Search

The gut microbiota and liver cancer have a complex interaction. However, the role of gut microbiome in liver tumor initiation remains unknown. Herein, liver cancer was induced using hydrodynamic transfection of oncogenes to explore liver tumorigenesis in mice. Gut microbiota depletion promoted liver tumorigenesis but not progression. Elevated sterol regulatory element-binding protein 2 (SREBP2) was observed in mice with gut flora disequilibrium. Pharmacological inhibition of SREBP2 or Srebf2 RNA interference attenuated mouse liver cancer initiation under gut flora disequilibrium. Furthermore, gut microbiota depletion impaired gut tryptophan metabolism to activate aryl hydrocarbon receptor (AhR). AhR agonist Ficz inhibited SREBP2 posttranslationally and reversed the tumorigenesis in mice. And, AhR knockout mice recapitulated the accelerated liver tumorigenesis. Supplementation with Lactobacillus reuteri , which produces tryptophan metabolites, inhibited SREBP2 expression and tumorigenesis in mice with gut flora disequilibrium. Thus, gut flora disequilibrium promotes liver cancer initiation by modulating tryptophan metabolism and up-regulating SREBP2.

The melatonin 1A receptor (MTNR1A) is a membrane receptor distributed across the mammalian gonadal axis-associated membrane. Melatonin (MT) can specifically bind with MTNR1A on the cell membrane and regulates mammalian reproductive activities. However, the role of MTNR1A in regulating the reproductive physiological activities of sheep in the Tibetan Plateau remains unclear. In this study, the MT content in Tibetan sheep blood during the estrous cycle was detected by ELISA. The distribution of MTNR1A in the hypothalamus-pituitary-gonadal axis (HPGA) was analyzed by immunohistochemistry and immunofluorescence. Western blot and qRT-PCR were used to detect dynamic changes of MTNR1A mRNA and protein expression, and the protein distributions in the HPGA. The results showed that the average secretion level of MT in Tibetan sheep blood was highest occurred during diestrus and the lowest during proestrus. Additionally, the secretion of MT at night was significantly higher than during the day. The immunopositive products of MTNR1A were primarily distributed around the glial cells in the dorsal hypothalamic nucleus region, chromophobe cells, and eosinophilic cytoplasm in the pituitary gland, follicular granular layer, follicular adventitia, tubal mucosa, cilia, endometrium, interstices, and glands in the uterus. The expression trends of MTNR1A mRNA and proteins in the HPGA during the estrous cycle were the same. The relative expression levels of MTNR1A mRNA and proteins in the hypothalamus and ovaries were the highest during proestrus and the lowest during metestrus; the highest during diestrus in the pituitary and oviducts; the highest during metestrus in the uterus. Collectively, the differences in the secretion of MT in Tibetan sheep blood and the expression of MTNR1A in HPGA suggest that they may be affected by steroid hormone secretion during the estrous cycle of Tibetan sheep, which has a potential impact on the regulation of animal estrous cycle.

Background: ABO hemolytic disease of the newborn (ABO HDN) is a main risk factor for neonatal hyperbilirubinemia, which is one of the most common causes for readmission in neonates after discharge. Our objective is to assess the risk factors for readmission in neonates with ABO hemolytic disease for phototherapy.Methords: 291 neonates at gestational age ≥ 35 weeks were enrolled with the diagnosis of ABO hemolytic disease by collecting their clinical and laboratory data retrospectively. All these infants were born in Women’s Hospital School of Medicine Zhejiang University between 2018 and 2019. . Among these neonates, 36 cases were readmitted due to hyperbilirubinemia, which is defined as the study group, while the other 255 cases as the control group.Results: The study and control groups were similar on maternal and infants basic parameters (P> 0.05), as well as the complications of both infants and mothers (P> 0.05). However, we found significant differences in the concentration of initial total serum bilirubin, the onset age for phototherapy, the positive direct antiglobulin test (DAT) between two groups (P Conclusions: For neonates with hyperbilirubinemia due to ABO HDN, positive direct antiglobulin test (DAT), small age for phototherapy and high initial level of bilirubin can increase the risk of readmission for phototherapy.

