Objective To investigate the protective effect of exogenous leptin against focal cerebral ischemia-reperfusion(I/R)injury in mice and explore the underlying mechanism.Methods A total of 100 C57BL/6 mice were randomly divided into 5 groups,including a sham-operated group,cerebral I/R model group,and 3 leptin treatment groups with intraperitoneal injections of 0.5,1.0 or 2.0 leptin immediately after occlusion of the internal carotid artery.At 24 h after reperfusion,neurological function scores of the mice were assessed,and TTC staining was used to determine the area of cerebral infarction.The pathological changes in the cortical brain tissue of the mice were observed using HE staining,and degenerative damage of the cortical neurons were assessed with Fluoro-Jade C staining.The expression of glial fibrillary acidic protein in cortical brain tissues was detected using immunohistochemistry and Western blotting.In another 45 C57BL/6 mice with sham operation,I/R modeling,or leptin(1 mg/kg)treatment,glutamic acid in the cortical brain tissue was detected using glutamate assay,and cortical glutamate-aspartate transporter(GLAST)and glutamate transporter-1(GLT-1)protein expressions were detected using immunohistochemistry.Results Compared with the I/R model mice,the leptin-treated mice had significantly lower neurological deficit scores,smaller cerebral infarct area,milder pathologies in the cortical brain tissue,and lessened cortical neuronal damage with normal morphology and less excessive proliferation of the astrocytes.Leptin treatment significantly up-regulated the expressions of GLT-1 and GLAST and lowered the content of glutamic acid in the brain tissue of the I/R mice.Conclusion Exogenous leptin has obvious neuroprotective effect against cerebral I/R injury in mice,mediated probably by controlling excessive astrocyte proliferation and up-regulating cortical GLT-1 and GLAST expressions to reduce glutamate-mediated excitotoxic injury of the astrocytes.

Objective To investigate the protective effect of exogenous leptin against focal cerebral ischemia-reperfusion(I/R)injury in mice and explore the underlying mechanism.Methods A total of 100 C57BL/6 mice were randomly divided into 5 groups,including a sham-operated group,cerebral I/R model group,and 3 leptin treatment groups with intraperitoneal injections of 0.5,1.0 or 2.0 leptin immediately after occlusion of the internal carotid artery.At 24 h after reperfusion,neurological function scores of the mice were assessed,and TTC staining was used to determine the area of cerebral infarction.The pathological changes in the cortical brain tissue of the mice were observed using HE staining,and degenerative damage of the cortical neurons were assessed with Fluoro-Jade C staining.The expression of glial fibrillary acidic protein in cortical brain tissues was detected using immunohistochemistry and Western blotting.In another 45 C57BL/6 mice with sham operation,I/R modeling,or leptin(1 mg/kg)treatment,glutamic acid in the cortical brain tissue was detected using glutamate assay,and cortical glutamate-aspartate transporter(GLAST)and glutamate transporter-1(GLT-1)protein expressions were detected using immunohistochemistry.Results Compared with the I/R model mice,the leptin-treated mice had significantly lower neurological deficit scores,smaller cerebral infarct area,milder pathologies in the cortical brain tissue,and lessened cortical neuronal damage with normal morphology and less excessive proliferation of the astrocytes.Leptin treatment significantly up-regulated the expressions of GLT-1 and GLAST and lowered the content of glutamic acid in the brain tissue of the I/R mice.Conclusion Exogenous leptin has obvious neuroprotective effect against cerebral I/R injury in mice,mediated probably by controlling excessive astrocyte proliferation and up-regulating cortical GLT-1 and GLAST expressions to reduce glutamate-mediated excitotoxic injury of the astrocytes.

