ObjectiveTo investigate the demyelination induced by Angiostrongylus cantonensis （AC） infection in the brain of Balb/c mice and analyze the untargeted metabolomic changes in the corpus callosum， aiming to elucidate the underlying mechanisms. MethodsBalb/c mice were randomly assigned to a control group （n=6） and an infection group （n=6）. The infection group was orally administered 30 third-stage larvae of AC， while the control group received an equal volume of saline. Body weight， visual function， and behavioral scores were measured on post-infection 3， 6， 9， 12， 15， 18， and 21 days to assess neurological alterations. After 21 days， brain tissues were harvested for immunofluorescence staining， hematoxylin-eosin （HE） staining， and transmission electron microscopy to examine morphological changes in brain myelin and retina. Metabolomics analysis was performed， and differential metabolites were identified using volcano plots and heatmaps. The distribution of fold changes and bar charts were used to profile the key metabolites. These differential metabolites were then subjected to Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and regulatory network analysis. ResultsOn the 9th day after AC infection， Balb/c mice showed a decline in neurological behavioral scores （P<0.05）. By day 15， visual scores decreased （P<0.05）， and by day 21， significant weight loss （P＜0.001） and mortality were observed. Concurrently， transmission electron microscopy and immunofluorescence staining revealed significant myelin damage in the corpus callosum and a marked reduction in oligodendrocytes （P<0.001）. HE staining showed severe retinal ganglion cell damage. Metabolomic analysis revealed that glycerophospholipids were the most abundant differential metabolites， with steroids and sphingolipids being relatively less abundant. Cholesteryl ester CE （20：2） was significantly upregulated （P<0.001）， while phosphatidylmethanol （18：0_18：1） was significantly downregulated （P<0.01）. KEGG enrichment and regulatory network analyses demonstrated that the differential metabolites were mainly enriched in metabolic pathways like steroid biosynthesis， bile secretion， and cholesterol metabolism， and were involved in key metabolic pathways such as sphingolipid metabolism， neural signal regulation， and glycerophospholipid metabolism. ConclusionsAC infection affects the metabolic state of mice via multiple pathways， modifying the levels of metabolites crucial for myelination and myelin stability. Demyelination may be closely linked to the disruption of these key metabolic pathways， particularly the dysregulation of cholesterol and sphingolipid metabolism， potentially playing a central role in demyelination onset. Furthermore， alterations in phospholipid metabolism and abnormal nerve signaling regulation may exacerbate myelin damage.

Hypothyroidism alone can lead to myocardial fibrosis and result in heart failure, but traditional hormone replacement therapy does not improve the fibrotic situation. Hydrogen sulfide (H 2 S), a new gas signaling molecule, possesses antiinflammatory, antioxidant, and anti-fibrotic capabilities. Whether H 2 S could improve hypothyroidism-induced myocardial fibrosis are not yet studied. In our study, H 2 S could decrease collagen deposition in the myocardial tissue of rats caused by hypothyroidism. Furthermore, in hypothyroidism-induced rats, we found that H 2 S could enhance cystathionine-gamma-lyase (CSE), not cystathionine β-synthase (CBS), protein expressions. Finally, we noticed that H 2 S could elevate autophagy levels and inhibit the transforming growth factor-β1 (TGF-β1) signal transduction pathway. In conclusion, our experiments not only suggest that H 2 S could alleviate hypothyroidism-induced myocardial fibrosis by activating autophagy and suppressing TGF-β1/ SMAD family member 2 (Smad 2) signal transduction pathway, but also show that it can be used as a complementary treatment to conventional hormone therapy.

