[Risk factors for bronchopulmonary dysplasia in twin preterm infants: a multicenter study]. / åŒèƒŽæ—©äº§å„¿æ”¯æ°”ç®¡è‚ºå‘è‚²ä¸è‰¯å±é™©å› ç´ åˆ†æžï¼šä¸€é¡¹å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early identification of BPD in twin preterm infants in clinical practice. METHODS: A retrospective analysis was performed for the twin preterm infants with a gestational age of <34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020. According to their conditions, they were divided into group A (both twins had BPD), group B (only one twin had BPD), and group C (neither twin had BPD). The risk factors for BPD in twin preterm infants were analyzed. Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins. RESULTS: A total of 904 pairs of twins with a gestational age of <34 weeks were included in this study. The multivariate logistic regression analysis showed that compared with group C, birth weight discordance of >25% between the twins was an independent risk factor for BPD in one of the twins (OR=3.370, 95%CI: 1.500-7.568, P<0.05), and high gestational age at birth was a protective factor against BPD (P<0.05). The conditional logistic regression analysis of group B showed that small-for-gestational-age (SGA) birth was an independent risk factor for BPD in individual twins (OR=5.017, 95%CI: 1.040-24.190, P<0.05). CONCLUSIONS: The development of BPD in twin preterm infants is associated with gestational age, birth weight discordance between the twins, and SGA birth.

miRNA-633 and KAI1 as Potential Biomarkers of Malignant Melanoma with Gastric Cancer.

OBJECTIVE: Malignant melanoma with gastric cancer is one of the most malignant tumors. However, there have been no reports on the effects of KAI1 and miRNA-633 on the survival and prognosis of patients with malignant melanoma with gastric cancer. METHODS: Fifty patients with malignant melanoma and gastric cancer were collected from October 2017 to December 2019. The clinical parameters included clinical information, such as sex, age, tumor size, and tumor staging. RT-qPCR was used to detect the expression of KAI1 and miRNA- 633. The role of KAI1 and miRNA-633 on the overall survival of melanoma was explored by the Pearson chi-square test, Spearman-rho correlation test, Univariate and multivariate cox regression analyses, and Kaplan-Meier method. Furthermore, the bioinformatic analysis was used to verify the role of KAI1 and miRNA-633 on malignant melanoma with gastric cancer. RESULTS: The expression of KAI1 and miRNA-633 was significantly related with the tumor size and staging of tumor (p<0.05) based on the Pearson chi-square test. Spearman's correlation coefficient displayed that KAI1 was significantly correlated with the miRNA-633 (ρ=-0.439, p=0.001). The result of multivariate cox proportional regression analysis showed that KAI1 (HR =0.109, 95% CI: 0.031-0.375, p< 0.001), and miRNA-633 (HR = 13.315, 95% CI: 3.844-46.119, p<0.001) were significantly associated with overall survival. CONCLUSION: The low expression level of KAI1 and high expression of miRNA-633 are significantly correlated with the poor overall survival prognosis of malignant melanoma with gastric cancer, to provide a basis for KAI1 and miRNA-633 to become novel molecular targets for malignant melanoma with gastric cancer.

A successful case of preimplantation genetic testing for monogenic disorder for aplasia cutis congenita.

Background: Aplasia cutis congenita (ACC), also called congenital cutaneous hypoplasia, is a serious disease in newborns. Children with ACC often die due to wound infections and bleeding. How the incidence of ACC can be reduced is a question that needs to be solved urgently. Case report: We reported a mother who had delivered two children with ACC, both of whom were diagnosed with ACC type VI, skin defects, limb deformities, and congenital heart malformations. One infant died a few days after birth, and another died in utero in the second trimester. Genetic testing in both children showed a heterozygous mutation in the ITGB4 gene [17q25 exon 8, c. 794 dupC, (p. Ala266fs) and exon 15, c. 1860G > A]. The mother later successfully gave birth to a healthy baby using Preimplantation Genetic Testing for Monogenic disorders(PGD-M). Conclusion: The PGD-M technique is highly valuable in reducing the incidence of ACC and improving the prognoses of newborns.

Lower expression of KAI1 as a biomarker of poor survival prognosis of melanoma combined with colorectal cancer metastasis.