Objective To investigate the effect of short-term blood glucose control on neurovascular coupling in pa-tients with diabetes mellitus type 2(T2DM).Methods The patients with T2DM who were admitted to Department of En-docrinology,The Second Affiliated Hospital of Hainan Medical University,from December 1,2021 to May 30,2023 were consecutively included in this study,and according to whether examination was performed before or after blood glucose control,they were divided into pre-blood sugar control T2DM group(T2DM-Pre-c group)and post-blood sugar control T2DM group(T2DM-Pro-c group).Healthy volunteers matched for age and sex were enrolled as healthy control(HC)group.Transcranial Doppler was used to monitor cerebral blood flow parameters,including mean blood flow velocity(Vm)of the middle cerebral artery during elbow flexion,and the T2DM group and the HC group were compared in terms of the changes in cerebral blood flow parameters after blood glucose control.Results A total of 52 T2DM patients and 36 healthy volunteers were enrolled in this study.Compared with the HC group,the T2DM-Pre-c group had significantly higher exercise-induced pulsatility index,resistance index,and time to peak of Vm(TTP-Vm)(all P<0.05).The T2DM-Pre-c group had a significantly lower Vm slope than the HC group(P=0.031).The T2DM-Pro-c group had a significant in-crease in Vm slope and a significant reduction in TTP-Vm after blood glucose control(P<0.05).Conclusion Impair-ment of neurovascular coupling is observed in patients with T2DM during the state of hyperglycemia,and short-term blood glucose control can improve neurovascular coupling.

Objective To investigate the relationship between cerebrovascular reactivity(CVR)and emotional disorders in the patients undergoing continuous hemodialysis for end-stage renal disease(ESRD).Methods The clinical data of the ESRD patients undergoing continuous hemodialysis were collected.Anxiety and depression of the patients were assessed by the Hamilton anxiety scale(HAMA)and Beck depression inven-tory,respectively.The cerebral hemodynamic changes during the breath holding test were monitored by transcrani-al Doppler sonography,and the breath-holding index(BHI)was calculated.The BHI≥0.69 and BHI＜0.69 indi-cate normal CVR and abnormal CVR,respectively.Binary Logistic regression was employed to analyze the factors affecting the depressive state of ESRD patients.Results The group with abnormal CVR exhibited higher total cholesterol level(P=0.010),low density lipoprotein level(P=0.006),and incidence of depression(P=0.012)than the group with normal CVR.Compared with the non-depression group,the depression group dis-played prolonged disease course(P=0.039),reduced body mass index(P=0.048),elevated HAMA score(P=0.001),increased incidence of anxiety(P＜0.001),decreased BHI(P=0.015),and increased incidence of abnormal CVR(P=0.012).Binary Logistic regression analysis indicated anxiety as a contributing factor(OR=22.915,95％CI=2.653-197.956,P=0.004)and abnormal CVR as a risk factor(OR=0.074,95％CI=0.008-0.730,P=0.026)for depression.Conclusion Impaired CVR could pose a risk for depression in the patients with ESRD.

Objective:A case of advanced nasopharyngeal carcinoma with autonomic dysfunction was reported and its pathophysiological mechanism was discussed.Methods:The diagnosis and treatment of a nasopharyngeal carcinoma patient with autonomic nervous dysfunction such as paroxysmal syncope was summarized, and the pathophysiological mechanism of this case was analyzed by searching related literature.Results:Nasopharyngeal carcinoma characterized by autonomic dysfunction was rare and had a poor prognosis. Autonomic dysfunction caused by nasopharyngeal carcinoma was associated with carotid sinus syndrome, parapharyngeal space syncope syndrome, glossopharyngeal nerve reflex and paraneoplastic neuropathy.Conclusions:Early detection and treatment is a key factor affecting the prognosis of nasopharyngeal carcinoma. Clinicians should consider nasopharyngeal carcinoma as one of the differential diagnoses in the diagnosis and treatment of patients with autonomic nervous dysfunction combined with cranial nerve damage.

A 25-year-old women was admitted to the department of Neurology in Affiliated 2nd Hospital of Hainan Medical University due to recurrent syncope for 8 years and return for 2 months. She had multiple episodes of syncope at onset. She presented with the feeling of weakness in both lower limbs, and fatigue in the past year. She experienced pain in the waist and limbs joint in recent three months. Physical examination showed joint hyperactivity in metacarpophalangeal joints of both upper limbs, increased skin elasticity. Active-standing transcranial Doppler (TCD) test showed that the average heart rate (HR) and the average middle cerebral artery (MCA) blood flow velocity in the supine position were 79 beats/min and 62 cm/s, respectively; while the average HR and the average MCA blood flow velocity in the standing position were 126 beats/min, 47 cm/s. Meanwhile,the blood pressure was normal during the test of supine-to-standing TCD. Genetic testing indicated LDB3 transgenation. The patient was diagnosed as postural tachycardia syndrome (joint-hypermobility-related), Ehlers-Danlos syndrome, and relieved by fluid infusion and rehabilitation therapy.

