1.Cannabidiol inhibits neuronal endoplasmic reticulum stress and apoptosis in rats with multiple concussions by regulating the PERK-eIF2α-ATF4-CHOP pathway.
Yujia YANG ; Lifang YANG ; Yaling WU ; Zhaoda DUAN ; Chunze YU ; Chunyun WU ; Jianyun YU ; Li YANG
Journal of Southern Medical University 2025;45(6):1240-1250
OBJECTIVES:
To explore the effects of cannabidiol on endoplasmic reticulum stress and neuronal apoptosis in rats with multiple concussions (MCC).
METHODS:
SD rats were randomized into sham group, MCC group, 1% tween20 (TW) treatment group, and low-dose (10 mg/kg) and high-dose (40 mg/kg) cannabidiol treatment groups. In all but the sham group, MCC models were established using a metal pendulum percussion device, after which the rats received daily intraperitoneal injections of the corresponding agents for 2 weeks. The expressions of PERK, eIF2α, ATF4, CHOP, TRIB3, p-Akt and pro-caspase-3 in the brain tissue of the rats were detected with qRT-PCR, Western blotting and immunofluorescence staining. The core targets of cannabidiol in treatment of traumatic brain injury (TBI) were identified by network pharmacology analysis, and molecular docking was carried out to simulate the interaction of cannabidiol with the factors related to endoplasmic reticulum stress and apoptosis.
RESULTS:
Compared with the sham-operated rats, the rat models of MCC showed significantly increased mRNA expressions of PERK, eIF2α and CHOP and protein expressions of PERK, eIF2α, ATF4, CHOP, TRIB3, p-AKT and pro-caspase-3 in the cerebral cortex. CBD treatment, especially at the high dose, obviously increased the expression of p-Akt and lowered the expression levels of the other factors tested in the rat models. Network pharmacology analysis indicated interactions of the core targets of CBD with the factors related to endoplasmic reticulum stress and TBI, and molecular docking study showed a high binding energy of CBD with multiple factors pertaining to endoplasmic reticulum stress and apoptosis.
CONCLUSIONS
MCC induce endoplasmic reticulum stress and apoptosis in rat brain tissues, for which CBD, especially at a high dose, provides neuroprotective effects by inhibiting endoplasmic reticulum stress and cell apoptosis.
Animals
;
Endoplasmic Reticulum Stress/drug effects*
;
Apoptosis/drug effects*
;
Rats, Sprague-Dawley
;
Activating Transcription Factor 4/metabolism*
;
Transcription Factor CHOP/metabolism*
;
Rats
;
Eukaryotic Initiation Factor-2/metabolism*
;
Signal Transduction/drug effects*
;
eIF-2 Kinase/metabolism*
;
Cannabidiol/pharmacology*
;
Neurons/metabolism*
;
Brain Concussion/metabolism*
;
Male
;
Molecular Docking Simulation
2.Clinical and genetic characteristics of four children with Kabuki syndrome due to de novo variants of KMT2D gene
Haizhen FAN ; Yanmei WANG ; Yunhong WU ; Lifang JIA ; Lihong WANG ; Yansheng SHEN
Chinese Journal of Medical Genetics 2024;41(5):546-550
Objective:To explore the clinical and genetic characteristics of four children with Kabuki syndrome (KS) due to variants of KMT2D gene. Methods:Four children with KS diagnosed at the Children′s Hospital of Shanxi Province between January 2020 and December 2022 were selected as the study subjects. Whole exome sequencing was carried out for the children and their family members. Candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results:The KS phenotype scores for the four children were 7, 8, 6, and 6, respectively. Child 2 also presented with a rare solitary kidney malformation. Genetic testing revealed that all children had harbored novel de novo variants of the KMT2D gene, including c. 16472_16473del, c. 858dup, c. 11899C>T, and c. 12844C>T, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were classified as pathogenic. Conclusion:For children showing phenotypes such as distinctive facial features, intellectual disability, developmental delay, cardiac abnormalities, and urinary system anomalies, KS should be considered. Early diagnosis and intervention can be achieved through genetic testing, especially in the presence of KMT2D gene mutations.
