Several mitochondrial dysfunctions in obesity and diabetes include impaired mitochondrial membrane potential, excessive mitochondrial reactive oxygen species generation, reduced mitochondrial DNA, increased mitochondrial Ca2+ flux, and mitochondrial dynamics disorders. Mitophagy, specialized autophagy, is responsible for clearing dysfunctional mitochondria in physiological and pathological conditions. As a paradox, inhibition and activation of mitophagy have been observed in obesity and diabetes-related heart disorders, with both exerting bidirectional effects. Suppressed mitophagy is beneficial to mitochondrial homeostasis, also known as benign mitophagy. On the contrary, in most cases, excessive mitophagy is harmful to dysfunctional mitochondria elimination and thus is defined as detrimental mitophagy. In obesity and diabetes, two classical pathways appear to regulate mitophagy, including PTEN-induced putative kinase 1 (PINK1)/Parkin-dependent mitophagy and receptors/adapters-dependent mitophagy. After the pharmacologic interventions of mitophagy, mitochondrial morphology and function have been restored, and cell viability has been further improved. Herein, we summarize the mitochondrial dysfunction and mitophagy alterations in obesity and diabetes, as well as the underlying upstream mechanisms, in order to provide novel therapeutic strategies for the obesity and diabetes-related heart disorders.

ObjectiveTo visualize the research trends of verbal and nonverbal cognitive functions in patients with post-stroke aphasia (PSA). MethodsPapers about verbal and nonverbal cognitive functions after stroke were extracted from Web of Science Core Collection from establishment to August, 2022, and a bibliometric analysis was conducted on the distribution of articles published by year, author, journal, institution, and country. Author cooperation, author co-citation, journal co-citation, country/institution cooperation, dynamic evolution, keyword hotspots, and trends were visually analyzed by using VOSviewer software. ResultsA total of 1 630 publications were identified for final analysis. The first article related to the topic was retrieved in 2004. After that, the number of published papers showed an increasing trend year by year, with some fluctuations after 2019. Matthew A. Lambon Ralph and Elizabeth Jefferies were the authors who produced the most, were cited the most, and were the most influential. Neuropsychologia was a highly productive and well-cited publication. The University of Manchester in the United Kingdom and Johns Hopkins University in the United States were the nations/institutions with high yield and high centrality. Although China had a high yield and was in the top five, the centrality was insufficient. The dynamic emergence of keywords revealed that the research had gone through the following stages: evaluating the mechanism of language and nonverbal cognitive function impairment based on neuroimage, exploring the role of nonverbal cognitive dysfunction in pathology and recovery mechanisms of patients with PSA, examining the therapeutic mechanism of non-invasive brain stimulation and electronic tele-rehabilitation equipment, and revealing not only the frontal and temporal areas but also brain network supporting nonverbal cognition. ConclusionIn recent years, some achievements have been made in the researches on verbal and nonverbal cognitive function, particularly in the studies of the neuroimaging-based mechanisms of common damage and the intervention effects of synergistic therapy. In the future, academic cooperation between different regions and different teams needs to be strengthened. Further exploration should be focused on refining the cognitive neuropsychology and exploring new technologies to improve the therapeutic effect of PSA.

