1.Clinical and genetic analysis of essential hypertension with mitochondrial tRNAMet 4435A>G and YARS2 mutation
Meili GUO ; Yunfan HE ; Ade CHEN ; Zaishou ZHUANG ; Xiaoyong PAN ; Minxin GUAN
Journal of Zhejiang University. Medical sciences 2024;53(2):184-193
Objective:To investigate the role of m.4435A>G and YARS2 c.572G>T(p.G191V)mutations in the development of essential hypertension.Methods:A hypertensive patient with m.4435A>G and YARS2 p.G191V mutations was identified from previously collected mitochondrial genome and exon sequencing data.Clinical data were collected,and a molecular genetic study was conducted in the proband and his family members.Peripheral venous blood was collected,and immortalized lymphocyte lines constructed.The mitochondrial transfer RNA(tRNA),mitochondrial protein,adenosine triphosphate(ATP),mitochondrial membrane potential(MMP),and reactive oxygen species(ROS)in the constructed lymphocyte cell lines were measured.Results:Mitochondrial genome sequencing showed that all maternal members carried a highly conserved m.4435A>G mutation.The m.4435A>G mutation might affect the secondary structure and folding free energy of mitochondrial tRNA and change its stability,which may influence the anticodon ring structure.Compared with the control group,the cell lines carrying m.4435A>G and YARS2 p.G191V mutations had decreased mitochondrial tRNA homeostasis,mitochondrial protein expression,ATP production and MMP levels,as well as increased ROS levels(all P<0.05).Conclusion:The YARS2 p.G191V mutation aggravates the changes in mitochondrial translation and mitochondrial function caused by m.4435A>G through affecting the steady-state level of mitochondrial tRNA and further leads to cell dysfunction,indicating that YARS2 p.G191V and m.4435A>G mutations have a synergistic effect in this family and jointly participate in the occurrence and development of essential hypertension.
2.Investigation and control of a suspected outbreak of healthcare acquired infection caused by carbapen-em-resistant klebsiella pneumonia in intensive care unit of neurology department
Shuqi WANG ; Ping ZHOU ; Meili ZHOU ; Dongqin CHEN
Modern Hospital 2024;24(7):1130-1133
Objective To investigate the cause of a suspected outbreak of carbapenem-resistant Klebsiella pneumoniae infection(CRKP)in the neurological ICU,to find out the reason for infection and the way of transmission to provide evidence for the prevention and control of nosocomial infection.Methods Four patients with CRKP infection in the department of neurological ICU of a hospital from Au-gust 4 to August 20,2020 were investigated epidemiologically and environmental hygiene monitoring of the ward was carried out.Compre-hensive measures were taken to control the outbreak.Results All four CRKP infection cases were hospital-acquired,and the isolated strains showed consistent drug susceptibility test results,indicating they were the same clone.Environmental hygiene monitoring revealed the presence of the same clone in samples from patient bedside items,suction devices,oxygen therapy equipment,and personal belongings of healthcare workers.After implementing comprehensive corrective measures,no new cases of CRKP infection occurred,and subsequent surface sampling did not isolate any CRKP strains.Conclusion Environmental surface contamination in the neurointensive care unit and inadequate disinfection procedures were likely the main causes of the suspected outbreak of CRKP infection.Prompt identification of the outbreak,activation of emergency response plans,and implementation of corrective measures are crucial for controlling the outbreak of multidrug-resistant bacterial infections in hospitals.After adopting comprehensive measures,there were no new CRKP infection cases.
3.Chronic intermittent hypoxia impairs learning and memory by upregulating HMGB1 and NF-κB in rat hippocampus
Zhengang WU ; Yao XIAO ; Yafang CHEN ; Jinying ZHANG ; Zeming GUO ; Jun LIN ; Meili YANG
Chinese Journal of Neuroanatomy 2024;40(2):224-230
Objective:To explore the effect of chronic intermittent hypoxia(CIH)on learning and memory dysfunc-tion in rats,as well as the expression of high mobility group box-1(HMGB1)and nuclear transcription factor-KB(NF-κB)in the hippocampus region.Methods:The CIH rat model was established,and forty SD rats were randomly divid-ed into four groups:normoxia group,hypoxia for 4 weeks group(CIH4 group),hypoxia for 8 weeks group(CIH8 group),and hypoxia for 12 weeks group(CIH12 group).Morris water maze was used to assess the learning memory ability of rats,and immunohistochemistry and ELISA were used to detect the expression of HMGB1 and NF-κB in the hippocampus of rats.Results:Compared with the normoxia group,the CIH12 and CIH8 groups had longer escape la-tency,the number of crossing the platform and the residence time in the quadrant of the platform were significantly shortened,but there was no significant difference in the CIH4 group.Additionally,there was no significant expression of HMGB1 and NF-κB in the hippocampal region of the normoxia group,but little expression was observed in CIH4 group,and significantly expressed in CIH8 group and CIH12 group,and the expression of CIH12 group was significantly higher than that of CIH8 group.Conclusion:CIH can lead to a decline in learning and memory function in rats,and the longer time of intermittent hypoxia led to the more significant effect on their learning and memory function.In addi-tion,CIH also leads to increased expression levels of HMGB1 and NF-κB in the hippocampus region,and the expres-sion increased more significantly after hypoxia for 12 weeks,comparing to hypoxia for 8 weeks.
