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Epilepsy is a disorder of the brain charac-terized by abnormal neuron excitability.However,the underlying molecular mechanism of neuron excitability modulation remains elusive.With the help of bioinformatic methods,we have identified receptor-type tyrosine-pro-tein phosphatase-like N(PTPRN)as a critical gene dur-ing epileptogenesis.PTPRN recruits NEDD4L ubiquitin E3 ligase to NaV1.2 sodium channels,facilitating NEDD4L-mediated ubiquitination and endocytosis.Knockout of PTPRN endows hippocampal granule cells with augmented depolarization currents and higher intrinsic excitability,which is reflected by increased seizure susceptibility of transgenic mice.On the contrary,reduced neuron excit-ability and decreased seizure susceptibility are observed after PTPRN overexpression.Meanwhile,we find that a 133 aa fragment recaptures modulation effect of PTPRN full-length,and this fragment shows therapeutic potential towards epilepsy caused by NaV1.2 gain of function vari-ants.In brief,our results demonstrate PTPRN playsa criti-calroleinregulatingneuronexcitability,providing a poten-tial therapeutic approach for epilepsy.
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Objective:To study the effects of plan-do-check-action (PDCA) cycle in quality improvement of neonatal resuscitation.Methods:From 2016 to 2020, the clinical data of neonates born in our hospital were analyzed. Neonates born during 2016 to 2017 were pre-PDCA group and neonates born during 2018 to 2020 were post-PDCA group. PDCA quality improvement included step-by-step, high-frequency and low-dose training, strengthening teamwork and adding equipment.Results:A total of 7 728 live-birth neonates were delivered before PDCA with 319 cases (4.1%) of asphyxia. 10 174 live-birth neonates were delivered after PDCA with 422 cases (4.1%) of asphyxia. The asphyxia rates showed no significant difference between the two groups ( P>0.05). The incidences of severe asphyxia before and after PDCA were both 0.8% without significant difference ( P>0.05). The success rates of resuscitation for severe asphyxia before and after PDCA was 27.9% and 44.9%, respectively, and the differences were statistically significant ( P<0.05). The mortality rates within 7 d before and after PDCA were 0.5‰ and 0.1‰ respectively, without significant differences ( P>0.05). Conclusions:The implementation of PDCA cycle and step-by-step, high-frequency, low-dose neonatal resuscitation training can effectively improve the success rate of resuscitation in newborns with severe asphyxia.
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BACKGROUND@#The molecular mechanisms driving tumorigenesis have continually been the focus of researchers. Cuproplasia is defined as copper-dependent cell growth and proliferation, including its primary and secondary roles in tumor formation and proliferation through signaling pathways. In this study, we analyzed the differences in the expression of cuproplasia-associated genes (CAGs) in pan-cancerous tissues and investigated their role in immune-regulation and tumor prognostication.@*METHODS@#Raw data from 11,057 cancer samples were acquired from multiple databases. Pan-cancer analysis was conducted to analyze the CAG expression, single-nucleotide variants, copy number variants, methylation signatures, and genomic signatures of micro RNA (miRNA)-messenger RNA (mRNA) interactions. The Genomics of Drug Sensitivity in Cancer and the Cancer Therapeutics Response Portal databases were used to evaluate drug sensitivity and resistance against CAGs. Using single-sample Gene Set Enrichment Analysis (ssGSEA) and Immune Cell Abundance Identifier database, immune cell infiltration was analyzed with the ssGSEA score as the standard.@*RESULTS@#Aberrantly expressed CAGs were found in multiple cancers. The frequency of single-nucleotide variations in CAGs ranged from 1% to 54% among different cancers. Furthermore, the correlation between CAG expression in the tumor microenvironment and immune cell infiltration varied among different cancers. ATP7A and ATP7B were negatively correlated with macrophages in 16 tumors including breast invasive carcinoma and esophageal carcinoma, while the converse was true for MT1A and MT2A . In addition, we established cuproplasia scores and demonstrated their strong correlation with patient prognosis, immunotherapy responsiveness, and disease progression ( P <0.05). Finally, we identified potential candidate drugs by matching gene targets with existing drugs.@*CONCLUSIONS@#This study reports the genomic characterization and clinical features of CAGs in pan-cancers. It helps clarify the relationship between CAGs and tumorigenesis, and may be helpful in the development of biomarkers and new therapeutic agents.
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Humanos , Feminino , Genômica , Carcinogênese , Carcinoma , Neoplasias da Mama , Transformação Celular Neoplásica , Nucleotídeos , Microambiente TumoralRESUMO
Objective To evaluate the efficacy and safety of frequently nebulized hypertonic saline(HS) in different concentration with Terbutaline in infants with moderate to severe bronchiolitis.Methods A total of 195 infants were randomly enrolled to either Group A(5% HS 4ml+Terbutaline 2.5mg,n=65),Group B(3% HS 4ml + Terbutaline 2.5mg,n=65) or Group C[0.9% normal saline(NS) 4ml + Terbutaline 2.5mg,n=65].All the infants were given inhalation treatment q6h after admission for 4 times,and then q8h till the remission of wheezing.The primary outcome was the hospital length of stay(LOS),and the secondary outcomes were the clinical severity score(CSS),remission time of wheezing,cost and side effects.
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Competition of teaching skills is regarded as an effective means to develop teacher's ability in teaching.This article briefly described a teaching competition at a medical school from participant identification,requirement clarification,training before competition,evaluation index screening and interviewer selection.Meanwhile the article further analyzed and analyzed the problems arising from the competition and proposed measures to promote teachers' awareness and ability of teaching.
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107 copies/mi group. Conclusion: The presence of high amount of HBVDNA in serum is associated with suppressed co-stimulatory and regulatory effect of IL-12 to Th1/Th2 profilation