3.Hierarchical fuzzy comprehensive evaluation of prevention and control level of occupational hazards in coal mines
Haixu WU ; Jinyu GUO ; Lifang YAN ; Xuetao WANG ; Junli ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(1):62-66
Objective:To establish an evaluation model for occupational hazard prevention and control levels in coal mines, to explore the combination of Analytic Hierarchy Process (AHP) and fuzzy comprehensive evaluation, to evaluate the overall situation of occupational hazard prevention and control in coal mines.Methods:In November 2021, Collect information of occupational hazards and their prevention and control status in 30 coal mines. AHP model was first constructed for the elements of occupational hazard prevention and control in coal mines. Then, the AHP and fuzzy comprehensive evaluation method was applied to comprehensively evaluate and grade the occupational hazard prevention and control in coal mines, using the principles of maximum membership and weighted average.Results:The hierarchical fuzzy comprehensive evaluation results for typical coal mine were basically consistent with its occupational hazard prevention and control situation. The dust prevention and control situation was good, the noise prevention and control situation is average, the occupational health monitoring situation was good, the occupational health management situation was average, and the overall level of occupational hazard prevention and control was good.Conclusion:The hierarchical fuzzy comprehensive evaluation model for occupational hazard prevention and control levels, combined with the principles of maximum membership and weighted average, can objectively evaluate and reflect the overall situation of occupational hazard prevention and control in coal mines.
4.The effects of scutellarin on P13K expression and phosphorylation level in activated microglia
Lifang YANG ; Zhaoda DUAN ; Yujia YANG ; Dongyao XU ; Chunyun WU ; Li YANG
Chinese Journal of Neuroanatomy 2024;40(3):320-326
Objective:To explore the impact of scutellarin on the levels of phosphatidylinositol 3-kinase(P13K)and phosphorylated P13K(p-PI3K)in activated microglia.Methods:A rat cerebral ischemia model was made by middle cerebral artery occlusion(MCAO)method.SD rats were randomly divided into three groups:sham operation group(Sham),cerebral ischemia group(MCAO),and cerebral ischemia with scutellarin group(MCAO+S).A model of ischemia-hypoxia injury of BV2 microglia was established by glucose-oxygen deprivation(OGD)and randomly assigned as control group(Control),OGD group and OGD+scutellarin group(OGD+S).Changes in PI3K and p-PI3K expres-sion in microglia were assessed using double immunofluorescence staining and Western Blot.Results:Immunofluores-cence staining and Western Blot analyses revealed a significant increase in p-PI3K levels in activated microglia both in vivo and in vitro(P<0.05).Furthermore,treatment with scutellarin led to a further elevation in p-PI3K(P<0.05).However,there were no significant alterations observed in PI3 K expression among the groups(P>0.05).Conclusion:Scutellarin may play a positive role in the treatment of cerebral ischemia by up-regulating the phosphorylation level of P13K in activated microglia.
