OBJECTIVE: To observe the effects of electroacupuncture (EA) at "Shenting" (GV24) and "Baihui" (GV20) on mitochondrial autophagy in hippocampal neurons and silent information regulator sirtuin 1 (Sirt1)/forkhead box O3 (FOXO3)/PTEN-inducible kinase 1 (PINK1)/Parkin pathway in rats with learning-memory impairment after cerebral ischemia reperfusion injury. METHODS: A total of 35 male SD rats were randomly divided into a sham operation group (9 rats) and a modeling group (26 rats). In the modeling group, middle cerebral artery occlusion method was used to establish the middle cerebral artery ischemia-reperfusion (MCAO/R) model, and 18 rats of successful modeling were randomly divided into a model group and an EA group, 9 rats in each one. EA was applied at "Shenting" (GV24) and "Baihui" (GV20) in the EA group, 30 min a time, once a day for 14 days. After modeling and on 7th and 14th days of intervention, neurologic deficit score was observed; the learning-memory ability was detected by Morris water maze test; the morphology of neurons in CA1 area of hippocampus was detected by Nissl staining; the mitochondrial morphology was observed by transmission electron microscopy; the protein expression of Beclin-1, microtubule-associated protein 1 light chain 3B (LC3B), P62, Sitrt1, FOXO3, PINK1 and Parkin was detected by Western blot. RESULTS: After modeling, the neurologic deficit scores in the model group and the EA group were higher than that in the sham operation group (P<0.001); on 7th and 14th days of intervention, the neurologic deficit scores in the model group were higher than those in the sham operation group (P<0.001), the neurologic deficit scores in the EA group were lower than those in the model group (P<0.05, P<0.01). After modeling, the escape latency in the model group and the EA group was prolonged compared with that in the sham operation group (P<0.001); on 9th-13th days of intervention, the escape latency in the model group was prolonged compared with that in the sham operation group (P<0.001), the escape latency in the EA group was shortened compared with that in the model group (P<0.05, P<0.01, P<0.001). The number of crossing plateau in the model group was less than that in the sham operation group (P<0.001); the number of crossing plateau in the EA group was more than that in the model group (P<0.05). In the model group, in CA1 area of hippocampus, the number of neurons was less, with sparse arrangement, nuclear fixation, deep cytoplasmic staining, and reduction of Nissl substance; the morphology of mitochondrion was swollen, membrane structure was fragmented, and autophagic lysosomes were formed. Compared with the model group, in the EA group, in CA1 area of hippocampus, the number of neurons was increased, the number of cells of abnormal morphology was decreased, and the number of Nissl substance was increased; the morphology of mitochondrion was more intact and the number of autophagic lysosomes was increased. Compared with the sham operation group, in the model group, the protein expression of Beclin-1, FOXO3, PINK1, Parkin and the LC3BⅡ/Ⅰ ratio in hippocampus were increased (P<0.01, P<0.001), while the protein expression of P62 was decreased (P<0.05). Compared with the model group, in the EA group, the protein expression of Beclin-1, Sirt1, FOXO3, PINK1, Parkin and the LC3BⅡ/Ⅰratio in hippocampus were increased (P<0.001, P<0.01), while the protein expression of P62 was decreased (P<0.001). CONCLUSION EA at "Shenting" (GV24) and "Baihui" (GV20) can relieve the symptoms of neurological deficits and improve the learning-memory ability in MCAO/R rats, its mechanism may relate to the modulation of Sirt1/FOXO3/PINK1/Parkin pathway and the enhancement of mitochondrial autophagy.
Animals ; Electroacupuncture ; Male ; Rats, Sprague-Dawley ; Rats ; Forkhead Box Protein O3/genetics* ; Reperfusion Injury/metabolism* ; Ubiquitin-Protein Ligases/genetics* ; Brain Ischemia/complications* ; Mitochondria/genetics* ; Autophagy ; Protein Kinases/genetics* ; Sirtuin 1/genetics* ; Humans ; Memory Disorders/psychology* ; Signal Transduction