To establish a reference nomogram for end-tidal CO corrected for ambient CO (ETCOc) levels in term and late-preterm Chinese newborns and then assess its efficacy to identify hemolytic hyperbilirubinemia.We conducted a prospective study by measuring concurrent ETCOc and total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) levels collected postnatally at 12, 24, 48, 72, 96, and 120 hours of age. ETCOc at the 25th, 50th, 75th, and 95th percentiles at each epoch were used to construct the reference nomogram. We then explored the ability of predischarge ETCOc and TSB/TcB metrics to predict the development of hyperbilirubinemia requiring phototherapy in early postnatal period and jaundice readmission in late postnatal period.Our nomogram, based on 990 measurements from 455 infants who were not nonhemolytic, displayed a steady line within 3 postnatal days, followed by a subsequent decline. From a cohort of infants with a serial ETCOc measurements (n = 130) and those readmitted (n = 21), we found that ETCOc and TSB/TcB ≥75th percentile can identify most hemolytic hyperbilirubinemia between 12 and 72 hours after birth with an area under the curve (AUC) of 0.741. An ETCOc ≥1.7 ppm alone between 96 and 120 hours after birth can identify most hemolytic hyperbilirubinemia with an AUC of 0.816. In addition, 90.5% of readmitted infants had an ETCOc ≥75th percentile.An ETCOc reference nomogram during the first 5 postnatal days in nonhemolytic term and late-preterm newborns can be used to identify hemolytic hyperbilirubinemia requiring phototherapy in the early postnatal period and readmission in the late postnatal period.

BACKGROUND The treatment efficacy of angiogenesis inhibitor could be underestimated at an early stage based on tumor volume changes. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can quantitatively assess tumors at the cellular level, but it is unclear whether it can provide useful information for assessing treatment response of anti-angiogenic treatment for lung adenocarcinoma. PURPOSE To determine the use of IVIM-DWI for non-invasive monitoring of the early response to anti-angiogenic treatment in the orthotopic transplantation of lung adenocarcinoma model. STUDY TYPE Prospective. POPULATION Thirty-seven nude mice were randomized into two groups: treatment group (received bevacizumab + cisplatin, N = 20) and control group (received saline, N = 17). FIELD STRENGTH/SEQUENCE Single-shot turbo spin-echo (TSE) IVIM-DWI, TSE T2-weighted imaging at 3.0 T. ASSESSMENT Tumor volume, IVIM parameters (apparent diffusion coefficient [ADC], diffusivity [D], perfusion fraction [f], and pseudo-diffusion coefficient [D*]) were measured before and 2 hours, 3, 7, 10 and 14 days after treatment. Regions of interest were manually drawn along the inner edge of the tumor by two radiologists with 5 and 10-year experience in magnetic resonance imaging. Pathological examinations (hematoxylin and eosin stain, cluster of differentiation 34) were performed. STATISTICAL TESTS Kolmogorov-Smirnov test, repeated-measure two-way analysis of variance test, Mann-Whitney U test, Pearson correlation analysis, receiver operating characteristic curve. P

Unlike other complications among very low birth weight infants (VLBW), the incidence of bronchopulmonary dysplasia (BPD) has not decreased substantially, partly because of the different definitions of BPD applied by different researchers. In this retrospective cohort study, we aimed to compare the 2018 revised definition and the 2001 consensus definition of BPD proposed by the National Institute of Child Health and Human Development (NICHD), as well as to identify which definition better predicts severe respiratory morbidities or death. We included 417 infants born at a gestational age

