Panvascular diseases are systemic diseases with atherosclerosis as the pathological core， involving multiple vascular beds and target organs throughout the body. Due to their wide range and complexity， the traditional single-discipline prevention and treatment model struggles to meet the needs of systematic management， while clinical diagnosis often remains one-sided and insufficient， leading to delayed treatment. Literature reviews show that panvascular diseases involve a wide range of lesion sites， numerous influencing factors， and are prone to endangering life and health. It is urgent to construct a comprehensive and whole-course prevention and treatment management system， with vascular health as the goal and patients as the core. First， early screening and risk assessment should be conducted for high-risk groups. In terms of treatment decisions for patients， multi-disciplinary collaboration is needed to establish a scientific and standardized prevention and treatment path. Second， it is important to attach great importance to a people-centered approach， enhance patients' familiarity with the disease through cognitive intervention， and shift from passive treatment to active health care. Thirdly， it is needed to leverage the advantages of modern science and technology， promote the deep integration of artificial intelligence innovations and modern medicine， and help traditional diagnosis and treatment plans evolve towards precision， intelligence， and personalization. This will open up new paths for the modernization of the whole-course management of pan-vascular diseases. Fourth， efforts should be made to continue to carry forward and innovate the characteristics of traditional Chinese medicine， adhere to equal emphasis on modern and traditional medicine， promote complementary advantages and coordinated development of Chinese and Western medicine， and form a unique Chinese model for the whole-course management of panvascular diseases. Fifth， through the reintegration and redistribution of government， medical insurance， and medical resources， comprehensive talents in the broad vascular disciplines should be cultivated and an efficient hierarchical management model established， providing reference and guidance for the whole-course management of comprehensive diseases in the future.

OBJECTIVES: To investigate the protective effects of dexmedetomidine (DEX) against heat stress (HS)-induced oncosis in human skeletal muscle cells (HSKMCs) and its underlying mechanisms. METHODS: A HSKMC model of HS-induced oncosis were established by 43 ℃ water bath for 4 h, and the effects of treatments with 30 μmol/L DEX, ML385 (a Nrf2 inhibitor) +DEX, si-Nrf2+HS, and si-Nrf2+DEX prior to modeling on cell viability was assessed using CCK-8 assay. Oncosis characteristics were evaluated using transmission electron microscopy and Annexin V-FITC/PI flow cytometry. The oxidative stress markers (GSH, GSH-Px, MDA, SOD and ROS), mitochondrial membrane potential, energy metabolism, and inflammatory cytokines (TNF-α, IL-6 and IL-1β) in the cells were quantified using standard kits, and the expressions of porimin, caspase-3 and Nrf2 pathway proteins were analyzed using Western blotting and qRT-PCR. RESULTS: HS induced typical oncotic features in HSKMCs including organelle swelling and cytoplasmic vacuolization. DEX pretreatment significantly attenuated these changes, reduced Annexin V⁺/PI⁺ cell ratio and cellular porimin expression, and lowered the levels of ROS and MDA while restoring GSH and SOD levels. DEX pretreatment also significantly increased the mitochondrial membrane potential and ATP level, upregulated the expressions of Nrf2, p-Nrf2, HO-1 and NQO1, and suppressed the expressions of TNF-α, IL-6 and IL-1β. The protective effects of DEX were obviously attenuated by interventions with ML385 or si-Nrf2. CONCLUSIONS DEX mitigates HS-induced HSKMC oncosis by activating the Nrf2/HO-1 pathway to relieve oxidative stress, mitochondrial dysfunction, and inflammatory responses.
Humans ; Dexmedetomidine/pharmacology* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress/drug effects* ; Heat-Shock Response/drug effects* ; Signal Transduction/drug effects* ; Membrane Potential, Mitochondrial ; Muscle, Skeletal/cytology* ; Heme Oxygenase-1/metabolism* ; Apoptosis/drug effects*