5.The effects of cannabidiol on the expression of NLRP3 inflammasome following multiple cerebral concussions in rats
Chunze YU ; Lifang YANG ; Zhaoda DUAN ; Yujia YANG ; Chunyun WU ; Jianyun YU ; Li YANG
Chinese Journal of Neuroanatomy 2024;40(1):98-104
Objective:To investigate the effects of cannabidiol(CBD)on the NOD-like receptor protein 3(NLRP3)inflammasome in the brains of rats with multiple cerebral concussions(MCC).Methods:Rats were subjec-ted to the MCC model and divided into Sham,MCC,vehicle(MCC+TW),CBD-L(10 mg/kg),and CBD-H(40 mg/kg)groups.Immunofluorescence double staining was used to observe changes in NLRP3 and microglial cells in the brain,and Western Blot was performed to detect the expression changes of the NLRP3 inflammasome.Results:A sig-nificant increase in lectin-positive microglial cells of the cortex with enlarged cell bodies and elevated immunofluores-cence intensity of NLRP3 in the activated microglial cells was revealed by immunofluorescence double staining following MCC(P<0.05).The immunofluorescence intensity of NLRP3 in the activated microglial cells was downregulated by the administration of CBD,with a more pronounced effect observed in the CBD-H group compared to the CBD-L group(P<0.05).The expression of NLRP3,caspase-1,and apoptosis-associated speck-like protein(ASC)in the cortex,hippocampus,and basal ganglia of rats following MCC was significantly increased,as shown by Western Blot analysis(P<0.05),and cortical areas are more elevated.The expression of these proteins in different brain regions was reduced by CBD-10 and CBD-40 intervention(P<0.05).Conclusion:Cannabidiol can reduce the inflammatory response of multiple cerebral concussions rats through NLRP3 inflammasome and protect nerve tissue.
6.Hierarchical fuzzy comprehensive evaluation of prevention and control level of occupational hazards in coal mines
Haixu WU ; Jinyu GUO ; Lifang YAN ; Xuetao WANG ; Junli ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(1):62-66
Objective:To establish an evaluation model for occupational hazard prevention and control levels in coal mines, to explore the combination of Analytic Hierarchy Process (AHP) and fuzzy comprehensive evaluation, to evaluate the overall situation of occupational hazard prevention and control in coal mines.Methods:In November 2021, Collect information of occupational hazards and their prevention and control status in 30 coal mines. AHP model was first constructed for the elements of occupational hazard prevention and control in coal mines. Then, the AHP and fuzzy comprehensive evaluation method was applied to comprehensively evaluate and grade the occupational hazard prevention and control in coal mines, using the principles of maximum membership and weighted average.Results:The hierarchical fuzzy comprehensive evaluation results for typical coal mine were basically consistent with its occupational hazard prevention and control situation. The dust prevention and control situation was good, the noise prevention and control situation is average, the occupational health monitoring situation was good, the occupational health management situation was average, and the overall level of occupational hazard prevention and control was good.Conclusion:The hierarchical fuzzy comprehensive evaluation model for occupational hazard prevention and control levels, combined with the principles of maximum membership and weighted average, can objectively evaluate and reflect the overall situation of occupational hazard prevention and control in coal mines.
7.Methodological investigation on bacterial endotoxin in betahistine hydrochloride injection
HAO Gang ; ZHANG Lifang ; WU Xing ; YAN Hao ; ZHAO Yating ; HAN Feng
Drug Standards of China 2024;25(1):082-089
Objective: Investigation on the quality control method of bacterial endotoxin in betahistine hydrochloride injection.
Methods: The method of bacterial endotoxin gel test of 23 batches of betahistine hydrochloride injection from 5 manufacturers was studied.
Results: The limit value of endotoxin in this product was 3 EU·mg-1, which was suitable for the bacterial endotoxin test of China Pharmacopoeia 2020.
Conclusion: The quality of betahistine hydrochloride injection can be controlled by bacterial endotoxin test, and the limit of bacterial endotoxin can be set as follows: the content of endotoxin in every 1mg of betahistine hydrochloride should not exceed 3 EU.
