Aim To explore the protective effect of PPARδ agonist GW501516 on neuro-vascular unit(NVU)injury induced by high glucose in vitro and its mechanism.Methods SD rat hippocampal neurons(Neu),astrocytes(Ast)and brain microvascular en-dothelial cells(BMEC)were isolated,purified and cultured in vitro,and NVU co-culture system was estab-lished.NVU co-culture system cells were divided into the control group,high glucose group(HG group),HG+GW501516 low,medium and high concentration groups(25,50 and 100 nmol·L-1)and HG+GW501516(100 nmol·L-1)+ANA12(TrkB inhibi-tor,5 μmol·L-1)group.NUV barrier function was e-valuated by transendothelial resistance(TEER)test and leakage test;the proliferative activity of Neu cells in co-culture system was detected by CCK-8 assay;the levels of inflammatory cytokines TNF-α,IL-6 and IL-1β in cell supernatant were detected by ELISA;the levels of SOD,MDA and NO in Neu cells were detected by chemical method;the apoptosis level was detected by flow cytometry;the protein expression levels of PPARδ,Bax,Bcl-2,cleaved caspase-3,and BDNF/TrkB pathway-related proteins BDNF,p-TrkB,and TrkB in Neu cells were detected by Western blot.Re-sults Compared with the control group,the TEER val-ue decreased and leakage value increased in HG group;the proliferation activity of Neu cells decreased,the levels of TNF-α,IL-6,IL-1β in supernatant and MDA and NO in Neu cells increased,and the SOD lev-el decreased;Neu cell apoptosis rate and expression levels of Bax and Cleaved caspase-3 increased,while the expression levels of PPARδ,Bcl-2,BDNF and p-TRKB/TrkB decreased(P＜0.05).Compared with the HG group,after treatment with different concentra-tions of GW501516,TEER value increased,leakage value decreased,proliferation activity of Neu cells in-creased,levels of TNF-α,IL-6,IL-1β in supernatant and MDA and NO in Neu cells decreased,and SOD level increased,and apoptosis rate of Neu cells and ex-pression levels of Bax and cleaved caspase-3 were de-creased,and expression levels of PPARδ,Bcl-2,BDNF and p-TRKB/TrkB increased(P＜0.05)in a dose-dependent manner.However,ANA12 intervention re-versed the effect of GW501516 on NVU damage under high glucose conditions.Conclusion PPARδ agonist GW501516 improves in vitro NVU injury induced by high glucose by activating BDNF/TrkB signaling path-way.

Objective To investigate the mechanism and protective effect of Humanin(HN)on rotenone(Rot)-induced toxic damage for dopamine neurons.Methods The Rot-poisened PC12 cell model was constructed,and the control group,the Rot poisening group,the HN pretreated Rot poisening group,and the HN treatment group were set up.ELISA was used to detect the content of HN inside and outside of Rot-infected cells,CCK-8 assay was used to detect cell viability,and ATP detection kit was used to detect the intracellular ATP content.Dichloro-dihydro-fluorescein diacetate(DCFH-DA)assay was used to detect the level of reactive oxygen species(ROS)in cells.Western blotting was performed to detect the expression level of mitochondrial autophagy regulatory proteins Pink1,Parkin,p62,LC3,mitochondrial biogenesis regulatory protein PGC1α,division/fusion regulatory proteins OPA1,MFN2,DRP1,p-DRP1 and antioxidant stress regulatory proteins Keap1 and Nrf2.HBAD-mcherry-EGFP-LC3 adenovirus transfected cells was used to observed the number of autophagosomes and autophagolysosomes.Results The results showed that the intracellular concentration of HN in PC12 in the Rot poisening group was significantly higher than that in the control group(P＜0.05);Compared with the control group,the Rot poisening group had significantly decreased activity of PC12 cells,decreased ATP content and increased production of ROS.After the poisen of Rot in PC12 cells,the expression of Pink1 and p-Parkin,the ratio of LC3Ⅱ/LC3Ⅰ and the expression of p-DRP1 in mitochondrial fusion protein was increased,while the expression of p62,the expression of mitochondrial biogenesis protein PGC1 α,mitochondrial fusion proteins MFN2 and OPA1,and antioxidant stress proteins Keap1 and Nrf2 were decreased(all P＜0.05).The number of autophagosomes and autophagolysosomes in PC12 cells in the Rot poisening group was higher than that in the control group(P＜0.05),and HN pretreatment(20 μmol/L)could significantly improve the changes mentioned above caused by Rot poisening(P＜0.05).Conclusion HN ameliorates Rot-induced toxic damage for dopamine neurons by inhibiting mitophagy and mitochondrial division and promoting mitochondrial biogenesis and fusion,and anti-oxidative stress.