Objective:To investigate the effects of exogenous hydrogen sulfide on myocardial fibrosis and apoptosis in rats after myocardial infarction and the underlying mechanisms.Methods:Forty-three Sprague Dawley(SD)rats were divided into 4 groups according to the random number table method: a control group(n=12), a myocardial infarction group(MI group, n=13), an hydrogen sulfide(H 2S)group(n=6)and an MI+ H 2S group(n=12). The rat model of acute myocardial infarction was established by intraperitoneal injections of isoproterenol(50 mg/kg, once a day, for 2 days). Electrocardiogram and troponin changes were recorded 48 h after the last drug administration to determine whether the rat model was successfully constructed.After successful establishment of the model, rats in the MI group and the MI+ H 2S group were intraperitoneally injected with sodium hydrosulfide(56 μmol/kg, once a day, for 6 weeks).6 weeks later, echocardiogram and Masson's trichrome staining were performed to assess changes in cardiac function and collagen volume fraction in each group.Terminal deoxynucleotidyl transferase(TdT)dUTP nick end labeling(TUNEL)was used to detect the myocardial apoptosis rate in each group, and Western-blot was used to detect protein expression of Yes-related protein 1(YAP1), WW domain containing transcriptional regulator1(TAZ), mammalian Ste20-like kinase 2(MST2), Bcl-2-associated X protein(Bax), cysteine protease 3(caspase-3), the ratio of matrix metalloproteinase 3(MMP3)/matrix metalloproteinase inhibitor 2(TIMP2), and B-cell lymphoma factor(Bcl-2). Results:Compared with the control group, myocardial collagen volume fraction was increased( P<0.05), the myocardial cell apoptosis rate was increased( P<0.05), and myocardial YAP1, TAZ, MST2, Bax, caspase-3 protein expression and MMP3/TIMP2 ratio were increased in the MI group(all P<0.05), while the expression of Bcl-2 protein was decreased( P<0.05). Compared with the MI group, collagen volume fraction and the cardiomyocyte apoptosis rate were significantly decreased in the MI+ H 2S group( P<0.05). Also, protein expression of YAP1(2.406±0.024 vs.2.830±0.063), TAZ(0.964±0.090 vs.1.329±0.018), MST2(0.780±0.082 vs.1.788±0.097), Bax(1.500±0.008 vs.0.613±0.003)and caspase-3(0.620±0.024 vs.0.780±0.012)and the MMP3/TIMP2 ratio were decreased(all P<0.05), while protein expression of Bcl-2 was increased( P<0.05)in myocardial tissue. Conclusions:H 2S can mitigate myocardial fibrosis after myocardial infarction, through inhibiting the activation of the YAP1/TAZ signaling pathway, thus reducing apoptosis of cardiomyocytes.

Objective:To observe the effects of acupuncture and moxibustion on phosphatase and PTEN-induced putative kinase 1(PINK1)/Parkin signaling pathway in the midbrain substantia nigra of Thy1-α synuclein(αSyn)transgenic model mice with Parkinson disease(PD). Methods:Twenty-four Thy1-αSyn transgenic mice were randomly divided into a model group,an acupuncture group,an acupuncture + moxibustion group,and a Western medicine group.Six wild-type mice in the same litter were used as the wild-type group.In the acupuncture group,Baihui(GV20)and Yanglingquan(GB34)were selected for acupuncture.In the acupuncture + moxibustion group,Guanyuan(CV4)was added on the basis of the acupuncture group.The Western medicine group was given rapamycin intraperitoneal injection at a dose of 10 mg/(kg·bw).The wild-type group and the model group were fixed without intervention.The overall rod performance(ORP)score of mice was observed in each group.The immunohistochemical method was used to detect the tyrosine hydroxylase(TH)positive neurons in the substantia nigra of mice in each group.The αSyn was detected by the immunofluorescence chemical method.The expression levels of αSyn,microtubule-associated protein 1 light chain 3(LC3)-Ⅱ/LC3-Ⅰ,autophagy protein sequestosome-1/protein 62(SQSTM-1/p62),PINK1,Parkin,and ubiquitin-specific protease 30(USP30)proteins were detected by Western blotting assay.The expression levels of LC3B,p62,PINK1,Parkin,and USP30 mRNAs were detected by fluorescence quantitative polymerase chain reaction. Results:Compared with the wild-type group,the ORP score,the p62,PINK1,and Parkin protein expression levels decreased significantly(P<0.01),the PINK1 mRNA expression level decreased(P<0.05),while the protein and mRNA expression levels of USP30 increased(P<0.05)in the model group.Compared with the model group,the ORP score in the acupuncture group and the acupuncture + moxibustion group increased(P<0.05);the expression level of LC3-Ⅱ/LC3-Ⅰ protein in the acupuncture + moxibustion group and the Western medicine group increased(P<0.05);the protein expression levels of p62,PINK1,and Parkin increased(P<0.05),while the USP30 protein expression level decreased significantly(P<0.01)in the acupuncture group,the acupuncture + moxibustion group,and the Western medicine group;the Parkin mRNA expression level in the acupuncture group and the acupuncture + moxibustion group increased(P<0.05);the USP30 mRNA expression level in the acupuncture + moxibustion group decreased(P<0.05). Conclusion:Acupuncture and moxibustion regulate the related molecule expression levels of PINK1/Parkin signaling pathway in the Thy1-αSyn transgenic PD model mice and promote the autophagy degradation of αSyn to exert the protective effect of dopaminergic neurons.