Objective To investigate the correlation between the severity of alcoholic fatty liver disease and the amount of fat in the abdominal cavity and the serum inflammatory factor IL-18 and IL-8. Methods From October 2016 to October 2017,one hundred and twenty patients with AFLD in the First Hospital of Hebei Medical University were divided into light,medium,heavy groups according to the severity of fatty lesions by color Doppler Ultrasound. There were 40 mild patients,50 moderate patients and 30 severe patients. Forty healthy subjects were selected as controls. All the participants underwent CT scanning. The intra-abdominal fat area (VAT),abdominal subcutaneous fat area (SAT) and total abdominal fat area (TA) were measured. The liver function was measured by biochemical analyzer and enzyme-linked immunoassay (ELISA). (ELSIA) IL-18 was detected and IL-8 was detected by radioimmunoassay. Results The VAT of the healthy control group and the mild,medium and severe AFLD group were (70. 28±10. 19),(114. 38 ± 9. 97),(146. 73±10. 19),(163. 38±12. 69) cm2. The TA of the healthy control group and the mild, medium and severe AFLD group were ( 256. 72± 34. 56),( 332. 19 ± 33. 28),( 387. 49± 32. 28),( 478. 19 ±31. 02) cm2. The SAT of the healthy control group and the light,medium and severe AFLD group were (156. 23±28. 19),(203. 43±27. 12),(246. 19±26. 89),(271. 19 ±27. 94) cm2,respectively. Aspartate aminotransferase (AST) of the healthy control group and the mild,medium and severe AFLD group were (18. 50±1. 12),(23. 50±1. 21),(25. 50±1. 24),(29. 50± 1. 43) U/L. Alanine aminotransferase (ALT) of the healthy control group and the light, medium and severe AFLD group were ( 18. 50 ± 2. 14), ( 26. 50 ±2. 22),(35. 50±2. 34),(38. 50±2. 11) U/L. γ-glutamyltransferaseof the healthy control group and the light,medium and severe AFLD group were ( 16. 50 ± 2. 11), ( 32. 50 ± 2. 23), ( 47. 50 ± 2. 31), ( 48. 00 ±2. 43) U/L,respectively. Compared with the healthy control group,VAT,TA,SAT,AST,ALT andγ-GT in the light,medium and heavy AFLD group showed statistically significant differences ( P＜0. 05) . Compared with the mild AFLD group, VAT, TA, SAT, AST, ALT and γ-GT in the medium and heavy AFLD group showed statistically significant differences ( P＜0. 05) . Compared with the moderate AFLD group,the VAT, TA,SAT, AST, ALT, and γ-GT of the severe AFLD group showed statistically significant differences ( P＜0. 05). The data of the three AFLD groups showed that the concentration of all indicators were increasing as the severity of fat deepened. IL-18 of the healthy control group and the light,medium and severe AFLD group were (45. 67±4. 51),(52. 18±5. 09),(59. 87±4. 98),(64. 18±5. 12) ng/L; IL-8 of the healthy control group and the light, medium and severe AFLD group were ( 78. 92 ± 5. 07), ( 115. 62 ± 4. 89), ( 223. 76 ± 6. 78),(286. 42±7. 02) g/L. Compared with every group,IL-18 and IL-8 of light,medium and severe AFLD group showed statistically significant differences (F＝1035. 67,2. 93×105,P＜0. 001); compared with mild AFLD group,IL-18 and IL-8 of medium and heavy group showed statistically significant differences;compared with moderate AFLD group,IL-18 and IL-8 of severe group AFLD showed statistically significant differences ( P＜0. 001) . The levels of inflammatory factors IL-18 and IL-8 increased with the severity of steatosis. The severity of AFLD was significantly positively correlated with VAT,TA,SAT,IL-18 and IL-8 ( r 0. 415(P＜0. 001), 0. 435 ( P＜0. 001), 0. 512 ( P＜0. 001), 0. 274 ( P＜0. 001 ), 0. 689 ( P ＜0. 001). Conclusion Fat control is an important measure to prevent AFLD. IL-18 and IL-8 can reflect the severity of liver injury in AFLD and have important significance in judging prognosis.

OBJECTIVE: To investigate the effect of working time on the prognosis of patients with ischemic stroke undergoing intravenous thrombolysis. METHODS: Clinical data of 3050 patients with ischemic stroke received intravenous thrombolysis from 71 hospitals in Zhejiang Province during June 2017 and September 2018 were retrospective analyzed. Whole day of Saturday and Sunday were defined as weekend; whole day of Monday to Friday were defined as weekdays; Monday to Friday 8:00-17:00 were defined as daytime of weekdays; Monday to Friday 17:01-07:59 on next day were defined as nights of weekdays; unconventional working time were defined as weekend and nights of weekdays. Good outcome was defined as mRS 0-2 at 3 months. Univariate analyses of baseline and prognostic variables in group of weekend and weekdays, nights of weekdays and daytime of weekdays, unconventional working time and daytime of weekdays were performed. Binary logistic regression was used to investigate whether weekend, nights of weekdays and unconventional working time were independent predicting factors of outcome after intravenous thrombolysis, respectively. RESULTS: There was no difference in 7-day mortality, 3-month mortality and good outcome at 3-month between weekend group and weekdays group, nights of weekdays group and daytime of weekdays group, unconventional working time group and daytime of weekdays group (all >0.05). Binary logistic regression results showed that weekends, nights of weekdays and unconventional working time were not independent predicting factors for outcome after intravenous thrombolysis (all >0.05). CONCLUSIONS The working time has not affected the outcomes of patients with ischemic stroke undergoing intravenous thrombolysis in studied hospitals of Zhejiang province.
Brain Ischemia ; drug therapy ; Humans ; Prognosis ; Retrospective Studies ; Stroke ; drug therapy ; Thrombolytic Therapy ; Time Factors

