Early predictors of refractory septic shock in neonates / 中国新生儿科杂志

Objective:To study the early predictors of refractory septic shock (RSS) in neonates.Methods:From July 2020 to December 2021, clinical data of neonates with septic shock admitted to the Neonatal Department of our hospital were retrospectively reviewed. According to the maximum septic shock score (SSS) during clinical course, the neonates were assigned into RSS group and non-RSS group. Perinatal data, laboratory results and hemodynamic parameters at diagnosis were compared between the two groups. Multiple logistic regression analysis was used to identify independent risk factors of RSS and septic shock-related death. Receiver operating characteristic (ROC) curve was constructed to evaluate the early predictors of poor prognosis.Results:A total of 130 neonates were enrolled, including 54 in RSS group and 76 in non-RSS group. Compared with the non-RSS group, the RSS group had significantly lower pH, base excess (BE), stroke volume index (SVI), cardiac output (CO) and cardiac index (CI).Meanwhile, the RSS group had significantly higher mean arterial pressure (MAP) to CI ratio (MAP/CI) and SSS [including bedside SSS (bSSS), computed SSS (cSSS) and modified version of cSSS (mcSSS)] (all P<0.05). Multiple logistic regression analysis showed that increased MAP/CI was an independent predictor of RSS. The cut-off value of MAP/CI was 11.6 [sensitivity 62%, specificity 87%, positive predictive value (PPV) 79% and negative predictive value (NPV) 77%], with an area under the curve (AUC) of 0.734. Increased mcSSS was an independent predictor of septic shock-related death. The cut-off value of mcSSS was 5.8 (sensitivity 83%, specificity 72%, PPV 21% and NPV 97%), with an AUC of 0.845. Conclusions:Increased MAP/CI (≥11.6) and mcSSS (≥5.8) may be early predictors of RSS and septic shock-related death in neonates.

Impacts of quality improvement in hemodynamic monitoring on fluid overload and prognosis in neonates with septic shock / 中国新生儿科杂志

Objective:To explore the effect of quality improvement of hemodynamic monitoring on fluid overload (FO) and outcome in newborns with septic shock.Methods:Non-invasive cardiac output monitoring and functional cardiac ultrasound quality improvement program was started during January 2020 in our hospital. Neonates with septic shock admitted before and after the program were retrospectively analyzed. From January 2018 to December 2019 was pre-improvement period when fluid resuscitation was routinely performed and vasoactive drugs was selected empirically. From January 2020 to December 2021 was post-improvement period when fluid resuscitation and/or use and adjustment of vasoactive drugs were guided by hemodynamic parameters. The 24 h, 48 h, 72 h FO, duration of invasive respiratory support, vasoactive-inotropic score, septic shock score, incidences of complications and all-cause mortality were compared between the two groups.Results:A total of 284 eligible cases were enrolled, including 136 cases in pre-improvement group and 148 cases in post-improvement group. Post-improvement group had significantly lower gestational age (GA), birth weight (BW) and body weight at disease onset than pre-improvement group ( P<0.05). Incidences of 48 h and 72 h FO, fluid resuscitation volume within 72 h, pulmonary hemorrhage and periventricular leukomalacia (PVL) were significantly lower in the post-improvement group ( P<0.05). No significant differences existed in 24 h FO, other complications and all-cause mortality between the two groups ( P>0.05). No significant differences existed in GA and BW for neonates with pulmonary hemorrhage and PVL between the two groups ( P>0.05). Conclusions:Quality improvement of hemodynamic monitoring can effectively improve FO and reduce the incidences of pulmonary hemorrhage and PVL.

