OBJECTIVES: Managing patients with refractory head and neck cancer pain is one of the more challenging issues in clinical practice, and traditional intrathecal drug delivery also fails to provide adequate analgesia. There are currently no comprehensive and effective treatment methods. This study aims to observe the efficacy and safety of treating intractable head and neck cancer pain with morphine pump via lumbar approach to the prepontine cistern. METHODS: A total of 18 patients with intractable head and neck cancer pain treated with prepontine cistern morphine pumps were selected from the Department of Pain Management, Second Xiangya Hospital, Central South University between September 2019 and July 2023. Statistical analysis was performed on patients' preoperative and postoperative (1 week, 1 month, and 2 months after surgery), Numerical Rating Scale (NRS) scores, Self-Rating Depression Scale (SDS) scores, daily oral morphine consumption, the number of daily breakthrough pain episodes, and postoperative daily intrathecal morphine dosage. RESULTS: The NRS scores, SDS scores, daily oral morphine consumption, and the number of daily breakthrough pain episodes of patients at each time point after surgery were significantly lower than before surgery (all P<0.05). With the gradual increase in the dosage of intrathecal morphine, the daily oral morphine consumption of patients at each postoperative time point was significantly reduced compared to preoperative levels (all P<0.05). The complications related to the operation were mild, including nausea in 5 cases (31.3%), headache in 2 cases (12.5%); hypotension, urine retention, hypersomnia and constipation in 1 case (6.3% each), and no serious adverse events occurred. All improved and were discharged after symptomatic treatment. CONCLUSIONS The implantation of prepontine cistern morphine pump effectively controls intractable head and neck cancer pain, demonstrating characteristics of minimal invasiveness, mild side effects, and low medication dosage under the premise of standardized procedures.
Humans ; Morphine/administration & dosage* ; Male ; Female ; Middle Aged ; Head and Neck Neoplasms/surgery* ; Analgesics, Opioid/administration & dosage* ; Cancer Pain/drug therapy* ; Pain, Intractable/etiology* ; Aged ; Adult ; Infusion Pumps, Implantable ; Pain Management/methods*

BACKGROUND:Mitochond rial biogenesis in skeletal muscle and its regulatory mechanisms during exercise have become focal points of research.Pathways such as AMP-activated protein kinase,peroxisome proliferator-activated receptory coactivator 1α,mitogen-activated protein kinase,calcium-regulated signaling play profound roles in exercise-induced mitochondrial biogenesis,impacting muscle metabolic optimization,enhanced athletic performance,and the prevention of metabolic diseases.However,the interactions among these pathways,their regulatory mechanisms,and their comprehensive effects on exercise-induced mitochondrial biogenesis in skeletal muscle remain unclear.OBJECTIVE:To explore the signaling pathways related to mitochondrial biogenesis in skeletal muscle,precisely analyze the induction and regulatory details of exercise within these pathways,and clearly elucidate the principles by which exercise-activated signaling pathways promote mitochondrial generation and functional enhancement.This will establish a theoretical foundation for improving muscle metabolism,enhancing exercise efficiency,and preventing metabolic diseases.METHODS:An extensive literature search was conducted using China National Knowledge Infrastructure(CNKI),WanFang,VIP,PubMed,and Web of Science.The latest publications related to mitochondrial biogenesis in skeletal muscle and its regulatory mechanisms were collected from inception to August 2024.By integrating findings from multiple signaling pathways,the regulatory mechanisms of exercise on mitochondrial biogenesis were systematically reviewed,with a focus on the interactions and synergistic mechanisms of AMP-activated protein kinase,peroxisome proliferator-activated receptor y coactivator 1α,protein kinase A,mitogen-activated protein kinase,calcium-regulated signaling pathways.RESULTS AND CONCLUSION:(1)Mitochondrial biogenesis in skeletal muscle is a complex biological process involving the coordinated regulation of multiple signaling pathways.This process aims to optimize the metabolic capacity,fatigue resistance,and overall athletic performance of skeletal muscle in response to changes in energy demand and external stress.The core mechanisms include the interactions and regulation of key factors such as AMP-activated protein kinase,peroxisome proliferator-activated receptor gamma coactivator 1α,and mitogen-activated protein kinase.(2)AMP-activated protein kinase senses the cellular energy status and activates peroxisome proliferator-activated receptor gamma coactivator 1α,thereby promoting mitochondrial biogenesis.Peroxisome proliferator-activated receptor gamma coactivator 1α,as the main regulator of mitochondrial biogenesis in skeletal muscle,can modulate the synthesis of mitochondrial proteins and DNA,enhance the antioxidant stress response,and improve mitochondrial function.(3)The mitogen-activated protein kinase signaling pathway,particularly p38 mitogen-activated protein kinase,further promotes mitochondrial generation by activating peroxisome proliferator-activated receptor gamma coactivator 1α during stress responses.(4)Additionally,calcium signaling and protein kinase A pathways play significant roles in the metabolic regulation of skeletal muscle.(5)Exercise can significantly enhance mitochondrial biogenesis capacity in skeletal muscle by activating these multiple signaling pathways,optimizing cellular metabolic efficiency,increasing muscle endurance,and improving athletic performance.(6)Future research should focus on in-depth exploration of the interaction mechanisms among AMP-activated protein kinase,peroxisome proliferator-activated receptor gamma coactivator1α,mitogen-activated protein kinases,and calcium signaling under different exercise intensities and modalities;strengthen studies across diverse age groups,genders,and health conditions;validate the universality and population-specificity of research findings;investigate the intricate mechanisms of emerging regulatory factors such as FNIP1 and PERM1 and their potential in exercise interventions;and promote the translation of exercise health research outcomes into clinical applications.

