Objective To explore the protection and mechanism of hydrogen sulfide (H2S) preconditioning against injury induced by cisplatin in human marrow mesenchymal stem cells (HMMSCs).Methods HMMSCs were treated by cisplatin at 0,5,10,20,40,60,80 mg/L concentrations for 24 h respectively and were exposed to cisplatin at 20 mg/L concentrations for 0,6,12,24,36,48 h respectively.HMMSCs were pretreated with NaHS at 0,0.4,0.6,0.8,1.0 mmol/L respectively for 30 min before exposed to cisplatin at 20 mg/L concentrations for 24 h.HMMSCs were treated by U0126 or combined with human epidermal growth factor (HEGF) together for 30 min before they were preconditioned with NaHS for 30 min.The cell survival rate,cell apoptosis rate,the expression of p-ERK1/2 and t-ERK1/2 were recorded.Results The cell survival rate decreased to 71.72％±2.72％,59.41％±5.44％,50.37％±4.55％,38.97％±2.92％,30.11％±4.64％ and 21.71％±5.35％ respectively after cells were treated with cisplatin at 5,10,20,40,60,80 mg/L concentrations respectively,and the differences were statistically significant compared with 0 mg/L group.The cell viability fell to 70.30％±6.20％,61.63％±2.70％,51.29％±3.13％,38.72％±3.66％ and 27.57％±2.32％ after HMMSCs were treated with cisplatin at 20 mg/L for 6,12,24,36,48 h respectively,and the differences were statistically significant compared with 0 h group.The cell viability increased to 65.99％±2.67％,72.93％±5.44％,75.10％±4.71％ and 76.56％± 5.25％ when HMMSCs got pretreatment of NaHS,and the differences had statistical significance compared with cisplatin group.The cell apoptotic rate decreased from 35.29％±2.77％ to 18.62％±0.97％ when HMMSCs were pretreated with NaHS at 0.6 mmo/L.Treatment of HMMSCs with cisplatin at 20 mg/L for 24 h reduced p-ERK1/2 expression.The pretreatment of NaHS could inhibit the inhibitory action to the expression of p-ERK1/2 induced by cisplatin.Pretreatment with U0126 or HEGF inhibited or promoted the protection and the upregulated expression ofp-ERK1/2 caused by NaHS pretreatment.Conclusion The preconditioning of H2S can protect cell damage caused by cisplatin via activating the ERK1/2 pathway of HMMSCs.

Objective To observe the effect of Yujin on cerebral function of acute hypoxia mice.MethodsThe acute hypoxia mice model was reproduced by cutting heads and establishing normal-pressure and closed hypoxic experimental settings. In yujin groups, the mice were treated with Yujin at the doses of 10 g/kg, 20 g/kg, 40 g/kg respectively through the intragastric tubes everyday. 6 days later, the mice survival time, the open-mouth times after cutting heads and the breathing time were observed. The activity of superoxide dismutase (SOD) and content of maleic dialdehyde (MDA) in cerebral tissues were measured. The morphological changes of the cerebral tissues under the microscope were examined.ResultsYujin could significantly prolong the survival time ( P<0.001) and the breathing time and increase the open-mouth times ( P<0.05～0.001), increase the activity of SOD ( P<0.001) and decrease the content of MDA ( P<0.01～0.001) in cerebral tissues. Compared with control group, the Yujin group mice had no obvious pathological alteration except some cerebral vascular dilatation.ConclusionYujin has an obvious protective effect on cerebral tissues of acute hypoxia mice.

Objective To investigate the effect of cortical 8-opioid receptor (DOR) on oxygen-glucose deprivation-induced (OGD-induced) neuronal injury. Methods Primary cultured cortical neurons incubated with selective DOR agonist (TAN-67) and antagonist (naltrindole) or PKC inhibitor (chelerythrine, CHE) were exposed to OGD. Lactate dehydrogenase (LDH) release was detected after 24 h reperfusion. The expression levels of DOR were measured by Western blot. Results Compared with OGD group, TAN-67 significantly decreased OGD-indueed LDH release, and increased the expression levels of DOR, while nahrindole aggravated neuronal injury and decreased the DOR protein expression. CHE could abolish the LDH down-regulation induced by TAN-67 plus OGD (P< 0.05, compared with TAN-67 treated group). Conclusions DOR activation protects neurons against OGD injury. PKC might take part in the neuroprotection pathways of DOR.

