OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies

OBJECTIVE: Plant-derived cytotoxic transgene expression, such as trichosanthin (tcs), regulated by recombinant adeno-associated virus (rAAV) vector is a promising cancer gene therapy. However, the cytotoxic transgene can hamper the vector production in the rAAV producer cell line, human embryonic kidney (HEK293) cells. Here, we explored microRNA-122 (miR122) and its target sequence to limit the expression of the cytotoxic gene in the rAAV producer cells. METHODS: A miR122 target (122T) sequence was incorporated into the 3' untranslated region of the tcs cDNA sequence. The firefly luciferase (fluc) transgene was used as an appropriate control. Cell line HEK293-mir122 was generated by the lentiviral vector-mediated genome integration of the mir122 gene in parental HEK293 cells. The effects of miR122 overexpression on cell growth, transgene expression, and rAAV production were determined. RESULTS: The presence of 122T sequence significantly reduced transgene expression in the miR122-enriched Huh7 cell line (in vitro), fresh human hepatocytes (ex vivo), and mouse liver (in vivo). Also, the normal liver physiology was unaffected by delivery of 122T sequence by rAAV vectors. Compared with the parental cells, the miR122-overexpressing HEK293-mir122 cell line showed similar cell growth rate and expression of transgene without 122T, as well as the ability to produce liver-targeting rAAV vectors. Fascinatingly, the yield of rAAV vectors carrying the tcs-122T gene was increased by 77.7-fold in HEK293-mir122 cells. Moreover, the tcs-122T-containing rAAV vectors significantly reduced the proliferation of hepatocellular carcinoma cells without affecting the normal liver cells. CONCLUSION HEK293-mir122 cells along with the 122T sequence provide a potential tool to attenuate the cytotoxic transgene expression, such as tcs, during rAAV vector production.
Animals ; Dependovirus/genetics* ; Genetic Therapy ; Genetic Vectors/genetics* ; HEK293 Cells ; Humans ; Mice ; MicroRNAs/genetics* ; Trichosanthin

Variation of maternal gut microbiota may increase the risk of autism spectrum disorders (ASDs) in offspring. Animal studies have indicated that maternal gut microbiota is related to neurodevelopmental abnormalities in mouse offspring, while it is unclear whether there is a correlation between gut microbiota of ASD children and their mothers. We examined the relationships between gut microbiome profiles of ASD children and those of their mothers, and evaluated the clinical discriminatory power of discovered bacterial biomarkers. Gut microbiome was profiled and evaluated by 16S ribosomal RNA gene sequencing in stool samples of 59 mother-child pairs of ASD children and 30 matched mother-child pairs of healthy children. Significant differences were observed in the gut microbiome composition between ASD and healthy children in our Chinese cohort. Several unique bacterial biomarkers, such as Alcaligenaceae and Acinetobacter, were identified. Mothers of ASD children had more Proteobacteria, Alphaproteobacteria, Moraxellaceae, and Acinetobacter than mothers of healthy children. There was a clear correlation between gut microbiome profiles of children and their mothers; however, children with ASD still had unique bacterial biomarkers, such as Alcaligenaceae, Enterobacteriaceae, and Clostridium. Candidate biomarkers discovered in this study had remarkable discriminatory power. The identified patterns of mother-child gut microbiome profiles may be important for assessing risks during the early stage and planning of personalized treatment and prevention of ASD via microbiota modulation.
Adult ; Animals ; Autism Spectrum Disorder ; microbiology ; Bacteria ; classification ; genetics ; isolation & purification ; Biomarkers ; Child ; Child, Preschool ; Cohort Studies ; Female ; Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mothers ; Risk Assessment