Objective:To investigate the risk factors for futile recanalization in patients with acute anterior circulation large vessel occlusion after endovascular mechanical thrombectomy (EMT), and establish a nomogram model predicting futile recanalization in these patients.Methods:One hundred and eighty-eight patients with acute anterior circulation large vessel occlusion after EMT were enrolled from Department of Neurology, Zhongshan Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine from January 2018 to December 2021. Patients were divided into futile recanalization group and effective recanalization group according to whether futile recanalization occurred; futile recanalization was defined as successful recanalization showed by immediate postoperative DSA (modified thrombolysis in cerebral infarction [mTICI] ≥2b), but poor functional outcome (modified Rankin Scale [mRS] scores>2 90 d after surgery). The clinical data were compared between futile recanalization group and effective recanalization group. Multivariate Logistic regression analysis was used to screen the risk factors for futile recanalization. R software was used to establish a nomogram model for futile recanalization. C-index was used to evaluate the differentiation of the model, and correction curve was used to evaluate the accuracy of the line graph model prediction. Receiver operating characteristic (ROC) curve was used to evaluate the predictive efficiency of the nomogram model.Results:Ninety-two patients had futile recanalization. Compared with the effective recanalization group, futile recanalization group had significantly older age, significantly higher hemoglobin A1c on admission, significantly longer time from puncture to vascular recanalization, significantly higher proportions of patients with hypertension history and poor collateral circulation, and significantly different severities of stroke and white matter hyperintensities (WMHs) and distribution of occlusive sites ( P<0.05). Multivariate Logistic regression analysis showed that age, history of hypertension, time from puncture to vascular recanalization, poor collateral circulation, severe WMHs, and moderate-severe stroke were independent risk factors for futile recanalization after EMT in patients with acute anterior circulation large vessel occlusion ( P<0.05). A nomogram model of futile recanalization was established according to the above 6 factors, with C-index of 0.862 ( 95%CI: 0.809-0.914); the calibration curve of the model was highly coordinated to the ideal model curve; area under the ROC curve of futile recanalization was 0.862 ( 95%CI: 0.809-0.914, P<0.001). Conclusions:Acute anterior circulation large vessel occlusion patients with older age, history of hypertension, longer time from puncture to vascular recanalization, poor collateral circulation, severe WMHs, and moderate-severe stroke trend to have futile recanalization after EMT. This nomogram can predict futile recanalization after EMT.