The predicting indices for the outcome of refractory septic shock in preterm infants / 中国新生儿科杂志

Objective:To study the predictive value of vasoactive-inotropic score (VIS), fluid overload (FO) and lactate level for the outcome of preterm infants with refractory septic shock.Methods:Preterm infants diagnosed with refractory septic shock and required hydrocortisone treatment in our Department from January 2016 to December 2021 were analyzed retrospectively. Preterm infants were assigned into three gestational age groups (<28 weeks, 28-31 weeks, 32-36 weeks). According to the outcome of the disease, the children were further divided into good prognosis group and poor prognosis group. The relationship between the maximum VIS, FO and the mean lactic acid before hydrocortisone and the outcome of refractory septic shock was analyzed by receiver operating characteristic (ROC) curve, the cut-off point of ROC curve was calculated to obtain the predictive efficacy of the three indicators for the outcome of refractory septic shock in preterm infants.Results:A total of 50 preterm infants with refractory septic shock and received hydrocortisone treatment were enrolled, including 20 in the good prognosis group and 30 in the poor prognosis group. There were no significant differences in the maximum VIS, FO and mean lactic acid before hydrocortisone treatment between the two groups of gestational age of <32 weeks ( P> 0.05). The maximum VIS, FO and mean lactic acid of gestational age of 32-36 weeks in the poor prognosis group were higher than those in the good prognosis group, VIS: 56.1±15.7 vs. 37.1±12.9, FO (%): 108.2 (78.6,137.7) vs. 55.5 (10.3, 100.7), and mean lactic acid (mmol/L): 8.3 (4.6, 12.0) vs. 4.8 (-0.8, 10.5), all P<0.05. The area under the ROC curve of the mean lactic acid was the largest, the cut-off value was 4.1 mmol/L, and the Youden index was 1.732. Conclusions:VIS, FO and lactate level are difficult to be used for determining the outcome of refractory septic shock in preterm infants of <32 weeks. While the mean lactic acid has the best predictive performance in preterm infants of 32-36 weeks.

A comparative study between two novel silicone/graphene-based nanostructured surfaces for maritime antifouling.

Two novel superhydrophobic nanocomposite series of polydimethylsiloxane (PDMS) enriched with reduced graphene oxide (RGO) and graphene oxide/boehmite nanorods (GO-γ-AlOOH) nanofillers were synthesized as maritime fouling-release (FR) surfaces. Controlling the nanofillers' structures and distribution in the silicone matrix influenced the self-cleaning and antifouling properties. γ-AlOOH nanorods had a single crystallinity with an average diameter of 10-20 nm and < 200 nm length. A hydrothermal method was used to prepare RGO, while the chemical deposition method was used to synthesis GO-γ-AlOOH nanocomposites for use as fouling-release coating materials. For studying the synergetic effects of graphene-based materials on the surface, mechanical, and FR features, these nanofillers were dispersed in the silicone matrix using the solution casting method. The hydrophobicity and antifouling properties of the surface were studied using water contact angle (WCA), scanning electron, and atomic force microscopes (SEM and AFM). Coatings' roughness, superhydrophobicity, and surface mechanical properties all improved for the homogeneity of the dispersion of the nanocomposite. Laboratory assessments were carried out for 30 days using selected microorganisms to determine the antifouling effects of the coating systems. PDMS/GO-γ-AlOOH nanorod composite had better antibacterial activity than PDMS/RGO nanocomposite against different bacterial strains. This is caused by the high surface area and stabilizing effects of the GO-γ-AlOOH hybrid nanofillers. The PDMS/GO-γ-AlOOH nanorod composite (3 wt%) had the lowest biodegradability percentage (1.6%) and the microbial endurability percentages for gram-positive, gram-negative, and fungi were 86.42%, 97.94%, and 85.97%, respectively. A field trial in natural seawater was conducted to confirm the coatings' FR performance based on the screening process and image analysis for 45 days in a tropical area. The most profound superhydrophobic antifouling nanostructured coating was the homogeneity of the GO-γ-AlOOH (3 wt%) dispersion, which had a WCA of 151° and a rough surface.

