Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China. / è¶ æœªæˆç†ŸåŒèƒŽå„¿ä¸´åºŠæ•‘æ²»ç»“å±€åŠå˜åŒ–åˆ†æžï¼šä¸€é¡¹å¹¿ä¸œçœå¤šä¸­å¿ƒå›žé¡¾æ€§ç ”ç©¶.

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.

Clinical characterization of NTCP deficiency in paediatric patients : A case-control study based on SLC10A1 genotyping analysis.

Na+ -taurocholate cotransporting polypeptide deficiency (NTCPD) is a newly described disorder arising from biallelic mutations of the SLC10A1 gene. As a result of a lack of compelling evidence from case-control studies, its genotypic and phenotypic features remain open for in-depth investigation. This study aimed to explore the genotypic and clinical phenotypic characteristics of paediatric patients with NTCPD. The SLC10A1 genotypes of all NTCPD patients were confirmed by screening for the prevalent variant c.800C>T and Sanger sequencing when necessary. The clinical presentations and laboratory changes were collected, reviewed and analysed, and then qualitatively and quantitatively compared with the relevant controls. A total of 113 paediatric NTCPD patients were diagnosed while c.374dupG and c.682_683delCT were detected as two novel pathogenic mutations. Hypercholanemia was observed in 99.12% of the patients. Indirect hyperbilirubinemia in affected neonates exhibited higher positive rates in comparison to controls. Moreover, transient cholestatic jaundice, elevated liver enzymes and 25-hydroxyvitamin D (Vit D) deficiency during early infancy were more commonly observed in patients than in controls. All NTCPD patients exhibited favourable clinical outcomes as a result of symptomatic and supportive treatment. The findings enriched the SLC10A1 mutation spectrum and provided comprehensive insights into the phenotypic characteristics of NTCPD. NTCPD should be considered and SLC10A1 gene should be analysed in patients with above age-dependent clinical features. Furthermore, over investigation and intervention should be avoided in the management of NTCPD patients.

miR-133 inhibits proliferation and promotes apoptosis by targeting LASP1 in lupus nephritis.

Lupus nephritis (LN) is a chronic autoimmune disease. Recently, microRNA (miR)-133 has been demonstrated to play an important role in renal cell carcinoma. Our current study was designed to test the role of miR-133 and its potential target in LN. First, significant correlation of LASP1 and miR-133 levels was observed in the human LN tissue. Modification of miR-133 level in the human mesangial cells (HMCs) by either overexpression or knockdown demonstrated a suppressive role of miR-133 in cell proliferation and an inductive role in cell apoptosis. Modification of LASP1 level in the HMCs demonstrated the opposing effects of LASP1 to miR-133 on proliferation and apoptosis. In addition, luciferase assay showed miR-133 directly regulates LASP1 expression through its binding site in the 3'UTR of LASP1. At last, our data showed that the changes in properties, such as suppression in proliferation and induction in apoptosis, induced by overexpression of miR-133 were restored by additional expression of LASP1. In summary, our obtained data demonstrated that miR-133 suppresses proliferation and promotes apoptosis through its binding with LASP1 in human mesangial cells. This study revealed a new mechanism involving the interaction of miR-133 and LASP1 in the pathogenesis of LN.

[Clinical features and MYO5B mutations of a family affected by microvillus inclusion disease].

Microvillus inclusion disease (MVID) is an autosomal recessive disorder caused by biallelic mutations in the MYO5B or STX3 gene. Refractory diarrhea and malabsorption are the main clinical manifestations. The aim of this study was to investigate the clinical features and MYO5B gene mutations of an infant with MVID. A 21-day-old female infant was referred to the hospital with the complaint of diarrhea for 20 days. On physical examination, growth retardation of the body weight and length was found along with moderately jaundiced skin and sclera. Breath sounds were clear in the two lungs and the heart sounds were normal. The abdomen was distended and the veins in the abdominal wall were observed. The liver and spleen were not palpable. Biochemical analysis revealed raised serum total bile acids, bilirubin, transaminases and γ-glutamyl transpeptidase while decreased levels of serum sodium, chloride, phosphate and magnesium. Blood gas analysis indicated metabolic acidosis. The preliminary diagnosis was congenital diarrhea, and thus parenteral nutrition was given along with other symptomatic and supportive measures. However, diarrhea, metabolic acidosis and electrolyte disturbance were intractable, and the cholestatic indices, including transaminases, γ-glutamyl transpeptidase, bilirubin and total bile acids, remained at increased levels. One month later, the patient was discharged and then lost contact. On genetic analysis, the infant was proved to be a compound heterozygote of the c.310+2Tdup and c.1966C>T(p.R656C) variants of the gene MYO5B, with c.310+2Tdup being a novel splice-site mutation. MVID was thus definitely diagnosed.

Short term outcomes of extremely low birth weight infants from a multicenter cohort study in Guangdong of China.

