Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Diabetic cardiomyopathy (DCM) is a medical condition characterized by cardiac remodeling and dysfunction in individuals with diabetes mellitus. Sarcoplasmic reticulum (SR) and mitochondrial Ca²⁺ overload in cardiomyocytes have been recognized as biological hallmarks in DCM; however, the specific factors underlying these abnormalities remain largely unknown. In this study, we aimed to investigate the role of a cardiac-specific long noncoding RNA, D830005E20Rik (Trdn-as), in DCM. Our results revealed the remarkably upregulation of Trdn-as in the hearts of the DCM mice and cardiomyocytes treated with high glucose (HG). Knocking down Trdn-as in cardiac tissues significantly improved cardiac dysfunction and remodeling in the DCM mice. Conversely, Trdn-as overexpression resulted in cardiac damage resembling that observed in the DCM mice. At the cellular level, Trdn-as induced Ca²⁺ overload in the SR and mitochondria, leading to mitochondrial dysfunction. RNA-seq and bioinformatics analyses identified calsequestrin 2 (Casq2), a primary calcium-binding protein in the junctional SR, as a potential target of Trdn-as. Further investigations revealed that Trdn-as facilitated the recruitment of METTL14 to the Casq2 mRNA, thereby enhancing the m⁶A modification of Casq2. This modification increased the stability of Casq2 mRNA and subsequently led to increased protein expression. When Casq2 was knocked down, the promoting effects of Trdn-as on Ca²⁺ overload and mitochondrial damage were mitigated. These findings provide valuable insights into the pathogenesis of DCM and suggest Trdn-as as a potential therapeutic target for this condition.
Animals ; Diabetic Cardiomyopathies/pathology* ; RNA, Long Noncoding/genetics* ; Myocytes, Cardiac/metabolism* ; Mice ; Calsequestrin/genetics* ; Calcium/metabolism* ; Male ; Sarcoplasmic Reticulum/metabolism* ; Methyltransferases/metabolism* ; Mice, Inbred C57BL ; Mitochondria, Heart/metabolism* ; Disease Models, Animal ; Mitochondria/metabolism*

Purpose/Significance To analyze the network security risk events monitored by the situational awareness platform of large hospitals,to find out the causes,and to put forward solutions and suggestions for improvement.Method/Process Taking the First Affiliated Hospital of Zhengzhou University as an example,the paper analyzes risk events on the situational awareness platform,screens the risky ter-minals on the hospital intranet,carries out rectification and reinforcement,analyzes the department distribution and causes of risky termi-nals,and puts forward suggestions for improvement.Result/Conclusion The number of risky terminals in medical and technical depart-ments is large,mainly due to the lack of management and the lack of full coverage of antivirus software.Through the rectification and rein-forcement of risky terminals,the number of network security risk events has been significantly reduced.Strengthening the hospital terminal security management,enhancing staff awareness of network security,and strengthening network security protection in different areas can ef-fectively reduce the incidence of hospital network security risk events and improve the hospital network security protection capability.

OBJECTIVE: The present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule (LTC) on ischemic stroke rats. METHODS: Twenty-six rats were randomly divided into four groups, including sham group, sham + LTC group, MCAO group, and MCAO + LTC group. Ischemic stroke rats were simulated by middle cerebral artery occlusion (MCAO), and LTC treatment group were orally administrated with 300 mg/kg of LTC once daily for seven consecutive days. LTC therapy was validated in terms of neurobehavioral abnormality evaluation, cerebral infarct area, and histological assessments. The plasma metabolome comparisons amongst different groups were conducted by UHPLC-Q Exactive MS in combination with subsequent multivariate statistical analysis, aiming to finding the molecules in respond to the surgery or LTC treatment. RESULTS: Intragastric administration of LTC significantly decreased not only the neurobehavioral abnormality scores but also the cerebral infarct area of MCAO rats. The interstitial edema, atrophy, and pyknosis of glial and neuronal cells occurred in the infarcted area, core area, and marginal area of cerebral cortex were improved after LTC treatment. A total of 13 potential biomarkers were observed, and Youden index of 11 biomarkers such as LysoPC, SM, and PE were more than 0.7, which were involved in neuroprotective process. The correlation and pathway analysis showed that LTC was beneficial to ischemic stroke rats via regulating glycerophospholipid and sphingolipid metabolism, together with nicotinate and nicotinamide metabolism. Heatmap and ternary analysis indicated the synergistic effect of carbohydrates and lipids may be induced by flavonoid intake from LTC. CONCLUSION The present study could provide evidence that metabolomics, as systematic approach, revealed its capacity to evaluate the holistic efficacy of TCM, and investigate the molecular mechanism underlying the clinical treatment of LTC on ischemic stroke.

