1.Immune infiltration mechanism of lupus nephritis and prediction of potential traditional Chinese medicine targeting based on CIBERSORT deconvolution algorithm
Xinzhu YUAN ; Lingqin LI ; Huan DU ; Changwei LIN ; Yanjiang WANG ; Boliang LI ; Baofu WANG ; Xisheng XIE
Chinese Journal of Immunology 2024;40(10):2121-2129,中插6
		                        		
		                        			
		                        			Objective:Using bioinformatics methods to study the immune infiltration mechanism of lupus nephritis(LN)and to explore potential target Chinese medicines,which can provide new directions for clinical treatment of LN.Methods:Gene expres-sion profile microarray dataset of LN was downloaded from GEO database,differential expressed genes(DEGs)were screened using R software,and GO and KEGG enrichment analysis were performed on these DEGs.Protein interaction network analysis of DEGs was performed by applying STRING database,key genes were screened by using Cytoscape,core gene expression was validated by Nephro-seq database,and the infiltration and correlation of 22 kinds of immune cells in LN were calculated by CIBERSORT deconvolution algorithm.Finally,herbal prediction of significantly enriched immune-related biological processes and key target genes were performed by Coremine Medical database.Results:A total of 367 LN-related DEGs were obtained,of which 253 were up-regulated and 114 were down-regulated.GO was mainly enriched in response to viruses,defense response to viruses,regulation of viral life cycle,regulation of viral processes,etc;KEGG was mainly enriched in S.aureus infection,COVID-19,influenza A,complement and coagulation cascade,pertussis,etc.Ten key genes were screened:IFIT3,OAS2,MX1,OAS1,RSAD2,XAF1,ISG15,IFIT1,ITGAM and PTPRC.Immune infiltration by CIBERSORT deconvolution algorithm showed that monocytes and initial B cells were highly expressed in LN,while memory B cells,naive CD4+T cells,follicular helper T cells and resting natural killer cells were lowly expressed in LN.Immune cell correlation analysis showed a positive correlation between initial B cells and plasma cells,a positive correlation between resting natural killer cells and resting dendritic cells,a negative correlation between monocytes and regulatory T cells,and a negative correlation between resting CD4+memory T cells and monocytes.Coremine Medical predicted that Salvia miltiorrhiza,Panax notogin-seng,Scutellaria baicalensis,ginseng,honey,monkey mushroom and peony were found to be most closely related to immunity in LN.Conclusion:The development and progression of LN are results of the combined involvement of multiple genes and pathways.Mono-cytes,memory B cells,initial CD4+T cells and initial B cells are most closely associated with LN.The predicted Salvia miltiorrhiza,Panax notoginseng,Scutellaria baicalensis,ginseng,honey,monkey mushroom and peony may be used as target herbs for the poten-tial treatment of LN.
		                        		
		                        		
		                        		
		                        	
2.miR-23b-3p regulates the differentiation of goat intramuscular preadipocytes by targeting the PDE4B gene.
Liyi ZHANG ; Xin LI ; Qing XU ; Xinzhu HUANG ; Yanyan LI ; Wei LIU ; Youli WANG ; Yaqiu LIN
Chinese Journal of Biotechnology 2023;39(12):4887-4900
		                        		