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective:To investigate the role of Fem-1 homolog C(FEM1C)in breast cancer progression and elucidate its underlying regulat-ory mechanism.Methods:The expression of FEM1C in breast cancer tissues and cells were detected with qPCR.The binding of FEM1C to ELAVL1 protein was predicted with an online database and validated by CoIP analysis;and the binding of ELAVL1 protein to OPA1 mRNA was predicted by using the starBase database and validated by RIP analysis.Next,breast cancer cell MDA-MB-231 was transfected with FEM1C shRNA(sh-FEM1C)or overexpression vector(FEM1C)or/and ELAVL1 overexpression vector(ELAVL1)or/and OPA1 overexpression vector(OPA1),or treated with 100 μM Mdivi-1,an DRP1 inhibitor,or MYLS22,an OPA1 inhibitor.Finally,nude mice were injected with sh-FEM1C lentiviral vectors to construct xenograft tumor models,and tumor growth was monitored.Results:The expression of FEM1C was upregu-lated in breast cancer tissues(P<0.01).Silencing FEM1C inhibited the proliferation,induced apoptosis,promoted the expression of auto-phagy protein LC3 Ⅱ/Ⅰ,inhibited p62 protein expression,upregulated the protein level of PINK1 in mitochondrial,promoted the expres-sion of mitochondrial fission proteins DRP1 and MIEF2,and inhibited the expression of fusion proteins OPA1 and MFN1 in MDA-MB-231 cells(P<0.01).Mdivi-1 treatment inhibited DRP1 expression(P<0.01),but had no effect on cell viability(P>0.05);MYLS22 treatment inhibited OPA1 expression and counteracted the effect of FEM1C overexpression on MDA-MB-231 cells(P<0.01).Mechanistic studies revealed that FEM1C binds to ELAVL1 protein and promotes its expression(P<0.01);ELAVL1 protein stabilizes OPA1 mRNA by binding to it and upregu-lates OPA1 protein levels(P<0.01).Overexpression of OPA1 reversed the effect of FEM1C silencing on MDA-MB-231 cells(P<0.01).In vivo results showed that knockdown of FEM1C inhibited tumor growth in vivo(P<0.01).Conclusions:FEM1C promotes the stability of OPA1 mRNA by upregulation of ELAVL1 protein to promote mitochondrial fusion and inhibit autophagy,thereby promoting breast cancer progression.

Objective The application effect of bedside ultrasound combined with joint movement protractor on the accurate monitoring and management of joint range of motion in extremely low birth weight infants was evaluated to reduce the incidence of secondary ectopic PICC in extremely low birth weight infants.Methods Convenience sampling was used to select 128 extremely low birth weight infants admitted to the neonatal intensive care unit of a tertiary hospital in Zhengzhou,Henan Province from February to September 2024.Among them,infants enrolled between June and September 2024 were assigned to an experimental group,while those enrolled between February and May 2024 were assigned to a control group,with 64 cases in each group.Whereas the experimental group,based on the control group,combined bedside ultrasound with a joint goniometer for precise monitoring and management of limb movement range in children with upper limb catheterization;the control group received routine prevention and management of PICC secondary displacement.After intervention,the incidence of PICC secondary displacement,the rate of PICC secondary displacement removal,the incidence of complications related to PICC secondary displacement,and the average length of stay of the infants were compared between the 2 groups.Results Ultimately,60 cases were included in each of the 2 groups.The incidence of secondary ectopic PICC in the post-intervention experimental group was 8.33％,lower of 23.33％in the control group;the extubation rate of secondary ectopic PICC was 3.33％,lower of 16.67％in the control group;the incidence of complications related to secondary ectopic PICC was 13.33％,lower of 51.67％in the control group;the average hospitalization day was 50(48,55)d,shorter of 61(55,65)d in the control group.The difference between the 2 groups was statistically significant(P＜0.05).Conclusion The combination of bedside ultrasound and joint movement protractor was used to accurately monitor and manage the range of motion of limbs in children with upper limb catheterization,which effectively guaranteed the safe position of the catheter tip and reduced the incidence of secondary ectopic complications related to PICC.It can be further promoted and applied in clinical practice.

Objective To design,develop,and implement a specialized nurse training information management platform to enhance the efficiency of training management and improve the quality of training.Methods A platform development team was formed to construct the platform architecture and develop functional modules based on the entire process of specialized nurse training management and the needs of various users.The platform was officially launched in 2020.Data on platform usage from 2020 to 2023 were collected,and in 2023,satisfaction surveys were conducted among specialized nurse training managers and trainees to assess the platform's effectiveness.Results The specialized nurse training information management platform includes 5 major modules,namely the Chinese Nursing Association,professional committees,hospitals,teaching bases,and trainees.It also includes 4 information databases,namely specialized nurses,teaching experts,teaching bases,and mentor faculty.The platform enables full-process digital management,integrating trainee management,project management,teaching base management,and evaluation management.From 2020 to 2023,the number of users across various categories of the platform showed a significant upward trend.By 2023,the platform had been applied to 28 specialized nurse training programs across professional committees.The highest frequency of use was among specialized nurse training managers at teaching bases.The satisfaction scores for platform usage among professional committees,hospital nursing departments,and specialized nurse training managers at teaching bases were(83.67±7.75)(82.69±8.08)and(84.69±7.75),respectively.The platform usage satisfaction score among 8 704 trainees was(33.07±3.01).Conclusion The specialized nurse training information management platform is comprehensive and has received high satisfaction ratings from various users.The use of the platform helps to improve the effectiveness and quality of training.