Objective:To investigate the clinical practice level and influencing factors of geriatric nursing specialist nurses.Methods:This study was a cross-sectional survey. Using the convenient sampling method, a total of 332 specialist nurses from 5 phases trained by Beijing Nursing Association from January to February 2021 were selected as the research objects. The general data questionnaire, Questionnaire on Clinical Practice Level of Geriatric Nursing Specialist Nurses, Questionnaire on Unit Support for Geriatric Nurses and Core Competence Self-Assessment Scale of Geriatric Nursing Specialist Nurses were used to investigate the nurses. Pearson correlation was used to analyze the relationship between unit support, self-assessment of core competence and practice level. Multiple linear regression was used to analyze the factors influencing the clinical practice level of geriatric nurses. A total of 332 questionnaires were distributed, 306 questionnaires were returned and 298 were valid questionnaires.Results:The total mean score of clinical practice of geriatric nursing specialist nurses was (3.42±0.83) . The results of multiple linear regression analysis showed that the work department, unit support and core competence were the influencing factors of the clinical practice level of geriatric nursing specialist nurses ( P<0.05) . Conclusions:Specialist nurses who work in the geriatric ward, have a high degree of unit support and have a high level of core competence have a higher clinical practice level.

Objective:To investigate the effect of sevoflurane anesthesia on electroencephalographic (EEG) seizures and long-term behavior and possible mechanism in neonatal rats.Methods:A total of 141 postnatal days 4-6 Sprague-Dawley rats (66 male, 75 female) were divided into 3 groups ( n=47 in each group) according to random number table method: control group, sevoflurane group, and NKCC1 inhibitor group, with 22 males and 25 females in each group. Rats in the control group were fed in normal cage without anesthesia; rats in the sevoflurane group were anesthetized with 2.1% sevoflurane for 6 hours; rats in the NKCC1 blocker group received intraperitoneal injection of 1.82 mg / kg bumetanide 30 minutes before anesthesia with 2.1% sevoflurane. The rats in the control group and sevoflurane group were injected subcutaneously with the same dose of DMSO at the same time when the NKCC1 blocker group received the drug intervention, so as to eliminate the influence caused by the solvent. The rats were observed for 30 minutes after recovery from anesthesia and then continued to breastfeed normally. Some of the new born rats received EEG monitoring from 9 to 11 days after being raised; the other rats received EPM and PPI respectively at 60 and 70 days after being raised. Results:The results of EEG showed that, compared with the control group, the number of epileptic waves((0.429±0.787), (1.571±0.787), t=2.753, P<0.01), the average duration of single epileptic wave ((1.575±2.349), (6.392±3.374), t=3.880, P< 0.01), the total duration increased significantly ((1.800±3.617), (10.957±6.028), t= 3.929, P<0.01) were all increased, the differences were statistically significant. Compared with sevoflurane group, the number of epileptic waves in EEG of male rats in NKCC1 blocker group decreased, the average duration of single epileptic wave decreased, and the total duration of epileptic wave shortened significantly, with statistical significance ((0.286±0.756), (0.925±1.733), (1.043±2.759), t=3.097, 4.404, 4.254, all P<0.01). There were no significant differences in female rat among the three groups (all P>0.05). Compared with male rats, the average duration of female rats in sevoflurane group decreased ((6.392±3.374), (2.515±2.992), t=3.044, P<0.01), the total duration shortened ((10.957±6.028), (3.270±5.883), t=2.626, P<0.01), the difference was statistically significant.The behavioral results showed that, compared with the control group, the open arm dwell time of male rats in sevoflurane group was significantly shorter ( P<0.05), and the panic response in PPI group was significantly lower ( P<0.05), the difference was statistically significant.Compared with the sevoflurane group, the open arm dwell time in NKCC1 blocker group was significantly longer ( P<0.05), and the panic response in PPI group was significantly increased.The difference was statistically significant ( P<0.05). The change trend in female rats of each group was similar to that of male rats, but there was no significant difference (all P>0.05). Comparison between male and female rats: compared with male rats in sevoflurane group, the female rats in sevoflurane group had a longer open arm stay time in EPM experiment ( P<0.05), the difference was statistically significant. Conclusion:Sevoflurane anesthesia for 6 hours can significantly increase the generation of epileptic waves in EEG of male newborn rats, and cause behavioral abnormalities in adult male rats, which may be related to NKCC1.And male rats are more vulnerable to the negative effects of sevoflurane anesthesia on brain nerve development.

