Objective To investigate the role of the NOP2/Sun RNA methyltransferase 2(NSUN2)gene in functions such as differentiation and apoptosis in PC12 cells,with the aim of exploring the function of the NSUN2 gene in nervous system development.Methods PC12 cells were divided into NSUN2-KO group and NSUN2 group.Immunofluorescence was used to detect neuronal characteristics of PC12 cells of each group.Enzyme-linked immunosorbent assay(ELISA),laser confocal and flow cytometry,nitroblue tetrazolium(NBT),thiobarbituric acid(TBA),cell counting kit-8(CCK-8)and flow cytometry were used to detect the content of cell neurotransmitters,intracellular calcium ion influx,superoxide dismutase activity,malondialdehyde content,cell proliferation,cell cycle and apoptosis,respectively.Results NSUN2-KO group showed reduced and shortened synapses(neuron-specific enolase 44.26 vs.63.21,P=0.002;neurofilament protein 10.12 vs.33.63,P<0.001);increased excitatory neurotransmitters(aspartic acid 618.83 nmol/L vs.372.38 nmol/L,P<0.001;glutamic acid 880.45 nmol/L vs.525.17 nmol/L,P<0.001)and decreased inhibitory neurotransmitters(glycine 197.40 nmol/L vs.286.15 nmol/L,P<0.001;γ-aminobutyric acid 134.91 nmol/L vs.208.25 nmol/L,P<0.001).NSUN2-KO group also exhibited increased fluorescence intensity value of intracellular calcium ions(51319.70 vs.24546.06,P<0.001);the prolonged G1 phase(73.38%vs.68.48%,P<0.001),shortened G2 phase(14.69%vs.16.99%,P=0.008)and S phase(11.92%vs.14.52%,P=0.002);increased oxidative stress levels(superoxide dismutase 11.05 U/mgprot vs.21.59 U/mgprot,P=0.002;malondialdehyde 1.42 nmol/mgprot vs.0.80 nmol/mgprot,P=0.008);increased apoptosis(21.55%vs.10.53%,P<0.001).Conclusion Knockout of the NSUN2 gene reduces and shortens synapses in NGF-induced PC12 cells,enhances the ability to release excitatory neurotransmitters,increases cytotoxicity,decreases cell viability,and promotes apoptosis,which indicates that the NSUN2 gene may be an important neuroprotective factor for neuronal proliferation,differentiation,and maintenance of their morphology and function.

Purpose: The causal relationship between the incidence and prognosis of chronic kidney disease (CKD) and serum testosterone levels in patients is not yet fully understood. This study aims to use the National Health and Nutrition Examination Survey (NHANES), a large-scale nationally representative sample, to investigate the relationship between CKD and testosterone. Materials and Methods: This study included six NHANES cycles for linear regression analysis, verified by multiple imputation methods. Stratified analysis and subgroup analysis were used to demonstrate the stability of CKD’s effect on testosterone. Furthermore, we used Kaplan-Meier plots and log-rank tests to evaluate differences in survival rates between CKD male patients with low and normal levels of testosterone. Results: From a total of 71,163 subjects, the cohort selected 28,663 eligible participants. Results showed that CKD patients had testosterone levels 28.423 ng/mL (24.762, 32.083) lower than non-CKD patients. The results of multiple imputations (β=27.700, 95% confidence interval: 23.427, 31.974) were consistent with those of linear regression analysis, and the numerical match was good. Stratified regression analysis, and subgroup analysis results showed that CKD had a significant impact on testosterone at different dimensions. Kaplan-Meier plots showed significantly reduced survival rates in low testosterone CKD male patients (p<0.0001). Conclusions The results of this big data analysis suggest that there may be a two-way risk between low levels of testosterone and CKD. The testosterone levels of CKD patients were significantly lower than those of the non-CKD population, and CKD patients with low testosterone levels had poorer prognoses. These results suggest that correcting testosterone levels in a timely manner can have preventive and therapeutic effects on the progression of CKD.