Objective: To analyze the developmental trajectories of middle school students loneliness and social support, as well as to explore the interaction between loneliness and social support, so as to provide the evidence based support for the mental health development of adolescents. Methods: A total of 989 first year students from four public middle schools in Xiangxi Tujia and Miao Autonomous Prefecture, Hunan Province were selected for three follow up surveys by a cluster random sampling method (T1:March 2023, T2:June 2023, T3:December 2023). The UCLA Loneliness Scale-20 (ULS-20) and Social Support Scale for University Students (SSSUS) were employed for questionnaire data collection. The growth mixture modeling was utilized to test the developmental trajectories of loneliness and social support among middle school students, while the cross lagged analysis was performed to investigate their mutual influence. Results: The scores for loneliness and social support in T1, T2 and T3 were (43.1±5.8, 42.5± 6.8 , 42.0±6.9; 55.9±12.0, 60.7±15.7, 60.4±16.7), respectively. Correlational analysis revealed a significant negative correlation between loneliness levels (T1, T2, T3) and social support (T1, T2, T3) ( r =-0.47 to -0.36, P <0.01). Growth mixture modeling indicated a linear declining trend of middle school students loneliness, and the developmental trajectory of social support showed a linear increasing trend, with significant individual differences in initial levels and rates of change ( P <0.05). Cross lagged analyses revealed that loneliness levels at T1 negatively predicted social support scores at T2 ( β =-0.16), and loneliness levels at T2 negatively predicted social support scores at T3 ( β =-0.12) ( P <0.05). Additionally, prior loneliness positively predicted its subsequent levels, with path coefficients of 0.58 and 0.47, respectively ( P <0.05). Social support scores at T1 negatively predicted loneliness levels at T2 ( β =-0.10), while scores at T2 negatively predicted loneliness levels at T3 ( β =-0.15) ( P <0.05). Prior loneliness also positively predicted its subsequent levels, with path coefficients of 0.43 and 0.44, respectively ( P <0.05). Conclusion The developmental trajectory of middle school students loneliness demonstrates a decreasing trend, while that of social support exhibits a linear increasing trend, indicating a longitudinal causal relationship between loneliness and social support.

Methods To investigate how the timing of cooling therapy affects organ injuries in rats with exertional heat stroke(EHS)and explore the possible mechanisms.Methods A total of 60 adult male Wistar rat models of EHS were randomized into model group without active cooling after modeling,immediate cooling group with cold water bath immediately after modeling,delayed cooling groups with cold water bath at 5,15 and 30 min after modeling,with another 12 mice without EHS as the normal control group.The changes in core body temperature of the mice were recorded and the cooling rate was calculated.After observation for 24 h,the mice were euthanized and blood samples were collected for detection of interleukin-1β(IL-1β),IL-2,IL-4,IL-6,IL-10,and interferon-γ,followed by pathological examination of the vital organs.The rats that died within 24 h were immediately dissected for examination.Results The number of deaths of the model rats within 24 h increased significantly with the time of delay of cooling treatment.The delay of cooling was positively correlated(r=0.996,P=0.004)while the cooling rate negatively correlated with the mortality rate(r=-0.961,P=0.009).The inflammatory cytokine levels presented with different patterns of variations among the cooling intervention groups.All the rat models of EHS had significant organ damages characterized mainly by epithelial shedding,edema,effusion,and inflammatory cell infiltration,and brain and renal injuries reached the peak level at 24 h after EHS.Conclusion EHS causes significant nonspecific pathologies of varying severities in the vital organs of rats,and the injuries worsen progressively with the delay of cooling.There is a significant heterogeneity in changes of serum inflammatory cytokines in rats with different timing of cooling intervention following EHS.