		                        			
		                        			This study aimed to explore the effect of miR-23b-3p on the differentiation of goat intramuscular preadipocytes, and to confirm whether miR-23b-3p plays its roles via targeting the PDE4B gene. Based on the pre-transcriptome sequencing data obtained previously, the miR-23b-3p, which was differentially expressed in goat intramuscular adipocytes before and after differentiation, was used as an entry point. real-time quantitative-polymerase chain reaction (qPCR) was used to detect the expression pattern of miR-23b-3p during the differentiation of goat intramuscular preadipocytes. The effects of miR-23b-3p on adipose differentiation and adipose differentiation marker genes were determined at the morphological and molecular levels. The downstream target genes of miR-23b-3p were determined using bioinformatics prediction as well as dual luciferase reporter assay to clarify the targeting relationship between miR-23b-3p and the predicted target genes. The results indicated that overexpression of miR-23b-3p reduced lipid droplet accumulation in goat intramuscular adipocytes, significantly down-regulated the expression levels of adipogenic marker genes AP2, C/EBPα, FASN, and LPL (P < 0.01). In addition, the expressions of C/EBPβ, DGAT2, GLUT4 and PPARγ were significantly downregulated (P < 0.05). After interfering with the expression of miR-23b-3p, lipid droplet accumulation was increased in goat intramuscular adipocytes. The expression levels of ACC, ATGL, AP2, DGAT2, GLUT4, FASN and SREBP1 were extremely significantly up-regulated (P < 0.01), and the expression levels of C/EBPβ, LPL and PPARγ were significantly up-regulated (P < 0.05). It was predicted that PDE4B might be a target gene of miR-23b-3p. The mRNA expression level of PDE4B was significantly decreased after overexpression of miR-23b-3p (P < 0.01), and the interference with miR-23b-3p significantly increased the mRNA level of PDE4B (P < 0.05). The dual luciferase reporter assay indicated that miR-23b-3p had a targeting relationship with PDE4B gene. MiR-23b-3p regulates the differentiation of goat intramuscular preadipocytes by targeting the PDE4B gene.
		                        		
		                        		
		                        		
		                        			Animals
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		                        			MicroRNAs/metabolism*
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		                        			Goats/genetics*
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		                        			PPAR gamma/metabolism*
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		                        			Adipogenesis/genetics*
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		                        			Cell Differentiation/genetics*
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		                        			Luciferases
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		                        			RNA, Messenger
		                        			
		                        		
		                        	
3.Analysis of Key Genes and Immune Infiltration Mechanism of Primary Sj?gren's Syndrome and Prediction of Targeted Traditional Chinese Medicine Based on Bioinformatics
Xinzhu YUAN ; Lingqin LI ; Huan DU ; Changwei LIN ; Zujun YUAN ; Yanjiang WANG ; Baofu WANG ; Xisheng XIE
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(11):3592-3604
		                        		
		                        			
		                        			Objective Using bioinformatics methods to study the immune infiltration mechanism of Primary Sj?gren's syndrome(pSS)and to explore potential target Chinese medicines,which can provide new directions for the clinical treatment of pSS.Methods Gene expression profile microarray dataset of pSS was downloaded from the GEO database,differential genes were screened using R software,and gene ontology(GO)and gene pathway enrichment(KEGG)enrichment analysis was performed on these differential genes.Protein interaction network analysis of differential genes was performed by applying the STRING database,key genes were screened by using Cytoscape,and ELISA for the verification of key genes expression.Immune infiltration and correlation of immune cells in pSS were calculated by CIBERSORT inverse convolution method in 22.Finally,the herbal prediction of key target genes was performed by using the Coremine Medical database.Results A total of 232 differential genes were obtained,of which 207 were up-regulated and 25 were down-regulated.GO was mainly enriched in:leukocyte mediated immunity,lymphocyte mediated immunity,leukocyte cell-cell adhesion,etc;KEGG was mainly enriched in Hematopoietic cell lineage,Primary immunodeficiency,Intestinal immune network for IgA production,Phagosome,Leishmaniasis.Ten key genes were screened:PTPRC,CD19,LCP2,CCR5 and CD69 etc.The hub genes expression in the pSS is the same as that of GSE40611.Immune infiltration showed that memory B cells,T cells CD4 memory activated,and T cells CD4 na?ve were highly expressed in the pSS.Immune cell correlation analysis showed a positive correlation between initial Monocytes and T cells regulatory(Tregs),a positive correlation between Macrophages M1 and B cell na?ve,and a negative correlation between Plasma cells and T cells CD4 memory activated.COREMINE Medical predicted that Ginseng,Panax notoginseng,Tripterygium wilfordii,Burnet,Magnolia,and Strychni may treat pSS.Conclusion The development and progression of pSS are the results of the combined involvement of multiple genes and pathways.Memory B cells,T cells CD4 memory activated,and T cells CD4 na?ve may promote the development of pSS.The predicted Ginseng,Panax notoginseng,Tripterygium wilfordii,Burnet,Magnolia,Strychni may be used as target herbs for the potential treatment of pSS.
		                        		
