 21 females, aged (35±4) years ) treated with Xingnaojing were included in Xingnaojing alone group, and forty-four patients (20 males and 24 females, aged (34±5) years) treated with medical ozone autologous blood transfusion combined with Xingnaojing were included in ozone autologous blood transfusion+Xingnaojing group. Heart rate, body temperature, mean arterial pressure, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score and Glasgow coma score (GCS) of patients in 2 groups were recorded before treatment and on 7 d after treatment. The blood-brain barrier injury markers including occludin, nitric oxide synthase (NOS), neuron-specific enolase (NSE), central nervous system specific protein S100ß, glial fibrillar acidic protein (GFAP), and excitatory amino acid (EAA) in serum of patients in 2 groups were detected before treatment and on 1, 3, and 7 d after treatment. Computer tomography perfusion imaging for brain was performed in patients of 2 groups to calculate the region of interest cerebral blood flow (rCBF), region of interest blood volume (rCBV), and region of interest mean transit time (rMTT) before treatment and on 1, 3, and 7 d after treatment. Data were statistically analyzed with chi-square test, analysis of variance for repeated measurement, independent sample t test, and Bonferroni correction. Results: On 7 d after treatment, heart rate, body temperature, and mean arterial pressure of patients in 2 groups were decreased compared with those before treatment, heart rate of patients in ozone autologous blood transfusion+Xingnaojing group was obviously higher than that in Xingnaojing alone group (t=2.886, P<0.01), body temperature of patients in ozone autologous blood transfusion+Xingnaojing group was obviously lower than that in Xingnaojing alone group (t=5.020, P<0.01), and mean arterial pressure of patients in 2 groups were close (t=0.472, P>0.05). On 7 d after treatment, APACHEⅡ score of patients in ozone autologous blood transfusion+Xingnaojing group was obviously lower than that in Xingnaojing alone group (t=3.797, P<0.01), and GCS of patients in ozone autologous blood transfusion+Xingnaojing group was obviously higher than that in Xingnaojing alone group (t=4.934, P<0.01). On 3 and 7 d after treatment, the levels of occludin, NOS, NSE, S100ß, GFAP, and EAA in serum of patients in ozone autologous blood transfusion+Xingnaojing group were significantly lower than those in Xingnaojing alone group (t=2.100, 2.090, 2.691, 2.013, 2.474, 2.635, 2.225, 4.011, 3.150, 2.691, 3.145, 2.781, P<0.05 or P<0.01). On 1, 3, and 7 d after treatment, rCBF and rCBV of patients in ozone autologous blood transfusion+Xingnaojing group were significantly increased compared with those in Xingnaojing alone group (t=3.127, 3.244, 3.883, 7.274, 3.661, 2.777, P<0.01). On 7 d after treatment, rMTT of patients in ozone autologous blood transfusion+Xingnaojing group was (3.02±0.57) s, which was significantly lower than (3.11±1.20) s in Xingnaojing alone group (t=2.409, P<0.05). Conclusions: Transfusion of medical ozone autologous blood combined with Xingnaojing therapy can effectively relieve brain injury and improve cerebral blood perfusion in patients with burn septic encephalopathy, which is with safety and credibility.

[Value of renal injury marker protein in early diagnosis of acute kidney injury in burn patients with delayed resuscitation].