The Clinical Medicine Proficiency Test developed by the National Medical Examination Center of China in 2020 aims to assess whether clinical medical students possess the necessary medical humanities and basic medical theoretical knowledge and skills required for clinical internships. Since 2002, Japan has implemented the pre-clinical clerkship objective structured clinical examination and computer-based testing, which share similarities with China's proficiency test in terms of examination objectives, content, format, and score evaluation. Through comparing the examinations of China and Japan, this article concludes that it is necessary to learn from Japan's experience to expedite the process of promoting the Clinical Medicine Proficiency Test as an industry admission examination in China. We suggest that medical schools should keep tracking the development of the proficiency test and fully leverage its role in urging students to pay more attention to clinical internships. We also urge medical schools to establish a three-level examination system based on post competency criteria in line with the standards of the National Medical Licensing Examination to improve the quality of medical education.

Methods To investigate how the timing of cooling therapy affects organ injuries in rats with exertional heat stroke(EHS)and explore the possible mechanisms.Methods A total of 60 adult male Wistar rat models of EHS were randomized into model group without active cooling after modeling,immediate cooling group with cold water bath immediately after modeling,delayed cooling groups with cold water bath at 5,15 and 30 min after modeling,with another 12 mice without EHS as the normal control group.The changes in core body temperature of the mice were recorded and the cooling rate was calculated.After observation for 24 h,the mice were euthanized and blood samples were collected for detection of interleukin-1β(IL-1β),IL-2,IL-4,IL-6,IL-10,and interferon-γ,followed by pathological examination of the vital organs.The rats that died within 24 h were immediately dissected for examination.Results The number of deaths of the model rats within 24 h increased significantly with the time of delay of cooling treatment.The delay of cooling was positively correlated(r=0.996,P=0.004)while the cooling rate negatively correlated with the mortality rate(r=-0.961,P=0.009).The inflammatory cytokine levels presented with different patterns of variations among the cooling intervention groups.All the rat models of EHS had significant organ damages characterized mainly by epithelial shedding,edema,effusion,and inflammatory cell infiltration,and brain and renal injuries reached the peak level at 24 h after EHS.Conclusion EHS causes significant nonspecific pathologies of varying severities in the vital organs of rats,and the injuries worsen progressively with the delay of cooling.There is a significant heterogeneity in changes of serum inflammatory cytokines in rats with different timing of cooling intervention following EHS.

Objective To investigate the frequency and distribution characteristics of gene mutations in children with phenylalanine hydroxylase(PAH)deficiency in Xinjiang.Methods A total of 230 children diag-nosed with PAH deficiency in Urumqi Maternal and Child Health Care Hospital from January 1st,2015 to February 28th,2023 were enrolled in the study.The variation of PAH gene was analyzed and the variation sites of PAH gene in children with different phenotypes were compared.Results A total of 441 PAH gene va-riants were detected in 230 children with PAH deficiency in Xinjiang,with a total detection rate of 95.87％.A-mong them,2 variants were detected in 227 cases,only 1 variant was detected in 2 cases,and 3 variants were detected in 1 case.217 cases were complex heterozygous variants,and 10 cases were homozygous variants.The high-frequency variant loci were c.158G＞A[23.39％(102/441)],c.728G＞A[11.70％(51/441)],c.688G＞A[5.05％(22/441)],c.721C＞T[3.90％(17/441)],c.611A＞G[3.67％(16/441)],c.1238G＞C[3.21％(14/441)].The high-frequency variant loci for classic PKU were c.728G＞A,c.331C＞T,and c.782G＞A;the high-frequency variant loci for mild PKU were c.721C＞T,c.1068C＞A,and c.1301C＞A;the high-frequency variant loci for children with mild HPA were c.158G＞A and c.688G＞A.There were significant differences in the frequency of high frequency mutations among the above three phenotypes(P＜0.05).Conclusion Mild HPA predominates in children with PAH deficiency in Xinjiang.The hotspot loci of the PAH gene in Xinjiang have been clarified,and specific PAH gene loci have been observed in the three different phenotypes,which can provide theoretical basis for prenatal diagnosis and clinical genetic counselling.