With the increase in extremely low birth weight (ELBW) infants, their outcome attracted worldwide attention. However, in China, the related studies are rare. The hospitalized records of ELBW infants discharged from twenty-six neonatal intensive care units in Guangdong Province of China during 2008-2017 were analyzed. A total of 2575 ELBW infants were enrolled and the overall survival rate was 55.11%. From 2008 to 2017, the number of ELBW infants increased rapidly from 91 to 466, and the survival rate improved steadily from 41.76% to 62.02%. Increased survival is closely related to birth weight (BW), regional economic development, and specialized hospital. The incidence of complications was neonatal respiratory distress syndrome (85.2%), oxygen dependency at 28 days (63.7%), retinopathy of prematurity (39.3%), intraventricular hemorrhage (29.4%), necrotizing enterocolitis (12.0%), and periventricular leukomalacia (8.0%). Among the 1156 nonsurvivors, 90.0% of infants died during the neonatal period (≤ 28 days). A total of 768 ELBW infants died after treatment withdrawal, for reasons of economic and/or poor outcome. The number of ELBW infants is increasing in Guangdong Province of China, and the overall survival rate is improving steadily.

L-type calcium channel blocker suppresses calcineurin signal pathway and development of right ventricular hypertrophy.

BACKGROUND AND PURPOSE: Many studies have shown that L-type calcium channel blockers can prevent and treat right ventricular hypertrophy (RVH). In order to identify the mechanism, we investigated the role of the calcineurin signal pathway in the progression of RVH induced by chronic hypoxia and the effects of an L-type calcium channel blocker on the pathway. METHODS: Rats were allocated to 1 of 3 groups (n=10 for each): chronic hypoxia group, amlodipine treatment group (30 mg/kg/day, administered via gavage); and control group. Rats in the amlodipine treatment group and the chronic hypoxia group were exposed to normobaric chronic hypoxia (9.5%-10.5% oxygen). We investigated the changes of right ventricle (RV) to left ventricle (LV) and interventricular septum (S) weight ratio [RV/(LV+S)], RV to body weight (BW) ratio (RV/BW), calcineurin A beta (CnAbeta) mRNA levels, cardiac myosin heavy chain beta (beta-MHC) mRNA levels and protein expression of CnAbeta, nuclear factor 3 of activated T cell (NFAT3), and beta-MHC. RESULTS: After 21 days, RV/(LV+S) and RV/BW were significantly higher in the chronic hypoxia group than in the control group and the amlodipine group (p<0.01). The expression of CnAbeta mRNA and protein, NFAT3 protein, beta-MHC mRNA and protein in RV of the chronic hypoxia group was higher than that of the control group and the amlodipine treatment group (p<0.01). CONCLUSIONS: The calcineurin signal pathway plays a critical role in the progression of RVH induced by chronic hypoxia. L-type calcium channel blockade suppresses the development of RVH by inhibiting this pathway.

[Effect of cyclosporine A on myocardial calcineurin activity of the right ventricle and plasma NO, nitric oxide synthase and endothelin-1 levels in rats with chronic hypoxia].

OBJECTIVE: To study the role of calcineurin in the progression of right ventricle myocardial hypertrophy in rats exposed to chronic hypoxia by examining the effect of Ca(2+) channel blockers on the activation of calcineurin and plasma levels of nitric oxide (NO), NO synthase, and endothelin-1 (ET-1). METHODS: Rat models of right ventricle myocardial hypertrophy were established by exposing the rats to chronic hypoxia in 10.0%+/-0.5% O(2) for 7 d. The 24 rat models were assigned into normoxic group, hypoxic group and cyclosporin A (CsA)-treated hypoxic group. The rats in normoxic group were kept under normoxic environment, while those in the other 2 groups were subjected to further hypoxic treatment for 14 d, with the rats in CsA group receiving intraperitoneal CsA injection at 20 mg/kg on a daily basis. On day 21 of the experiment, all the rats were killed to collect the hearts for measuring the weight ratio of the right ventricle to the left ventricle and interventricular septum [RV/ LV+S ], as well as the right ventricle to body weight ratio (RV/BW); blood samples were also drawn from the ventricles for measuring plasma NO, iNOS, and ET-1 levels, with the ventricular myocardial [Ca(2+)](i) and the activity of calcineurin also determined. RESULTS: The RV/(LV+S) and RV/BW were significantly higher in hypoxic group than those of the normoxic and CsA groups (P<0.01); the right ventricular myocardial [Ca(2+)](i) in CsA group was significantly higher than that in the other two groups (P<0.01). In comparison with the normoxic group, the right ventricular myocardial calcineurin activity was significantly increased in the hypoxic group. CsA treatment significantly suppressed calcineurin activity (P<0.01). CONCLUSIONS: Calcineurin possibly plays a role in the progression of right ventricle myocardial hypertrophy in rats with chronic hypoxia. Blocking L-type Ca(2+) channels with CsA effectively prevents the development of myocardial hypertrophy possibly by inhibiting calcium influx and suppressing calcineurin activity.