Efficacy of norepinephrine in the treatment of neonatal septic shock: an observation study / 中国新生儿科杂志

Objective:To study the efficacy of norepinephrine in the treatment of neonates with septic shock.Methods:A prospective observation study of neonates with septic shock, who received norepinephrine in the neonatal intensive care unit of Guangdong Women and Children's Hospital from January 2019 to November 2020. All infants had functional echocardiography for hemodynamic monitoring before norepinephrine treatment and 1 hour thereafter blood pressure, heart rate, arterial blood gas analyses were recorded at the same time. The intravenous fluid volume and urine volume from the diagnosis of shock to the commencement of norepinephrine therapy (T0) and 24 hours thereafter (T1) were recorded, and the hemodynamic parameters, vasoactive drugs and clinical outcomes were analyzed.Results:A total of 66 newborns were enrolled, including 27 cases of mild shock, 33 cases of moderate shock and 6 cases of severe shock. 48 were male infants, 38 cases were premature infants. The gestational age was (35.2±4.1) weeks and the birth weight was (2 476±909) g. The median time of shock diagnosis was 2 days after birth, and the median shock score was 4 points. The median time from the diagnosis of shock to the start of norepinephrine treatment was 7.5 hours. Compared with that before norepinephrine treatment, stroke volume, stroke volume index, cardiac output, cardiac index, left ventricular ejection fraction, shortening fraction, systolic blood pressure, diastolic blood pressure, mean arterial pressure, blood pH and BE at 1 hour after treatment were increased, heart rate and blood lactic acid were decreased, the differences were statistically significant ( P<0.05). Urine volume was increased 24 hours after treatment ( P<0.05), and fluid overload decreased ( P<0.05). The maximum dopamine dose, the down-regulation time and duration of vasoactive drugs were positively correlated with the time to start norepinephrine therapy ( r=0.325、 r=0.383、 r=0.319, P<0.05). Among the 66 infants, 58 infants with shock had been corrected and 14 infants died within 28 days. Conclusions:Norepinephrine is effective and feasible in the treatment of neonatal septic shock and can significantly improve hemodynamic parameters.

Comparison of the predictive value of vasoactive-inotropic score, shock score and lactate level for the outcome of septic shock in term infants / 中国新生儿科杂志

Objective:To study the predictive value of vasoactive-inotropic score (VIS), shock score and lactate level for the outcome of term infants with septic shock.Methods:From January 2019 to October 2020, clinical data of term infants with septic shock admitted to our department were reviewed. According to their clinical outcome, the infants were assigned into the survival group and the deceased group and the differences of the two groups were compared. Logistic regression was used to determine the risk factors of mortality in term infants with septic shock. Receiver operating characteristic curve was used to compare the predictive efficacy of VIS, shock score and lactate level for the outcome of septic shock.Results:Significant differences existed between the survival group and the deceased group in the following: maximum VIS, maximum shock score, maximum lactate level, the mean value of VIS during the second 24 h, the mean value of lactate during the first and second 24 h ( P < 0.05). Meanwhile, maximum VIS ( OR = 1.038, 95% CI 1.014~1.063), maximum shock score ( OR = 2.372, 95% CI 1.126~4.999) and the mean value of lactate during the first 24h ( OR = 2.983, 95% CI 1.132~7.862) were correlated with mortality in the infants ( P < 0.05). The area under the curve of maximum VIS was the most prominent, with 58.5 as cut-off. Conclusions:Among the three indicators, VIS has the best predictive value for mortality outcome in term infants with septic shock, followed by shock score and lactate level.

Threshold and risk factors of fluid overload in neonatal septic shock / 中国新生儿科杂志

Objective:To study the threshold of fluid overload (FO) and its risk factors in neonatal septic shock.Methods:From January 2019 to November 2020, clinical data of infants with septic shock hospitalized in the neonatal department of our hospital were reviewed. With poor prognosis as the outcome, ROC curve was drawn based on 24 h (from the beginning of septic shock), 48 h and 72 h FO value. FO cutoff value was determined as area under curve (AUC) reached maximum. Risk factors of FO were analyzed between FO<cutoff value group and FO≥cutoff value group.Results:A total of 152 eligible cases were included and the cutoff value of 48 h FO was determined as 43.3%. 116 cases were in FO<43.3% group and 36 cases were in FO≥43.3% group. FO≥43.3% group had smaller gestational age (GA), birth weight (BW), 1 min Apgar score, 5 min Apgar score and lower PLT, PCT, pH, and ALB level compared with FO<43.3% group. Meanwhile, FO≥43.3% group had significantly higher shock score, bedside septic shock scores (bSSS), lactic acid level, higher incidences of WBC <5×10 9/L and albumin infusion compared with FO<43.3% group. As for prognostic outcome, FO≥43.3% group had significantly higher incidences of neonatal persistent pulmonary hypertension, severe cerebral hemorrhage, periventricular leukomalacia, acute kidney injury, severe brain injury, multiple organ dysfunction syndrome, disseminated intravascular coagulation and 28 d all-cause mortality rate than FO<43.3% group ( P<0.05). Logistic regression analysis showed risk factors associated with FO≥43.3% were BW ( OR=0.998, 95% CI 0.998~0.999, P<0.05), pH ( OR=0.018, 95% CI 0.000~0.990, P<0.05) and bSSS ( OR=1.619, 95% CI 1.134~2.311, P<0.05). The cutoff values were BW 1 830 g, pH 7.15 and bSSS 0.5. Conclusions:The 48 h FO with cutoff value of 43.3% has the highest predictive value for prognostic outcome in neonates with septic shock. FO≥43.3% is associated with more adverse outcomes. Infants with septic shock who have lower BW, lower pH and higher bSSS are more likely to develop FO≥43.3%.