Myocardial fibrosis is a key link in the occurrence and development of diabetic cardiomyopathy. Its etiology is complex, and the effect of drugs is not good.Cardiomyocyte apoptosis is an important cause of myocardial fibrosis. The purpose of this study was to investigate the effect of gaseous signal molecule sulfur dioxide (SO2 ) on diabetic myocardial fibrosis and its internal regulatory mechanism. Masson and TUNEL staining, Western-blot, transmission electron microscopy, RT-qPCR, immunofluorescence staining, and flow cytometry were used in the study, and the interstitial collagen deposition, autophagy, apoptosis, and changes in phosphatidylinositol 3-kinase (PI3K)/AKT pathways were evaluated from in vivo and in vitro experiments. The results showed that diabetic myocardial fibrosis was accompanied by cardiomyocyte apoptosis and down-regulation of endogenous SO2 -producing enzyme aspartate aminotransferase (AAT)1/2 . However, exogenous SO2 donors could up-regulate AAT1/2 , reduce apoptosis of cardiomyocytes induced by diabetic rats or high glucose, inhibit phosphorylation of PI3K/AKT protein, up-regulate autophagy, and reduce interstitial collagen deposition. In conclusion, the results of this study suggest that the gaseous signal molecule SO2 can inhibit the PI3K/AKT pathway to promote cytoprotective autophagy and inhibit cardiomyocyte apoptosis to improve myocardial fibrosis in diabetic rats. The results of this study are expected to provide new targets and intervention strategies for the prevention and treatment of diabetic cardiomyopathy.

Objective To study the alterations of renal function in patients with acute ischemic stroke and diabetes and to analyze the risk factors of contrast-induced nephropathy (CIN) after digital subtraction angiography (DSA).Methods Eight hundred and seventy-one cerebral infarction patients with diabetes who underwent DSA were selected in the Third Affiliated Hospital of Chongqing Medical University and Nanjing Brain Hospital Affiliated to Nanjing Medical University from August 2012 to August 2016.The patients were divided into diabetic group (n =178) and non-diabetic group (n =693).The alterations of renal function and the incidence rate of CIN were observed between two groups 3 days after DSA.Univariate analysis and multi-factor Logistic regression analysis were used to analyze the independent risk factors of CIN.Results The levels of estimated glomerular filtration rate (eGFR,ml · min-1 · 1.73 m-2) in diabetic group at 1,2 and 3 days after DSA(81.94 ±9.38,75.36 ±8.21,84.43 ±9.72) were lower than that in non-diabetic group (84.62 ± 10.06,79.08 ±9.84,87.62 ± 10.15,t =3.213,4.645,3.772,all P ＜ 0.05).The levels of serum creatinine (Scr) and cystatin (CysC) in diabetic group at 1,2 and 3 days after DSA (Scr:85.63 ±9.83,92.37 ±10.07,83.43 ±9.07;CysC:1.08 ±0.12,1.35 ±0.14,0.95 ±0.10) were higher than that in non-diabetic group (Scr:81.36 ± 8.98,87.84 ± 9.85,80.31 ± 8.64,t =5.548,5.448,4.253;CysC:0.97 ±0.11,1.21 ±0.12,0.88 ±0.09;t =11.677,13.400,9.043;all P ＜ 0.05).The incidence rate of CIN in diabetic group (25.84％ (46/178)) was higher than that in nondiabetic group (7.07％ (49/693),x2 =51.358,P =0.001).Multi-factor Logistic regression analysis showed allergies,plasma brain natriuretic peptide,heart failure,the original renal insufficiency,NIHSS score,contrast agent dosage,preoperative eGFR,preoperative Scr and preoperative CysC were the independent risk factors of CIN in cerebral infarction patients with diabetes.Conclusions The renal function decreased significantly and the incidence rate of CIN was high in cerebral infarction patients with diabetes after DSA.Allergies,plasma brain natriuretic peptide,heart failure,the original renal insufficiency,contrast agent dosage,preoperative eGFR,preoperative Scr and preoperative CysC were the independent risk factors of CIN in cerebral infarction patients with diabetes.