BACKGROUND:Parkinson's disease has the main pathological changes in the midbrain,especially in the dense substantia nigra,leading to impaired motor and non-motor function in patients.At present,research is limited by cellular heterogeneity,and its pathogenesis still needs to be further elucidated.In recent years,single-cell RNA sequencing(scRNA-seq)has gradually been applied in neurodegenerative diseases,which is of great significance for understanding intercellular heterogeneity,disease development mechanisms,and treatment strategies. OBJECTIVE:To review the research progress of scRNA-seq technology applied to Parkinson's disease in recent years,providing a theoretical basis for the application of scRNA-seq in the treatment and diagnosis of Parkinson's disease. METHODS:The first author used a computer system to search for relevant literature in the CNKI,WanFang,PubMed,and Web of Science databases,with the Chinese search terms"single-cell RNA sequencing,Parkinson's disease,cell heterogeneity,cell subtypes,dopaminergic neurons,glial cells"and English search terms"single-cell RNA seq,Parkinson disease,heterogenicity,subtypes,dopaminergic neurons,glial cells."71 articles were ultimately included for review and analysis. RESULTS AND CONCLUSION:(1)scRNA-seq is a high-throughput experimental technique that utilizes RNA sequencing at the single-cell level to quantify gene expression profiles in specific cell populations,revealing cellular mysteries at the molecular level.Compared with traditional sequencing techniques,scRNA-seq technology is used to reveal the diversity of cell types and changes in specific gene expression in complex tissues under various physiological and pathological conditions through automatic clustering analysis of cell transcriptome.(2)By using scRNA-seq,the development process of dopaminergic neurons and the unique functional characteristics of various cell subtypes are elucidated,in order to better understand potential therapeutic molecular targets.(3)The use of scRNA-seq analysis has improved our understanding of the response of Parkinson's disease glial cells,enabling us to comprehensively map and characterize different cell type populations,identify specific glial cell subpopulations related to neurodegeneration,and draw valuable single cell maps as reference data for future research.(4)The application of scRNA-seq to detect embryonic mice and stem cells will help improve the in vitro differentiation protocol and quality control of cell therapy,as well as evaluate the overall cell quality and developmental stage of dopaminergic neurons derived from stem cells.