4.Association of neutrophil gelatinase-associated lipocalin and severity of coronary stenosis in patients with stable coronary artery disease
Li ZHU ; Minghao HE ; Meili ZHOU ; Shengchao WANG ; Kun CHEN
China Modern Doctor 2024;62(23):57-62
Objective To investigate the association of neutrophil gelatinase-associated lipocalin(NGAL)and severity of coronary stenosis in patients with stable coronary artery disease(SCAD).Methods Totally 144 patients who underwent coronary angiography firstly due to suspected coronary artery disease were enrolled.The patients were divided into SCAD group(n=101)and non-CAD group(n=43),and the clinical data were compared.The SCAD group was fuether divided into three subgroups accoding to Gensini score:mild stenosis group(Gensini<16,n=32),moderate stenosis(16≤Gensini<30,n=33)and severe stenosis group(Gensini≥36,n=35).The clinical data of each group were compared.Odinal Logistic regression was used to analysis the influencing factors of severe stenosis.The receiver operating characteristic(ROC)curve was performed to evaluated the ability of NGAL in discriminating severe stenosis.Results Serum NGAL,high sensitive C-reactive protein(hs-CRP)level in SCAD group were higher than those in non-CAD group(P<0.01).Comparing with mild and moderate stenosis groups,NGAL and hs-CRP level were more higher in severe stenosis group(P<0.01).Multivariable Logistic regression analysis showed that NGAL and hs-CRP were independent risk factors for severe coronary stenosis(both P<0.05).Receiver operating characteristic(ROC)curve analysis showed that the areas under the curve of NGAL and hs-CRP were 0.771,0.702 respectively(both P<0.01).The difference between two AUCs was 0.069 which was insignificant(P>0.05).Conclusion Serum NGAL increased is closely associated with severe coronary stenosis in patients with SCAD,which has a certain ability of discriminating severity of coronary stenosis.
5.Pharmacological Interventions for Cirrhotic Ascites: From Challenges to Emerging Therapeutic Horizons
Yuan GAO ; Xin LIU ; Yunyi GAO ; Meili DUAN ; Bing HOU ; Yu CHEN
Gut and Liver 2024;18(6):934-948
Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited. A comprehensive understanding of the underlying pathophysiological mechanism of ascites is crucial for its optimal management. The renin-angiotensin-aldosterone system (RAAS) is increasingly believed to play a pivotal role in the formation of cirrhotic ascites, as RAAS overactivation leads to a reduction in urine sodium excretion then a decrease in the ability of the kidneys to excrete water. In this review, the authors provide an overview of the pathogenesis of cirrhotic ascites, the challenges associated with current pharmacologic treatments, and the previous attempts to modulate the RAAS, followed by a description of some emerging targeted RAAS agents with the potential to be used to treat ascites.
6.Pharmacological Interventions for Cirrhotic Ascites: From Challenges to Emerging Therapeutic Horizons
Yuan GAO ; Xin LIU ; Yunyi GAO ; Meili DUAN ; Bing HOU ; Yu CHEN
Gut and Liver 2024;18(6):934-948
Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited. A comprehensive understanding of the underlying pathophysiological mechanism of ascites is crucial for its optimal management. The renin-angiotensin-aldosterone system (RAAS) is increasingly believed to play a pivotal role in the formation of cirrhotic ascites, as RAAS overactivation leads to a reduction in urine sodium excretion then a decrease in the ability of the kidneys to excrete water. In this review, the authors provide an overview of the pathogenesis of cirrhotic ascites, the challenges associated with current pharmacologic treatments, and the previous attempts to modulate the RAAS, followed by a description of some emerging targeted RAAS agents with the potential to be used to treat ascites.
7.Pharmacological Interventions for Cirrhotic Ascites: From Challenges to Emerging Therapeutic Horizons
Yuan GAO ; Xin LIU ; Yunyi GAO ; Meili DUAN ; Bing HOU ; Yu CHEN
Gut and Liver 2024;18(6):934-948
Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited. A comprehensive understanding of the underlying pathophysiological mechanism of ascites is crucial for its optimal management. The renin-angiotensin-aldosterone system (RAAS) is increasingly believed to play a pivotal role in the formation of cirrhotic ascites, as RAAS overactivation leads to a reduction in urine sodium excretion then a decrease in the ability of the kidneys to excrete water. In this review, the authors provide an overview of the pathogenesis of cirrhotic ascites, the challenges associated with current pharmacologic treatments, and the previous attempts to modulate the RAAS, followed by a description of some emerging targeted RAAS agents with the potential to be used to treat ascites.