Objective To analyze the common causes of fatty liver in Chinese adults.Methods The CNKI, WANFANG database and VIP database were searched by computer , and the etiology of fatty liver was published from January 2008 to December 2017.Meta-analysis of pre-valence, influencing factors, and blood biochemical indicators were per-formed using R software and Stata software .Results Twenty-four stu-dies were finally included,with a total of 49,275 cases.Meta-analysis showed that the prevalence of fatty liver in the population were : total prevalence 19.31%, male prevalence 26.44%, female prevalence 15.31%.The prevalence rates at different ages were :＜30 years old 13.20%, 31-40 years old 16.73%, 41-50 years old 20.98%, 51-60 years old 21.85%,＞60 years old 17.46%.The risk ratio of influen-cing factors in patients with fatty liver compared with normal population was: high cholesterol 2.03, high triglyceride 3.02, aspartate transaminas increased 3.70, alanine transaminase increased 4.55, hyperglycemia 2.54, obesity 10.73 , greasy food 3.93, alcohol consumption 2.85, hy-pertension 2.06, quality index fat 2.52.The differences in mean blood biochemical results between patients with and without fatty liver were as follows: total cholestero 1.23,triglyceride 1.18,high-density lipoprotein -0.55,low-density lipoprotein 0.28, aspartate transaminase 1.09, alanine transaminase 1.45,total bilirubin 1.09, fasting blood glucose 1.16.Conclusion The preva-lence of fatty liver in Chinese men is higher than that in females ; common factors are high cholesterol , high triglycerides, elevated aspartate transaminase, elevated alanine transaminase, hyperglycemia, obesity, greasy food, hypertension, body mass index; patients with fatty liver fatty biochemical indicators than the normal population were abnormal.

Objective The active ingredient was used as index to optimize the extraction and enrichment process of anti-in-flammatory and analgesic active-fraction(ARF)of Dianbaizhu. Methods Methyl salicylate triglycoside-B was chosen as index com-ponent to extract and enrich methyl salicylate glycosides. Extraction and elution solvents were optimized. The HPLC fingerprint was ob-tained with Thermo Hypersil Gold C18(250 mm×4.6 mm,5μm)column and a gradient elution with the mobile phase consisting of ace-tonitrile(A)-0.2％acetic acid(B)at a flow rate of 1.0 ml/min. And the detection wavelength was set at 294 nm. Results The opti-mized extraction solvent of Dianbaizhu was the 30％ethanol and the optimized elution solvent of ARF enriched by AB-8 macroporous resins was the 35％ethanol. The methodological study on similarity and RSD in ARF HPLC fingerprint of three batches of samples cor-responded to related regulations. Conclusion The extraction and enrichment process of ARF is stable and repeatable.

Objective: To investigate the genetic cause for a family with multiorgan dysplasia and "molar tooth sign" on MRI image. Method: The patient, a 3 months and 21 days old boy, was clinically examined and the medical history of his family was collected. Next generation sequencing was performed to analyze his clinical and genetic causes. Result: Clinical manifestation of the child displayed multiorgan dysplasia, such as six finger deformity, short limbs, coloboma of optic disc and choroid, situs inversus.Cranial MRI showed "molar tooth sign" . The gene sequencing confirmed that the child carried a de novo deletion of c. 2843_2844 delAA in OFD1 gene. Conclusion The child has typical clinical features of Joubert syndrome, such as MRI "molar syndrome" , developmental abnormalities of ocular tissue and limb, visceral inversion, and so on.The OFD1 gene had a novel deletion mutation through gene detection. Combined clinical features with gene detection, it was clear that the child was a rare case of Joubert syndrome type 10 which was the first case of Joubert syndrome caused by OFD1 gene mutation in China.

Hypertension is the leading risk factor for death resulted from cardiovascular diseases.According to the statistics,the number of patients with hypertension in China is 270 million.At present,15 classes and 69 drugs have been approved for the treatment of hypertension,however,the treatment rate and the control rate remain low.Therefore,the research tocusing on new antihypertensive drugs are how to effectively reduce the blood pressure in patients with refractory hypertension,reduce the target organ damage in patients with complications,and reduce adverse drug reactions.This paper summarized the recent research progress of anti-hypertensive drugs on the market or in development,so as to provide references for development and application of antihypertensive drugs.