OBJECTIVE: This study aimed to investigate the correlation between KAI1 (CD82) and miR-633 expression and prognosis and survival time of patients with melanoma combined with colorectal cancer (CRC). METHODS: Clinical and follow-up data of melanoma and CRC patients were recorded, and the expression levels of KAI1 and miR-633 were detected. Pearson chi-square tests and Spearman correlation coefficient were used to analyze the relationship between prognosis and related parameters in these patients. Cox proportional risk regression and receiver operating characteristic curve analyses were used. RESULTS: Overall, 195 patients were included. KAI1 and miR-633 expression levels were significantly correlated with the prognosis of patients with melanoma combined with CRC. Spearman correlation analysis showed that the expression levels of KAI1 and miR-633 were significantly correlated with the prognosis of patients. Multivariate Cox regression analysis suggested that low expression levels of KAI1 and high expression levels of miR-633 indicated shorter survival time for patients. CONCLUSIONS: KAI1 expression was significantly correlated with melanoma and CRC patient prognosis. When KAI1 expression levels were low, the patient survival time was poor.

[Application of extracorporeal membrane oxygenation in the treatment of persistent pulmonary hypertension of the newborn]. / 体外膜肺氧合技术在持续肺动脉高压新生儿救治中的临床应用.

OBJECTIVES: To study the clinical value of extracorporeal membrane oxygenation (ECMO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN). METHODS: A retrospective analysis was performed on the medical data of 11 neonates with PPHN who were treated with ECMO in the Neonatal Intensive Care Unit of Zhongshan People's Hospital from January 2015 to December 2021, involving the neonates' general information, clinical diagnosis, laboratory results, duration of ECMO treatment, complications during ECMO treatment, length of hospital stay, and outcome. RESULTS: Of the 11 neonates, 10 (91%) had successful weaning from ECMO, and 8 (73%) survived. For the 11 neonates, the mean duration of ECMO treatment was (81±50) hours (range: 26 to 185 hours), the mean duration of ventilator use was (198±105) hours (range: 57 to 392 hours), and the mean length of hospital stay was (22±15) days (range: 2 to 49 days). The oxygenation index and blood lactate level were significantly improved after 24 hours of ECMO treatment among the 11 neonates (P<0.05). Ten neonates had significantly reduced pulmonary artery pressure after 24 hours of ECMO treatment (P<0.05). One neonate had a progressive increase in the pulmonary artery pressure during EMCO treatment, succumbing to death. This neonate was diagnosed with alveolar capillary dysplasia based on the histopathological findings of the lung tissue and whole-exome sequencing results. Among the 11 children, 5 had intracranial hemorrhage, 1 had disseminated intravascular coagulation, 1 had gastric hemorrhage, 2 had pulmonary hemorrhage, 1 had renal insufficiency, and 3 had bleeding at the puncture site during ECMO treatment. CONCLUSIONS: ECMO is effective for the treatment of PPHN, however, the high incidence of complications of ECMO treatment suggests that it is important to carefully assess the indications and timing of ECMO treatment and improve the management of ECMO, which can improve the weaning rate and survival rate.

Anodal transcranial direct current stimulation alleviates cognitive impairment in an APP/PS1 model of Alzheimer's disease in the preclinical stage.

Anodal transcranial direct current stimulation (AtDCS) has been shown to alleviate cognitive impairment in an APP/PS1 model of Alzheimer's disease in the preclinical stage. However, this enhancement was only observed immediately after AtDCS, and the long-term effect of AtDCS remains unknown. In this study, we treated 26-week-old mouse models of Alzheimer's disease in the preclinical stage with 10 AtDCS sessions or sham stimulation. The Morris water maze, novel object recognition task, and novel object location test were implemented to evaluate spatial learning memory and recognition memory of mice. Western blotting was used to detect the relevant protein content. Morphological changes were observed using immunohistochemistry and immunofluorescence staining. Six weeks after treatment, the mice subjected to AtDCS sessions had a shorter escape latency, a shorter path length, more platform area crossings, and spent more time in the target quadrant than sham-stimulated mice. The mice subjected to AtDCS sessions also performed better in the novel object recognition and novel object location tests than sham-stimulated mice. Furthermore, AtDCS reduced the levels of amyloid-ß42 and glial fibrillary acidic protein, a marker of astrocyte activation, and increased the level of neuronal marker NeuN in hippocampal tissue. These findings suggest that AtDCS can improve the spatial learning and memory abilities and pathological state of an APP/PS1 mouse model of Alzheimer's disease in the preclinical stage, with improvements that last for at least 6 weeks.