VIPR1 promoter methylation promotes transcription factor AP-2α binding to inhibit VIPR1 expression and promote hepatocellular carcinoma cell growth in vitro / 南方医科大学学报

OBJECTIVE@#To explore the transcriptional regulation mechanism and biological function of low expression of vasoactive intestinal peptide receptor 1 (VIPR1) in hepatocellular carcinoma (HCC).@*METHODS@#We constructed plasmids carrying wild-type VIPR1 promoter or two mutant VIPR1 promoter sequences for transfection of the HCC cell lines Hep3B and Huh7, and examined the effect of AP-2α expression on VIPR1 promoter activity using dual-luciferase reporter assay. Pyrosequencing was performed to detect the changes in VIPR1 promoter methylation level in HCC cells treated with a DNA methyltransferase inhibitor (DAC). Chromatin immunoprecipitation was used to evaluate the binding ability of AP-2α to VIPR1 promoter. Western blotting was used to assess the effect of AP-2α knockdown on VIPR1 expression and examine the differential expression of VIPR1 in the two cell lines. The effects of VIPR1 overexpression and knockdown on the proliferation, cell cycle and apoptosis of HCC cells were analyzed using CCK8 assay and flow cytometry. We also observed the growth of HCC xenograft with lentivirus-mediated over-expression of VIPR1 in nude mice.@*RESULTS@#Compared with the wild-type VIPR1 promoter group, co-transfection with the vector carrying two promoter mutations and the AP-2α-over-expressing plasmid obviously restored the luciferase activity in HCC cells (P < 0.05). DAC treatment of the cells significantly decreased the methylation level of VIPR1 promoter and inhibited the binding of AP-2α to VIPR1 promoter (P < 0.01). The HCC cells with AP-2α knockdown showed increased VIPR1 expression, which was lower in Huh7 cells than in Hep3B cells. VIPR1 overexpression in HCC cells caused significant cell cycle arrest in G2/M phase (P < 0.01), promoted cell apoptosis (P < 0.001), and inhibited cell proliferation (P < 0.001), while VIPR1 knockdown produced the opposite effects. In the tumor-bearing nude mice, VIPR1 overexpression in the HCC cells significantly suppressed the increase of tumor volume (P < 0.001) and weight (P < 0.05).@*CONCLUSION@#VIPR1 promoter methylation in HCC promotes the binding of AP-2α and inhibits VIPR1 expression, while VIPR1 overexpression causes cell cycle arrest, promotes cell apoptosis, and inhibits cell proliferation and tumor growth.

Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China.@*METHODS@#A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups.@*RESULTS@#Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05).@*CONCLUSIONS@#There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.

