1.NAD+ Ameliorates Endothelial Dysfunction in Hypertension via Activation of SIRT3/IDH2 Signal Pathway
Yumin QIU ; Xi CHEN ; Jianning ZHANG ; Zhangchi LIU ; Qiuxia ZHU ; Meixin ZHANG ; Jun TAO ; Xing WU
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(1):70-80
ObjectiveTo investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism. MethodsC57BL/6J mice were randomly divided into saline group (Saline) and hypertension group (Ang Ⅱ, which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps), and supplemented daily with nicotinamide mononucleotide (300 mg/kg), a precursor of NAD+. Blood pressure, endothelial relaxation function and pulse wave velocity were measured after 4 weeks. Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro. mtROS levels were detected by immunofluorescence staining. RT-PCR was used to detect the mRNA expression of mtDNA, SIRT3 and isocitrate dehydrogenase 2 (IDH2). 8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay. The protein expression levels of p-eNOS, eNOS, SIRT3 and IDH2 were detected by Western blot. ResultsNMN supplementation reduced blood pressure (P<0.001) and improved endothelial function and arterial stiffness (P<0.001) in hypertensive mice. In vitro, NMN improved endothelial function in AngII-stimulated endothelial cells (P<0.05) and attenuated mitochondrial oxidative stress levels (P<0.001). Mechanistically, NMN elevated SIRT3 activity (P<0.001), which subsequently enhanced IDH activity (P<0.001) and reduced oxidative stress levels in endothelial cells. Conversely, knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function (P<0.001). ConclusionNAD+ lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.
2.Effects of MUC13 on the prognosis and biological behavior of gastric cancer
Xi-Long WANG ; Hong-Xing WANG ; Zhao-Gang DONG ; Yi TAN ; Yi ZHANG
Chinese Journal of Current Advances in General Surgery 2024;27(2):92-97
Objective:To explore the prognostic value of MUC13 expression in gastric cancer(GC)patients and its impact on the biological behavior of GC cells.Methods:Comprehensive anal-ysis of the expression pattern of MUC genes in GC tissues based on the TCGA database to screen for differentially expressed genes.Spearman correlation analysis determined the correlation of ex-pression between MUC genes in GC tissues.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway(KEGG)enrichment analysis were used to explore the potential biological functions of MUC genes.Univariate COX regression analysis was performed to explore the relationship between all differentially expressed MUC genes and the prog-nosis of GC patients to screen out MUC genes that were significantly related to the prognosis of GC.Clinical GC tissue samples were used to further verify the expression of MUC13 through im-munofluorescence,and its relationship with the clinicopathological characteristics and prognosis of GC was analyzed.siRNA was used to silence the expression of MUC13 in GC cells,and the effect of MUC13 on cell proliferation,migration and invasion was analyzed through CCK-8,colony forma-tion and Transwell experiments.Results:Among all MUC members,the expression levels of MUC1,MUC2,MUC3A,MUC4,MCU5B,MUC12,and MUC13 were significantly upregulated in GC tissues(P<0.05).There are certain interactions between these MUC genes,and they are mainly en-riched in pathways related to digestive system processes,epithelial structure maintenance,apical plasma membrane,saliva secretion,etc.Importantly,upregulation of MUC13 in GC tissues indicates poor patient prognosis(Log-rank P<0.05).In addition,MUC13 expression was significantly correlat-ed with the age(P<0.001)of GC patients and tumor size(P=0.035).Further cell function experiments showed that after silencing MUC13,the proliferation ability of GC cells was significantly reduced(P<0.05),while their migration and invasion abilities were not significantly affected(P>0.05).Con-clusions:Highly expressed MUC13 is closely related to the poor prognosis of gastric cancer,par-ticipates in the regulation of tumor progression and is a potential therapeutic target and prognostic marker for gastric cancer.