Case report: Recombinant human epidermal growth factor gel plus kangfuxin solution in the treatment of aplasia cutis congenita in a case with Adams-Oliver syndrome.

Background: Aplasia cutis congenita is a congenital disorder with the absence of skin, muscle and(or) bone. It usually affects the scalp. The presence of a large scalp defect can be potentially serious when complicated with hemorrhage and infection. Early healing of this condition is beneficial to improve the prognosis of infants. Study case: A full-term newborn male was born with a round-shaped defect at the vertex of the scalp and skull (dimensions, 8 cm × 9 cm). The infant had a large deletion encompassing the 15.1 region of chromosome 15, including the DLL4 gene. Genetic testing was positive for Adams-Oliver syndrome (AOS). After two months of recombinant human epidermal growth factor gel combined with kangfuxin solution therapy, the skin defects of the scalp healed remarkably. The infant had regular follow-up appointments. At the age of 5 months, the defect became smaller, hairless, and showed good granulation tissue. At 2 years of age, the child's Gesell Developmental Schedules was 70. Conclusion: Recombinant human epidermal growth factor gel combined with kangfuxin solution was a successful conservative treatment for an infant with a large scalp defect accompanied by AOS.

Highly efficient electrocatalysts for overall water splitting: mesoporous CoS/MoS2 with hetero-interfaces.

Mesoporous CoS/MoS2 with abundant heterogeneous interfaces was faciley synthesized from a bimetallic hybrid zeolitic imidazolate framework, which showed excellent catalytic activity and reaction kinetics in both the HER and OER in 1 M KOH. Meanwhile, as a cathode and anode in water splitting electrocatalysis, it delivers a low cell voltage of 1.61 V at 10 mA cm-2 and excellent durability.

[Application value of whole exome sequencing in critically ill neonates with inherited diseases].

OBJECTIVE: To study the application value of whole exome sequencing (WES) in critically ill neonates with inherited diseases. METHODS: A total of 66 critically ill neonates with suspected inherited diseases or unclear clinical diagnosis who were admitted to the neonatal intensive care unit were enrolled as subjects. The clinical data of the neonates were collected, and venous blood samples were collected from the neonates and their parents for WES. The clinical manifestations of the neonates were observed to search for related pathogenic gene mutations. RESULTS: Among the 66 critically ill neonates with suspected inherited diseases or unclear clinical diagnosis (34 boys and 32 girls), 14 (21%) were found to have gene mutations by WES. One neonate had no gene mutation detected by WES but was highly suspected of pigment incontinence based on clinical manifestations, and multiplex ligation-dependent probe amplification detected a heterozygous deletion mutation in exons 4-10 of the IKBKG gene. Among the 15 neonates with gene mutations, 10 (67%) had pathogenic gene mutation, 1 (7%) was suspected of pathogenic gene mutation, and 4 (27%) had gene mutations with unknown significance. Among the 15 neonates, 13 underwent chromosome examination, and only 1 neonate was found to have chromosome abnormality. CONCLUSIONS: Chromosome examination cannot be used as a diagnostic method for inherited diseases, and WES detection technology is an important tool to find inherited diseases in critically ill neonates with suspected inherited diseases or unclear clinical diagnosis; however WES technology has some limitation and it is thus necessary to combine with other sequencing methods to achieve an early diagnosis.

Primary carnitine deficiency in two sisters with intractable epilepsy and reversible metabolic cardiomyopathy: Two case reports.