Objective:To investigate the present situation and influencing factors of hearing loss among noise exposed workers in a gas production plant, and to provide basis and guidance for enterprises to prevent hearing loss.Methods:In November 2023, a cross-sectional survey was conducted among personnel exposed to noise in a gas production plant. A total of 380 questionnaires were collected, among which 319 were valid resulting in an effective recovery rate of 83.9%. Ultimately, 292 were included in the study. The questionnaire covered demographic characteristics, work conditions, behavioral and lifestyle habits, hearing loss, and medical history. The noise exposure levels of the research subjects were determined based on the occupational disease hazard factor detection reports provided by the gas production plant for 2022 and 2023. Whether hearing loss occurred was determined based on the pure tone audiometry results from the occupational health examination. Chi-square tests were used to analyze the influence of demographic characteristics, work conditions, and behavioral and lifestyle habits on hearing loss. A multivariate logistic regression model was used to analyze the relationship between hearing loss and related influencing factors.Results:Among the noise-exposed workers in the gas production plant, the incidence of high-frequency hearing loss was 14.4% (42/292) . The rate of hearing loss among men was higher than that among women ( P=0.010) , and the rate of hearing loss among those with a history of smoking was higher than that among those who had never smoked ( P=0.015) . Conclusion:Gas production enterprises should prioritize targeted interventions for workers with prolonged employment histories and smoking habits. Training programs should be implemented to cultivate proper ear protection practices, enhance knowledge of hearing conservation, and promote healthier lifestyle behaviors among employees.

Myocardial ischemia-reperfusion(I/R)injury refers to the irreversible cardiac damage and cardio-myocyte apoptosis that occur upon the restoration of blood flow following ischemia in ischemic heart disease(IHD).Given its high incidence,elevated mortality rate,and poor clinical outcomes,the prevention and treatment of I/R injury are of considerable clinical significance.Mitochondrial dynamics dysfunction,characterized by abnormalities in mitochondrial morphology,fission,and fusion,has emerged as a critical pathological feature.Evidence indicates that correcting these dysfunctions can enhance myocardial energy metabolism,mitigate oxidative stress,calcium overload,and inflammatory responses,and inhibit the pathological opening of the mitochondrial permeability transition pore and vascular remodeling.These effects position mitochondrial dynamics as a promising therapeutic target for IHD and I/R injury.This paper ex-plores the pathophysiological mechanisms by which mitochondrial dynamics dysfunction in cardiomyocytes,vascular endo-thelial cells,and vascular smooth muscle cells contributes to the development and progression of I/R injury,aiming to of-fer novel insights into its prevention and treatment.

Myocardial ischemia-reperfusion(I/R)injury refers to the irreversible cardiac damage and cardio-myocyte apoptosis that occur upon the restoration of blood flow following ischemia in ischemic heart disease(IHD).Given its high incidence,elevated mortality rate,and poor clinical outcomes,the prevention and treatment of I/R injury are of considerable clinical significance.Mitochondrial dynamics dysfunction,characterized by abnormalities in mitochondrial morphology,fission,and fusion,has emerged as a critical pathological feature.Evidence indicates that correcting these dysfunctions can enhance myocardial energy metabolism,mitigate oxidative stress,calcium overload,and inflammatory responses,and inhibit the pathological opening of the mitochondrial permeability transition pore and vascular remodeling.These effects position mitochondrial dynamics as a promising therapeutic target for IHD and I/R injury.This paper ex-plores the pathophysiological mechanisms by which mitochondrial dynamics dysfunction in cardiomyocytes,vascular endo-thelial cells,and vascular smooth muscle cells contributes to the development and progression of I/R injury,aiming to of-fer novel insights into its prevention and treatment.

Objective The application effect of bedside ultrasound combined with joint movement protractor on the accurate monitoring and management of joint range of motion in extremely low birth weight infants was evaluated to reduce the incidence of secondary ectopic PICC in extremely low birth weight infants.Methods Convenience sampling was used to select 128 extremely low birth weight infants admitted to the neonatal intensive care unit of a tertiary hospital in Zhengzhou,Henan Province from February to September 2024.Among them,infants enrolled between June and September 2024 were assigned to an experimental group,while those enrolled between February and May 2024 were assigned to a control group,with 64 cases in each group.Whereas the experimental group,based on the control group,combined bedside ultrasound with a joint goniometer for precise monitoring and management of limb movement range in children with upper limb catheterization;the control group received routine prevention and management of PICC secondary displacement.After intervention,the incidence of PICC secondary displacement,the rate of PICC secondary displacement removal,the incidence of complications related to PICC secondary displacement,and the average length of stay of the infants were compared between the 2 groups.Results Ultimately,60 cases were included in each of the 2 groups.The incidence of secondary ectopic PICC in the post-intervention experimental group was 8.33％,lower of 23.33％in the control group;the extubation rate of secondary ectopic PICC was 3.33％,lower of 16.67％in the control group;the incidence of complications related to secondary ectopic PICC was 13.33％,lower of 51.67％in the control group;the average hospitalization day was 50(48,55)d,shorter of 61(55,65)d in the control group.The difference between the 2 groups was statistically significant(P＜0.05).Conclusion The combination of bedside ultrasound and joint movement protractor was used to accurately monitor and manage the range of motion of limbs in children with upper limb catheterization,which effectively guaranteed the safe position of the catheter tip and reduced the incidence of secondary ectopic complications related to PICC.It can be further promoted and applied in clinical practice.