The core pathological feature of Parkinson's disease(PD)is the abnormal aggregation of α-synuclein and the result ing neuronal damage.α-Synuclein exhibits toxic effects when it forms oligomers or fibrils,leading to neuronal death via multiple pathways,including mitochondrial dysfunction,impaired vesicular trafficking,dopamine auto-oxidation,and neuroinflammation.In addition,α-synuclein can propagate between cells via exosomes,endocytosis/exocytosis,tunneling nanotubes,or vagal nerve axonal transport,creating a cascade of pathological effects.Animal models of PD that recapitulate the key pathological hallmark of α-synuclein accumulation are indispensable tools for elucidating disease mechanisms and developing novel therapeutic interventions.To date,various strategies,including transgenic techniques,bacterial artificial chromosome(BAC)-mediated expression,viral vector-mediated overexpression,and gene editing,have been employed to develop α-synuclein overexpression animal models.These models have significantly advanced our exploration of the relationship between PD and α-synuclein.This systematic review considers the structure and function of α-synuclein,its mechanisms of toxicity,intercellular propagation pathways,animal models of overexpression,and potential therapeutic targets based on its pathogenic mechanisms.

Postoperative acute pain can significantly hinder early postoperative recovery if inadequately managed,and may even progress to chronic postsurgical pain(CPSP).The current clinical practice primarily relies on multimodal analgesia strategies,with intravenous opioids being the cornerstone.Although effective in alleviating postoperative pain,the associated adverse effects of opioids have limited their widespread use.In recent years,with the development of integrative medicine combining Western and traditional Chinese medicine,numerous studies have demonstrated that incorporating transcutaneous electrical acupoint stimulation(TEAS)into multimodal analgesia protocols confers significant benefits for postoperative pain management.TEAS not only reduces postoperative pain and opioid consumption but also mitigates opioid-related side effects,thereby facilitating patient recovery.This review aims to provide a comprehensive overview of the analgesic mechanisms of TEAS,its application within multimodal analgesia for postoperative pain,and its potential to serve as a valuable reference for clinicians seeking to optimize postoperative pain management strategies.

The core pathological feature of Parkinson's disease(PD)is the abnormal aggregation of α-synuclein and the result ing neuronal damage.α-Synuclein exhibits toxic effects when it forms oligomers or fibrils,leading to neuronal death via multiple pathways,including mitochondrial dysfunction,impaired vesicular trafficking,dopamine auto-oxidation,and neuroinflammation.In addition,α-synuclein can propagate between cells via exosomes,endocytosis/exocytosis,tunneling nanotubes,or vagal nerve axonal transport,creating a cascade of pathological effects.Animal models of PD that recapitulate the key pathological hallmark of α-synuclein accumulation are indispensable tools for elucidating disease mechanisms and developing novel therapeutic interventions.To date,various strategies,including transgenic techniques,bacterial artificial chromosome(BAC)-mediated expression,viral vector-mediated overexpression,and gene editing,have been employed to develop α-synuclein overexpression animal models.These models have significantly advanced our exploration of the relationship between PD and α-synuclein.This systematic review considers the structure and function of α-synuclein,its mechanisms of toxicity,intercellular propagation pathways,animal models of overexpression,and potential therapeutic targets based on its pathogenic mechanisms.

Postoperative acute pain can significantly hinder early postoperative recovery if inadequately managed,and may even progress to chronic postsurgical pain(CPSP).The current clinical practice primarily relies on multimodal analgesia strategies,with intravenous opioids being the cornerstone.Although effective in alleviating postoperative pain,the associated adverse effects of opioids have limited their widespread use.In recent years,with the development of integrative medicine combining Western and traditional Chinese medicine,numerous studies have demonstrated that incorporating transcutaneous electrical acupoint stimulation(TEAS)into multimodal analgesia protocols confers significant benefits for postoperative pain management.TEAS not only reduces postoperative pain and opioid consumption but also mitigates opioid-related side effects,thereby facilitating patient recovery.This review aims to provide a comprehensive overview of the analgesic mechanisms of TEAS,its application within multimodal analgesia for postoperative pain,and its potential to serve as a valuable reference for clinicians seeking to optimize postoperative pain management strategies.