[Effect of the proteasome inhibitor MG-132 on hyperoxic lung injury and its mechanism in rats].

OBJECTIVE: To observe the effects of proteasome inhibitor MG-132 on hyperoxic lung injury in rats and explore the mechanism. METHODS: Thirty SD rats were randomly divided into 3 groups, namely the normoxic group, hyperoxic group, and hyperoxic with MG-132 treatment group, and rat models of hyperoxic exposure-induced lung injury were established in the latter two groups. After pathological grading of the lung injury under optical microscope and determination of the wet/dry weight ratio of the lung tissue, the expressions of ubiquitin protein and nuclear factor-kappaB (NF-kappaB) p56 and the activity of proteasome 20S and myeloperoxidase (MPO) were detected. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) expressions in the lung tissue were also detected. RESULTS: The rats with hyperoxic exposure showed obvious pulmonary edema and increased wet/dry weight ratio of the lung tissue (P<0.01), which were significantly alleviated with MG-132 treatment (P<0.01). Compared with the normoxic group, hyperoxic exposure resulted in significant lung pathologies (P<0.01), which was reduced after MG-132 treatment. Immunohistochemistry and Western blotting demonstrated increased expression of ubiquitin protein in the lung tissue after hyperoxic exposure (P<0.01), which was lowered by MG-132 treatment (P<0.01). Proteasome 20S activity was obviously enhanced in the hyperoxic group (P<0.01) but lowered by MG-132 treatment (P<0.01). Hyperoxic exposure also caused obviously enhanced MPO activity and expressions of NF-kappaB, TNF-alpha, and IL-6 (P<0.01), which were all reduced by MG-132 treatment (P<0.05). CONCLUSION: MG-132 alleviates hyperoxic lung injury probably by inhibiting the NF-kappaB/inflammatory factor pathways.

[Effect of adenosine on activity of transcription factor NF-kappa B and cytokines in myocardial tissue of experimental rats with pneumonia].

OBJECTIVE: Recent studies have shown that cytokines TNF-alpha and IL-6 play important roles in myocardial injury or dysfunction. Transcription nuclear factor (NF-kappa B) have been implicated in the regulation of a variety of cytokines in response to cellular defense. The authors observed the activity of NF-kappa B and cytokines TNF-alpha, IL-6 mRNA expression in myocardium to further investigate the mechanism of myocardial injury caused by infectious pneumonia. The therapeutic effect of exogenous adenosine was also studied by observing the influence on NF-kappa B and cytokines. METHODS: Thirty rats were divided into three experimental groups at random, each group had 10 rats. The model of pneumonia was induced by the injection of Staphylococcus aureus into the trachea of rats. Adenosine-treated rats were given daily slow intravenous injection of adenosine at a dose of 150 microg/kg.min for 3 days from the second day. All rats were killed on the fifth day. Myocardial tissues were preserved in liquid nitrogen for examination. Pathological examination of myocardium was done and TNF-alpha and IL-6 mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR). NF-kappa B activity was measured by electrophoretic mobility shift assay (EMSA). RESULTS: (1) The myocardium in pneumonia group showed significant pathological lesion when compared with control group (P < 0.01). The pathological lesion of myocardium in adenosine-treated group significantly decreased when compared to pneumonia group (P < 0.05). (2) Significant increase of TNF-alpha and IL-6 mRNA expression was observed in myocardium of pneumonic rats when compared with control group (2.27 +/- 0.27 vs. 1.05 +/- 0.16; 1.89 +/- 0.31 vs. 1.12 +/- 0.25: P < 0.01, respectively). NF-kappa B activity of myocardium in pneumonia group was significantly higher than that in control group (13,033 +/- 1286 vs. 383 +/- 15: P < 0.01). (3) TNF-alpha and IL-6 mRNA expression was significantly decreased in adenosine-treated group when compared with pneumonia group (1.25 +/- 0.18 vs. 2.27; 1.31 +/- 0.25 vs. 1.89 +/- 0.31, P < 0.01, respectively). Comparing to that in pneumonia group, NF-kappa B activity of myocardium in adenosine-treated group was significantly decreased (4 487 +/- 562 vs. 13033 +/- 1286, P < 0.01), but it was still significantly higher than that in control group (4487 +/- 562 vs.383 +/- 15, P < 0.01). CONCLUSIONS: Increased activity of NF-kappa B and subsequent upregulation of TNF-alpha and IL-6 mRNA expression probably play a pivotal role in the mechanism of myocardial injury in rats with pneumonia. Exogenous adenosine can inhibit inflammatory change by lowering NF-kappa B activity and subsequent down-regulation of TNF-alpha and IL-6 expression. Our findings provide novel therapeutic evidence of adenosine in myocardial injury induced by pneumonia in clinic.