OBJECTIVE: To explore the feasibility of remote monitoring of neonatal jaundice in newborns with ABO hemolytic disease. METHODS: Forty six neonates of gestational age >35 weeks with ABO hemolytic disease admitted to Women's Hospital, Zhejiang University School of Medicine from January 20th, 2020 to February 29th, 2020 were enrolled in the study (study group). The newborns were followed up at home after discharge, the transcutaneous bilirubin (TCB) levels were measured by parents using the provided device and the results were sent to the doctor by smart phone using the installed APP. Fifty six newborns with ABO hemolytic disease admitted in 2018 who received conventional outpatient follow-up after discharge served as the control group. The demographic characteristics, total serum bilirubin (TSB) level during hospitalization, number of outpatient visit and rate of re-admission due to rebound hyperbilirubinemia were compared between the two groups. RESULTS: There were no significant differences between the two groups in gestational age, birth weight, delivery mode, gender, length of the first hospitalization, TSB level before phototherapy and before discharge, and the managements during the first hospitalization (all P>0.05). Compared with the control group, TSB level before readmission [(265±16) μmol/L vs. (295±15) μmol/L] and the number of outpatient visits (1.3±0.8 vs. 3.8±0.5) were significantly lower in the study group (all P < 0.01), while the rate of readmission (17.4%vs. 12.5%) and the weight at the time of readmission[(3398±452) g vs. (3477±324) g] were not significantly different (all P>0.05). No cases of acute bilirubin encephalopathy occurred in both groups. CONCLUSION: The remote follow-up for neonatal jaundice at home can effectively reduce the number of outpatient visits without increasing the risk of readmission and severe neonatal hyperbilirubinemia for newborns with ABO hemolytic disease.

Diffusion kurtosis imaging (DKI) has been proven to provide additional value for assessing many central nervous system diseases compared with conventional diffusion tensor imaging (DTI); however, whether it has the same value in peripheral nerve injury is unclear. This study aimed to investigate the performance of DKI, DTI, and electromyography (EMG) in evaluating peripheral nerve crush injury (PNCI) in rabbits. A total of 27 New Zealand white rabbits were selected to establish a PNCI model. Longitudinal DTI, DKI, and EMG were evaluated before surgery and 1 day, 3 days, 1 week, 2 weeks, 4 weeks, 6 weeks, and 8 weeks after surgery. At each time point, two rabbits were randomly selected for pathological examination. The results showed that fractional anisotropy (FA) derived from both DKI and DTI demonstrated a significant difference between injured and control nerves at all time points (all P < 0.005) mean kurtosis of the injured nerve was lower than that on the control side after 2–8 weeks (all P

Background Less invasive surfactant administration (LISA) is a way of giving surfactant without endotracheal intubation and has shown to be promising in reducing the incidence of bronchopulmonary dysplasia (BPD) in preterm infants. However, the mechanism underlying its beneficial effect and variations in the technique of administration may prevent its widespread use. This trial aims to evaluate the effects of two methods of surfactant administration, LISA or endotracheal surfactant administration followed by low peak pressure (LPPSA) ventilation, in preterm infants with respiratory distress syndrome (RDS). Methods The LISA Or Low Peak Pressure trial is to be conducted in 14 tertiary neonatal intensive care units in China. A total of 600 preterm infants born with gestational age between 250/7 and 316/7 weeks and with a primary diagnosis of RDS will be involved in the study. Infants will be randomized to the LISA or LPPSA group when surfactant therapy is indicated. Primary outcomes include mortality, severity of bronchopulmonary dysplasia at 36 weeks of postmenstrual age (PMA), and mechanical ventilation (MV) in the first 72 h of life. Secondary outcomes include the days of MV, duration of all sorts of non-invasive respiratory support, fraction of inspired oxygen, oxygen saturation before and after surfactant administration, and time required to perform the procedure for surfactant administration. The incidence of comorbidities, including retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), hemodynamically significant patent ductus arteriosus (hsPDA), pneumothorax, and massive pulmonary hemorrhage within 48 h of surfactant administration, and the failure rates of each technique will be determined. Discussion Data from recent systematic review and meta-analysis have suggested a possible improvement in outcomes of preterm infants with RDS by the LISA technique. However, robust evidence is lacking. Why LISA plays a potential role in reducing respiratory morbidity, mainly BPD in preterm infants, remains unclear. The possible explanations are the active and uninterrupted delivery of continuous positive airway pressure during the LISA procedure and the avoidance of complications caused by intubation and relatively high pressure/volume ventilation following surfactant administration. We hypothesized that LISA’s effectiveness lies mainly in avoiding relatively high-pressure positive ventilation immediately following surfactant administration. Thus, this multicenter randomized controlled trial will focus on issues of endotracheal intubation and the pressure/volume used during conventional surfactant administration. The effectiveness, safety and comorbidities of preterm infants following LISA or LPPSA will be evaluated. Trial registration Chinese Clinical Trial Registry: ChiCTR1900020970. Registered on 23 January 2019.

