Objective To detect the impact of Diltiazem on the major adverse cardiac events (MACE) in six months after percutaneous coronary intervention (PCI).Methods A total of 192 patients after PCI with coronary atherosclerotic heart disease were enrolled in this study.The patients were randomly divided into Diltiazem therapy group (101 patients) and non-Diltiazem therapy group (91 patients).The high-sensitivity C-reactive protein (hs-CRP) was assessed before and 24 h after PCI,and the incidence of Major adverse cardiovascular events(MACEs) were assessed at the sixth month after PCI.Results Compared with before PCI,hs-CRP level increased significantly in both group after PCI (P＜0.01),but hs-CRP level was lower in Diltiazem therapy group than in non-Diltiazem therapy group (P＜0.05).Compared with non-Diltiazem therapy group,there was lower incidence of MACEs during six months follow-up in Diltiazem therapy group.Conclusions Diltiazem can decrease the incidence of MACEs during six months after PCI.

Objective:To investigate the effect of verapamil on the endotoxin-induced cytokine production and nuclear factor kappa B(NF-?B) activation in the liver. Methods:Fifty six adult male Sprague-Dawley rats were randomly divided into seven groups: group A: saline;group B:endotoxin(10 mg/kg,intraperitoneally,i.p.);group C,D,E,F:endotoxin(10 mg/kg) after treatment with verapamil(1,2.5,5,10 mg/kg i.p.respectively),and group G:verapamil alone(10 mg/kg).Tumor necrosis factor(TNF-?),interleukin-6(IL-6), interleukin-10(IL-10) and NF-?B in the liver tissues and the serum levels of ALT and AST were investigated at 1 h afer LPS injection. Results:Endotoxin stimulated production of TNF-?,IL-6 and IL-10,and activated NF?B in the liver.Verapamil attenuated acute liver injury,down-regulated endotoxin-induced pro-inflammatory cytokine production,up-regulated ant-inflammatory cytokines production and inhibited NF-?B activation in the liver in a dose-dependent manner.Conclusion:Verapamil can attenuate acute liver injury by down-regulating the production of TNF-?,IL-6 and up-regulating IL-10 in the liver in a dose-dependent manner,possibly via inhibition of NF-?B.

Objective To explore the clinical effect of the endoscopic electrocoagulation combined with nasal micro packing in the treatment of refractory epistaxis .Methods 120 patients with refractory epistaxis were selected as the research subjects ,and they were divided into two groups by the single blind randomly methods ,60 cases in each group.The control group was given vaseline gauze for hemostasis of nasal cavity ,and the observation group received endoscopic electrocoagulation combined with nasal packing hemostasis micro treatment .The cure rate ,the incidence of complications ,recovery of nasal mucosa of nasal ventilation time , recovery time , the total amount of bleeding , pain score and recurrence rate of the two groups were compared .Results The cure rate in the observation group was 96.67％,which was significantly higher than 81.67％ in the control group(χ2 =6.988,P<0.05).The incidence rate of complications and pain score in the observation group were 8.33％,(3.65 ±1.09)points,respectively,which were significantly lower than 21.67％,(5.23 ±1.72) points in the control group (χ2 =4.183,t =6.010,all P<0.05).The total amount of bleeding significantly reduced (t=6.344,P<0.05),the recovery of nasal ventilation time and recovery time of nasal mucosa significantly decreased (t=7.119,6.183,all P<0.05).The patients were followed up for 6 months,the recurrence rate in the observation group was 1.67％,which was significantly lower than 11.67％in the control group(χ2 =4.821,P<0.05).Conclusion The endoscopic electric coagulation combined with nasal micro packing in the treatment of refractory epistaxis has significant effect ,it can effectively promote the recovery of patients,reduce complications and recurrence ,the prognosis is good .