The clinical value of different shock scoring systems on the prognosis of neonatal refractory septic shock / 中国新生儿科杂志

Objective:To study the clinical value of neonatal shock score (NSS) and septic shock score (SSS) in the evaluation of mortality and serious complications of neonatal refractory septic shock.Method:From January 2019 to November 2020, clinical data of neonates with septic shock admitted to Neonatal Department of our hospital were retrospectively reviewed. According to the final outcomes, neonates were assigned into good prognosis group (neonates survived without serious complications) and poor prognosis group (neonates were dead within 28 days after birth and/or had serious complications). The NSS and SSS were calculated according to the worst value of each index during the septic shock course. SSS included computed septic shock score (cSSS) and bedside septic shock score (bSSS). The receiver operating characteristic (ROC) curve was used to analyze the efficacy of each scoring system evaluating the risk of poor prognosis due to septic shock. The correlation of each scoring system with the duration of vasoactive drugs was analyzed using Spearman rank correlation analysis.Result:A total of 72 neonates were enrolled, including 45 in good prognosis group and 27 in poor prognosis group. The vasoactive drug score, serum lactate level, NSS and cSSS in poor prognosis group were significantly higher than good prognosis group ( P<0.05).And bSSS score showed no significant differences between the two groups ( P>0.05). The area under the ROC curve (AUC) of NSS and cSSS predicting the adverse prognosis of neonates with septic shock were 0.644 (95% CI 0.510~0.777, P<0.05) and 0.765 (95% CI 0.654~0.877, P<0.05). The best cut-off values for NSS and cSSS predicting poor prognosis were 4.0 and 80.5, respectively. The positive predictive value (PPV) (81.3% vs. 47.5%) and negative predictive value (NPV) (75.0% vs. 70.6%) of cSSS were higher than NSS. Spearman rank correlation analysis showed that cSSS was positively correlated with the duration of vasoactive drugs( r=0.487, P<0.01). Conclusion:Both shock scoring systems have an evaluation value for the prognosis of neonatal septic shock. The evaluation value of cSSS is better than NSS, and can be used as a main tool for the evaluation of neonatal refractory septic shock.

Midterm outcome comparison between patients with bicuspid or tricuspid aortic stenosis undergoing transcatheter aortic valve replacement / 中华心血管病杂志

Objective: To compare the prognosis of transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) stenosis. Methods: This was a retrospective study. Patients with symptomatic severe aortic stenosis, who underwent TAVR with follow-up time more than one year in Guangdong Provincial People's Hospital from April 2016 to August 2018, were included. According to aortic CT angiography, the patients were divided into BAV group and TAV group. The primary endpoint was the composite event of all-cause death and stroke, and the secondary endpoints were TAVR-related complications. Incidence of clinical endpoints and parameters derived from echocardiography were compared between the groups, and Kaplan-Meier survival analysis was used to compare the composite event between the two groups. Results: A total of 49 patients were included. The age was (73.6±6.3) years, and 25(51.0%) were male. There were 32 patients in BAV group and 17 in TAV group, the follow-up time was 466 (390, 664) days. The incidence of composite endpoint of death and stroke at one year were comparable in BAV and TAV groups (6.3% (2/32) vs. 5.9% (1/17), P=1.00). Kaplan-Meier curves also showed a similar risk of the composite endpoint(HR=1.03，95%CI 0.09-11.24，Log-rank P=0.98) between two groups. The incidence of all-cause death, stroke, myocardial infarction, severe bleeding, major vascular complications, new-onset atrial fibrillation or atrial flutter, and permanent pacemaker implantation were all similar between the two groups(all P>0.05), and there was no acute kidney injury (stage 2 or 3) in both groups. Echocardiographic parameters at one year were similar between the two groups (all P>0.05). Conclusions: The midterm prognosis of TAVR in patients with BAV and TAV stenosis is similar. Clinical trials of large sample size with long-term follow-up are warranted to verify our findings.

Predictive value of plasmacytoid dendritic cells and Toll-like receptor-9 regarding the treatment efficacy of interferon-α in HBeAg-positive chronic hepatitis B patients.