8.Progress of interruption of schistosomiasis transmission and prospects in Yunnan Province
Yun ZHANG ; Lifang WANG ; Xiguang FENG ; Mingshou WU ; Meifen SHEN ; Hua JIANG ; Jing SONG ; Jiayu SUN ; Chunqiong CHEN ; Jiaqi YAN ; Zongya ZHANG ; Jihua ZHOU ; Yi DONG ; Chunhong DU
Chinese Journal of Schistosomiasis Control 2024;36(4):422-427
Schistosomiasis was once hyper-endemic in Yunnan Province. Following concerted efforts for over 70 years, remarkable achievements have been made for schistosomiasis control in the province. In 2004, the Mid- and Long-term Plan for Schistosomiasis Prevention and Control in Yunnan Province was initiated in Yunnan Province, and the target for transmission control of schistosomiasis was achieved in the province in 2009. Following the subsequent implementation of the Outline for Key Projects in Integrated Schistosomiasis Control Program (2009—2015) and the 13th Five - year Plan for Schistosomiasis Control in Yunnan Province, no acute schistosomiasis had been identified in Yunnan Province for successive 12 years, and no local Schistosoma japonicum infections had been detected in humans, animals or Oncomelania hupensis snails for successive 6 years in the province by the end of 2020. The transmission of schistosomiasis was interrupted in Yunnan Province in 2020. This review summarizes the history of schistosomiasis, changes in schistosomiasis prevalence and progress of schistosomiasis control in Yunnan Province, and proposes the future priorities for schistosomiasis control in the province.
9.Quantitative Evaluation of High-Quality Development Policies of Public Hospitals at Provincial Level Based on PMC Index Model
Zihan LANG ; Yixuan WU ; Lifang ZHOU ; Lingfeng XU ; Qianqian YU
Chinese Hospital Management 2024;44(10):1-4,9
Objective It evaluates the high-quality development policies of public hospitals at the provincial level in China,and provides theoretical basis and countermeasures for formulating and optimizing the high-quality develop-ment policies of public hospitals.Methods The ROST CM 6.0 software was used to conduct text mining for 11 sample policies,and the Policy Modeling Consistency(PMC)index model was constructed to evaluate the sample policies quantitatively.Results The average PMC index of 11 sample policies included in the study was 7.16 points,of which 8 were excellent grades and 3 were qualified grades.The first-level variables X5 service system(0.82),X8 Party leadership(0.91)and X6 organization and operation(0.94)scored higher;X2 policy timeliness(0.52),X7 cultural construction(0.68)and X4 service capability(0.71)scored low.Conclusion The content of the high-quality develop-ment policy of public hospitals at the provincial level is basically in line with the national policy,and is relatively excel-lent in the aspects of organization and operation,service system and party leadership,etc.,but there are some weaknesses in the aspects of policy timeliness,cultural construction and service capacity,etc.,which can be op-timized and improved from the aspects of improving service capacity,supplementing long-term policies and strengthening hospital cultural construction.
10.Research on the High-Quality Development Path of Tertiary Public Hospitals Based on fsQCA
Na XU ; Lingfeng XU ; Lifang ZHOU ; Junjie NIU ; Zihan LANG ; Yixuan WU ; Xiaoli JIANG ; Haibo PENG ; Wenqiang YIN ; Chengliang YIN ; Qianqian YU
Chinese Hospital Management 2024;44(10):5-9
Objective To explore the high-quality development path of tertiary public hospitals and provide scientific reference for deepening the reform of public hospitals.Methods Based on SPO theory,it constructed an analytical framework for the high-quality development of tertiary public hospitals,collected data of a quarterly monitoring in-dex for the performance assessment and high-quality development of tertiary public hospitals in a certain province in 2023,and analysed 73 tertiary public hospitals participating in the performance assessment as the object of analy-sis,and adopted the fuzzy-set Qualitative Comparative Analysis to explore different condition sets of high-quality de-velopment of tertiary public hospitals and reveal the path of high-quality development of public hospitals.Results High-quality development is the result of multi-factor interaction.Four configurations were identified to promote the high-quality development of tertiary public hospitals:service quality-technology-driven path,service quality-driven path,comprehensive service-driven path,and service quality-benefit-driven path.Quality safety and functional orientation were found to be the core elements in promoting high-quality development of public hospitals.Conclusion Hospitals at all levels should strengthen the guidance of party building,combine with the actual functional positioning,take quality and safety as the core,and optimize the combination conditions of technical level,personnel structure,service process,and cost control.It is essential to clarify the development strategy of hospitals,implement the dynamic concept,and realize the high-quality development of public hospitals.

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