Sphingosine-1-phosphate(S1P)is a highly active membrane phospholipid metabolite with important physiological roles in the cardiovascular system.Sphingosine kinase(SphK)is a lipase that is important for main-taining stable S1P levels in vivo.S1P exerts different physiological effects in cardiovascular diseases by catalytically regulating the binding of S1P to G protein-coupled receptors(S1PR1-5)on the cell surface,thus exerting different physiological effects in cardiovascular diseases.For example,they are involved in regulating the development of dis-eases such as atherosclerosis,myocardial ischemia-reperfusion injury,myocardial infarction,heart failure and other diseases,maintaining the barrier function of vascular endothelial cells,protecting the endothelial glycocalyx layer,leukocyte adhesion,inflammatory reactions and other pathophysiologic processes.

Objective:To establish a UPLC method for the simultaneous determination of paeoniflorin,naringin,hesperidin,neohesperidin,costunolide and dehydrocostuslactone to improve the quality standard of Shangke Dieda Tablets.Methods:An Agilent Poroshell 120 C18 column(100 mm × 4.6 mm;2.7 μm)was used with a mobile phase of acetonitrile and 0.1％phosphate solution with binary gradient system at a flow rate of 1.0 mL·min-1.The detection wavelength was 230 nm and the column temperature was 30 ℃.Results:Paeoniflorin,naringin,hesperidin,neohesperidin,cosinolide and dehydrocosinolide showed a good linear relationship between injection concentration and peak area(r＞0.999).The linear ranges of six components were 0.854 2-256.272 μg·mL-1(r=0.999 9),1.057 5-317.247 μg·mL-1(r=0.999 9),and 0.989 5-269.850 μg·mL-1(r=0.999 9),1.055 6-316.689 μg·mL-1(r=0.999 9),0.905 1-271.527 μg·mL-1(r=0.999 8),and 1.064 7-319.395 μg·mL-1(r=0.999 9),respectively.The average recoveries of six components were 99.4％(RSD=1.2％),104.0％(RSD=1.2％),101.6％(RSD=1.0％),102.9％(RSD=0.4％),97.0％(RSD=1.9％),and 104.2％(RSD=1.0％),respectively.A total of 74 batches of samples were collected from 10 manufacturers.The contents of paeoniflorin,naringin,hesperidin,neohesperidin,coxinolactone,and dehydro-cosinolactone were 0.250 8-0.653 2,0.042 2-0.930 9,0.590 9-3.978 0,0.021 2-0.592 6,0.002 4-0.156 7,0.009 2-0.231 3 mg per tablet,respectively.Conclusion:The validated results showed that the method can be used to control the quality of Shangke Dieda Tablets.

Objective Exploring the relationship between changes in serum Golgi apparatus transmem-brane glycoprotein 73(GP73)and chitosanase 3-like protein 1(CHI3L1)levels and liver fibrosis and lesion sever-ity in patients with hepatitis B(CHB).Methods Using a case-control study,80 patients diagnosed with CHB infection and developing liver fibrosis in the Infectious Disease Department of Changsha First Hospital from June 2020 to June 2023 were selected as the liver fibrosis group,while 120 patients diagnosed with CHB infection but not developing liver fibrosis in the Infectious Disease Department of our hospital were selected as the control group.The serum GP3,CHI3L1,liver function,and fibrosis indicators of the two groups of patients were compared,and the liver fibrosis group was divided into mild according to Scheuer system standards Perform stratified analysis on patients with significant liver fibrosis.Results The serum GP3 and CHI3L1 levels in the liver fibrosis group were significantly higher than those in the control group,with statistical significance(P＜0.05);The ROC curves were plotted using serum GP3,CHI3L1,and GP3+CHI3L1,respectively.The sensitivity for diagnosing liver fibrosis in CHB patients was 62.81%,60.94%,and 96.33%,with specificity of 80.66%,80.05%,and 75.30%.The AUC values under the curves were 0.792,0.756,and 0.908,respectively;The levels of ALT,AST,HA,LN,PC III NP,C IV,and CG in the liver fibrosis group were higher than those in the control group,and the PLT measurement values were lower than those in the control group,with statistical significance(P＜0.05);49 patients with moderate to severe liver fibrosis(33 in S2 phase and 16 in S3 phase)and 31 patients with mild liver fibrosis(all in S1 phase)had significantly higher serum GP3 and CHI3L1 levels than mild patients,with statistical significance(P＜0.05);The levels of DBIL,ALT,AST,HA,LN,PC III NP,C IV,and CG in patients with moderate to severe liver fibrosis were higher than those in the mild group,and the PLT measurement values were lower than those in the mild group,with statistical significance(P＜0.05).Conclusion The serum GP3 and CHI3L1 levels in CHB patients with liver fibrosis are significantly elevated,and there is a certain correlation with the degree of liver fibro-sis.The combination of these two indicators is beneficial for diagnosing liver fibrosis in CHB patients.

