AIM:To investigate the mechanism of reduced tear secretion in depression-related dry eye rats based on 5-HT/TRPV4/AQP5.METHODS:Healthy SD male rats were established with chronic unpredictable mild stress(CUMS)method to establish a depression-induced dry eye model(n=8), and the control group was blank rats(n=8). The ELISA method was used to compare the 5-hydroxytryptamine(5-HT)in serum and hippocampal tissue of the two groups, and the HE sections of lacrimal gland and AQP5 immunohistochemistry were observed. Western blot and RT-PCR were used to detect the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland tissue of the two groups of rats.RESULTS:The tear secretion in the depression-induced group was significantly reduced(P=0.001), the serum and hippocampal 5-HT levels were significantly reduced(all P<0.05), the expression of AQP5 antibody in the lacrimal gland immunohistochemistry was significantly lower than that in the control group(P<0.001), the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland was significantly reduced(all P<0.05), and no obvious inflammatory cells were found in the lacrimal gland tissue sections.CONCLUSION:Depression-related dry eye may occur through a non-inflammatory 5-HT/TRPV4/AQP5 mechanism.

AIM:To investigate the mechanism of reduced tear secretion in depression-related dry eye rats based on 5-HT/TRPV4/AQP5.METHODS:Healthy SD male rats were established with chronic unpredictable mild stress(CUMS)method to establish a depression-induced dry eye model(n=8), and the control group was blank rats(n=8). The ELISA method was used to compare the 5-hydroxytryptamine(5-HT)in serum and hippocampal tissue of the two groups, and the HE sections of lacrimal gland and AQP5 immunohistochemistry were observed. Western blot and RT-PCR were used to detect the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland tissue of the two groups of rats.RESULTS:The tear secretion in the depression-induced group was significantly reduced(P=0.001), the serum and hippocampal 5-HT levels were significantly reduced(all P<0.05), the expression of AQP5 antibody in the lacrimal gland immunohistochemistry was significantly lower than that in the control group(P<0.001), the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland was significantly reduced(all P<0.05), and no obvious inflammatory cells were found in the lacrimal gland tissue sections.CONCLUSION:Depression-related dry eye may occur through a non-inflammatory 5-HT/TRPV4/AQP5 mechanism.

Objective To investigate the effect of total paeony glycoside(TPG)on cerebral ischemia-reperfusion injury(CI/RI)of rats.Methods The rats were randomly divided into sham surgery(sham)group,CI/RI model group(simple CI/RI group),positive control group(nimodipine group,5 mg/kg),low-dose TPG group(TPG-L group,27 mg/kg),a high-dose TPG group(TPG-H group,54 mg/kg)and a high-dose TPG+NOD-like receptor thermal protein domain associated protein 3(NLRP3)activator diethyl dithiocarbamate(DDC)group(TPG-H+DDC group,54 mg/kg TPG and 30 mg/kg DDC),with 18 rats in each,administered once a day for 7 consecutive days.After the administration,the neurological deficit score of the rats was evaluated.Nissl staining microscopy was applied to observe neuronal activity in brain tissue.2,3,5-triphenyltetrazolium chloride(TTC)staining microscopy was applied to detect the area of cerebral infarction in rats.The level of interleukin-1β and IL-18 in brain tissue was measured by ELISA method.Western blot was applied to detect the expression of purinergic receptor P2X ligand-gated ion channel 7(P2X7R)/NLRP3 signaling pathway related proteins and pyroptosis related proteins such as apoptosis associated speck like protein containing a CARD(ASC)and cysteine protease 1(caspase-1)proteins in brain tissue.Results Compared with the sham group,the neurological deficit score,infarct area,level of IL-1β and IL-18 in brain tissue and protein expression of P2X7R,NLRP3,ASC,and caspase-1 in brain tissue of rats in the simple CI/RI group were significantly increased(P<0.05),while the proportion of Nissl body positive cells in brain tissue was significantly reduced(P<0.05).The change in corresponding indicators of rats in the nimodipine group,TPG-L group,and TPG-H group was opposite to those in the simple CI/RI group(P<0.05).NLRP3 acti-vator DDC antagonized the inhibitory effect of TPG on cell pyroptosis in CI/RI rats.Conclusions TPG may inhibit brain injury in CI/RI rats by down-regulating the P2X7R/NLRP3 pathway.