Reactive gliosis and inflammatory reaction are common pathological change to spinal cord injury (SCI). Whereas, the effects of melatonin (MT) on the astro- and microgliosis and their related inflammatory response in the injured spinal cord are not fully understood. In this study, MT's effects on the accumulation and proliferation of microglia and astrocytes and their related inflammatory response were investigated in an acute SCI model. The effects of MT on oxidative stress, neuronal survival and behavioral performance were also tested. It was found that MT treatment significantly suppressed the accumulation and the proliferation of microglia and astrocytes. Quantitative PCR data showed that MT significantly down-regulated the pro-inflammatory markers iNOS, IL-1β and TNF-α expressions. The data showed that MT led to the rise in SOD, CAT and GSH-Px contents and the decrease in MDA content. Western blotting analysis verified that MT significantly down-regulated caspase-3, Bax and GFAP expressions, up-regulated Bcl-2 expression. Compared with the SCI vehicle-treated group, the SCI MT-treated group exhibited a greater Basso Mouse Scale (BMS) locomotor rating score. On the whole, these findings implied that MT exerts its neuroprotective effects by suppressing the accumulation and the proliferation of microglia and astrocytes and reducing the release of pro-inflammatory cytokines, which might be one of the underlying mechanisms of the MT's neuroprotective effect after SCI. Accordingly, MT may be a promising therapeutic candidate for acute SCI.

To quantitatively compare the diagnostic values of various diffusion parameters obtained from mono- and biexponential diffusion-weighted imaging (DWI) models and diffusion kurtosis imaging (DKI) in differentiating between benign and malignant solitary pulmonary lesions (SPLs). Multiple b-value DWIs and DKIs were performed in 89 patients with SPL by using a 3-T magnetic resonance (MR) imaging unit. The apparent diffusion coefficient (ADC) of various b-value sets, true diffusivity (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), apparent diffusional kurtosis (Kapp), and kurtosis-corrected diffusion coefficient (Dapp) were calculated and compared between the malignant and benign groups using a Mann-Whitney U test. Receiver-operating characteristic analysis was performed for all parameters. The ADC(0, 150) values of malignant tumors were lower than those of the benign group (p = 0.01). The ADC(0, 300), ADC(0, 500), ADC(0, 600), ADC(0, 800), ADC(0, 1000), ADCtotal, D, and Dapp of malignant tumors were significantly lower than those of benign lesions (all p 0.05). Intravoxel incoherent motion (IVIM) and DKI-derived parameters have similar performance compared with conventional ADC in differentiating SPLs. • Mono- and biexponential DWI and DKI are feasible for differentiating SPLs. • ADC (0, ≥500) has better performance than ADC (0