Objective: To investigate the sleep and mental health status of adolescents in Shandong Province, to explore the correlation between sleep and mental health, so as to provide a basis for adolescent physical and mental health management. Methods: From February to March 2023,a multistage stratified whole cluster sampling method was used to randomly select 3 cities in Shandong Province, one urban area and one township in each city, one junior high school and one senior high school in the urban area and the township, respectively, and then 4 classes were randomly selected from each grade level of each school, and all 3 667 students in the classes were surveyed by using the Pittsburgh Sleep Quality Index Scale (PSQI) short form and the Chinese Middle School Students Mental Health Inventory (MMHI-60). Results: The prevalence of sleep deprivation among adolescents in Shandong Province was 37.44%, and the detection rate of psychological problems was 46.41%. Adolescent psychology could be divided into four latent categories:psychological immune group (39.6%), psychological low risk group (12.2%), psychological medium risk group (13.2%) and psychological high risk group (35.0%). Multifactorial Logistic regression analyses showed that gender, school year, sleep duration and sleep quality were influencing factors for the psychological latent categories ( OR =1.39-9.55, P < 0.05 ), and that adolescents with sleep deprivation and poor sleep quality were more inclined to be classified as being in the psychological medium and high risk groups. Conclusions The sleep and mental health of adolescents in Shandong Province is not very good. Comprehensive prevention and control of psychological problems should not only focus on personality and psychological characteristics, but also need to be combined with the sleep condition of adolescents.

Objective To explore the changes and significance of serum vitamin A levels in children with community acquired pneumonia. Methods A total of 80 children with community-acquired pneumonia (pneumonia group) were selected from October 2015 to March 2016 and were divided into Mycoplasma pneumoniae (MP) infection group, bacteria infection group, MP and bacteria mixed infection group (mixed infection group) according to different pathogens. Thirty healthy children in the same period were selected as the control group. The serum vitamin A concentration was detected by ultra-high-performance liquid chromatography-tandem mass spectrometry. Results The level of serum vitamin A was (0.567±0.163) μmol/L in pneumonia group, (0.578±0.162) μmol/L in MP infection group, (0.557±0.153) μmol/L in bacteria infection group and (0.554±0.186) μmol/L in mixed infection group, and all of them were lower than that in control group (0.759±0.160) μmol/L, and there were significant differences (P<0.05). There was no difference in serum vitamin A level among MP infection group, bacteria infection group and mixed infection group (P>0.05). There was a significant difference in the distribution of vitamin A deficiency between pneumonia group and control group ( P<0.001). The proportion of suspected subclinical vitamin A deficiency in control group was higher, while vitamin A deficiency and subclinical vitamin A deficiency in pneumonia group were higher. Conclusions The serum vitamin A level decreased in children with community-acquired pneumonia, But there was no significant differences in serum vitamin A levels among the children with pneumonia caused by different pathogens.

Since the first Drug Administration Law was issued in 1984， the drug regulation of China has undergone a forty- year process. During these four decades， China’s drug regulatory system has gradually transitioned from being extensive to refined， and the concept of supervision has become increasingly scientific. This paper first outlines the historical evolution of China’s drug regulatory laws and regulations since the founding of the People’s Republic of China， with a focus on the historical origins of the revision of the Drug Administration Law during 1984-2001. It also clarifies the new challenges faced by drug regulation as the industry innovates and develops， as well as the corresponding reform of the drug review and approval system. The paper summarizes the reform achievements of drug regulation. By studying and analyzing the challenges faced by drug regulation in terms of regulatory capacity， regulatory resources， and regulatory system in the context of internationalization of the industry， the paper proposes policy suggestions such as establishing a cross-regional regulatory system， reforming the review mechanism， strengthening the construction of the review team， and enhancing transparency in regulatory practices， with the aim of promoting the high-quality development of the pharmaceutical industry.