OBJECTIVE: To compare the time delay between in-hospital stroke and out-of-hospital stroke patients, and to explore the influence factors for the prognosis of in-hospital stroke patients treated by intravenous thrombolysis. METHODS: Clinical data of 3050 patients with ischemic stroke who received intravenous thrombolysis in 71 hospitals in Zhejiang province from June 2017 to September 2018 were analyzed. Differences of time delay including door to imaging time (DIT), imaging to needle time (INT) and door to needle time (DNT) between in-hospital stroke (=101) and out-of-hospital stroke (=2949) were observed. The influencing factors for the outcome at 3 month after intravenous thrombolysis in patients with in-hospital stroke were analyzed using binary logistic regression analysis. RESULTS: Patients with in-hospital stroke had longer DIT[53.5 (32.0-79.8) min vs. 20.0 (14.0-28.0) min, <0.01], longer IDT[47.5(27.3-64.0)min vs. 36.0(24.0-53.0)min, <0.01], and longer DNT[99.0 (70.5-140.5) min vs. 55.0 (41.0-74.0) min, <0.01], compared with patients with out-of-hospital stroke; patients in comprehensive stroke center had longer DIT[59.5(44.5-83.3) min vs. 37.5(16.5-63.5) min, <0.01], longer DNT[110.0(77.0-145.0) min vs. 88.0 (53.8-124.3) min, <0.05], but shorter INT[36.5(23.8-60.3)min vs. 53.5 (34.3-64.8) min, <0.05], compared with patients in primary stroke center. Age (=0.934, 95% 0.882-0.989, <0.05) and baseline National Institute of Health Stroke Scale score (=0.912, 95% 0.855-0.973, <0.01) were independent risk factors for prognosis of in-hospital stroke patients. CONCLUSIONS In-hospital stroke had longer DIT and DNT than out-of-hospital stroke, which suggests that a more smooth thrombolysis process of in-hospital stroke should be established.
Administration, Intravenous ; Brain Ischemia ; drug therapy ; Fibrinolytic Agents ; therapeutic use ; Hospitals ; statistics & numerical data ; Humans ; Prognosis ; Stroke ; drug therapy ; Thrombolytic Therapy ; statistics & numerical data ; Time Factors ; Treatment Outcome

OBJECTIVE: To investigate the association of atrial fibrillation (AF) with hemorrhagic transformation (HT) in patients with ischemic stroke treated by intravenous thrombolysis. METHODS: Clinical data of 3272 patients treated by intravenous thrombolysis from 71 hospitals in Zhejiang Province during June 2017 and December 2018 were retrospectively reviewed. Intracranial HT was defined as intracranial hemorrhage suggested by imaging examination 24 hours after intravenous thrombolysis. Patients were dichotomized into HT group (=533) and non-HT group (=2739). The association of AF and HT was analyzed by univariate analysis and binary logistic regression. RESULTS: Compared with the non-HT group, the HT group were older, had longer onset to needle time (ONT), higher baseline National Institute of Health Stroke Scale (NIHSS) score, higher baseline glucose level, and higher AF rate (<0.05 or <0.01). Binary logistic regression analysis revealed that AF was independently associated with HT (=2.527, 95%:2.030-3.146, <0.01). CONCLUSIONS AF is independently associated with the occurrence of HT in ischemic stroke patients treated with intravenous thrombolysis.
Antifibrinolytic Agents ; adverse effects ; pharmacology ; Atrial Fibrillation ; complications ; Brain Ischemia ; complications ; drug therapy ; Humans ; Retrospective Studies ; Stroke ; complications ; drug therapy ; Thrombolytic Therapy ; adverse effects ; Treatment Outcome

OBJECTIVE: To investigate the effect of treatment time on the outcome of patients with ischemic stroke undergoing reperfusion therapy. METHODS: The clinical data of 3229 ischemic stroke patients who received intravenous thrombolysis with or without arterial thrombolysis from 71 hospitals in Zhejiang province from June 2017 to September 2018 were retrospectively reviewed. The good outcome was defined as modified Rankin Scale (mRS) ≤ 2. Binary logistic regression analysis was used to investigate the association of door to needle time (DNT), or door to reperfusion time (DRT) with the outcomes in patients treated by intravenous thrombolysis or bridging arterial thrombolysis, respectively. RESULTS: Binary logistic regression showed that DNT (=0.994, 95%:0.991-0.997, <0.01) or DRT (=0.989, 95%:0.983-0.995, <0.01) were independently associated with good outcomes, respectively. Every hour decreases in DNT resulted in a 4.7%increased probability of functional independence (mRS 0-2) in patients treated by intravenous thrombolysis; Every hour decreases in DRT was associated with a 11.4%increased probability of functional independence in patients treated by intravenous thrombolysis with arterial thrombolysis. CONCLUSIONS Good outcomes are associated with lower DNT in ischemic stroke patients treated by intravenous thrombolysis or lower DRT in patients treated by intravenous thrombolysis bridging arterial thrombolysis.
Brain Ischemia ; drug therapy ; Fibrinolytic Agents ; therapeutic use ; Humans ; Reperfusion ; Retrospective Studies ; Stroke ; drug therapy ; Thrombolytic Therapy ; Time Factors ; Treatment Outcome