Objective: To explore the value of renal injury marker protein in early diagnosis of acute kidney injury (AKI) in burn patients with delayed resuscitation. Methods: The retrospective case-control research was conducted. Forty-three burn patients with delayed resuscitation (27 males and 16 females, with age of 18-75 (35±3) years)who were admitted to Zhengzhou First People's Hospital from May 2018 to May 2020 met the inclusion criteria. The patients were divided into AKI group with 23 patients and non-AKI group with 20 patients according to whether AKI occurred within 7 days after burns. The gender, age, deep partial-thickness burn area, full-thickness burn area, and acute physiology and chronic health evaluation Ⅱ of patients were compared between the two groups.The fluid supplement volume and serum creatinine at 12, 24, and 48 h after burn, serum albumin/fibrinogen ratio (AFR), urinary heat shock protein 70 (HSP70), tissue inhibitor of metalloproteinase-2 (TIMP-2)×insulin-like growth factor binding protein 7 (IGFBP-7), and neutrophil gelatinase associated lipocalin (NGAL)at 12, 24, 48, 72, 120, and 168 h after burn were detected.Data were statistically analyzed with Mann-Whitney U test, analysis of variance for repeated measurement, independent-samples t test, chi-square test and Bonferroni correction. The independent variable to predict the occurrence of AKI was screened by multi-factor logistic regression analysis. The receiver's operating characteristic curve was drawn for predicting the occurrence of AKI in burn delayed resuscitation patients, and the area under the curve (AUC), the best threshold, and the sensitivity and specificity under the best threshold were calculated. Results: The gender, age, deep partial-thickness burn area, full-thickness burn area, acute physiology and chronic health evaluation Ⅱ of patients in two groups were similar (χ(2)=1.98, t=1.98, 1.99, 1.99, 1.99, P>0.05). The fluid supplement volume of patients in AKI group at 24 and 48 h after burn was significantly less than that in non-AKI group (t=15.37, 6.51, P<0.01). The serum creatinine of patients in AKI group at 12, 24, and 48 h after burn was significantly higher than that in non-AKI group (Z=2.16, 5.62, 6.72, P<0.01). The serum AFR of patients in AKI group at 12, 24, 48, 72, 120, and 168 h after burn was significantly lower than that in non-AKI group (t=16.14, 35.35, 19.60, 20.47, 30.20, 20.17, P<0.01). The levels of urinary HSP70 of patients in AKI group at 12, 24, 48, 72, 120, and 168 h after burn were (6.89±0.87), (6.42±0.73), (5.81±0.72), (5.17±0.56), (4.63±0.51), (3.89±0.51) µg/L, which were significantly higher than (3.89±0.75), (3.57±0.63), (2.66±0.41), (1.83±0.35), (1.48±0.19), (1.28±0.19) µg/L in non-AKI group (t=12.00, 13.61, 17.39, 22.98, 26.34, 21.59, P<0.01). Urinary TIMP-2×IGFBP-7 and NGAL of patients in AKI group at 12, 24, 48, 72, 120, 168 h after burn were significantly higher than those in non-AKI group (t=26.94, 101.11, 35.50, 66.89, 17.34, 14.30, 14.00, 13.78, 12.32, 14.80, 21.36, 22.62, P<0.01). Urinary HSP70 and serum AFR at 12 h after burn, urinary TIMP-2×IGFBP-7 and NGAL at 24 h after burn were included into multi-factor logistic regression analysis (odds ratio=2.42, 3.47, 7.52, 5.61, 95% confidence interval=1.99-2.95, 1.86-3.92, 2.87-9.68, 2.14-14.69, P<0.01). For 43 patients with burn delayed resuscitation, the AUC of receiver's operating characteristic curve of serum AFR at 12 h after burn for predicting AKI was 0.739 (95% confidence interval=0.576-0.903), the optimal threshold was 9.90, the sensitivity was 82%, and the specificity was 90%. The AUC of urinary HSP70 at 12 h after burn was 0.990 (95% confidence interval=0.920-1.000), the optimal threshold was 1.40 µg/L, the sensitivity was 98%, and the specificity was 96%. The AUC of urinary TIMP-2×IGFBP-7 at 24 h after burn was 0.715 (95% confidence interval=0.512-0.890), the optimal threshold was 114.20 µg(2)/L(2), the sensitivity was 91%, and the specificity was 95%. The AUC of urinary NGAL at 24 h after burn was 0.972 (95% confidence interval=0.860-1.000), the optimal threshold was 78 µg/L, the sensitivity was 95%, and the specificity was 96%. Conclusions: Urinary HSP70 and NGAL have higher value in early diagnosis of AKI in burn patients with delayed resuscitation.