This study aimed to investigate the potential of intravoxel incoherent motion (IVIM) diffusion-weighted MR imaging in assessing solitary pulmonary lesions (SPLs). Sixty-two patients with pathologically confirmed SPLs, including 51 and 11 cases of malignant and benign lesions, respectively, were assessed. Diffusion weighted imaging (DWI) with 13 b values was used to derive apparent diffusion coefficient (ADC) and IVIM parameters, including true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f). Our results showed that, there was an excellent inter-observer agreement on the measurements of D and ADC between observers (inter-class correlation coefficient, ICC = 0.902 and 0.884, respectively). Meanwhile, f and D* showed good and substantial reproducibility (ICC = 0.787 and 0.623, respectively). D and ADC of malignant lesions were significantly lower than those of benign lesions (both P ≤ 0.001), while similar values were obtained in both groups for D* and f (both P > 0.05). In receiver operating characteristic (ROC) analysis, D showed the highest area under curve (AUC) for distinguishing malignant from benign lesions, followed by ADC. Accompanying signs of SPLs have specific features on IVIM maps. In conclusion, IVIM provides functional information in characterizing SPLs which is helpful to differential diagnosis. D and ADC have a significantly higher diagnostic value than f and D*.

Gas vesicles are hollow, air-filled polyprotein structures that provide the buoyancy to cells. They are found in a variety of prokaryotes. In this study, we isolated a partial gas vesicle protein gene cluster containing gvpA and gvpC20Ψ from Planktothrix rubescens, and inserted it into an expression vector and expressed it in E. coli. The gas vesicle was developed in bacterial cells, which made bacterial cells to float on medium surface. We also amplified gvpA and gvpC20Ψ separately and synthesized an artificial operon by fusing these two genes with the standardized gene expression controlling elements of E. coli. The artificial operon was expressed in E. coli, forming gas vesicles and floating bacteria cells. Our findings verified that the whole set of genes and the overall structure of gas vesicle gene cluster are not necessary for developing gas vesicles in bacteria cells. Two genes, gvpA and gvpC20Ψ, of the gas vesicle gene cluster are sufficient for synthesizing an artificial operon that can develop gas vesicles in bacteria cells. Our findings provided a wide range of applications including easing the harvest of cultured microalgae and bacteria, as well as enriching and remediating aquatic pollutants by constructing gas vesicles in their cells.

To determine the relationship between total serum bilirubin (TSB) during the first 2 days of life and subsequent neonatal morbidity in very low birth weight (VLBW, less than 1500 g) infants. We performed a prospective study of 582 VLBW infants born between July 1, 2005 and December 31, 2009. TSB was measured in umbilical cord blood (UCB), at 24 and 48 h after birth. Demographic and clinical characteristics of infants in hospital were recorded. The interaction between TSB variables during the first 48 h of life and subsequent neonatal morbidity were assessed in logistic regression analyses adjusted for multiple risk factors. It was found that TSB in UCB was in a negative correlation with occurrence of respiratory distress syndrome (RDS) [OR 0.626, 95% confidence interval (95% CI): 0.446-0.879, p = 0.007], and there was also a negative correlation between TSB in UCB and occurrence of intraventricular hemorrhage (IVH) [OR 0.695, 95% CI 0.826-0.981, p = 0.020]. However, TSB in UCB positively correlated with hyperbilirubinemia [OR 2.471, 95% CI 1.326-3.551, p = 0.012], and TSB at 24 h after birth was also in a positive correlation with early onset sepsis (EOS) [OR 1.299, 95% CI 1.067-1.582, p = 0.011]. VLBW infants with low TSB levels in UCB were more likely to develop RDS and IVH, and those with low TSB levels in UCB were less likely to develop hyperbilirubinemia. Infants with high TSB levels at 24 h after birth were more likely to develop EOS. The protective effect of raised TSB in UCB with respect to RDS and IVH warrants further investigation.