OBJECTIVE: To observe the effects of electroacupuncture (EA) on improving motor function and regulating microglial activation based on Notch receptor 1 (Notch1)/Hes family bHLH transcription factor 1 (Hes1) pathway in mice with Parkinson's disease (PD). METHODS: Thirty-six male C57BL/6 mice were randomly divided into a control group, a model group and an EA group, 12 mice in each group. PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days in the model group and the EA group. From the 1st day of modeling, EA was applied at "Baihui" (GV20) and bilateral "Shenshu" (BL23) in the EA group, with continuous wave, in frequency of 2 Hz and current of 2 mA, 15 min a time, once a day for 14 days continuously. The behavioral performance was evaluated by gait test, pole climbing test and hanging test, the number of positive cells of tyrosine hydroxylase (TH) and the co-expression positive cells of Notch1/ionized calcium binding adaptor molecule 1 (Iba-1) in the substantia nigra of midbrain was assessed by immunofluorescence, the protein expression of TH, α-synuclein (α-syn), Notch1, Hes1, Iba-1, inducible nitric oxide synthase (iNOS), Arginase-1 (ARG1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 was detected by Western blot, the mRNA expression of Notch1 and Hes1 was detected by real-time PCR. RESULTS: Compared with the control group, in the model group, the stride frequency was accelerated (P<0.001) and the stride length was shortened (P<0.001) for the four limbs, the pole climbing test time was prolonged (P<0.01) and the grip level was reduced (P<0.01); in the substantia nigra of midbrain, the number of positive cells of TH was decreased (P<0.001), the number of co-expression positive cells of Notch1/Iba-1 was increased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-1βand IL-6 was increased (P<0.01, P<0.05, P<0.001), the protein expression of TH, ARG1 and IL-10 was decreased (P<0.01, P<0.001), the mRNA expression of Notch1 and Hes1 was increased (P<0.01). Compared with the model group, in the EA group, the stride frequency was decelerated (P<0.001) and the stride length was increased (P<0.05, P<0.01, P<0.001) for the four limbs, the pole climbing test time was shortened (P<0.05) and the grip level was increased (P<0.05); in the substantia nigra of midbrain, the number of positive cells of TH was increased (P<0.01), the number of co-expression positive cells of Notch1/Iba-1 was decreased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-6 and IL-1β was decreased (P<0.05, P<0.01), the protein expression of TH, ARG1 and IL-10 was increased (P<0.05, P<0.001, P<0.01), the mRNA expression of Notch1 and Hes1 was decreased (P<0.05). CONCLUSION EA can improve the behavioral performance and protect the dopaminergic neurons in PD mice, its mechanism may relate to the inhibition of Notch1/Hes1-mediated neuroinflammation, thus inhibiting the microglial activation.
Animals ; Electroacupuncture ; Microglia/metabolism* ; Male ; Receptor, Notch1/metabolism* ; Parkinson Disease/physiopathology* ; Transcription Factor HES-1/metabolism* ; Mice ; Mice, Inbred C57BL ; Humans ; Signal Transduction

Objective To systematic evaluate the impact of applying the clinical nursing pathway(CNP)on epidural anesthetic analgesia natural delivery.Methods The randomized controlled trial(RCT)and quasi-experimental researches on the application of CNP in epidural anesthetic analgesia natural delivery were retrieved from PubMed,Cochrane Library,Embase,Web of Science,China Knowledge Network database,Wanfang database,VIP and the Chinese Biomedical Literature Database.The retrieval time limit was from January 1,2014,to July 31,2024 with no language limitation.The meta analysis on the included studies was performed by applying RevMan5.4.1.Results A total of 5 RCTs and 2 quasi-experimental studies were in-cluded,involving 979 parturients with deliveries.The meta analysis showed that compared with the conven-tional nursing,CNP could shorten the duration of the first stage of labor(MD=—1.06,95％CI:—1.95——0.17,P=0.02)and the duration of the second stage of labor(MD=—0.12,95％CI:—0.21——0.03,P=0.006);decreased the rate of perineal lateral incision(RR=0.73,95％CI:0.65-0.83,P＜0.001)and inci-dence rate of postpartum urinary retention(RR=0.35,95％CI:0.20-0.63,P＜0.001);and shortened the time to lactation initiation(SMD=—1.52,95％CI:—2.38——0.66,P＜0.001).There was no influence on reducing postpartum 24 h hemorrhage amount(SMD=—0.51,95％CI:—1.23-0.21,P=0.16).The study subjects were divided into the primipara women subgroup and unclassified parturients subgroup.Compared with the conventional nursing group,compared with the conventional nursing,CNP had no impact on the dura-tion of the first stage of labor(MD=—0.32,95％CI:—0.61-0.98,P=0.63)and the duration of the second stage of labor(MD=—0.11,95％CI:—0.25-0.04,P=0.15)in the primipara women subgroup.CNP could reduce the postpartum 24 h hemorrhage volume in the unclassified parturients subgroup(SMD=—1.47,95％CI:—1.72——1.21,P＜0.001).Conclusion Application of CNP in parturients labor analgesia could reduce the perineal lateral incision rate and incidence rate of postpartum urinary retention and shorten the time to lac-tation initiation.Due to the heterogeneity among studies,the impact of CNP on the labor duration and the bleeding amount within postpartum 24 h still requires more high-quality studies to be conducted in the future for verification.