Primary carnitine deficiency (PCD) is a disorder of the carnitine cycle that results in defective fatty acid oxidation. When carnitine cannot be transported into the cells, fatty acid oxidation is impaired, resulting a variety of symptoms, such as chronic muscle weakness, cardiomyopathy, hypoglycemia and liver dysfunction. The clinical manifestations and outcomes of different cases with PCD vary among patients. The present case report focused on two sisters with PCD. The younger sister presented with intractable epilepsy, and the older sister presented with reversible metabolic cardiomyopathy. Potential mutations in the SLC22A5 gene were investigated within the family, and a nonsense mutation [c.760C>T (p.R254X)] was identified in four family members. The two sisters harbored homozygous mutations, whereas their parents presented heterozygous mutations. Metabolic disease screening revealed low plasma free carnitine levels (<5 µmol/l) in the two sisters. The plasma free carnitine levels of their parents were normal, and they were asymptomatic. PCD in the two patients was managed using oral levocarnitine. The metabolic cardiomyopathy of the older sister improved following 3 months of treatment. However, the epilepsy of the younger sister was recurrent with oral antiepileptic therapy lasting one year and eight months, and epilepsy was finally controlled following right cerebral resection. The present case report demonstrated that the clinical manifestations presented by patients with PCD within the same family were different. The results indicated that treatment with levocarnitine supplementation should be initiated as soon as possible before irreversible organ damage occurs. In addition, metabolic decompensation and cardiac muscle functions were improved following carnitine supplementation. The resection of the severely diseased unilateral brain combined with carnitine supplementation and antiepileptic therapy may be an effective treatment for PCD with intractable epilepsy complications.

CoMo-bimetallic N-doped porous carbon materials embedded with highly dispersed Pt nanoparticles as pH-universal hydrogen evolution reaction electrocatalysts.

The hydrogen evolution reaction is a key half reaction for water electrolysis and is of great significance. Pt-based nanomaterials are promising candidates for HER electrocatalysts. However, the high price of platinum and poor durability impede their practical applications. Herein, a new CoMo-bimetallic hybrid zeolite imidazolate framework is employed to load Pt nanoparticles in a highly dispersed manner as a precursor to synthesize an efficient pH-universal HER electrocatalyst (PtCoMo@NC), which displays overpotentials of 26, 51, and 66 mV at a current density of 10 mA cm-2 in acidic, basic, and neutral media, respectively. The strong synergistic effect of highly dispersed multi-type catalytic species, including cobalt, molybdenum carbide, and platinum (4.7%) promotes the catalytic activity in the HER process. Meanwhile, the aggregation of Pt nanoparticles is greatly restrained by the carbon matrix so that a brilliant long-time durability of 12 hours and a negligible current decrease in the LSV curve after 10 000 CV cycles are achieved.

Aspirin Versus Clopidogrel Monotherapy for the Secondary Prevention of Recurrent Cerebrovascular Attack Following Previous Ischemic Stroke in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) and stroke are two different diseases, but have many aspects in common. Aspirin is recommended as an initial treatment for the secondary prevention of recurrent ischemic stroke in patients with T2DM. However, clopidogrel is an oral antiplatelet drug that might be another choice in case of aspirin intolerance. In this analysis, we aimed to systematically compare aspirin versus clopidogrel monotherapy for the secondary prevention of recurrent cerebrovascular attack following previous ischemic stroke in patients with T2DM. METHODS: Online medical databases including Web of Science, MEDLINE, Cochrane central, EMBASE and http://www.ClinicalTrials.com were searched for published articles that satisfied the inclusion and exclusion criteria of this study. Recurrent stroke, fatal stroke, cerebral hemorrhage, myocardial infarction and mortality were considered the main end points in these patients with T2DM. RevMan 5.3 software was used to statistically analyze the data representing each subgroup. Risk ratios (RRs) with 95% confidence intervals (CIs) were used to represent the results following analysis. RESULTS: A total of 9218 participants with T2DM who were previously affected by ischemic stroke were included in this analysis, whereby 4917 were assigned to aspirin and 4301 to clopidogrel. This current analysis showed that there was no significant difference in recurrent stroke rate (RR: 0.79, 95% CI: 0.61-1.02; P = 0.07) observed with aspirin versus clopidogrel in these patients with T2DM. The risk of fatal stroke (RR: 0.88, 95% CI: 0.39-1.98; P = 0.76), cerebral hemorrhage (RR: 0.65, 95% CI: 0.38-1.11; P = 0.12), myocardial infarction (RR: 0.88, 95% CI: 0.43-1.79; P = 0.71) and mortality (RR: 1.07, 95% CI: 0.90-1.27; P = 0.44) were also similarly manifested. CONCLUSION: Clopidogrel monotherapy was neither inferior nor superior to aspirin monotherapy for the secondary prevention of recurrent cerebrovascular attack following previous ischemic stroke in patients with T2DM. Hence, clopidogrel or aspirin monotherapy is equally safe and effective in these patients with T2DM.