		                        		
		                        		
		                        	
4.Prediction of short term clinical outcomes in low Apgar score neonates using umbilical artery blood gas analysis plus amplitude integrated electroencephalography
Jiangbiao XIE ; Xinzhu LIN ; Zhuxin ZHANG ; Lixia TANG
Chinese Journal of Neonatology 2023;38(8):465-470
		                        		
		                        			
		                        			Objective:To study the predictive values of umbilical artery blood gas analysis(UABG) plus amplitude-integrated electroencephalography(aEEG) monitoring within 6 h after birth for early complications and short term neurological outcomes in low Apgar score neonates.Methods:From January 2020 to February 2022, neonates with gestational age (GA) ≥35 weeks and 1 min or 5 min Apgar score ≤7 admitted to NICU of our hospital were retrospectively reviewed. According to UABG pH values, the neonates were assigned into pH<7.2 group and pH ≥7.2 group, and further grouped into abnormal aEEG group and normal aEEG group. The ttest, rank sum test and χ2 test were used to compare laboratory results, incidences of diseases, physical growth and neurological prognosis at 6 month of age. Results:A total of 105 neonates with low Apgar scores were enrolled, including 73 cases in the pH<7.2 group and 32 cases in the pH≥7.2 group. In the pH<7.2 group, 52(71.2%) had abnormal aEEG and 21 had normal aEEG. In the pH≥7.2 group, 6(18.8%) had abnormal aEEG and 26 had normal aEEG. The incidence of abnormal aEEG in the pH<7.2 group was higher than the pH≥7.2 group ( P<0.001). The degree of aEEG abnormality was negatively correlated with UABG pH ( r=-0.463, P<0.001). In the pH<7.2 group, the levels of creatine kinase isozymes (CK-MB), activated partial thromboplastin time and the incidence of hypoxic-ischemic encephalopathy (HIE) in neonates with abnormal aEEG were significantly higher than those with normal aEEG, and the head circumference (HC) at 6 month was significantly smaller in neonates with abnormal aEEG (all P<0.05). In the pH≥7.2 group, the level of CK-MB, incidences of HIE and respiratory failure in neonates with abnormal aEEG were higher than those with normal aEEG, HC at 6 month was smaller and the incidence of adverse neurological prognosis was higher in neonates with abnormal aEEG (all P<0.05). Conclusions:UABG plus aEEG monitoring within 6 h after birth shows predictive values for early complications and short term neurological outcomes in low Apgar scores neonates.
		                        		
		                        		
		                        		
		                        	
5.Progress on fluid and nutritional management in the prevention of bronchopulmonary dysplasia
Yasen WANG ; Wei SHEN ; Xinzhu LIN
Chinese Pediatric Emergency Medicine 2022;29(6):418-422
		                        		
		                        			
		                        			Bronchopulmonary dysplasia(BPD)is one of the most common and serious complications of very/extremely preterm infants, which may negatively affect their short-term and long-term prognosis.Nutritional imbalance is one of the important factors in the development of BPD and adequate nutrition plays a key role in lung development.Optimal nutritional management improves growth and neurocognitive function, and reduces the incidence of BPD.This review included the following sections: fluid intake, energy intake, early parenteral nutrition and enteral nutrition of preterm infants with high risk of BPD.
		                        		
		                        		
		                        		
		                        	
6.Risk factors of bronchopulmonary dysplasia in very preterm infants: a national multicenter study
Ruihua BA ; Lixia TANG ; Wei SHEN ; Lian WANG ; Zhi ZHENG ; Xinzhu LIN ; Fan WU ; Qianxin TIAN ; Qiliang CUI ; Yuan YUAN ; Ling REN ; Jian MAO ; Yumei WANG ; Bizhen SHI ; Ling LIU ; Jinghui ZHANG ; Yanmei CHANG ; Xiaomei TONG ; Yan ZHU ; Rong ZHANG ; Xiuzhen YE ; Jingjing ZOU ; Huaiyu LI ; Baoyin ZHAO ; Yinping QIU ; Shuhua LIU ; Li MA ; Ying XU ; Rui CHENG ; Wenli ZHOU ; Hui WU ; Zhiyong LIU ; Dongmei CHEN ; Jinzhi GAO ; Jing LIU ; Ling CHEN ; Cong LI ; Chunyan YANG ; Ping XU ; Yayu ZHANG ; Sile HU ; Hua MEI ; Zuming YANG ; Zongtai FENG ; Sannan WANG ; Eryan MENG ; Lihong SHANG ; Falin XU ; Shaoping OU ; Rong JU
Chinese Pediatric Emergency Medicine 2022;29(6):433-439
		                        		
		                        			
		                        			Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.
		                        		