Rational Epithelioid hemangioendothelioma (EHE) is a rare neoplasm commonly known to arise from the soft tissue, lung, and liver. EHE arising from right innominate vein (RIV) has scarcely been reported in English literature. Patient concerns Herein, we present a rare case of EHE of RIV in a 51-year-old woman with right-lower chest pain for 4 days. Computed tomography of the chest revealed a spherical mass with calcification and fatty foci located in the anterior mediastinum, thus a presumptive diagnosis of teratoma was made. Diagnoses, interventions, and outcomes Video-assisted thoracoscopic explorations and resection of mediastinal tumor were then performed. The pathological examination showed that the tumor was EHE. Postoperative radiotherapy was delivered to the patient. Pulmonary metastases were found by chest CT a year after surgery. Lessons A diagnosis of EHE might be considered, when a mediastinal tumor closely related to veins showing intratumoral calcification and obvious enhancement, despite the presence of a clear boundary and visible fat content.

Background Less invasive surfactant administration (LISA) to spontaneously breathing preterm infants has been reported to reduce the duration of mechanical ventilation and the incidence of bronchopulmonary dysplasia (BPD) in previous study. The objective of this study was to explore the feasibility and potential benefits of LISA in early preterm infants on nasal continuous positive airway pressure (nCPAP) compared to conventional endotracheal instillation. Methods All infants with respiratory distress born at 28–32 weeks’ gestational age from January 2012 to December 2012 (n=90), who were eligible for exogenous pulmonary surfactant (PS) therapy were randomized to receive PS by intubation with an endotracheal tube (Intubation group, n=43), or by intubation using a catheter while on nCPAP (LISA group, n=47). Respiratory indices were recorded every 30 seconds during PS administration, and every 1 hour thereafter for the first day. The rate of mechanical ventilation (MV) in the first 72 hours, mean duration of both MV and nCPAP, mean duration of oxygen requirement and neonatal outcomes were recorded. Results PS was successfully administered in 43 (100%) out of 43 babies using the conventional approach and in 46 (97%) out of 47 babies using LISA. The duration of both MV and nCPAP was significantly shorter in LISA group, when compared with intubation group. However, there were no significant differences in both the rate of MV in the first 72 hours and mean duration of oxygen requirement. There were also no differences in the mortality or in the incidence of bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity and necrotizing enterocolitis, or in the duration of respiratory support. Conclusions LISA in spontaneously breathing infants on nCPAP is an alternative therapy for PS delivery, avoiding intubation with an endotracheal tube. The method is feasible and potentially effective, and deserves further clinical trials. Trial registration Current Controlled Trials ChiCTR-ICR-15006001. Registered 20 February 2015.

Idiopathic basal ganglia calcification (IBGC) is a rare neurodegenerative disorder characterized by the deposition of calcium in the brain and variable combinations of movement disorders, gait impairment and neuropsychiatric symptoms. Few reports have described psychiatric manifestations as early symptoms of IBGC. The present study reports the case of a middle-aged man with schizophrenia-like psychosis and obsessive-compulsive symptoms as the first manifestations of IBGC. The response of the patient to olanzapine and fluoxetine suggests that low-dose olanzapine is effective and should be increased cautiously to avoid worsening parkinsonism and that fluoxetine is an effective drug for the treatment of obsessive-compulsive symptoms in IBGC.

To compare neonatal mortality and neurodevelopmental outcomes at two years of age in very low birth weight infants (≤1500 g) born by cesarean with those by vaginal delivery. In this retrospective, case-control study, we evaluated neonatal mortality, medical conditions and neurodevelopmental outcomes at two years of corrected age in 710 very low birth weight (VLBW) infants born between January 2005 and December 2010. Of the 710 infants, 351 were born by the cesarean and 359/710 by vaginal route. There were no significant differences in neonatal mortality between the cesarean delivery group and vaginal delivery group [56/351 (15.9%) vs. 71/359 (19.8%), P=0.20]. VLBW infants delivered by the cesarean procedure had a higher incidence of respiratory distress syndrome than those born by the vaginal route [221/351 (63.0%) vs. 178/359 (49.6%), P