Objective · To explore the correlation of serum S100B protein with depressive episode of bipolar disorder (BD) and its prognosis.Methods· Based on BD criteria of Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-Ⅳ),80 patients with depressive episode of BD (case group) and 42 healthy controls (control group) were enrolled.Patients were randomly assigned into quetiapine group who were treated with lithium and quetiapine and modified electroconvulsive therapy (MECT) group who received lithium and MECT.The serum S100B level and Hamilton Rating Scale for Depression (HAMD) were assayed before and after 4-week treatment.Results· The serum S100B levels before treatment in patients with depressive episode of BD were significantly higher than those in healthy controls (P=0.000).The levels of S100B in both drug and MECT groups decreased after 4-week treatment.The HAMD score after treatment significantly decreased than that before treatment (P=0.000).Pearson correlation analysis showed that the change of S 100B level was positively correlated with the change of HAMD score before and after treatment in case group (r=0.33,P=0.013).Conclusion· S100B may be associated with depressive episode of BD and its prognosis.

Objective To evaluate the efficacy of dezocine for prevention of postoperative cognitive dysfunction (POCD) in elderly patients undergoing total knee arthroplasty under remifentanil-based anesthesia.Methods Sixty-eight patients of both sexes, aged 65-85 yr, weighing 48-78 kg, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ , undergoing elective unilateral total knee arthroplasty under general anesthesia, were randomly divided into 2 groups (n =34 each) using a random number table: control group (group C) and dezocine group (group D).After induction of anesthesia, the patients were tracheally intubated and mechanically ventilated.Anesthesia was maintained with iv infusion of propofol 0.05-0.06 mg · kg-1 · min-1 and remifentanil 0.05-0.10 μg · kg-1 · min-1, and intermittent iv boluses of vecuronium 0.04 mg/kg.Dezocine 0.1 mg/kg was injected intravenously at 30 min before skin incision in group D.At 1 day before operation (T0) , and 1, 3, 5, 7 days after operation (T1 , T2, T3 , T4) , the blood samples from the central vein were collected for determination of serum cortisol (Cor), neuron specific enolase (NSE) and S-100β protein concentrations.Before operation, and 5 and 7 days after operation, the patients' cognitive function was assessed using Mini-Mental State Examination, and the occurrence of POCD was recorded.Results Compared with the baseline value at T0, the serum Cor, NSE and S-100β protein concentrations were significantly increased at T1-3, and MMSE scores were decreased at T3,4 in the two groups.Compared with group C, the serum Cot, NSE and S-100β protein concentrations were significantly decreased at T1-4, and Mini-Mental State Examination scores were increased at 5 and 7 days after operation, and the incidence of POCD was decreased in group D.Conclusion Dezocine 0.1 mg/kg intravenously injected at 30 min before skin incision can prevent the occurrence of POCD in elderly patients undergoing total knee arthroplasty under remifentanil-based anesthesia.

Objective To observe the growth and proliferation capabilities of MPCs in primary OA articular cartilage and their differen-tiation properties into chondrocytes by applying related genes SOX6 and SOX9, so as to provide theoretical evidence in preventing and curing primary OA. Methods SOX6 and SOX9 genes were respectively ligated into adenovirus shuttle plasmids pAdTrack-CMV-SOX6 and pAdTrack-CMV-SOX9, then the recombinant plasmids were used to infect MPCs derived from primary OA articular cartilage. TB and the ex-pressions of collagen type Ⅱ protein and mRNA in differentiated MPCs were compared between the infected group and the uninfected group. Results Either SOX6 gene or SOX9 gene could stably infect MPCs from primary OA cartilage. TB and collagen typeⅡwere strongly posi-tive in the SOX6-infected or SOX9-infected MPCs, while they were weekly positive in the uninfected MPCs. Collagen typeⅡmRNA expres-sion in SOX6-infected MPCs derived from primary OA cartilage was 3. 8 times of that in uninfected cells (P<0. 01), and that in SOX9-in-fected MPCs was 5. 15 times of that in the uninfected cells (P<0. 01). Conclusion The stable transfection of SOX6 and SOX9 genes into MPCs derived from primary OA cartilage could significantly promote chondrogenic differentiation of MPCs. There must be feasible methods of gene technology to promote cell proliferation and differentiation of MPCs for repairing articular cartilage injury.