3.Correlation of ATF6 and IFN-α Expression with Clinicopathological Features and Prognosis in Laryngeal Squamous Cell Carcinoma
Kai XI ; Miaomiao ZHANG ; Xi ZHANG ; Tengteng ZHANG ; Bingwen XING
Journal of Modern Laboratory Medicine 2024;39(2):12-17
Objective To investigate the expression of activating transcription factor 6(ATF6)and interferon α(IFN-α)and their significance in laryngeal squamous cell carcinoma(LSCC)tissue.Methods A total of 100 LSCC patients admitted to Clinical Medical College of Henan University of Science and Technology/the First Affiliated Hospital of Henan University of Science and Technology from March 2015 to March 2020 were selected,and their clinicopathological features such as tumor location,degree of differentiation,and lymph node metastasis were collected and organized.Immunohistochemical method was applied to detect the expression of ATF6 and IFN-α in tissues.Spearman method was used to analyze the correlation between ATF6 and IFN-α expression in LSCC tissue.Kaplan-Meier method was applied to analyze the relationship between ATF6 and IFN-α expression in LSCC tissue and 3-year survival rate of patients.Cox regression was used to analyze the influencing factors of 3-year mortality in LSCC patients.Results The positive rate of ATF6 in LSCC tissue(76.00%)was higher than that in normal tissues adjacent to cancer(13.00%),the positive rate of IFN-α in LSCC tissue(29.00%)was lower than that in normal tissues adjacent to cancer(74.00%),and the difference was statistically significant(χ2=80.352,40.536,all P<0.05).The proportions of ATF6 positive expression in LSCC patients with TNM stage Ⅲ+Ⅳ,deep infiltration depth,and lymph node metastasis were significantly higher than those in LSCC patients with TNM stage Ⅰ+Ⅱ,shallow infiltration depth,and no lymph node metastasis(χ2=7.310,9.223,5.123,all P<0.05).The proportions of IFN-α negative expression in LSCC patients with TNM stage Ⅲ+Ⅳ,deep infiltration depth,and lymph node metastasis were significantly higher than those in LSCC patients with TNM stage Ⅰ+Ⅱ,shallow infiltration depth,and no lymph node metastasis(χ2=8.564,5.021,5.203,all P<0.05).There was a negative correlation between ATF6 and IFN-α expression in LSCC tissues(r=-0.415,P<0.05).The 3-year survival rate of LSCC patients in the ATF6 positive expression group(50.00%)was significantly lower than that in the ATF6 negative expression group(83.33%),while the 3-year survival rate of LSCC patients in the IFN-α positive expression group(82.76%)was significantly higher than that in the IFN-α negative expression group(47.89%)(Log rank χ2=8.002,10.854,all P<0.05).ATF6(HR=1.735,95%CI:1.159~2.598)and IFN-α(HR=0.624,95%CI:0.439~0.886)were influencing factors for the mortality of LSCC patients.Conclusion The positive expression rate of ATF6 increased and the positive expression rate of IFN-α decreased in LSCC tissues.They were closely related to the clinical pathological characteristics and prognosis of patients.
4.The Regulatory Function of ADAR1-mediated RNA Editing in Hematological Malignancies
Xing-Yu WAN ; Huan-Ping GUO ; Rui-Hao HUANG ; Xiao-Qi WANG ; Ling-Yu ZENG ; Tao WU ; Lin XIA ; Xi ZHANG
Progress in Biochemistry and Biophysics 2024;51(2):300-308
RNA editing, an essential post-transcriptional reaction occurring in double-stranded RNA (dsRNA), generates informational diversity in the transcriptome and proteome. In mammals, the main type of RNA editing is the conversion of adenosine to inosine (A-to-I), processed by adenosine deaminases acting on the RNAs (ADARs) family, and interpreted as guanosine during nucleotide base-pairing. It has been reported that millions of nucleotide sites in human transcriptome undergo A-to-I editing events, catalyzed by the primarily responsible enzyme, ADAR1. In hematological malignancies including myeloid/lymphocytic leukemia and multiple myeloma, dysregulation of ADAR1 directly impacts the A-to-I editing states occurring in coding regions, non-coding regions, and immature miRNA precursors. Subsequently, aberrant A-to-I editing states result in altered molecular events, such as protein-coding sequence changes, intron retention, alternative splicing, and miRNA biogenesis inhibition. As a vital factor of the generation and stemness maintenance in leukemia stem cells (LSCs), disordered RNA editing drives the chaos of molecular regulatory network and ultimately promotes the cell proliferation, apoptosis inhibition and drug resistance. At present, novel drugs designed to target RNA editing(e.g., rebecsinib) are under development and have achieved outstanding results in animal experiments. Compared with traditional antitumor drugs, epigenetic antitumor drugs are expected to overcome the shackle of drug resistance and recurrence in hematological malignancies, and provide new treatment options for patients. This review summarized the recent advances in the regulation mechanism of ADAR1-mediated RNA editing events in hematologic malignancies, and further discussed the medical potential and clinical application of ADAR1.