Objective To investigate the role of the NOP2/Sun RNA methyltransferase 2(NSUN2)gene in functions such as differentiation and apoptosis in PC12 cells,with the aim of exploring the function of the NSUN2 gene in nervous system development.Methods PC12 cells were divided into NSUN2-KO group and NSUN2 group.Immunofluorescence was used to detect neuronal characteristics of PC12 cells of each group.Enzyme-linked immunosorbent assay(ELISA),laser confocal and flow cytometry,nitroblue tetrazolium(NBT),thiobarbituric acid(TBA),cell counting kit-8(CCK-8)and flow cytometry were used to detect the content of cell neurotransmitters,intracellular calcium ion influx,superoxide dismutase activity,malondialdehyde content,cell proliferation,cell cycle and apoptosis,respectively.Results NSUN2-KO group showed reduced and shortened synapses(neuron-specific enolase 44.26 vs.63.21,P=0.002;neurofilament protein 10.12 vs.33.63,P<0.001);increased excitatory neurotransmitters(aspartic acid 618.83 nmol/L vs.372.38 nmol/L,P<0.001;glutamic acid 880.45 nmol/L vs.525.17 nmol/L,P<0.001)and decreased inhibitory neurotransmitters(glycine 197.40 nmol/L vs.286.15 nmol/L,P<0.001;γ-aminobutyric acid 134.91 nmol/L vs.208.25 nmol/L,P<0.001).NSUN2-KO group also exhibited increased fluorescence intensity value of intracellular calcium ions(51319.70 vs.24546.06,P<0.001);the prolonged G1 phase(73.38%vs.68.48%,P<0.001),shortened G2 phase(14.69%vs.16.99%,P=0.008)and S phase(11.92%vs.14.52%,P=0.002);increased oxidative stress levels(superoxide dismutase 11.05 U/mgprot vs.21.59 U/mgprot,P=0.002;malondialdehyde 1.42 nmol/mgprot vs.0.80 nmol/mgprot,P=0.008);increased apoptosis(21.55%vs.10.53%,P<0.001).Conclusion Knockout of the NSUN2 gene reduces and shortens synapses in NGF-induced PC12 cells,enhances the ability to release excitatory neurotransmitters,increases cytotoxicity,decreases cell viability,and promotes apoptosis,which indicates that the NSUN2 gene may be an important neuroprotective factor for neuronal proliferation,differentiation,and maintenance of their morphology and function.

Objective To study the mechanism of Shexiang Baoxin pill in the treatment of atherosclerosis, and to provide a theoretical basis for long-term clinical application. Methods The chemical components and targets of Shexiang Baoxin pill were collected and screened by TCMSP, TCMID, ETCM and BATMAN databases. The targets related to atherosclerosis were collected and screened by DisGeNet, OMIM, TCMSP, DrugBank and DisGeNet. Drug-compound target network and protein-protein interaction network were constructed. Go and KEGG enrichment analysis of Shexiang Baoxin pill in the treatment of atherosclerosis were carried out on MetaScape platform. Results 114 potential therapeutic components of Shexiang Baoxin pill on atherosclerosis were selected, corresponding to 175 targets. The results of network analysis showed that the main active components of Shexiang Baoxin pill were chenodeoxycholic acid, ursodeoxycholic acid, cinnamaldehyde and ginsenoside R_b1. The results of pathway enrichment showed that the anti-atherosclerotic mechanism of Shexiang Baoxin pill was related to the regulation of immunity, inflammation, and metabolism. Conclusion The active components of Shexiang Baoxin pill could act on ALB, INS, AKT1, ACTB, TNF, IL-6 and other targets, regulating multiple pathways to achieve the therapeutic effect on atherosclerosis.

In recent years, the management of respiratory diseases related to preterm birth has received extensive attention.In 2021, the American Thoracic Society brought together multidisciplinary experts in respiratory, neonato-logy, otolaryngology, sleep medicine, radiology and nursing specialties to develop Guidelines for outpatient respiratory management in infants, children, and adolescents with post-preterm respiratory disease (hereinafter referred to as the " Guideline" ), aiming to provide evidence-based medical evidence for standardized outpatient management of respiratory diseases associated with preterm birth at different ages.The Guideline was interpreted and summarized so that pediatric clinicians could correctly diagnose and treat these diseases, and understand and implement standardized outpatient management on the basis of evidence.