8.Pharmacological Interventions for Cirrhotic Ascites: From Challenges to Emerging Therapeutic Horizons
Yuan GAO ; Xin LIU ; Yunyi GAO ; Meili DUAN ; Bing HOU ; Yu CHEN
Gut and Liver 2024;18(6):934-948
Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited. A comprehensive understanding of the underlying pathophysiological mechanism of ascites is crucial for its optimal management. The renin-angiotensin-aldosterone system (RAAS) is increasingly believed to play a pivotal role in the formation of cirrhotic ascites, as RAAS overactivation leads to a reduction in urine sodium excretion then a decrease in the ability of the kidneys to excrete water. In this review, the authors provide an overview of the pathogenesis of cirrhotic ascites, the challenges associated with current pharmacologic treatments, and the previous attempts to modulate the RAAS, followed by a description of some emerging targeted RAAS agents with the potential to be used to treat ascites.
9.Glycyrrhizic acid⁃mediated protective effect of miRNAs on alcoholic liver inj ury in rats
Meili Cong ; Mayire Nuermaimaiti ; Bei Zhou ; Ruihua Chen ; Zhong Wang ; Huhu Zhu ; Xiaoguo Zhao
Acta Universitatis Medicinalis Anhui 2023;58(8):1374-1379
Objective :
To investigate the mechanism of miRNAs in glycyrrhizic acid treatment of alcohol⁃induced
liver injury in rats .
Methods :
45 male SD rats were randomly divided into glycyrrhizin group , model group and control group . The rats in glycyrrhizin group were given 56% liquor and glycyrrhizin , the rats in model group were
given 56% liquor , and the rats in control group were given distilled water for 8 weeks . The blood was collected and the serum was separated by centrifugation to detect the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) . RNA were extracted from liver tissues , miRNAs were detected by rat miRNA microarray , and their expression levels were analyzed . The miRNA target genes of differential miRNA were predicted . Gene Ontology (GO) and KEGG Pathway enrichment analysis were used to understand the function of differential miRNA , and the differential miRNA⁃mRNA⁃Pathway regulatory network was constructed using Cytoscape to further screen the regulatory key miRNA and key pathways . qRT⁃PCR was used to verify the expression of selected miRNA .
Results :
Compared with the model group , the glycyrrhizin group could significantly improve the liver tissue lesions , and reduce the liver serum AST and ALT levels (P < 0. 05) . Compared the microarray data of glycyrrhizin group and model group , a total of 13 differentially expressed miRNA were screened ( P < 0. 05 , fold change ≥ 1 . 5) , of which 10 were up⁃regulated and 3 were down⁃regulated . The GO classification annotation of differential miRNA target genes showed that differential miRNA were related to cell adhesion , antioxidant activity , metabolic process , biological process regulation , cell killing , immune system and other functions . The KEGG Pathway analyling pathway , Hippo signaling pathway , PI3K⁃Akt signaling pathway , wnt signaling pathway , apoptosis and other signaling pathways might play an important regulatory role in the improvement of alcoholic liver injury by glycyrrhic acid .
Conclusion
This study established the miRNA expression profile of glycyrrhizin in the treatment of alcoholic liver injury in rats , suggested that miR⁃615 , miR⁃107 ⁃3p and miR⁃292⁃5p might play an important role in the treatment of alcoholic liver injury by glycyrrhizin .
10.Application of pediatric early warning score ruler of children in the nursing of critically ill children in neurology department
Yan LI ; Meili LIU ; Meng LIANG ; Yuewei CHEN ; Wei LIU
Chinese Journal of Practical Nursing 2022;38(4):284-289
Objective:To design a pediatric early warning score (PEWS) ruler and observe the effect of its application in the nursing of critically ill children hospitalized in neurology department.Methods:A total of 200 critically ill children admitted to Department of Neurology of Hunan Children′s Hospital from 2018 to 2019. 98 cases who were hospitalized from January to September 2019 were selected as the observation group, and 102 cases who were hospitalized from January to September 2018 were set as the control group. The control group received conventional care, while the observation group conducted PEWS ruler for nursing intervention on the basis of conventional care. The differences in hospital days, ICU transfer rate, and frequency of medical intervention between the two groups were compared.Results:The hospital days of the control group and observation group were 18.17 ± 6.33 and 13.33 ± 6.38 respectively, and the difference between the two groups was significant ( t=5.38, P<0.01). The ICU transfer rate was significantly different between the control group 17.6% (18/102) and observation group 8.2% (8/98) ( χ2=3.98, P<0.05). The reduction of increased intracranial pressure, cooling, calm, sedation and oxygen breathing in the control group were 6.86% (7/102), 13.73% (14/102), 6.86% (7/102), 7.84% (8/102), while the observation group were 17.35% (17/98), 27.55% (27/98), 24.49% (24/98), 28.57% (28/98), and the differences between the two groups were significant ( χ2 values were 5.20-14.55, all P<0.05). Conclusions:The application of PEWS ruler is helpful for nurses to recognize the progress of diseases of the critically ill children. Also, it can shorten the hospitalization days of these children, reduce the ICU transfer rate, as well as improve the nursing quality for them.


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