5.Implementation of surveillance,prevention and control of healthcare-asso-ciated infection in maternal and child healthcare institutions:A nation-wide investigation report
Shuo LI ; Xi YAO ; Hui-Xue JIA ; Wei-Guang LI ; Xun HUANG ; Shu-Mei SUN ; Xi CHENG ; Qing-Lan MENG ; Xiang ZHANG ; Jing-Ping ZHANG ; Ya-Wei XING ; Qing-Qing JIANG ; Lian-Xuan WU ; Bing-Li ZHANG ; Xiao-Jing LIU ; Liu-Yi LI
Chinese Journal of Infection Control 2024;23(3):323-329
Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24%of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66%,85.96%,80.77%,and 74.19%,respectively.51.22%MCH institutions adopted information surveillance system on HAI cases.94.31%MCH institutions carried out surveillance on hand hygiene compliance.Over 90%MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54%MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90%MCH insti-tutions established three-level pre-examination triage systems.86.18%set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50%.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.
6.The Application of Sugen Theory in the Pathogenesis of Asthma
Qiongqiong XING ; Rongyi ZHOU ; Leying XI ; Yiwen YU ; Shuzi ZHANG ; Suping YU ; Rui LIN ; Xianqing REN
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(6):645-652
Asthma is a common chronic respiratory disease characterized by repeated attacks and prolonged illness.Traditional Chinese medicine believes that the formation of Sugen is the core pathogenesis of repeated asthma attacks.By tracing the origin of Sug-en theory,summarizing the connotation of ancient asthma Sugen theory and the innovative understanding of modern medical scholars on asthma Sugen,this paper explores the potential connection between the traditional Chinese medicine Sugen theory and the pathogenesis of modern asthma,in order to provide new ideas and methods for the treatment and research of asthma.
7.Correlation between serum Irisin,pentraxin3,metastasis-associated lung ad-enocarcinoma transcript 1 levels and the severity of diabetic retinopathy and the value of combined diagnosis
Bo LI ; Mingyuan LIU ; Xing LI ; Xinqiao ZHANG ; Tingting CAO ; Xi WANG ; Zhaoxia LI ; Ling BAI
Recent Advances in Ophthalmology 2024;44(6):470-475
Objective To investigate the correlation between serum Irisin,long pentraxin 3(PTX3),human metas-tasis-associated lung adenocarcinoma transcript 1(MALAT1)levels and the severity of diabetic retinopathy(DR)and the value of combined diagnosis.Methods Eighty-five patients with type 2 diabetes mellitus(T2DM)combined with DR at Cangzhou Central Hospital from April 2022 to April 2023 were selected as the DR group,85 patients with T2DM alone were selected as the non-DR group,and 85 healthy volunteers were selected as the control group during the same period.Pa-tients in the DR group were further divided into the proliferative DR(PDR)group(38 patients)and the non-PDR group(47 patients)based on whether DR was in the proliferative phase.Clinical data of patients in the DR group were collected,including gender,diastolic pressure,age,systolic pressure,disease course,fasting plasma glucose(FPG),body mass in-dex,hemoglobin A1c(HbA1c),smoking history,triglyceride(TG),drinking history,peak systolic velocity(PSV),peak end-diastolic velocity(PEDV),resistance index(RI),fasting insulin(FINS),family history of diabetes,total cholesterol(TC),and homa-insulin resistance(HOMA-IR).Enzyme-linked immunosorbent assay was used to detect serum levels of Irisin and PTX3 in each group of patients,and real-time quantitative polymerase chain reaction was used to detect the ser-um level of MALAT1.The correlations between serum levels of Irisin,PTX3 and MALAT1 and the severity of DR were ana-lyzed using the Pearson correlation coefficient.The influencing factors of the DR severity were identified using the Logistic regression.The value of serum Irisin,PTX3,and MALAT1 levels in diagnosing DR alone was analyzed using the receiver operating characteristic(ROC)curve.The value of regimens containing and not containing serum Irisin,PTX3,and MAL-AT1 levels in diagnosing DR was analyzed using the ROC curve,net reclassification index(NRI),and integrated discrimina-tion improvement(IDI)index.Results The serum levels of Irisin,PTX3,and MALAT1 were compared among the