Objective:To search, evaluate and summarize the best evidences related to induction of labor by oxytocin infusion in pregnant women with full-term pregnancy, and to provide reference for clinical practice in order to reduce the complications during labor, such as the proportion of instrument delivery, prolonged labor duration, uterine rupture, postpartum hemorrhage, etc. Standardize the management process of induction of labor with oxytocin, improve the satisfaction of pregnant women to participate in the decision of induction of labor, and improve the outcome of the newborn.Methods:Take the evidence-based nursing method, in view of the full-term pregnancy pregnant women oxytocin drip induced labor evidence-based labor management problems, nearly 10 years related literature retrieval from January 1st 2011 to April 9th, 2021, the Australian JBI evidence-based health care center of literature quality evaluation criteria and evidence classification system, all kinds of research evaluation and classification of retrieval.Results:Early detection to 340 articles, and eventually into 9 articles, including 1 clinical decision, 6 guides, 2 pieces of system evaluation. Totally 45 pieces evidences related to induction of labor by oxytocin infusion in pregnant women with full-term pregnancy were sumarized, including induced labor time, oxytocin side effects, induced labor before evaluation, induced labor of guardianship, infusion solution, such as health education, and other seven aspects.Conclusions:The present study summarized 45 pieces of best evidence on the management of labor induced by oxytocin infusion during term pregnancy, which provided some evidence-based basis for midwives, obstetric nurses and managers. Through the application of the best evidence, it is beneficial to improve the outcome of pregnant women in the neonatal perinatal period, standardize the process of inducing labor with oxytocin, and improve the quality of obstetric care.

OBJECTIVE：To improve the quality standard of Taraxaci Herba ，and to evaluate the quality of T. officinale from different origins. METHODS ：Based on the provisions of the 2020 edition of Chinese Pharmacopoeia （part Ⅰ）under the item “Taraxaci Herba ”，the method of content determination was added for the detection of water-soluble extracts （hot extraction method）and alcohol-soluble extracts （hot extraction method ），total flavonoids ，chlorogenic acid ，caffeic acid ，cichoric acid and isochlorogenic acid A. HPLC fingerprint was established by using 42 batches of T. officinale from 8 producing areas as object ，and principal component analysis was performed on the basis of above results. RESULTS ：The contents of alcohol-soluble extracts in 42 batches of T. officinale were 15.30％-30.40％，and those of water-soluble extracts were 27.59％-38.96％. The concentration of total flavonoids（UV spectrophotometry ），chlorogenic acid ，caffeic acid ，cichoric acid and isochlorogenic acid A （HPLC method ）were 0.016-0.096，0.003-0.196，0.004-0.117，0.025-1.578，0.002-0.152 mg/mL，respectively （all R2＞0.999）；RSDs of precision ， stability and repeatability tests were all lower than 2.00％（n＝6）；average sample recovery were 98.97％-103.53％，and RSDs were 1.19％-1.58％. The contents of total flavonoids ，chlorogenic acid ，caffeic acid ，cichoric acid and isochlorogenic acid A were 0.734％ -3.700％ ，0.004％ -0.123％ ，0.006％ - 0.087％ ，0.073％ -1.499％ ，0.005％ -0.109％ respectively in 42 batches of T. officinale. For 42 batches of T. officinale samples in HPLC fingerprint ，RSDs of the relative retention time of the common peak were 0-0.94％，and RSDs of the relative peak area were 0-125.57％. Among them ，the similarity of 39 batches of samples was all higher than 0.900. Results of principal component analysis showed that the quality of T. officinale from Shaanxi province was better，followed by medicinal materials from Hebei province. CONCLUSIONS ：Tentatively，the contents of alcohol-soluble extract，water-soluble extract ，total flavonoids ，chlorogenic acid ，caffeic acid ，cichoric acid and isochlorogenic acid A shall not be less than 17.0％，27.0％，1.383％，0.024％，0.021％，0.450％，0.021％ for Taraxaci Herba. In addition to the low content of caffeic acid in T. officinale from Shaanxi province ，the other indexes were better ；the content of caffeic acid in T. officinale from Hebei province was higher than that from Shaanxi province ，and other indicators were slightly lower than that from Shaanxi province. The quality of comprehensive evaluation of T. officinale from other origins was relatively poor ，and the quality of different batches of medicinal materials from the same origin was unstable.