[mRNA expression of MDR3 gene in the blood of preterm infants with parenteral nutrition-associated cholestasis].

OBJECTIVE: To study the association between the expression of the MDR3 gene and the pathogenesis of parenteral nutrition-associated cholestasis (PNAC) in preterm infants. METHODS: Among the preterm infants who were admitted to the hospital from June 2011 to November 2017 and received parenteral nutrition for more than 14 days, 80 who did not develop PNAC were enrolled as non-PNAC group, and 76 who developed PNAC were enrolled as PNAC group. On days 1, 14, 30, 60 and 90 after birth, serum hepatobiliary biochemical parameters [alanine aminotransferase (ALT), total bilirubin (TBil), direct bilirubin (DBil), total bile acid (TBA) and gamma-glutamyl transpeptidase (γ-GT)], fibrosis indices [hyaluronic acid, laminin, procollagen III N-terminal peptide and type IV collagen] and clinical manifestations were observed. Real-time quantitative PCR was used to measure the mRNA expression of MDR3 in both groups, and the correlation between the mRNA expression of MDR3 and serum hepatobiliary biochemical parameters was analyzed. RESULTS: In the PNAC group, serum levels of hepatobiliary biochemical parameters and fibrosis indices increased on day 14 after birth and reached the peak on day 30 after birth, followed by a reduction on day 60 after birth. On days 14, 30, 60 and 90 after birth, the PNAC group had significantly higher serum levels of hepatobiliary biochemical parameters and fibrosis indices than the non-PNAC group (P<0.05). The PNAC group had higher relative mRNA expression of MDR3 in peripheral blood cells than the non-PNAC group (P<0.05). In the PNAC group, the relative mRNA expression of MDR3 in peripheral blood cells was negatively correlated with serum levels of hepatobiliary biochemical parameters (ALT, TBil, DBil, TBA and γ-GT) (P<0.001). CONCLUSIONS: High mRNA expression of MDR3 in preterm infants may be associated with the development of PNAC, and further studies are needed to identify the mechanism.

A new furan derivative from an endophytic Aspergillus tubingensis of Decaisnea insignis (Griff.) Hook.f. & Thomson.

A new furan derivative named 3-(5-oxo-2,5-dihydrofuran-3-yl) propanoic acid (1) was isolated for the first time. Its structure was elucidated by UV, IR, NMR, HR-ESI-MS and the single-crystal X-ray diffraction spectroscopic data. Meanwhile, the antifungal and antibacterial activities of compound 1 was tested, it exhibited potent antifungal activity against Fusarium graminearum with MIC value of 16 µg/mL and medium antibacterial activity against Streptococcus lactis with MIC value of 32 µg/mL.

A new analog of pyrrolezanthine from the roots of Reynoutria ciliinervis (Nakai) Moldenke.

In the present study, a new analogue of pyrrolezanthine (1) was isolated from the roots of Reynoutria ciliinervis (Nakai) Moldenke. Its structure was elucidated mainly by NMR, HR-ESI-MS and the single-crystal X-ray diffraction spectroscopic data. Meanwhile, the antimicrobial activity of compound 1 was measured, it exhibited potent antifungal activity against Sclerotinia sclerotiorum with MIC value of 31.2 µg/mL.

MicroRNA138 regulates keratin 17 protein expression to affect HaCaT cell proliferation and apoptosis by targeting hTERT in psoriasis vulgaris.