Objective To investigate the correlation between HLA-DM gene polymorphism and antibody response induced by poliomyelitis vaccine.Methods 355 healthy infants aged 2 to 3 months in Guangxi Zhuang Autonomous Region were selected as the study objects,and 10 SNPs of DMA exon 3 and DMB exon 2/3 were genotyped by Sanger sequencing.The correlation between DMA and DMB genes and poliomyelitis vaccine-induced antibody response was analyzed at allele,genotype and haplotype levels.Results In the type Ⅰ antibody response induced by polio vaccine,the frequencies of DMA*01:02,DMB*01:01,DMB*01:01/DMB*01:01 and DMA*01:02-DMB*01:01 were higher in the non-seroconversion group than in the seroconversion group(P<0.05).In the polio type Ⅱ antibody response,the frequencies of DMA*01:02,DMA*01:02/DMA*01:02,DMB*01:01/DMB*01:01 and DMA*01:02-DMB*01:01 were higher in the non-seroconversion group than in the seroconversion group(P<0.05).Conclusion Alleles DMA*01:02 and DMB*01:01 may be associated with type Ⅰ and type Ⅱ antibody responses induced by poliomyelitis vaccine.

BACKGROUND:Traditional Chinese medicine compound prescription has a long history in the treatment of primary osteoporosis,and the curative effect is definite,but the medication rule and mechanism are not clear. OBJECTIVE:Using the methodology of data mining and network pharmacology,to explore and verify the law of drug use and molecular mechanism of modern traditional Chinese medicine in the treatment of primary osteoporosis. METHODS:The relevant documents included in CNKI,WanFang,VIP and PubMed were used as data sources,and the relevant data were statistically counted and extracted by Microsoft EXCEL2019,IBMSPSS25.0 and other software.The high-frequency drugs obtained from the data statistics were analyzed by association rules analysis and cluster analysis,and the core drug combination of traditional Chinese medicine compound prescription in the treatment of primary osteoporosis was obtained by combining the two results.The therapeutic mechanism of this combination was explained by network pharmacology and verified by molecular docking. RESULTS AND CONCLUSION:Finally,151 articles were included and 207 prescriptions were selected,involving 285 flavors of Chinese herbs.(1)Ten groups of important drug combinations were obtained through the above two analyses,among which the core drug combination with the highest confidence and improvement was"Drynaria-Eucommia-Angelica."The key components of the combination in the treatment of primary osteoporosis were quercetin,kaempferol,naringenin and so on.The core targets were SRC proto-oncogene,phosphoinositide-3-Kinase regulatory subunit 1 and RELA proto-oncogene.The main pathways were cancer signaling pathway,JAK-STAT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.(2)The key active components were docked with the core targets,and the two showed a good combination.To conclude,Chinese herbal compound therapy in the treatment of primary osteoporosis can use a variety of active components to exert its efficacy through multiple signal pathways and acting on multiple targets,which can provide a theoretical basis for the research and development of new drugs for the follow-up treatment of primary osteoporosis.

The ezrin,radixin,moesin(ERM)protein family plays a pivotal role in cell morphology,migration,and signal transduction.Ezrin,as a prominent member of this family,is highly involved in these processes.Ezrin phosphorylation is particularly crucial,by regulating the interaction between ezrin and the actin cytoskeleton.This interaction is a key mediator of cytotoxicity in host cells infected with Helicobacter pylori,significantly impacting cell morphology.In this review,we comprehensively summarize the multifaceted role of ezrin protein in H.pylori-induced nodular gastritis.We consider the relationships between ezrin's structure,function,signaling pathways,and phosphorylation in the context of nodular gastritis.Moreover,this review highlights the role of ezrin protein as a potential therapeutic target,offering novel insights for the prevention and treatment of nodular gastritis.