BACKGROUND:Mitochond rial biogenesis in skeletal muscle and its regulatory mechanisms during exercise have become focal points of research.Pathways such as AMP-activated protein kinase,peroxisome proliferator-activated receptory coactivator 1α,mitogen-activated protein kinase,calcium-regulated signaling play profound roles in exercise-induced mitochondrial biogenesis,impacting muscle metabolic optimization,enhanced athletic performance,and the prevention of metabolic diseases.However,the interactions among these pathways,their regulatory mechanisms,and their comprehensive effects on exercise-induced mitochondrial biogenesis in skeletal muscle remain unclear.OBJECTIVE:To explore the signaling pathways related to mitochondrial biogenesis in skeletal muscle,precisely analyze the induction and regulatory details of exercise within these pathways,and clearly elucidate the principles by which exercise-activated signaling pathways promote mitochondrial generation and functional enhancement.This will establish a theoretical foundation for improving muscle metabolism,enhancing exercise efficiency,and preventing metabolic diseases.METHODS:An extensive literature search was conducted using China National Knowledge Infrastructure(CNKI),WanFang,VIP,PubMed,and Web of Science.The latest publications related to mitochondrial biogenesis in skeletal muscle and its regulatory mechanisms were collected from inception to August 2024.By integrating findings from multiple signaling pathways,the regulatory mechanisms of exercise on mitochondrial biogenesis were systematically reviewed,with a focus on the interactions and synergistic mechanisms of AMP-activated protein kinase,peroxisome proliferator-activated receptor y coactivator 1α,protein kinase A,mitogen-activated protein kinase,calcium-regulated signaling pathways.RESULTS AND CONCLUSION:(1)Mitochondrial biogenesis in skeletal muscle is a complex biological process involving the coordinated regulation of multiple signaling pathways.This process aims to optimize the metabolic capacity,fatigue resistance,and overall athletic performance of skeletal muscle in response to changes in energy demand and external stress.The core mechanisms include the interactions and regulation of key factors such as AMP-activated protein kinase,peroxisome proliferator-activated receptor gamma coactivator 1α,and mitogen-activated protein kinase.(2)AMP-activated protein kinase senses the cellular energy status and activates peroxisome proliferator-activated receptor gamma coactivator 1α,thereby promoting mitochondrial biogenesis.Peroxisome proliferator-activated receptor gamma coactivator 1α,as the main regulator of mitochondrial biogenesis in skeletal muscle,can modulate the synthesis of mitochondrial proteins and DNA,enhance the antioxidant stress response,and improve mitochondrial function.(3)The mitogen-activated protein kinase signaling pathway,particularly p38 mitogen-activated protein kinase,further promotes mitochondrial generation by activating peroxisome proliferator-activated receptor gamma coactivator 1α during stress responses.(4)Additionally,calcium signaling and protein kinase A pathways play significant roles in the metabolic regulation of skeletal muscle.(5)Exercise can significantly enhance mitochondrial biogenesis capacity in skeletal muscle by activating these multiple signaling pathways,optimizing cellular metabolic efficiency,increasing muscle endurance,and improving athletic performance.(6)Future research should focus on in-depth exploration of the interaction mechanisms among AMP-activated protein kinase,peroxisome proliferator-activated receptor gamma coactivator1α,mitogen-activated protein kinases,and calcium signaling under different exercise intensities and modalities;strengthen studies across diverse age groups,genders,and health conditions;validate the universality and population-specificity of research findings;investigate the intricate mechanisms of emerging regulatory factors such as FNIP1 and PERM1 and their potential in exercise interventions;and promote the translation of exercise health research outcomes into clinical applications.

The incidence of breast cancer is on the rise annually, and chemotherapy is potentially effective in prolonging the lifespan of young breast cancer patients which also irreversibly harm the ovaries. Recently, increasingly more studies have focused on the role of gonadotropin-releasing hormone agonist (GnRH-a) for protecting ovarian function in patients undergoing chemotherapy with disputable findings. This review addresses four perspectives including the impact of chemotherapy on ovarian function, the introduction of GnRH-a and the possible mechanism of protecting ovarian function, the advances of clinical research on the ovarian protection by GnRH-a in chemotherapy for patients with breast cancer and other related issues, with the aim of providing thoughts for clinical diagnosis and associated research.

Overweight and obesity are getting more commonplace worldwide and increasingly developing serious health and social issues. Weight loss intervention is regarded as an effective way to improve the fertility outcomes of overweight or obese women of childbearing age who have a substantial impact on their ability to conceive as well as an elevated risk of various perinatal complications. The effectiveness of weight loss therapies in improving fertility outcomes in overweight or obese infertile women is still being investigated. This article aims to investigate the impact of weight loss therapies on overweight or obese women from multiple perspectives, including the effects of weight loss intervention on fertility, assisted reproductive outcomes, and perinatal outcomes to provide more ideas and references for the clinical practice of weight loss interventions.

AIM:This study investigated the protective effects and underlying mechanisms of rosuvastatin(RST)in mitigating high glucose(HG)-induced damage in human umbilical vein endothelial cells(HUVECs),comple-mented by bioinformatics analysis.METHODS:Network pharmacology was employed to identify the potential targets and signaling pathways of RST in treating HG-induced vascular endothelial dysfunction.Molecular docking techniques were used to evaluate the binding affinity of RST to these core targets.The HUVECs were cultured in vitro and assigned into control,HG,and HG+RST(0.01,0.1,1,2,5 and 10 μmol/L)groups.Cell viability was determined using the MTS as-say.Levels of lactate dehydrogenase(LDH)and nitric oxide(NO)were quantified using chemical colorimetric assays.The mRNA levels of endothelial nitric oxide synthase(eNOS),claudin-1(CLDN-1),occludin(OCLN),zonula oc-cludens-1(ZO-1),aldose reductase(AR),Janus kinase 2(JAK2),mitogen-activated protein kinase 1(MAPK1),Ras homologous gene family member A(RHOA)and heat shock proteins 90AB1(HSP90AB1)were assessed by RT-qPCR.Western blot analysis was used to evaluate protein levels of eNOS,OCLN and ZO-1.RESULTS:Network pharmacology analysis suggested that RST may improve HG-induced vascular endothelial dysfunction by influencing the chemokine sig-naling pathway,tyrosine metabolism,MAPK signaling pathway,and hypoxia-inducible factor 1 alpha signaling pathway.The MTS assay indicated that RST significantly enhanced cell viability in an HG environment(P＜0.01)and reduced HG-induced damage in HUVECs.Compared with the control group,the HG group showed a significant increase in LDH levels(P＜0.01)and decreases in NO,eNOS,CLDN-1,OCLN and ZO-1 levels(P＜0.05).Additionally,the mRNA levels of AR,JAK2,MAPK1 and RHOA were elevated(P＜0.01),and HSP90AB1 was reduced in the HG group(P＜0.05).Rel-ative to the HG group,RST treatment significantly decreased LDH levels(P＜0.01)and increased the levels of NO,eNOS,CLDN-1,OCLN and ZO-1(P＜0.01).Moreover,the mRNA levels of AR,JAK2,MAPK1 and RHOA were re-duced(P＜0.01),and HSP90AB1 expression was increased in the HG+RST group(P＜0.01).CONCLUSION:RST ef-fectively attenuates HG-induced endothelial injury.This protective effect is potentially mediated by downregulating AR,JAK2,MAPK1,and RHOA expression and upregulating HSP90AB1 expression.