Objective To investigate the genetic cause for a family with multiorgan dysplasia and“molar tooth sign” on MRI image.Method The patient,a 3 months and 21 days old boy, was clinically examined and the medical history of his family was collected .Next generation sequencing was performed to analyze his clinical and genetic causes .Result Clinical manifestation of the child displayed multiorgan dysplasia, such as six finger deformity , short limbs, coloboma of optic disc and choroid , situs inversus.Cranial MRI showed “molar tooth sign”.The gene sequencing confirmed that the child carried a de novo deletion of c.2843_2844 delAA in OFD1 gene.Conclusion The child has typical clinical features of Joubert syndrome , such as MRI “molar syndrome”, developmental abnormalities of ocular tissue and limb , visceral inversion , and so on.The OFD1 gene had a novel deletion mutation through gene detection . Combined clinical features with gene detection , it was clear that the child was a rare case of Joubert syndrome type 10 which was the first case of Joubert syndrome caused by OFD 1 gene mutation in China .

OBJECTIVETo investigate the effect of premature rupture of the membrane (PROM) on neonatal complications in premature infants.

METHODSThe registration information of 7684 preterm infants with gestational age <37 weeks were collected from the cooperative units in the task group between January 1, 2014 to December 31, 2014. Specially trained personnel from each cooperative units filled in the unified form in a standardized format to record the gender, gestational age, birth weight, PROM, placental abruption, antenatal corticosteroid, Apgar score, amniotic fluid pollution, and complications of the infants. The data were analyzed comparatively between the cases with PROM and those without (control).

RESULTSThe preterm mortality rate was significantly lower but the incidences of ICH, NEC, ROP and BPD were significantly higher in PROM group than in the control group (P<0.05). The 95% confidence interval of the OR value was <1 for mortality, and was >1 for ICH, NEC, ROP and BPD. After adjustment for gestational age, birth weight, gender, mode of delivery, placental abruption, placenta previa, prenatal hormones, gestational diabetes mellitus (GDM), gestational period hypertension and 5-min Apgar score <7, the incidences of NEC, ROP and BPD were significantly different between the two groups (P<0.05) with 95% confidence interval of OR value >1, but the mortality rate and incidence of ICH were not significantly different between the two groups (P>0.05).

CONCLUSIONPROM is a risk factor for NEC, ROP and BPD in preterm infants, and adequate intervention of PROM can reduce the incidences of such complications as NEC, ROP and BPD in the infants.

Apgar Score ; Birth Weight ; Female ; Fetal Membranes, Premature Rupture ; pathology ; Gestational Age ; Humans ; Incidence ; Infant, Newborn ; Infant, Newborn, Diseases ; etiology ; Infant, Premature ; Pregnancy ; Risk Factors

BACKGROUNDThe N400 component of event-related potentials (ERP) has recently drawn widespread attention at home and abroad. This study was to explore the relationship between N400 changes and risperidone treatment and rehabilitation infirst-episode schizophrenia (FES).

METHODSERP component N400 was recorded by Guangzhou Runjie WJ-1 ERP instruments, in 58 FES before and 6 months, 15 months after risperidone treatment, and in 62 normal controls. The patients' syndromes were assessed by Positive and Negative Syndrome Scale (PANSS). And the stimuli are Chinese sentences with matching (congruent) or mismatching (incongruent) ending words.

RESULTSN400 latencies were prolonged, and amplitudes were decreased in Cz, Pz, Fz, C3, C4, in FES compared with in NC, before treatment. The prolonged N400 latencies and decreased amplitudes were negatively correlated with the patients' positive scale and total scale of PANSS. There are significant differences of N400 amplitudes and latencies in 6 months and 15 months follow-up after treatment. Before treatment, 6 months and 15 months after treatment, N400 latencies are 446 ± 35 ms, 440 ± 37 ms, 414 ± 31 ms (F = 9.72, P < 0.01) in incongruent situation; N400 amplitudes are 5.2 ± 4.6 μV, 5.7 ± 4.8 μV, 7.3 ± 5.0 μV (F = 2.06, P > 0.05) in congruent situation, and 8.5 ± 5.9 μV, 10.1 ± 5.0 μV, 11.9 ± 7.0 μV (F = 3.697, P < 0.05) in incongruent situation.

CONCLUSIONSN400 could be used to predict the effects of treatment of schizophrenia to some degree. The linguistic and cognitive impairment in schizophrenia can be improved by antipsychotic drugs.

Adult ; Evoked Potentials ; Follow-Up Studies ; Humans ; Middle Aged ; Risperidone ; therapeutic use ; Schizophrenia ; drug therapy ; rehabilitation