Objective: To explore the action mechanism of miR-139-5p inhibiting proliferation and invasion of epithelial ovarian cancer (EOC) cells by targetedly regulatingNotch1.Methods: A total of 24 pairs of EOC tissues and its corresponding para-cancerous tissues from patients, who underwent surgical resection in the DepartmentofGynecology,Nanyang Central Hospital of Henan Province, were collected for this study; in addition, human ovarian cancer cell lines (SKOV3, ES2, HEY-T30) and human ovarian epithelial cell line IOSE80 were also collected. Real-time quantitative PCR (qPCR) was applied to detectmRNAexpressionofmiR-139-5pandNotch1 in EOC tissues and cell lines. The miR-139-5p over-expression vector and recombinant plasmid pLV-Notch1 were transfected into SKOV3 cells. Blank control group (Ctrl group) and negative control group (NC group) were set up. Dual luciferase reporter gene assay was applied to verify the targeting relationship between miR-139-5p and Notch1 3'-UTR. CCK-8, Transwell and Scratch healing experiments were applied to detect cell proliferationinvasionandmigration, respectively. Western blotting was applied to detect expressions of proliferation and migration related proteins in cells. Results: Compared with para-cancerous tissues and IOSE80 cells, the expression of miR-139-5p was significantly decreased in EOC tissues and cell lines, while the expression of Notch1 mRNA was significantly increased (all P<0.01). The results of Dual luciferase reporter showed that Notch1 was the downstream target gene of miR-139-5p. Compared with NC group, cell proliferation, invasion and migration ability, expression levels of Notch1, NICD, Cyclin D1, Cyclin A1, Snail1, β-catenin and N-cadherin were all significantly decreased on 3 d in miR-139-5p mimic group (all P<0.01), while expression of E-cadherin was significantly increased (P<0.01); meanwhile, over-expression of Notch1 could reverse the inhibitory effect of miR-1395p on proliferation, invasion and migration of SKOV3 cells. Conclusion: miR-139-5p can targetedly regulate Notch1 to inhibit proliferation, invasion and migration of EOC cells, which may be related to its down-regulation of NICD, Cyclin D1, Cyclin A1, Snail1, βcatenin and N-cadherin, and up-regulation of E-cadherin.

The lung is the second most common site of neuroendocrine tumors (NETs). Typical and atypical carcinoids are low-grade NETs of the lung. These rare tumors have received little attention and education is needed for treating physicians. The article describes the classifcation of lung NETs, the epidemiology and pathological characteristics. When lung NETs are diagnosed at an early stage, surgical intervention is often curative. For advanced lung NETs patients, different treatment methods including chemotherapy, somatostatin analogs, m-TOR inhibition, peptide receptor radioligand therapy, and biologic systemic therapy are discussed. The conclusions are generally extrapolated from the outcome of extra-pulmonary carcinoids. Prospective randomized well-designed trials are urgently needed to inform current recommendations on systemic treatment.
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Disease-Free Survival ; Drug Therapy ; methods ; Humans ; Lung ; drug effects ; radiation effects ; surgery ; Lung Neoplasms ; pathology ; surgery ; therapy ; Neoplasm Grading ; Neuroendocrine Tumors ; pathology ; surgery ; therapy ; Outcome Assessment (Health Care) ; Radiotherapy ; methods

Objective: To explore the molecular and genetic mechanism of transcription factor GATA-6 in nonsyndromic conotruncal defect (CTD) in order to provide evidence for early prevention and inheritance consultation of CTD. Methods: A total of 32 cases of patients with nonsyndromic CTD and 100 healthy individuals were enrolled in the study.A total of 7 exons and bilateral partial intron-exon boundaries of GATA-6 were amplified by means of polymerase chain reaction (PCR). The PCR products were purified and directly sequenced by using an ABI Genetic Analyzer 3100 Automatic DNA sequence equipment.The acquired GATA-6 gene sequence was compared with standard gene sequence published in National Center for Biotechnology Information database, as well as the healthy control group to observe the GATA-6 gene mutations.The mutations were introduced into pcDNA3.1(+ ) by site-directed mutagenesis PCR on the basis of pcDNA3.1(+ )-GATA-6 in order to generate the GATA6-G245R mutant constructs.Wild type GATA-6, GATA-6-G245R and atrial natriuretic factor-luciferase(ANF-luciferase) were cotransfected into HEK 293T cells in vitro, and the CMV-LacZ were cotransfected as internal reference.Luciferase and galactosidase activity were measured by using luminometer 24 h after transfection and detected in the downstream ANF-luciferase reporter gene. Results: A heterozygous missense mutation in the GATA-6 gene was identified in a patient with double outlets of the right ventricle.The mutation was located in Gly245Arg(G245R) in exon 2 of GATA-6.The mutation of pcDNA3.1(+ )-GATA-6 expression vectors were successfully constructed.Through the detection of luciferase reporter gene activity, it was found that GATA-6-G245R and wild-type GATA-6 decreased by 41.3%, and the comparison between them was statistically significant (P<0.001). Conclusions Transcription factor GATA-6 gene mutation is associated with the occurrence of nonsyndromic CTD.Transcription factor GATA-6 gene may be susceptible gene in human nonsyndromic CTD.