OBJECTIVE: To investigate the efficacy and safety of venetoclax (VEN) combined with demethylating agents (HMA) in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML). METHODS: The clinical data of 26 adult R/R AML patients who received the combination of VEN with azacitidine (AZA) or decitabine (DAC) in Huai'an Second People's Hospital from February 2019 to November 2021 were retrospectively analyzed. The treatment response, adverse events as well as survival were observed, and the factors of influencing the efficacy and survival were explored. RESULTS: The overall response rate (ORR) of 26 patients was 57.7% (15 cases), including 13 cases of complete response (CR) and CR with incomplete count recovery (CRi) and 2 cases of partial response (PR). Among the 13 patients who got CR/CRi, 7 cases achieved CRm (minimal residual disease negative CR) and 6 cases did not, with statistically significant differences in overall survival (OS) and event-free survival (EFS) between the two groups (P=0.044, 0.036). The median OS of all the patients was 6.6 (0.5-15.6) months, and median EFS was 3.4 (0.5-9.9) months. There were 13 patients in the relapse group and refractory group, respectively, with response rate of 84.6% and 30.8% (P=0.015). The survival analysis showed that the relapse group had a better OS than the refractory group (P=0.026), but there was no significant difference in EFS (P=0.069). Sixteen patients who treated for 1-2 cycles and 10 patients who treated for more than 3 cycles achieved response rates of 37.5% and 90.0%, respectively (P=0.014), and patients treated for more cycles had superior OS and EFS (both P<0.01). Adverse effects were mainly bone marrow suppression, complicated by various degrees of infection, bleeding, and gastrointestinal discomfort was common, but these could be all tolerated by patients. CONCLUSION VEN combined with HMA is an effective salvage therapy for patients with R/R AML and is well tolerated by patients. Achieving minimal residual disease negativity is able to improve long-term survival of patients.
Adult ; Humans ; Retrospective Studies ; Neoplasm, Residual/drug therapy* ; Bridged Bicyclo Compounds, Heterocyclic/adverse effects* ; Recurrence ; Leukemia, Myeloid, Acute/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective: To investigate the association of plasma vitamin B₁₂ level with plasma uric acid level among the elderly over 65 in 9 longevity areas of China. Methods: The elderly over 65 years old with complete information on plasma vitamin B₁₂ and plasma uric acid from Healthy Aging and Biomarkers Cohort Study (2017 to 2018) were recruited in this study. Information on socio-demographic characteristics, life styles, diet intake, and health status were collected by questionnaire and physical examination; and fasting venous blood was collected to detect the levels of plasma vitamin B₁₂, uric acid and other indicators. Multiple linear regression models were used to analyze the association of plasma vitamin B₁₂ level per interquartile range increase with plasma uric acid level. The association trend of plasma vitamin B₁₂ level with plasma uric acid level was described by restrictive cubic splines fitting multiple linear regression model. Multiple logistic regression models were used to analyze the association of plasma vitamin B₁₂ level stratified by quartiles with hyperuricemia. Results: A total of 2 471 participants were finally included in the study, the age was (84.88±19.76) years old, of which 1 291 (52.25%) were female. The M (Q₁, Q₃) level of plasma vitamin B₁₂ was 294 (203, 440) pg/ml and the plasma uric acid level was (341.01±90.46) μmol/L. A total of 422 participants (17.08%) were defined with hyperuricemia. The results of multiple linear regression model showed that there was a positive association of plasma vitamin B₁₂ level with plasma uric acid level after adjustment for covariates (P<0.05). An IQR increase in plasma vitamin B₁₂ (237 pg/ml) was associated with a 6.36 (95%CI: 2.00-10.72) μmol/L increase in the plasma uric acid level. The restrictive cubic splines curve showed a positive linear association of log-transformed plasma vitamin B₁₂ with uric acid level (P<0.001). Conclusion: There is a positive association of plasma vitamin B₁₂ level with plasma uric acid level among the elderly over 65 years old in 9 longevity areas of China.
Humans ; Female ; Aged ; Aged, 80 and over ; Male ; Vitamin B 12 ; Uric Acid ; Cohort Studies ; Hyperuricemia ; Vitamins ; Folic Acid

Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 μg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q₁) of blood selenium, the ORs (95%CI) of Q₃ and Q₄ blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (P_nonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.
Aged, 80 and over ; Female ; Humans ; Selenium ; Cohort Studies ; Cross-Sectional Studies ; Metals/analysis* ; Cognitive Dysfunction/epidemiology* ; China/epidemiology*

Objective:To evaluate the feasibility and the application values of quantitative susceptibility mapping (QSM) for the assessment of meniscal injury and in distinguishing meniscus degeneration and tears.Methods:The clinical and imaging data of 70 patients suspected of meniscus injury and scheduled for arthroscopy in Shandong Medical Imaging Research Institute, Cheeloo College of Medicine, Shandong University from November 2019 to June 2020 were analyzed retrospectively. Thirty age-and sex-matched healthy subjects were also examined as controls. All subjects received knee joint QSM and routine MR imaging. According to the results of arthroscopy, the patients was divided into meniscus degeneration and meniscus tear groups, respectively. The conventional MR was evaluated by two radiologists. The meniscus injury area was delineated on the original QSM magnitude images (the central area of the posterior corner of the lateral meniscus was selected in the healthy controls) and mapped to the corresponding QSM maps, and the magnetic susceptibility values were measured. Kruskal-Wallis H test was used to analyze the magnetic sensitivity values of meniscal degeneration, meniscal tear and healthy control groups; and Bonferroni was used to correct the pairwise comparison. ROC curve was established to evaluate the threshold and efficacy of magnetic susceptibility value in the diagnosis of meniscal tear. The results were compared with those of conventional MRI. Results:The magnetic susceptibility values of meniscus of healthy controls, meniscal degeneration and meniscal tear groups were (0.035±0.016)ppm, -0.031(-0.040,-0.005)ppm, and(-0.122±0.115)ppm, respectively, with significant difference found among the three groups (χ2=44.419, P<0.05). The magnetic susceptibility values of meniscus of healthy controls was significantly higher than those of meniscus degeneration patients and meniscus tear patients (χ2=-23.843, -48.253, P<0.05). The magnetic susceptibility values of meniscus of meniscus tear group was significant lower than those of meniscus degeneration group (χ2=-24.410, P<0.05). Taking magnetic susceptibility values of -0.062 5 ppm as threshold, the area under the ROC curve for the diagnosis of meniscal tears was 0.949, with the sensitivity as 87% and the specificity as 100%. The sensitivity and specificity of conventional MRI in the diagnosis of meniscal tears were 86.8% and 87.5%, respectively. Conclusion:QSM can quantitatively evaluate meniscus injury and can be used as an effective supplement method to conventional MRI, which is helpful to improve the diagnosis of meniscus tear.