The incidence of breast cancer is on the rise annually, and chemotherapy is potentially effective in prolonging the lifespan of young breast cancer patients which also irreversibly harm the ovaries. Recently, increasingly more studies have focused on the role of gonadotropin-releasing hormone agonist (GnRH-a) for protecting ovarian function in patients undergoing chemotherapy with disputable findings. This review addresses four perspectives including the impact of chemotherapy on ovarian function, the introduction of GnRH-a and the possible mechanism of protecting ovarian function, the advances of clinical research on the ovarian protection by GnRH-a in chemotherapy for patients with breast cancer and other related issues, with the aim of providing thoughts for clinical diagnosis and associated research.

Overweight and obesity are getting more commonplace worldwide and increasingly developing serious health and social issues. Weight loss intervention is regarded as an effective way to improve the fertility outcomes of overweight or obese women of childbearing age who have a substantial impact on their ability to conceive as well as an elevated risk of various perinatal complications. The effectiveness of weight loss therapies in improving fertility outcomes in overweight or obese infertile women is still being investigated. This article aims to investigate the impact of weight loss therapies on overweight or obese women from multiple perspectives, including the effects of weight loss intervention on fertility, assisted reproductive outcomes, and perinatal outcomes to provide more ideas and references for the clinical practice of weight loss interventions.

Objective:To explore the application prospect of a new pH-responsive tertiary amine monomer dodecylmethylaminoethyl methacrylate (DMAEM) modified resin adhesive (DMAEM@RA) in the prevention and treatment of secondary caries.Methods:Five percents DMAEM was added to the resin adhesive to synthesize DMAEM@RA for modifying. Streptococcus mutans (Sm) and Lactobacillus casei (Lc) biofilms were cultured on resin adhesive and DMAEM@RA, respectively. The culture systems were set up at pH=7.4, 6.0, 5.5, and 5.0. The antimicrobial activity of DMAEM@RA was evaluated by quantitative PCR. The effects of DMAEM@RA on biofilm thickness, bacterial amount, and extracellular polysaccharides were studied by scanning electron microscope (SEM) and extracellular polysaccharide staining. Real-time fluorescence quantitative PCR was used to study the effect of DMAEM@RA on the expression levels of cariogenic genes in Sm. Results:DMAEM@RA could significantly reduce the amount of Sm and Lc under acidic conditions, especially Lc. At pH=5.0, the logarithm value of co-cultured Sm bacteria [lg (CFU/ml)] in DMAEM@RA group (7.58±0.01) was significantly lower than that in control group (7.87±0.03) ( t=14.32, P<0.001), and the logarithm value of Lc bacteria [lg (CFU/ml)] (7.29±0.04) was also significantly lower than that in control group (7.93±0.15) ( t=6.93, P=0.002). SEM observed that the bacteria decreased and the cell fragments appeared in DMAEM@RA group. In addition, DMAEM@RA significantly reduced the biomass of extracellular polysaccharides in the dual-species biofilm under acidic conditions. At pH=5.0, the biomass of extracellular polysaccharides in DMAEM@RA group [(25.13±3.14) mm 3/mm 2] was significantly lower than that in the control group [(42.66±7.46) mm 3/mm 2] ( t=3.75, P=0.020). DMAEM@RA could significantly up-regulate the expressions of gtfB and gtfC genes in Sm under acidic conditions. At pH=5.0, gtfB and gtfC genes were significantly up-regulated by (14.64± 0.44) times and (2.99±0.20) times, respectively ( t=-42.74, P<0.001; t=-13.55, P<0.001). Conclusions:The DMAEM@RA has a good antibacterial effect under acidic conditions, demonstrating that it has a good potential to prevent the occurrence and development of secondary caries.