Hepatitis B virus (HBV) infection represents a public health threat and a challenge for the medical community. Untimely treatment may lead to liver cirrhosis and even liver cancer. At present, the major treatment for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients includes administration of interferon-α (IFN-α), which has anti-viral and immunomodulatory effects. Plasmacytoid dendritic cells (pDCs) and Toll-like receptor-9 (TLR-9) have important roles in anti-viral therapy. However, their predictive value regarding the efficacy of IFN-α treatment of HBeAg-positive chronic hepatitis B (CHB) patients has remained elusive. A total of 178 patients with CHB and HBeAg-positive status, who had not received any previous anti-HBV treatment, were enrolled in the present study. All patients were treated with IFN-α. HBV DNA load, hepatitis B surface antigen and serum alanine aminotransferase were measured prior to and following 48 weeks of treatment. According to HBV levels, the patients were divided into a response group and non-responders group. To determine the amount of pDCs, blood dendritic cell antigen 2 (BDCA-2)- and immunoglobulin-like transcript 7 (ILT7)-expressing cells in liver biopsies were detected using immunohistochemistry. TLR-9 expression in peripheral blood mononuclear cells was determined by reverse transcription-quantitative PCR. There was no significant difference in the proportion of pDCs (BDCA-2; ILT7) and TLR-9 mRNA expression between the response group and the non-responders group prior to IFN-α treatment. After IFN-α treatment, BDCA-2, ILT7 and TLR-9 mRNA expression was obviously increased in the response group compared with that in the non-responders group (P<0.05). Increased expression of BDCA-2, ILT7 and TLR-9 mRNA was negatively correlated with HBV DNA (P<0.05). Increased levels of pDCs and TLR-9 were negatively correlated with HBV DNA, and were thus capable of predicting the IFN-α treatment response in patients with CHB and HBeAg-positive status.

Sodium butyrate increases P-gp expression in lung cancer by upregulation of STAT3 and mRNA stabilization of ABCB1.

As a new type of anticancer drug, the effect of histone deacetylase inhibitors (HDACIs) in cancer clinical therapy is disappointing owing to drug resistance. P-glycoprotein (P-gp) is clearly recognized as a multidrug resistance protein. However, the relationship between P-gp and sodium butyrate (SB), a kind of HDACIs, has not been investigated. In this study, we found that SB increased mRNA and protein expression of P-gp in lung cancer cells and the underlying mechanisms were elucidated. We found that SB treatment enhanced the mRNA and protein expression of STAT3 rather than that of ß-catenin, Foxo3a, PXR, or CAR, which were reported to directly regulate the transcription of ABCB1, a P-gp-encoding gene. Interestingly, inhibition of STAT3 expression obviously attenuated SB-increased P-gp expression in lung cancer cells, indicating that STAT3 played an important role in SB-mediated P-gp upregulation. Furthermore, we found that SB increased the mRNA stability of ABCB1. In summary, this study showed that SB increased P-gp expression by facilitating transcriptional activation and improving ABCB1 mRNA stability. This study indicated that we should pay more attention to HDACIs during cancer clinical therapy.

Antifungal effects of three medicinal crops on Phytophthora nicotianae / 中国中药杂志

Tobacco black shank is one of the most harmful soil-borne diseases infected by Phytophthora parasitica. In order to probe the control method to this disease, in this study, the mycelial growth rate method was employed to investigate the antifungal effects of extracts from stem-leaf and root, root exudates, and their combination of Scrophularia ningpoensis, Chuanmingshen violaceum and Pinellia ternata The results showed that: ①Stem-leaf and root extracts of S. ningpoensis, C. violaceum and P. ternata exhibited different antifungal activities, and the inhibition increased with the increase of extract concentration. The antifungal effect of S. ningpoensis extracts at 0.5 g•mL⁻¹ was the strongest than other medicinal plants, the inhibition rate of steam-leaf and root extracts reached 74.88%, 69.27%, respectively. The inhibitory effect of C. violaceum and P. ternata was relatively lower, however, there is a significant gain effect after combination of steam-leaf and root extracts of C. violaceum. ②The root exudates of S. ningpoensis, C. violaceum and P. ternata showed fungistasis to Phytophthora nicotianae, and fungistasis was enhanced with the increase of root exudate concentration. The antifungal effect in the order of C. violaceum > S. ningpoensis > P. ternata. ③The antifungal activity of combination of extract and root exudate from S. ningpoensis was similar with the effect of C. violaceum, they were both stronger than P. ternata, and the antifungal activity for three combination were located between the antifungal activity of their extracts and root exudates. S. ningpoensis and C. violaceum can be potentially applied to prevent and control the tobacco black shank.