To explore the prevalence and related factors of orthostatic intolerance in patients with Type 2 diabetes. Methods Patients with Type 2 diabetes were enrolled，admitted to the Department of Neurology from September 2020 to October 2021.General clinical data were collected. The active standing TCD test were performed on all the patients，and the changes of blood pressure，heart rate and cerebral hemodynamics were recorded from supine to standing for 1 min，3 min，5 min and 10 min. Orthostatic intolerance questionnaire were completed. Association between Orthostatic intolerance questionnaire score and results of supine to standing TCD test were analyzed. Results A total of 161 patients were enrolled for this study，70 （43.5%） with Symptoms of orthostatic intolerance and 91 （56.5%） without. Correlation analysis showed that Orthostatic intolerance questionnaire score have positive correlation with the magnitude of systolic pressure fall，diastolic pressure fall，Cerebral blood flow velocity fall and cerebral blood flow response to tilt score.（r=0.57、P= 0.000，r=0.44、P=0.000，r=0.30、P=0.022，r=0.24、P=0.044）.Conclusion The proportion of OI in patients with Type 2 diabetes is high，which is associated with orthostatic blood pressure and cerebral blood flow decline.

Weight loss is common in non-motor symptoms in Parkinson disease (PD).It may predate motor symptom onset,and may be associated with the development of disease.However,it was less accounted of clinically.The pathophysiology of weight loss in PD is very complicated.This review discusses the pathogenesis of PD weight loss from dopaminergic dysfunction,energy expenditure/intake imbalance,central mechanisms of feeding behavior regulation,and neuroendocrine abnormalities.

Objective To study the application of 99Tcm in rabbit cerebral thromboembolic stroke and thrombolysis effect of recombinant tissue plasminogen activator (rt-PA).Methods The 0.5 mL radioactive pertechnetate sodium (specification:5 mCi/2mL and radiation intensity 92.5 MBq/mL) was combined with 30 μL stannous chloride (5 mg/mL),and the 20 μL mixture was joined to whole blood,red blood cells,and plasma for labelling.Then 50 μL CaCl2 (0.5 mol/L) and bovine thrombin (50 IU/mL) were doped in mixture,and rapidly sucked into a polyethylene plastic pipe (PE80).Thrombus was formed for 2 h at 37 ℃ and cut into small pieces of 10 mm.Autologous blood clots combined with 99Tcm from external carotid artery were injected to internal carotid artery of rabbit,the radioactivity (counts per minute,CPM) was measured by gamma counting instrument,and the improvement of rt-PA 4.5 mg/kg (clinical equivalent dose) on this model was observed.Results After thromboembolism,CPM increased approximately by (5.1 ± 1.3) times,which suggested that the model was reliable.The rt-PA 4.5 mg/kg had significant progressive thrombolysis effect.Conclusion 99Tcm tracer technology could be applied to rabbit cerebral stroke model,which is stable and reliable

OBJECTIVETo investigate the effects of small interfering RNA (siRNA) targeting YAP on the proliferation and apoptosis of human periodontal ligament stem cells (hPDLSCs).

METHODSSynthesized sequences of siRNA were transfected into hPDLSCs by Lipofectamine™ 2000. The expression of YAP was identified by using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Proliferation activity was detected by using cell counting kit-8 (CCK-8). Changes in the cell cycle and apoptosis rate were detected by using flow cytometry. Results were analyzed by using SPSS 19.0, and P < 0.05 was considered statistically significant.

RESULTSExpression of YAP mRNA and protein were significantly downregulated after 48 h of transfection (P < 0.001). No obvious difference was found in the expression levels of YAP protein between 48 and 72 h, thus indicating that siRNA could inhibit the expression of YAP persistently and effectively. Proliferation activity was inhibited, and apoptosis rate was increased. Cell cycle was changed as the proportion of G₁and S phases increased (P < 0.01) and G₂ phase decreased (P < 0.05).

CONCLUSIONKnocking down YAP gene by siRNA could inhibit proliferation activity, induce apoptosis, and change the cell cycle of hPDLSCs. Thus, YAP could regulate the proliferation and apoptosis of hPDLSCs.

Adaptor Proteins, Signal Transducing ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Down-Regulation ; Humans ; Periodontal Ligament ; drug effects ; Phosphoproteins ; RNA, Messenger ; RNA, Small Interfering ; pharmacology ; Stem Cells ; drug effects ; Transfection