OBJECTIVE: To explore the effect of delta-opioid receptor (DOR) in electroacupuncture (EA) protecting the brain against acute ischemic injury. METHODS: Fifty-one rats were randomly divided into sham ischemia group, ischemia group, sham EA group, EA group, and EA+DOR antagonist (naltrindole) group. Transient focal cerebral ischemia (1 hour) was induced in rat brain by middle cerebral artery occlusion (MCAO) method. EA was applied on Shuigou (GV 26) and Neiguan (PC 6) for 30 min, starting immediately after the onset of reperfusion. Neurological deficit scores and volume of cerebral infarction were detected after 24-hour reperfusion. Other 12 rats were randomly divided into sham ischemia group, ischemia group, EA group and EA + naltrindole group. DOR protein expressions were assessed by Western blotting after 24-hour reperfusion. RESULTS: In comparison with the ischemia group and sham EA group, EA significantly reduced ischemic infarction and neurological deficits (P<0.05); EA significantly increased the expression of 60 kD DOR protein (P<0.05) and tended to increase that of 36 kD DOR protein (P>0.05). When naltrindole was combined with EA, the naltrindole completely abolished the EA-induced protection in ischemic infarction and neurological deficits, and also arrested the expression of DOR. CONCLUSION: EA can up-regulate DOR expression and protect the brain from ischemia-reperfusion injury.

Objectives:To investigate the predictive effect of regional homogeneity (ReHo) from resting-state functional magnetic resonance imaging (rs-fMRI) in acute phase on memory function of chronic phage in ischemic stroke patients and the effects of residual learning (REL) on the predictive performance of machine learning models.Methods:From June 2019 to June 2021, rs-fMRI data of one-week after stroke (acute phase) were collected from 35 first-time ischemic stroke patients, and their memory scores were assessed by the Rey auditory verbal learning test (RAVLT) at 6 months after stroke (chronic phase). Using ReHo from rs-fMRI data in acute phase of ischemic stroke patients, the support vector regression (SVR) and the REL-based SVR (REL-SVR) were constructed to predict the patients’ memory scores at 6 months after stroke, and the performance of the two models was compared using Pearson correlation coefficient.Results:Based on the ReHo from acute phase, the correlation coefficient between the predicted values and the true scores from the SVR model was r=0.524, P=0.001, while the correlation coefficient obtained by the REL-SVR model was r=0.671, P<0.001. Brain regions with relatively higher weights such as Temporal_Pole_Mid_R (weight value: 1.03), Temporal_Mid_R(weight value: 1.03), Temporal_Inf_R (weight value: 1.03), Occipital_Mid_R (weight value: 0.57), Frontal_Mid_L (weight value: 0.32), Frontal_Sup_Medial_L (weight value: 0.53), SupraMarginal_L (weight value: 1.54), Calcarine_L (weight value: 0.65), Lingual_L (weight value: 0.58), Cuneus_L (weight value: 0.65), Precuneus_L (weight value: 0.83), cerebellum(weight value>1.0) made larger contributions to the prediction model. Conclusions:ReHo in the acute-phase can effectively predict memory in the chronic phase of ischemic stroke patients. Furthermore, REL can improve the performance of the traditional SVR model and achieve higher predictive accuracy.