Objective To investigate the prognostic value of the platelet-to-lymphocyte ratio(PLR)at different early time points in adult patients undergoing veno-arterial extracorporeal membrane oxygenation(VA-ECMO).Methods A retrospective study was conducted,selecting 55 adult patients who underwent VA-ECMO treatment at the First Hospital of Jiaxing from June 2020 to October 2022 as the study subjects.Then,the patients'gender,age,past history[including hypertension,diabetes,heart disease,chronic obstructive pulmonary disease(COPD)],and the reason for extracorporeal membrane pulmonary oxygenation(ECMO)adjuvant therapy[including severe myocarditis,acute myocardia infarction,in-hospital and out-of-hospital cardiac arrest,severe closed craniocerebral injury,severe pneumonia,pelvic fracture,other(pulmonary embolism,electrocution,traumatic hepatic rupture,post-partum hemorrhage,severe acute pancreatitis,crush syndrome)],acute physiology and chronic health evaluationⅡ(APACHEⅡ),sequential organ failure assessment(SOFA)at the time of admission,and ECMO peripheral blood tests[creatinine,alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood lactate acid(Lac),white blood cell count(WBC),neutrophil count(NEU),lymphocyte count(LYM),hemoglobin(Hb),and platelet count(PLT)]and the last time prior to ECMO assistance,24 hours prior to the occurrence of acute kidney injury(AKI),and 24 hours after the occurrence of AKI.PLR levels at 24 hours ECMO,and the proportion of continuous renal replacement therapy(CRRT).The patients were divided into a death group and a survival group based on their 30-day prognosis and further categorized into a CRRT group and a non-CRRT group based on whether CRRT was administered.Clinical indicators of patients with different prognosis and the differences in PLR levels between CRRT and non-CRRT groups were compared.Logistic regression analysis was used to identify independent risk factors affecting the 30-day prognosis of VA-ECMO patients.The receiver operator characteristic(ROC curves)were plotted to evaluate the prognostic predictive value of each risk factor.Results Compared to the survival group,the death group had significantly higher APACHEⅡscores,SOFA scores,LYM and proportion receiving CRRT[APACHEⅡscore:34.00(28.50,36.00)vs.25.00(14.75,34.00),SOFA score:5.00(4.00,6.50)vs.3.00(2.00,5.25),LYM(×109/L):3.40±1.97 vs.2.24±2.11,proportion receiving CRRT:91.30%(21/23)vs.62.50%(20/32)],and a significantly lower level of the last PLR prior to ECMO adjuvant[30.00(21.06,48.17)vs.58.82(41.80,145.72)],and the differences were statistically significant(all P<0.05).Logistic regression analysis showed that the levels of the last PLR before ECMO assistance[odds ratio(OR)=0.965,95%confidence interval(95%CI)was 0.938-0.993,P=0.013],APACHEⅡscore at the time of admission(OR=1.121,95%CI was 1.018-1.234,P=0.020),and CRRT(OR=7.734,95%CI was 1.042-57.401,P=0.045)were independent risk factors affecting the prognosis of the VA-ECMO patients at 30 days after adjuvant;the ROC curve analysis showed that APACHEⅡscore,CRRT and the last PLR level before ECMO assistance had a predictive value for the prognosis of VA-ECMO patients 30 days after assistance,in which the APACHEⅡscore+the last PLR level before ECMO assistance had the greatest predictive value in predicting the prognosis of the patients,with area under the curve(AUC)of 0.846,with a sensitivity of 62.5%and a specificity of 95.7%.Higher early PLR levels were associated with better prognosis.In the CRRT group,PLR levels at 24 hours before ECMO initiation,24 hours before AKI onset,and 24 hours after AKI onset were significantly lower than those in the non-CRRT group(all P<0.05).Conclusion Early PLR levels and CRRT administration have significant predictive value for the prognosis of patients undergoing VA-ECMO therapy.