Objective Comprehensive evaluated the characteristics and differences of prevalence of hypertension in cold and non-cold areas,to provide evidence-based prevention strategies for establishment and perfection hypertension prevention and control suitable for China's national conditions in cold area.Methods Northeast China (Heilongjiang,Jilin,Liaoning),Inner Mongolia,Ningxia,Gansu,Qinghai,Tibet and Xinjiang were classified as cold area,and the rest were non-cold area.Use hypertension as a search term,literatures on the prevalence of hypertension were retrieved in WanFang Data,CqVip,CNKI,SinoMed and Pubmed database from January 1 1995 to May 1 2017,then the relevant data were screened and extracted.Heterogeneity was estimated and corresponding effect model was selected.Publication bias was evaluated by funnel plot,Egger test and Begg test.Comprehensive meta-analysis V2 was used for Meta analysis,stratified analysis of age,gender,province and region was did.Results In China,the pooled prevalence of hypertension was 27.00％.The pooled awareness rate of hypertension was 50.80％,the pooled treatment rate of hypertension was 40.40％,and the pooled control rate was 6.80％.The pooled prevalence in cold area was 29.70％ and 26.30％ in non-cold area,respectively,the difference of prevalence between cold and non-cold areas was significant (P ＜ 0.05).After the stratified analysis of age and gender,the pooled prevalence in men and women in cold area had a increased trend than that in non-cold area;the pooled prevalence in ＜ 30,40-,50-,and 60-＜ 70 years old groups in cold area was higher than that in non-cold area.The pooled prevalence was the highest in Tibet (40.70％) and north and northeast China area (30.40％,29.20％),and the lowest in Hainan (16.70％) and southern China area (20.70％).Conclusions In China,the pooled prevalence of hypertension is 27.00％,which is higher in cold area than non-cold area.The pooled prevalence is the highest in Tibet and north and northeast China,and the lowest in Hainan and Southern China.

Objective The amyloid β-protein precursor contains a domain highly homologous to Kunitz-type serine protease inhibitors. We have successfully established and characterized the recombinant human rhKD/APP in vitro. The aim of this study is to investigate the potential neuroprotective role of rhKD/APP on cerebral ischemia/reperfusion injury in rats. Methods Rats pretreated with rhKD/APP (4, 8, 16 mg/kg) were subjected to prepare models of cerebral ischemia/reperfusion (I/R) injury and those rats treated with Nimodipine were used as positive control. Comparison of the scores of neurological deficits, TTC-stained infarct volume and cerebral water content between the groups was performed. The activities of SOD, Na+-K+-ATPase and the content of MDA in the cortex tissues were measured and the activities of serum myeloperoxidase ( MPO) enzyme were also compared. The expressions of adhesion molecules ( ICAM-1 and E-selectin) were compared by immunohistochemistry. End-labeling of nuclear DNA fragmentation (TUNEL) and qualification of caspase-3, Bcl-2 and Bax were also employed to evaluate the local apoptosis in cortex tissues. Results By pretreatment with the rhKD/APP at three doses, cerebral infarct volume, water content and neurological deficits were all reduced. The activities of SOD, and Na+-K+-ATPase were increased, the contents of MDA were decreased in the cortex tissues, and the serum MPO activity was reduced. The expressions of adhesion molecules were downregulated and the apoptotic signaling of neurons were inhibited. All the changes induced by rhKD/APP treatment in the ischemia/reperfusion injury models showed statistical significance compared with the control rats. However, no significant difference was shown between the rhKD/APP group and Nimodipine group excepted for the reduced MPO in sera. Conclusions The result of this study suggest that rhKD/APP has neuroprotective effect on the cerebral ischemia/reperfusion injury through inhibiting multiple signaling pathways and is promising to be a potential neuroprotective drug.

Objective To summarize the diagnosis and treatment of congenital pulmonary airway malformation in children.Methods The clinical data of 68 children with congenital pulmonary airway malformations from June 2014 to June 2017 were analyzed retrospectively,including 39 males and 29 females with mean age(1.1 ±:0.5) years old(from 2 months 12 days to 15 years),7 cases of pulmonary cyst resection in 68 cases,3 cases with lung segment resection,1 cases with lingulectomy,57 cases with lobectomy.Results 68 cases were cured and discharged without death.Postoperative short-term complications included subcutaneous emphysema in 5 cases,pleural effusion in 2 cases,pneumothorax in 2 cases.All cases were followed up well between 3 months and 1 year.Conclusion The diagnosis of congenital pulmonary airway malformation in children mainly depends on imaging examination.Because it is easy to repeat infection,and can not rule out malignant transformation,early diagnosis and early treatment should be done.Surgical resection is the only way to treat the disease.