		                        		
		                        		
		                        	
7.Neurodevelopmental outcomes and risk factors of premature infants at corrected gestational age 18~24 months
Zhi ZHENG ; Wei SHEN ; Lixia TANG ; Yao ZHU ; Lihan HUANG ; Zhenzhen WANG ; Xinzhu LIN
Chinese Journal of Neonatology 2022;37(5):423-428
		                        		
		                        			
		                        			Objective:To study the neurodevelopmental outcomes and risk factors of premature infants with gestational age (GA) <34 weeks.Methods:From June 2016 to June 2018, premature infants with GA<34 weeks admitted to the Neonatology Department of our hospital were retrospectively reviewed. Bayley Scales of Infant DevelopmentⅡwas used to assess the neurodevelopmental outcomes at corrected GA 18~24 months. The incidence of neurodevelopmental impairment (NDI) was determined. Mental developmental index (MDI) and psychomotor developmental index (PDI) were calculated. The infants were assigned into three groups according to their MDI and PDI scores:≥85 group, 70~84 group and <70 group. Risk factors of low MDI and PDI scores were analyzed.Results:A total of 202 premature infants with GA<34 weeks were included, including 131 males (64.9%) and 71 females (35.1%). 91 cases (45.0%) developed NDI, including 77 mild NDI (38.1%) and 14 severe NDI (6.9%). Univariate analysis found that the incidences of severe asphyxia, multiple births, Grad≥3 ROP and endotracheal intubation in the MDI<70 group were higher. At corrected GA 40 weeks, 3, 6, 12 months, MDI<70 group showed less cases of head circumference >-2SD. PDI<70 group had higher incidences of intrauterine distress, maternal gestational hypertension, multiple birth, Grade 3~4 RDS, Grade 3~4 germinal matrix-intraventricular hemorrhage and tracheal intubation ( P<0.05). Logistic regression showed gestational hypertension, history of tracheal intubation and invasive ventilation were the risk factors for low PDI score ( OR=9.176, 4.547 and 3.227, P<0.05). The head circumference >-2SD at corrected age 6m was protective factor for low MDI and PDI scores ( OR=0.063 and 0.041, P<0.001). Conclusions:Preterm infants with GA<34 weeks are likely to develop severe NDI. Avoiding unnecessary tracheal intubation and invasive ventilation and improving gestational hypertension management may be beneficial to the neurodevelopmental outcomes of preterm infants.
		                        		
		                        		
		                        		
		                        	
8.Risk factors of extrauterine growth retardation in very preterm infants with bronchopulmonary dysplasia
Yasen WANG ; Wei SHEN ; Lixia TANG ; Qing YANG ; Xinzhu LIN
Chinese Journal of Neonatology 2022;37(3):208-213
		                        		
		                        			
		                        			Objective:To study the nutritional status of very preterm infants (VPIs) with bronchopulmonary dysplasia (BPD) during hospitalization and the risk factors of extrauterine growth retardation (EUGR).Methods:From January 2017 to June 2020, clinical data of VPIs with BPD hospitalized in the department of neonatology of our hospital were retrospectively studied. The infants were assigned into EUGR group and non-EUGR group and their nutritional status and the risk factors of EUGR were compared.Results:A total of 225 VPIs were enrolled, including 143 cases of EUGR (63.6%) and 82 non-EUGR (36.4%). The EUGR group had significantly lower birth weight (BW) than non-EUGR group ( P<0.001). No significant difference existed in the gestational age (GA) between the two groups ( P=0.733). The incidences of EUGR in VPIs with mild, moderate and severe BPD were 41.9%, 70.8% and 90.7%, respectively and the differences were statistically significant ( P<0.001). Compared with non-EUGR group, EUGR group received less full-course antenatal corticosteroids (47.6% vs. 63.4%, P=0.022). EUGR group had longer duration of parenteral nutrition, fasting time and achieving full enteral nutrition ( P<0.05). EUGR group also showed slower increment of enteral feed volumes, slower growth velocity and higher incidence of feeding intolerance ( P<0.05). Multivariate logistic regression analysis showed that moderate/severe BPD, BW <1 000 g and feeding intolerance were independent risk factors for EUGR in VPIs. The use of pulmonary surfactant at birth was a predictive factor for EUGR in VPIs with BPD. Growth velocity >13 g/(kg·d) and full-course of antenatal corticosteroids were protective factors of EUGR for BPD infants. Conclusions:It is necessary to improve the use of full-course antenatal corticosteroids to reduce the application of pulmonary surfactant at birth in VPIs. Better enteral nutrition and improved growth velocity will help reducing the incidence of EUGR in VPIs with BPD.
		                        		