Objective To explore the application value and related factors of serum carbonic anhydraseⅢ(CAⅢ)in the clinical diagnosis of mild to moderate Alzheimer disease(AD).Methods A total of 106 elderly patients initially diagnosed with mild to moderate AD at Huashan Hospital,Fudan University from October 2020 to November 2022 were enrolled as the AD group,and 89 healthy elderly people during the same period were enrolled as the control group.The serum biochemical indicators including liver and kidney function,blood lipids,blood glucose,folic acid and homocysteine were detected in both groups.Cognitive function was assessed by Mini-mental State Examination(MMSE).Patient Health Questionnaire-9(PHQ-9)and Generalized Anxiety Disorder-7(GAD-7)were used to assess psychological status.The activities of daily living(ADL)were assessed by modified Barthel Index(BI).Serum CAⅢlevels were measured by enzyme-linked immunosorbent assay(ELISA).Correlation analysis and multivariate linear regression analysis were used to identify factors influencing serum CAⅢlevels,and receiver operating characteristic(ROC)curve analysis was performed to evaluate the diagnostic value of serum CAⅢlevels in elderly patients with mild to moderate AD.Results The MMSE score of the AD group was significantly lower than that of the control group(P＜0.001),and the PHQ-9 and GAD-7 scores were significantly higher than those of the control group(P＜0.001).The serum CAⅢlevel in the AD group was significantly lower than that in the control group(P＜0.000 1).In patients with AD,serum CAⅢlevels in patients with a disease course＞3 years,accompanied by depression or anxiety,moderate AD,and serum creatinine≤111 μmol/L were significantly lower than those in patients with a disease course≤3 years,normal emotions,mild AD,and serum creatinine＞111 μmol/L(P＜0.05).Correlation analysis and multivariate linear regression analysis showed that serum CAⅢlevels were negatively correlated with disease duration,PHQ-9 score,GAD-7 scores and severity degree,positively correlated with serum creatinine level(P＜0.05).The PHQ-9 score,severity degree,and serum creatinine level were independent related factors for serum CAⅢlevel in mild to moderate AD elderly patients(P＜0.05).ROC curve result showed that the area under the curve(AUC)of serum CAⅢin diagnosing mild to moderate AD in elderly patients was 0.946,with sensitivity and specificity of 88.79% and 96.74%,respectively.Conclusions Serum CAⅢlevels in elderly patients with mild to moderate AD are higher than those in healthy individuals.Mild AD,without depressive mood,and elevated serum creatinine levels are related factors for elevated serum CAⅢlevels in elderly AD patients.Serum CAⅢmay serve as a novel biological marker for the diagnosis of mild to moderate AD in the elderly.

Objective: To explore the influence of the location of the infarction lesion on the resting-state functional connectivity (rsFC) of the motor execution network. Methods: A total of 144 patients with infarction of the motor pathway were involved in the study, including 97 patients with capsule stroke (CS) and 47 patients with pontine stroke (PS).50 age-matched healthy subjects were enrolled.After acquiring the structural images and the resting-state functional MRI data of all the subjects by 3.0-Tesla MR scanner, the functional connectivity was calculated in different regions of interest and the differences of the rsFC within the motor execution network among patients with different infarction location were compared. Results: Left CS patients exhibited increased rsFC in L_PMd (MNI x, y, z: -22, -13, 57) -R_M1 (MNI x, y, z: 38, -22, 56) (F=3.951, P=0.022), the increased rsFC than healthy controls (P=0.031); Left CS patients exhibited increased rsFC in R_PMv (MNI x, y, z: 53, 0, 25)-L_SPL (MNI x, y, z: -22, -64, 54) than healthy controls (F=4.017, P=0.021), left CS patients exhibited decreased rsFC in R_PCG (MNI x, y, z: 37, -34, 53) -R_PMv (MNI x, y, z: 53, 0, 25) than healthy controls(F=-3.788, P=0.025). Right CS patients exhibited increased rsFC than healthy controls in R_PMd(MNI x, y, z: 28, -10, 54)-L_M1(MNI x, y, z: -38, -22, 56) (F=4.438, P=0.014), right CS patients exhibited increased rsFC than healthy controls in R_PMv(MNI x, y, z: 53, 0, 25)-R_PCG(MNI x, y, z: 37, -34, 53)(F=4.830, P=0.010), right CS patients exhibited decreased rsFC in L_M1(MNI x, y, z: -38, -22, 56)-L_SMA(MNI x, y, z: -5, -4, 57) than healthy controls (F=-5.102, P=0.007). And the left PS patients showed increased rsFC than healthy controls in R_DN -L_SMA (F=4.939, P=0.009), left PS patients exhibited increased rsFC than healthy controls in L_DN-R_SMA (F=3.431, P=0.036), left PS patients exhibited reduced rsFC than healthy controls in R_AICb -R_PMd (F=-4.114, P=0.019). Right PS patients showed increased rsFC compared with healthy controls in L_DN-R_M1(F=3.075, P=0.049), and increased rsFC compared with healthy controls in L_AICb-R_SCb (F=3.725, P=0.027). Conclusion The infarction location poses influence on the FC alteration of the motor network after stroke.