The purpose of this study is to explore the how microRNA-138 (miR-138) affects the expression of keratin 17 (K17) and psoriasis development. Twenty-eight skin lesions from patients with psoriasis vulgaris and twenty-four normal skin tissues from healthy controls were collected. The HaCaT cells were assigned into blank, negative control (NC), miR-138 mimic, miR-138 inhibitor, hTERT siRNA and miR-138 inhibitor+hTERT siRNA groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the miR-138 expression. The hTERT and K17 protein expression were testified by Western Blotting. MTT assay, flow cytometry with PI single staining and Annexin V/PI double staining were performed to detect the cell proliferation activity, cell cycle and apoptosis, respectively. Compared with the healthy skin, the expression of miR-138 decreased in the psoriatic skin, but hTERT and K17 protein expressions increased. The miR-138 mimic and hTERT siRNA groups showed significantly decreased hTERT and K17 protein expressions, inhibited cell proliferation, increased number of cells at G1 phase and elevated apoptosis rate in comparison to the rest three groups. The hTERT and K17 protein expressions in the miR-138 inhibitor group were up-regulated with promoted cell proliferation and reduced apoptosis rate as compared with the other four groups. In the miR-138 inhibitor+hTERT siRNA group, the hTERT and K17 protein expressions, cell proliferation and apoptosis were intermediate between the miR-138 inhibitor and hTERT siRNA groups. These findings indicated that the expression of miR-138 was lower in the psoriatic skin, which was negatively correlated to K17 expression. MiR-138 may regulate K17 protein expression to affect HaCaT cell proliferation and apoptosis by targeting hTERT gene.

Analysis of mutations of MDR3 exons 9 and 23 in infants with parenteral nutrition-associated cholestasis.

The aim of this study was to investigate mutations of multidrug resistance 3 (MDR3) exons 9 and 23 in infants with parenteral nutrition-associated cholestasis (PNAC). A total of 41 infants with PNAC were enrolled in the study. Genomic DNA was extracted from the peripheral venous blood leukocytes of each patient and MDR3 exons 9 and 23 were amplified by polymerase chain reaction. One patient was identified who carried a frameshift mutation in MDR3 exon 23 (C.2793) that was caused by the insertion of a single adenine residue, while mutations were not found in MDR3 exon 23 in the other 40 patients. The clinical features of the patient with the MDR3 exon 23 frameshift mutation included high serum γ-glutamyl transferase levels, the absence of biliary dilatation and deformity in magnetic resonance cholangiopancreatography, and abnormal electrical capacitance tomography imaging of the liver. No mutations in MDR3 exon 9 were identified in any of the patients. All 41 PNAC patients recovered following oral ursodeoxycholic acid treatment. The C.2793 frameshift mutation in MDR3 exon 23 is potentially associated with the development of PNAC in infants.

Correlation between mutation of MDR3 gene exon 6 and parenteral nutrition-associated cholestasis of preterm infants.

The aim of this study was to investigate the association between the mutation of multidrug resistance 3 (MDR3) exon 6 and parenteral nutrition-associated cholestasis (PNAC) in preterm infants. A total of 41 preterm infants with PNAC formed the experimental group, and 56 preterm infants receiving total parenteral nutrition (TPN) for >14 days but without cholestasis formed the control group. Genomic DNA was extracted from peripheral venous blood leukocytes. Polymerase chain reaction was used to amplify exon 6 of the MDR3 gene. The target band of MDR3 gene exon 6 was identified in all blood samples from all cases. We identified five cases with C. 504 C>T heterozygous mutations of exon 6 of the MDR3 gene and 14 cases with C. 504 C>T homozygous mutations in the experimental group. In the control group, we identified seven cases with the C. 504 C>T homozygous mutation and six cases with the C. 504 C>T heterozygous mutation. The distribution of the T/C allele frequency of C. 504 in exon 6 of the MDR3 gene between the experimental group and control group was statistically significant (P<0.05). Further analysis revealed the odds ratio of the T/C allele frequency of the C. 504 mutation in exon 6 of the MDR3 gene between the experimental group and control group to be 0.316. Point mutation C. 485 T>A was detected in one case in the experimental group. The C. 504 C>T and C. 485 T>A MDR3 mutations in exon 6 are possibly responsible for the development of PNAC in infants. C. 504 C>T may not be the only risk factor of neonatal PNAC. In order to further confirm the association between exon 6 of the MDR3 gene and PNAC, a large-sample multicenter study should be carried out.