Prostaglandin E
Angiotensin II ; Animals ; Humans ; Hypertension/chemically induced* ; Mice ; Mice, Inbred C57BL ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle

Knee osteoarthritis-associated bone marrow edema-like lesions (KOA-BMLs) is a common MRI imaging feature, which is mainly manifested as abnormal bone marrow hyperintensity in subchondral bone on T2 imaging. The formation of KOA-BMLs may be related to the abnormality of lower limb force line and subchondral bone perfusion, and related histopathological studies showed that the remodeling of bone and bone marrow in these damaged areas was abnormally increased. In KOA patients, the size of BMLs can fluctuate or even disappear in a relatively short period of time, and was closely related to pain, subchondral bone cyst formation, and the progression of KOA. However, the current treatment methods for KOA-BMLs are limited, and there is no uniform guideline or expert consensus, mainly includingmedication, physical therapy and surgical treatment. This article reviews the research progress of the disease characteristics and treatment of KOA-BMLs in order to provide guidance for the clinical diagnosis and treatment of KOA-BMLs.
Bone Marrow/diagnostic imaging* ; Bone Marrow Diseases/diagnostic imaging* ; Edema/diagnostic imaging* ; Humans ; Knee Joint ; Magnetic Resonance Imaging ; Osteoarthritis, Knee/diagnostic imaging*

Objective:To explore the effect of marital self-disclosure nursing on the fear and quality of life of maintenance hemodialysis patients.Methods:From January to December 2019, 106 maintenance hemodialysis patients who were treated at Jinhua Municipal Central Hospital in Zhejiang Province were selected as the research object. The patients were divided into the control group and the intervention group by random number table method, with 53 cases in each group. The control group conducted routine nursing, and the intervention group implemented marital self-disclosure nursing on this basis. The Fear of Progression Questionnaire-Short Form (FoP-Q-SF) and the Kidney Disease Questionnaire (KDQ) were used to compare the fear of disease progression and quality of life between the two groups before and after intervention.Results:After 12 weeks of intervention, the scores of physiological health dimension and social family dimension in the fear of disease progression in the intervention group were (15.2±1.8) and (13.0±2.1) respectively, which were lower than those of the control group, and the difference was statistically significant ( P<0.05) . After 12 weeks of intervention, the total KDQ score of the intervention group was (152.8±15.2) , and that of the control group was (138.9±15.7) , and the difference was statistically significant ( P<0.05) . Conclusions:The application of marital self-disclosure nursing in maintenance hemodialysis patients can reduce the fear and improve the quality of life of patients.

Objective To investigate the clinical features, laboratory findings, chest CT findings and treatment of patients with COVID-19, and to analyze their relationship with prognosis. Methods From January to February 2020, the clinical data on the 42 patients with COVID-19 admitted to the Wenzhou Sixth People′s Hospital were analyzed retrospectively. Results The clinical symptoms of the 42 cases included fever (35 cases), cough (26 cases), fatigue (14 cases), aspiration (9 cases), sore throat (4 cases), muscle ache (5 cases), headache (2 cases), nausea (4 cases), diarrhea (6 cases) and abdominal pain (1 case).The absolute number of blood lymphocyte decreased to different degrees in 22 cases.Fourteen cases had lactate dehydrogenase obviously, with no obvious change in procalcitonin.The imaging manifestations were cloud-like and ground-glass-like high density shadows scattered outside the lungs, small flaky consolidation and bronchus inflating sign were seen locally.A few images showed diffuse high density, most of the lesions showed consolidation or striate change, and local fibrosis was formed in the lower lobes of both lungs. Conclusion Fever and cough are the first symptoms of COVID-19, and a few cases are associated with shortness of breath and diarrhea, accompanied by different degrees of systemic symptoms, but most of the patients improve their conditions after active antivirus, anti-infection, systematic symptoms improvement and supportive treatment.The disease is highly infectious and its condition changes rapidly.Therefore, early detection, early diagnosis and comprehensive treatment of the whole body as soon as possible are the keys to treatment.