		                        		
		                        		
		                        	
9.Progress in pathogenesis of perinatal group B streptococcal infection
Yao ZHU ; Chao CHEN ; Xinzhu LIN
Chinese Journal of Perinatal Medicine 2022;25(12):919-924
		                        		
		                        			
		                        			Group B Streptococcus (GBS) is a major cause of severe perinatal infection, stillbirth, premature delivery, and neonatal infectious diseases. Ascending infection after vaginal colonization is the main route of prenatal GBS transmission. The pathogenic mechanism of GBS from asymptomatic colonization to invasive infection mainly relates to virulence factors, the regulation of two-component systems and immune escape. This paper reviews progress in pathogenic mechanism of perinatal GBS infection in recent years, aiming to provide a theoretical basis for the development of vaccines and new treatment approaches against GBS.
		                        		
		                        		
		                        		
		                        	
10.Clinical application of three non-invasive ventilation strategies in initial treatment of neonatal respiratory distress syndrome
Jing HUANG ; Xinzhu LIN ; Ruihua BA
Chinese Pediatric Emergency Medicine 2021;28(7):603-608
		                        		
		                        			
		                        			Objective:To evaluate the clinical effectiveness and safety of three different non-invasive ventilation strategies in initial treatment of neonatal respiratory distress syndrome(RDS).Methods:A total of 111 premature infants with RDS who were admitted to the NICU from Jan 2019 to Dec 2019 were divided into nasal continuous positive airway pressure(NCPAP)group( n=35), bi-level positive airway pressure(BiPAP)group( n=30)and nasal intermittent positive pressure ventilation(NIPPV)group( n=46)as an initial respiratory support.A retrospective study was conducted to compare pH, PaCO 2, PaO 2, P/F value(PaO 2/FiO 2)before 4 to 6 hours after treatment, the incidence of non-invasive ventilation failure, non-invasive ventilation time, invasive ventilation time, duration of oxygen therapy and the incidence of complications among the three groups. Results:Four to 6 hours after treatment, the blood gas indexes of pH, PaO 2 and P/F were significantly higher and PaCO 2 was significantly lower than those before the treatment in the three groups ( P<0.05). PaO 2 and P/F in both BiPAP group and NIPPV group were higher than those in NCPAP group ( P<0.05). PaCO 2 was lower in BiPAP group than that in NCPAP group ( P<0.05), but there were no statistical differences of the blood gas indexes between BiPAP group and NIPPV group ( P>0.05). The incidence of non-invasive ventilation failure was significantly lower in the BiPAP group and NIPPV group than that in NCPAP group ( P<0.012 5), while no signifficant difference was observed between BiPAP group and NIPPV group ( P>0.05). Moreover, no signifficant differences were found among three groups regarding non-invasive ventilation time, ventilation time of successful non-invasive ventilation, invasive ventilation time, duration of oxygen therapy and the incidence rates of bronchopulmonary dysplasia, necrotizing enterocolitis, periventricular-intraventricular hemorrhages, retinopathy of prematurity( P>0.05). Conclusion:NIPPV and BiPAP as an initial respiratory support for RDS in preterm infants augment the beneficial effects of NCPAP contributing to improvement of oxygenation, reduction of the rate of intubation within five days postnatal life without the relevant complications.
		                        		
		                        		
		                        		
		                        	
            
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