three groups of patients,and the differences were statistically significant(all P<0.001).The disease course of patients in the PDR group was longer than that in the non-PDR group,the PSV,PEDV and serum Irisin level were lower than those in the non-PDR group,while the RI,FPG,HbA1c,TG,FINS,HOMA-IR,and serum PTX3 and MALAT1 levels were higher than those in the non-PDR group(all P<0.05).The serum Irisin level in DR patients was negatively correlated with the severity of DR(r=-0.512,P<0.001),while the PTX3 and MALAT1 levels were positively correlated with the severity of DR(r=0.497,0.573,both P<0.05).The Logistic regression analysis showed that the disease course,FPG,HbA1c,TG,FINS,HOMA-IR,PSV,PEDV,RI,and serum levels of Irisin,PTX3 and MALAT1 were influencing factors for the DR progression(allP<0.05).The area under the curve(AUC)of serum Irisin,PTX3,and MALAT1 levels in diagnosing DR was 0.743,0.811,and 0.773,respectively.Compared with conventional diagnostic protocols,the AUC of the new diagnostic protocol containing serum levels of Irisin,PTX3,and MALAT1 significantly increased(Z=2.708,P=0.007),and the NRI and IDI were 0.039(95%CI:0.022-0.069)and 0.026(95%CI:0.014-0.047),respectively(all P<0.05).Conclusion The serum Irisin level in DR patients decreases,while the serum PTX3 and MALAT1 levels increase,which are closely related to the severity of DR.Diagnostic plans containing serum Irisin,PTX3,and MALAT1 indicators have high diagnostic value.
8.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
9.Curative effect analysis of anterior cervical discectomy and fusion in patients with cervical spondylosis of vertebral artery type
Yi-Xiang AI ; Jian-Tao LIU ; Ding-Jun HAO ; Xi GONG ; Yi-Han ZHU ; Xing-Yuan LI ; Xi-Wei ZHANG ; Kao WANG ; Jia-Jun SUN ; Shu-Yuan ZHANG
China Journal of Orthopaedics and Traumatology 2024;37(7):670-675
Objective To investigate the clinical effect of anterior cervical discectomy and fusion(ACDF)in the treatment of cervical spondylosis of vertebral artery type(CSA).Methods The clinical data of 42 patients with CSA from January 2020 to January 2022 were retrospectively analyzed.There were 25 males and 17 females,aged from 30 to 74 years old with an average of(53.9±11.0)years old.There were 18 cases with single-segment lesions,17 cases with two-segment lesions,and 7 cases with three-segment lesions.The American Academy of Otolaryngology-Head and Neck Surgery's Hearing and Balance Committee score(CHE),the Neck Disability Index(NDI)and the cervical curvature Cobb angle were recorded before surgery and after surgery at 6 months.Results All 42 ACDF patients were followed up for 6 to 30 months with an average of(14.0±5.2)months.The operative time ranged from 95 to 220 min with an average of(160.38±36.77)min,the intraoperative blood loss ranged from 30 to 85 ml with an average of(53.60±18.98)ml.Tow patients had mild postoperative dysphagia,which improved with symptomatic treatment such as nebulized inhalation.CHE score decreased from(4.05±0.96)preoperatively to(2.40±0.70)at 6 months postoperatively(t=12.97,P<0.05).The number of improved vertigo at 6 months postoperatively was 38,with an im-provement rate of 90.5%.NDI score was reduced from(34.43±8.04)preoperatively to(20.76±3.91)at 6 months postopera-tively(t=1 1.83,P<0.05).The cervical curvature Cobb angle improved from(8.04±6.70)° preoperatively to(12.42±5.23)° at 6 months postoperatively(t=-15.96,P<0.05).Conclusion The ACDF procedure has outstanding clinical efficacy in treating CSA.The operation can rapidly relieve patients'episodic vertigo symptoms by relieving bony compression and reconstructing cervical curvature.However,it is necessary to strictly grasp the indications for surgery and clarify the causes of vertigo in pa-tients,and ACDF surgery is recommended for CSA patients for whom conservative treatment is ineffective.
10.Porcine SIRT5 promotes replication of foot and mouth disease virus type O in PK-15 cells
Guo-Hui CHEN ; Xi-Juan SHI ; Xin-Tian BIE ; Xing YANG ; Si-Yue ZHAO ; Da-Jun ZHANG ; Deng-Shuai ZHAO ; Wen-Qian YAN ; Ling-Ling CHEN ; Mei-Yu ZHAO ; Lu HE ; Hai-Xue ZHENG ; Xia LIU ; Ke-Shan ZHANG
Chinese Journal of Zoonoses 2024;40(5):421-429
The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

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