Development of thoracolumbar vertebra (TLV) and rib primordium (RP) is a common evolutionary feature across vertebrates, although whole-organism analysis of the expression dynamics of TLV- and RP-related genes has been lacking. Here, we investigated the single-cell transcriptome landscape of thoracic vertebra (TV), lumbar vertebra (LV), and RP cells from a pig embryo at 27 days post-fertilization (dpf) and identified six cell types with distinct gene expression signatures. In-depth dissection of the gene expression dynamics and RNA velocity revealed a coupled process of osteogenesis and angiogenesis during TLV and RP development. Further analysis of cell type-specific and strand-specific expression uncovered the extremely high level of HOXA10 3'-UTR sequence specific to osteoblasts of LV cells, which may function as anti-HOXA10-antisense by counteracting the HOXA10-antisense effect to determine TLV transition. Thus, this work provides a valuable resource for understanding embryonic osteogenesis and angiogenesis underlying vertebrate TLV and RP development at the cell type-specific resolution, which serves as a comprehensive view on the transcriptional profile of animal embryo development.

To establish the experts consensus on the management of delirium in critically ill patients.A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group.Each statement was assessed based on the GRADE (Grading of Recommendations Assessment,Development,and Evaluation) principle.Then the Delphi method was adopted by 36 experts to reassess all the statements.(1) Delirium is not only a mental change,but also a clinical syndrome with multiple pathophysiological changes.(2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function.(3) Pain is a common cause of delirium in critically ill patients.Analgesia can reduce the occurrence and development of delirium.(4) Anxiety or depression are important factors for delirium in critically ill patients.(5) The correlation between sedative and analgesic drugs and delirium is uncertain.(6) Pay attention to the relationship between delirium and withdrawal reactions.(7) Pay attention to the relationship between delirium and drug dependence/ withdrawal reactions.(8) Sleep disruption can induce delirium.(9) We should be vigilant against potential risk factors for persistent or recurrent delirium.(10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases,and can also be alleviated with the improvement of primary diseases.(11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis.(12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium,especially subclinical delirium.(13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium.(14) Daily assessment is helpful for early detection of delirium.(15) Hopoactive delirium and mixed delirium are common and should be emphasized.(16) Delirium may be accompanied by changes in electroencephalogram.Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant.(17) Pay attention to differential diagnosis of delirium and dementia/depression.(18) Pay attention to the role of rapid delirium screening method in delirium management.(19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium.(20) The key to the management of delirium is etiological treatment.(21) Improving environmental factors and making patient comfort can help reduce delirium.(22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium.(23) Communication with patients should be emphasized and strengthened.Family members participation can help reduce the incidence of delirium and promote the recovery of delirium.(24) Pay attention to the role of sleep management in the prevention and treatment of delirium.(25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium.(26) When using antipsychotics to treat delirium,we should be alert to its effect on the heart rhythm.(27) Delirium management should pay attention to brain functional exercise.(28) Compared with non-critically illness related delirium,the relief of critically illness related delirium will not accomplished at one stroke.(29) Multiple management strategies such as ABCDEF,eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients.(30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment.(31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management.Consensus can promote delirium management in critically ill patients,optimize analgesia and sedation therapy,and even affect prognosis.

Objective To investigate the application value of functional MRI in the differential diagnosis between breast mucinous carcinoma and phyllodes tumor(≥ 3 cm). Methods 55 cases of breast mucinous adeno-carcinoma and phyllodes tumors(≥ 3 cm)from January 2012 to December 2017 were retrospectively analyzed. MRI features of 20 mucinous carcinomas and 35 phyllodes tumors were analyzed,compared with pathology. Re-sults There were 20 cases of breast mucinous carcinoma in current study,including 14 cases of pure mucinous carcinoma and 6 cases of mixed mucinous carcinoma. There were 35 cases of phyllodes tumors,including 9 be-nign,18 borderline and 8 malignant cases. There was no significant difference in T1WI signal and enhancement mode between breast mucinous carcinoma and phyllodes tumors. There were significant differences in age,long di-ameter,morphology,lobulation,border,ADC value,EER,T2WI signal and TIC curve pattern(P < 0.05). The area under ROC(AUC)of ADC value and EER for breast mucinous adenocarcinoma and phyllodes tumor was 0.7036 and 0.8029,respectively. Conclusions Multi-model functional MRI can effectively distinguish breast mucinous adenocarcinoma from phyllodes tumor(≥ 3 cm),and EER is more accurate than ADC value.