Early predictive value of platelet related indicators in patent ductus arteriosus in extremely low birth weight infants / 临床儿科杂志

Objective To analyze the predictive value of platelet related indicators for patent ductus arteriosus (PDA) in extremely low birth weight infants (ELBW). Methods The data of 79 ELBW infants born from June 2013 to June 2016 were retrospective analyzed. There were 48 cases without PDA (nPDA group) and 31 cases with PDA (PDA group). Among 31 cases with PDA, there were 17 cases of non-haemodynamically significant PDA (nhsPDA group) and 14 cases of haemodynamically significant PDA (hsPDA group). The clinical feature and platelet related indicators among nPDA group, PDA group, nhsPDA group and hsPDA group were compared. Multivariate logistic regression was used to analyze the effects of various factors on the occurrence of PDA. ROC curve analysis was performed to evaluate the early predictive value of platelet related indicators for PDA. Results Compared with the nPDA group, the PDA group had a smaller gestational age, a higher proportion of male infants, and a smaller platelet distribution width (PDW), and there were statistically significant differences in all of those (P all0.05). Conclusion PDW has certain early predictive value for PDA in ELBW. ELBW infants with PDW<13.4 GSD need to be watched closely for the occurrence of PDA.

[Study on transcriptome of Oncomelania hupensis before and after Schistosoma japonicum invasion I De novo assembly of data by RNA-Seq].

OBJECTIVE: To produce a comprehensive transcript dataset of Oncomelania hupensis before and after Schistosoma japonicum infection, so as to provide experimental data for perfecting genetic structural information and excavating related molecular markers of O. hupensis infected by S. japonicum. METHODS: O. hupensis snails were divided into the following 3 groups: one week after S. japonicum miracidium infection, 4 weeks after S. japonicum miracidium infection, and normal condition. Million high-quality reads were obtained from the normalized cDNA of the pooled samples, which were assembled into transcripts. RESULTS: A total of 63 686 unigenes were identified and were classified into 4 main categories, including general functional prediction (15.36%), signal transduction mechanism (11.75%), posttranslational modification (8.89%), and functional unknown (12.20%). CONCLUSIONS: The transcriptome information of O. hupensis snail after the invasion of S. japonicum shows that several genes are significantly up-regulated or down regulated expression, and that the availability of transcriptome information might provide a strong foundation for further understanding the schistosome-snail interaction at the molecular level.

Histone deacetylase inhibitors regulate P-gp expression in colorectal cancer via transcriptional activation and mRNA stabilization.

Histone deacetylase inhibitors (HDACIs) are emerging as a novel class of anti-tumor drugs. But the effect of HDACIs in tumors treatment has been disappointing, which mainly due to the acquisition of resistance to HDACIs. However, the underlying mechanisms have not been clearly understood. In this study, it was found that HDACIs SAHA and TSA increased P-gp expression in CRC cells, which has been well known to contribute to drug resistant. The mechanisms underlying these effects were investigated. We showed that HDACIs enhanced transcriptional activity of P-gp protein encoding gene ABCB1. HDACIs treatment also increased the protein and mRNA expression of STAT3, but not PXR, CAR, Foxo3a or ß-catenin, which are known to be involved in ABCB transcription regulation. Interestingly, knockdown of STAT3 significantly attenuated HDACIs-induced P-gp up-regulation in colorectal cancer cells, suggesting that STAT3 plays a crucial role in HDACIs-up-regulated P-gp. Furthermore, this study revealed for the first time that HDACIs enhanced the stability of ABCB1 at post-transcriptional level. Taken together, these results proved that HDACIs induced P-gp expression by two distinct ways, transcriptional activation and mRNA stabilization. Our results suggested that more attention should be paid to the cancer treatment using HDACIs since they will induce multidrug resistance in cancer cells.

Melatonin Upregulates the Activity of AMPK and Attenuates Lipid Accumulation in Alcohol-induced Rats.