OBJECTIVE: To investigate the effect of emergency medical service (EMS) on the prognosis of ischemic stroke patients treated with intravenous thrombolysis. METHODS: Clinical data of 2123 ischemic stroke patients treated with intravenous thrombolysis in 70 hospitals in Zhejiang province were retrospectively analyzed. There were 808 patients sent to the hospital by ambulance (EMS group) and 1315 patients by other transportations (non-EMS group). Good outcome was defined as modified Rankin Scale (mRS) ≤ 2 at 3-month. The onset to needle time (ONT), onset to door time (ODT), door to needle time (DNT) and outcome were compared between EMS group and non-EMS group. Binary logistic regression was used to explore the influencing factors for the outcome at 3-month. RESULTS: Compared with the non-EMS group, patients in the EMS group were older, with higher baseline National Institute of Health Sroke Scale (NIHSS) score, and had a higher proportion of atrial fibrillation (all <0.05), but there were no significant differences in ONT, ODT and DNT between two groups (all >0.05). Binary logistic regression showed that EMS was not independently associated with good outcome (=0.856, 95%:0.664-1.103, >0.05). CONCLUSIONS EMS had not improve the outcome of patients receiving intravenous thrombolysis in Zhejiang province.
Administration, Intravenous ; Brain Ischemia ; drug therapy ; Emergency Medical Services ; Fibrinolytic Agents ; therapeutic use ; Humans ; Prognosis ; Retrospective Studies ; Stroke ; drug therapy ; Thrombolytic Therapy ; statistics & numerical data ; Treatment Outcome

Objective To observe the safety and clinic effect of umbilical blood stem cell transplantation for the patients with chronic liver failure (CLF).Methods 44 patients with CLF were included in the research and divided into two groups,22 in control group received internal medicine treatment,the other 22 in treatment group received umbilical blood stem cell transplantation in addition to internal medicine treatment.The biochemical index,MELD scores,clinical symptoms,survival situation and adverse reaction of the patients were observed within 2,4,12 and 24 weeks.Results Albumin and prothrombin activity of treatment group were higher than those of control group,the MELD scores of the treatment group was lower than that of control group,the survival rate was higher than the control group,and the difference is significant between the two groups (P ＜ 0.05).There was no significant difference between the two groups in terms of alanine aminotransferase and total bilirubin (P ＞ 0.05).After 4 weeks treatment,fatigue,inappetite,abdominal distention and ascitic fluid of the treatment group were better than that of control group,the difference was statistically significant (P ＜ 0.05).Besides,the patients of the both groups did not have any adverse reaction or hepatocellular carcinoma.Conclusion Umbilical blood stem cell transplantation is safe and effective for the patients with CLF and can improve the survival rate of the patients.

BACKGROUND:Umbilical cord mesenchymal stem cells are plentifully and conveniently obtained with a high proliferative ability, and have opened up a new way to treat patients with liver failure as they can differentiate into hepatocyte-like cells.OBJECTIVE:To observe the safety and efficacy in the treatment of chronic liver failure by transplanting umbilical cord mesenchymal stem cells.METHODS:Using parallel contrast method, 50 patients with chronic liver failure were divided into two groups, namely a stem cell group and a control group, containing 25 patients in each group. For the first group, transplantation of umbilical cord mesenchymal stem cells, (1.4-2.3)×106/kg, 100 mL, was given on the basis of medical comprehensive treatment,while for the second group only simple medical comprehensive treatment was given. The injection was done every 15 days, totally three times. Liver functions, prothrombin activity, Model for End-Stage Liver Disease (MELD) score, clinical symptoms, survival and side effects of the patients were observed before and 2, 4, 12 and 24 weeks after the treatment.RESULTS AND CONCLUSION:Compared with the control group, the albumin level and prothrombin activity were significantly increased in the stem cell group 12 and 24 weeks after treatment (P < 0.05), while the MELD score was significantly decreased in the stem cell group at 4, 12 and 24 weeks after treatment (P < 0.05). There was no significant difference in alanine aminotransferase and total bilirubin levels between the two groups (P > 0.05). Four weeks after treatment, clinical symptoms of the stem cell group improved significantly in comparison with the control group (P < 0.05).During the 24-week follow-up, the survival rate in the stem cell group was significantly higher than that in the control group (P < 0.05). Additionally, there were no adverse reactions and liver cancer associated with the stem cell therapy.Results show that it is safe and effective to treat patients with chronic liver failure through the transplantation of umbilical cord mesenchymal stem cells, and the cell transplantation can significantly improve patients' survival rate.