Traumatic brain injury (TBI) contributes to the key causative elements of neurological deficits. However, no effective therapeutics have been developed yet. In our previous work, extracellular vesicles (EVs) secreted by stem cells from human exfoliated deciduous teeth (SHED) offered new insights as potential strategies for functional recovery of TBI. The current study aims to elucidate the mechanism of action, providing novel therapeutic targets for future clinical interventions. With the miRNA array performed and Real-time PCR validated, we revealed the crucial function of miR-330-5p transferred by SHED-derived EVs (SHED-EVs) in regulating microglia, the critical immune modulator in central nervous system. MiR-330-5p targeted Ehmt2 and mediated the transcription of CXCL14 to promote M2 microglia polarization and inhibit M1 polarization. Identified in our in vivo data, SHED-EVs and their effector miR-330-5p alleviated the secretion of inflammatory cytokines and resumed the motor functional recovery of TBI rats. In summary, by transferring miR-330-5p, SHED-EVs favored anti-inflammatory microglia polarization through Ehmt2 mediated CXCL14 transcription in treating traumatic brain injury.
Animals ; Brain Injuries, Traumatic/therapy* ; Chemokines, CXC/metabolism* ; Extracellular Vesicles/metabolism* ; Histocompatibility Antigens/metabolism* ; Histone-Lysine N-Methyltransferase/metabolism* ; Humans ; MicroRNAs/metabolism* ; Microglia/metabolism* ; Rats ; Stem Cells/metabolism*

BACKGROUND: Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules. METHODS: Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model. RESULTS: In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53-24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06-1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16-2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25-2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36-14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08-3.91). No significant difference in the risk for SAEs was found in any comparisons. CONCLUSIONS: Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42021278149.
Adult ; Humans ; BNT162 Vaccine ; 2019-nCoV Vaccine mRNA-1273 ; Network Meta-Analysis ; Immunization Schedule ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; Viral Vaccines ; mRNA Vaccines ; Antibodies, Neutralizing ; Antibodies, Viral

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a genetic cardiac muscle disease that accounts for approximately 30% sudden cardiac death in young adults. The Ser358Leu mutation of transmembrane protein 43 (TMEM43) was commonly identified in the patients of highly lethal and fully penetrant ARVD subtype, ARVD5. Here, we generated TMEM43 S358L mouse to explore the underlying mechanism. This mouse strain showed the classic pathologies of ARVD patients, including structural abnormalities and cardiac fibrofatty. TMEM43 S358L mutation led to hyper-activated nuclear factor κB (NF-κB) activation in heart tissues and primary cardiomyocyte cells. Importantly, this hyper activation of NF-κB directly drove the expression of pro-fibrotic gene, transforming growth factor beta (TGFβ1), and enhanced downstream signal, indicating that TMEM43 S358L mutation up-regulates NF-κB-TGFβ signal cascade during ARVD cardiac fibrosis. Our study partially reveals the regulatory mechanism of ARVD development.

Neurostimulation remarkably alleviates the symptoms in a variety of brain disorders by modulating the brain-wide network. However, how brain-wide effects on the direct and indirect pathways evoked by focal neurostimulation elicit therapeutic effects in an individual patient is unknown. Understanding this remains crucial for advancing neural circuit-based guidance to optimize candidate patient screening, pre-surgical target selection, and post-surgical parameter tuning. To address this issue, we propose a functional brain connectome-based modeling approach that simulates the spreading effects of stimulating different brain regions and quantifies the rectification of abnormal network topology in silico. We validated these analyses by pinpointing nuclei in the basal ganglia circuits as top-ranked targets for 43 local patients with Parkinson's disease and 90 patients from a public database. Individual connectome-based analysis demonstrated that the globus pallidus was the best choice for 21.1% and the subthalamic nucleus for 19.5% of patients. Down-regulation of functional connectivity (up to 12%) at these prioritized targets optimally maximized the therapeutic effects. Notably, the priority rank of the subthalamic nucleus significantly correlated with motor symptom severity (Unified Parkinson's Disease Rating Scale III) in the local cohort. These findings underscore the potential of neural network modeling for advancing personalized brain stimulation therapy, and warrant future experimental investigation to validate its clinical utility.
Adult ; Aged ; Brain Mapping ; Connectome ; Deep Brain Stimulation ; methods ; Female ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neural Pathways ; diagnostic imaging ; physiology ; Oxygen ; blood ; Parkinson Disease ; diagnostic imaging ; pathology ; therapy ; ROC Curve ; United Kingdom