AIMS: Melatonin is supposed to be an effective hepatoprotective agent. The effects and mechanisms of melatonin on alcoholic fatty liver (AFL) have not been well explored. The aim of this study was to investigate the preventive and therapeutic effects of melatonin on alcohol-induced fatty liver rats. METHODS: The AFL rats were induced by intragastric infusion of alcohol plus a high-fat diet for 6 weeks, and melatonin (10, 20, 40 mg/kg) was administered by gastric perfusion. We also established fatty acid overload cell model in HepG2 cells to investigate the effect of melatonin on AMP-activated protein kinase (AMPK) activity. RESULTS: The results showed that melatonin (20 and 40 mg/kg) administration significantly reduced alcohol-induced hepatic steatosis with lowering activities of serum alanine aminotransferase, aspartate aminotransferase and levels of serum and hepatic triglyceride. The activity of superoxide dismutase was increased and the content of malondialdehyde was decreased in liver homogenates of rats treated with melatonin. Melatonin increased the phosphorylation of AMPK in the liver tissues of alcohol-induced rats as well. Additionally, in vitro studies showed that melatonin increased the expression of melatonin1A receptor (MT1R), whereas luzindole, a receptor antagonist of melatonin, had no effect on its expression. In addition, melatonin reduced the levels of adenosine 3',5'-cyclic monophosphate (cAMP) and increased the phosphorylation of AMPK, and melatonin treatment could markedly reverse these effects. CONCLUSION: In conclusion, melatonin could protect against liver injury caused by alcohol gastric perfusion. The effect may be related to alleviating lipid peroxidation and upregulating the activity of AMPK mediated by MT1R signaling pathway.

Influence of tobacco-Chuanminshen violaceum rotation on microbe community in soil / 中国中药杂志

Soil microbes are the important indicator of soil quality. For exploring Chuanminshen violaceum planting to microbial effects in tobacco soil, this paper adopted Illumina MiSeq high-throughput sequencing to research the change of bacteria and fungi at the phylum and genus in the soil. The results showed that the Ch. violaceum planting increased the biodiversity of bacteria and fungi. The influence on fungi was greater than that on bacteria. It greatly increased the sequence of fungi, it obtained 32 978 16S rDNA and 32 229 18S rDNA sequence number. There was no change of the top three phylums in bacteria, but the content changed, Proteobacteria and Acidobacteria reduced by 1.73% and 1.4% respectively, and Actinobacteria increased by 0.65%. The advantage phylum Ascomycete in tobacco reduced by 27.99% to be second advantage phylum after Ch. violaceum planting, and the second advantage phylum Basidiomycete increased by 23.69% to become the first dominant fungi. At the genus, Ch. violaceum planting changed the order of dominant genus and the abundance was also changed. Some changed largely such as uncultured Acidobacteriaceae Subgroup-1, Gemmatimonas, Subgroup-2,uncultured Nitrosomonadaceae for bacteria, norank Sordariales, norank Agaricomycetes, Phialophora for fungi. Especially the rotation increased antagonistic microbes and physiological microbes and decreased pathogenic microbes. So the Ch. violaceum planting can improve the microbe community in tobacco soil.

Elevated dopamine D2 receptor in prefrontal cortex of CUMS rats is associated with downregulated cAMP-independent signaling pathway.

Because depression is associated with significant morbidity and functional disability, it is important to reveal the mechanism of action. A variety of studies have suggested the involvement of dopaminergic receptors in the pathophysiological mechanism of non-stress-associated depression-like behavior in rodents. Nevertheless, controversy exists about whether chronic stress acts on dopaminergic receptors in the prefrontal cortex. Thus, we investigated the level of dopamine D2 receptors (DRD2) and the possible mechanisms involved in a chronic unpredictable mild stress (CUMS) rat model of depression. The results showed CUMS-induced, depression-like symptoms in the rat, characterized by reduced sucrose consumption and body mass, and increased duration of immobility in a forced swimming test. Moreover, chronic stress upregulated the expression of DRD2 but downregulated protein kinase A (PKA), transcription factor cAMP response element binding protein (CREB), and phospho-CREB (p-CREB) in the prefrontal cortex, as demonstrated by Western blot. Notably, in the rat model of depression, decreased cyclic adenine monophosphate (cAMP) levels and PKA activity were present at the same time, which is consistent with clinical findings in depressed patients. Our findings suggested that dopaminergic system dysfunction could play a central role in stress-related disorders such as depression.