Objective:To construct the user personas of the patients who practice self-management home rehabilitation after lower limb bone transport by exploring their self-management experiences and needs in rehabilitation at home so as to provide targeted countermeasures for related medical staff.Methods:A purposive sampling method was employed to select the 21 patients who had undergone home rehabilitation after lower limb bone transport at Department of Orthopedic Trauma, Nanfang Hospital from September to December 2024. The cohort included 12 males and 9 females, with an age of (39.8±15.1) years. The phenomenological research method was used to conduct semi-structured interviews with this cohort. After the data from interviews were explored by the Colaizzi 7-step analysis to extract the factual labels, role dimension models were built, covering 3 dimensions: description, characteristics (basic, cognitive, behavioral, social support, and psychological adjustment characteristics) and needs.Results:All patients were interviewed. Four user personas were constructed, including self-awareness growth type (5 cases), emotional dependency-driven type (4 cases), risk-aversion procrastination type (7 cases), and management motivation-impaired type (5 cases). The patients of self-awareness growth type were 21 to 36 years old and received high school or university education, characterized by high self-efficacy, active measures to improve and maintain their state of rehabilitation, good management of negative emotions, and a low sense of stigma. The patients of emotional low-driven type were 42 to 74 years old and received their education in a primary school or junior high school, characterized by lack of independence, dependence on others for rehabilitation management, common management of negative emotions, low self-efficacy, and a strong sense of stigma. The patients of risk-aversion procrastination type were 33 to 56 years old and received their education in a junior or senior high school, characterized by a willingness to cooperate but insufficient motivation for rehabilitation management, an awareness of rehabilitation which was vulnerable to external factors, common management of negative emotions, low self-efficacy, and a strong sense of stigma. The patients of management motivation-impaired type were 51 to 61 years old, received primary school education or lower, characterized by insufficient knowledge and poor self-management behavior, constant failure to follow the prescribed rehabilitation exercises, poor management of negative emotions, low self-efficacy, and a low sense of stigma.Conclusion:The user personas we have constructed for the patients who practice self-management home rehabilitation after lower limb bone transport can help healthcare professionals with specific targeted interventions to enhance self-management efficacy to facilitate the rehabilitation process for the patients.

A ketogenic diet(KD)refers to an eating pattern designed to achieve a low-calorie content,minimum carbohydrate intake,high-fat consumption,and standard protein levels.A ketogenic diet is used in clinical practice to treat conditions including heart disease,diabetes,obesity,autism,glioblastoma,and other cancers.Although a ketogenic diet has not been recommended for any neurological disorders except epilepsy,extensive recent research suggests that such a diet may have a neuroprotective effect and may thus represent a new dietary therapy for the treatment of Parkinson's disease(PD).In this review,we discuss in detail the mechanisms responsible for the neuroprotective effects of a ketogenic diet in Parkinson's disease,with the aim of providing references for future clinical and experimental studies.

Parkinson's disease(PD)is a common progressive neurodegenerative disease mainly affecting the motor system.Various genetic factors and cellular mechanisms underlying PD have recently been discovered.Emerging evidence suggests that epigenetic modifications play a very important role in the pathogenesis,prevention,and treatment of PD.Epigenetic modification mediates genetic and environmental interactions mainly through complex interactions of DNA methylation,histone modification,and non-coding RNA,thereby affecting expression in the absence of changes in DNA sequence.In this review,we summarize the epigenetic modification mechanisms involved in the pathogenesis of Parkinson's disease.In this review,we summarize the epigenetic modification mechanisms involved in the pathogenesis of Parkinson's disease.Recent studies have found that traditional Chinese medicine can participate in the regulation of abnormal epigenetic modifications in the treatment of PD.Traditional Chinese medicine benefits from its multi-level and multi-target regulatory effects,and various traditional Chinese medicine monomers,compound prescriptions,and techniques have been evaluated,confirming that this is a promising approach for improving symptoms in PD.This review summarizes the mechanisms by which epigenetic modifications contribute to P D,explores the role of traditional Chinese medicine,and provides new ideas for clinical treatment and drug development in PD through epigenetic intervention.

Serotonin syndrome (SS), also known as serotonin toxicity, is a rare but life-threatening drug reaction syndrome. This case involves a 17-year-old female patient who developed tremors, fatigue, and tachycardia after taking fluoxetine combined with bupropion and tandospirone for five days. SS was highly suspected, and her symptoms improved following treatment targeted at serotonin syndrome. This case is reported to raise awareness among clinicians about the potential adverse reactions of drug combinations, the importance of early identification of SS symptoms, and precautions when prescribing combined medications to avoid serious consequences.