Objective: To evaluate the value of quantitative and heterogeneous analysis of radionuclide myocardial perfusion in diagnosis of viral myocarditis (VMC). Methods: 99mTc-MIBI myocardial perfusion imaging data of 37 patients suspected with VMC were analyzed retrospectively. Eighteen patients were clinical diagnosed as VMC (VMC group) and 19 patients excluded VMC were served as non-VMC group. Summed rest score (SRS) and the total perfusion deficit (TPD) were obtained by using QPS software. Heterogeneity parameters of radioactive count (segmental coefficient of variation [CVs] and ventricular wall coefficient of variation [CVw]) were also calculated. Perfusion parameters were compared between the two groups, and the diagnostic value on discrimination of VMC patients was evaluated by ROC analysis. Results: Compared with non-VMC group, myocardial perfusion in anterior and inferior walls decreased significantly in VMC group (all P<0.05); TPD and CVs were significantly higher in VMC group (P<0.05). Efficiency of CVs in diagnosis of VMC was best (AUC=0.83, P<0.01). When the threshold of CVs was 10.5%, the diagnostic sensitivity was 94.4% and the specificity was 73.7%. Conclusion: Heterogeneous analysis of myocardial perfusion is helpful for differential diagnosis of VMC.

Objective .To prove aristolochic (AA) caused vascular endothelial cells (VEC) injury via intracellular calcium overloa-ding and investigate the mechanism of calcium dobesilate antagonism. Methods Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and randomly divided into three groups: Control group, AA group, intervention group. Microscope and transmission elec-tron microscopy were used to observe changes of cell morphology and ultrastructure. ELISA method were applied to determine thrombomedu-lin (TM) in cell culture supernatant, fluorescent indicator FLuo-3/AM and intracellular calcium concentration ([Ca2+]. Results TM val-ue and average [Ca2+] i of AA group were significantly higher than that of control group (P < 0.05). Compared with the AA group, when the concentration of calcium dobesilate was 25 μM or 50 μM, TM value and average [Caz +] significantly decreased in intervention group (P < 0.05). Compared with control group, endoplasmic reticulum was pool expansion shaped, and mitochondrial cristae was absent in AA group cells. Endoplasmic reticulum and mitochondria patterns in the intervention group cells showed some improvement, compared with AA group. Conclusion AA induced VEC calcium overloading, 'I'M secretion and injury of endothelial ceils, endoplasmic reticulum and mito-chondria destruction. Dabesilate calcium could protect endoplasmic reticulum and mitochondria and reduce AA induced VEC calcium over-loading, and these could protect VEC.

Amyloidosis is a local or systemic disease caused by the deposition of misfolded proteins outside the cell,with rapid progression,and dire prognosis.Common types of cardiac amyloidosis are monoclonal immunoglobulin light chain amyloidosis(AL-CA)and transthyretin cardiac amyloidosis(ATTR-CA).Nuclear medicine examinations can be accurate,rapid,and non-invasive to help diagnose diseases and can effectively predict the prognosis of patients with CA.Technetium(99Tcm)-labeled bisphosphonate imaging has been included in the consensus of experts and has become the first-line imaging method for the diagnosis of ATTR-CA.123I-metaiodoenzylguanidine(MIBG)as a norepinephrine analogue can effectively assess cardiac sympathetic innervation in patients with CA.Aβ-amyloid imaging agents such as 11C-pittsburgh compound B and 18F-flubetaben are expected to be new techniques for diagnosing AL-CA and incorporating them into cardiac staging systems for AL-CA patients in the future.New imaging agents such as 18F-NaF has been widely used in the diagnosis,treatment response monitoring,and prognosis assessment of CA.Summarizing the research value of nuclide imaging in CA may provide new ideas for clinical realization of early detection of CA and accurate assessment of disease prognosis.

Purpose: Plasma osmolality, a marker of dehydration, is associated with cardiovascular mortality. We aimed to investigate whether elevated plasma osmolality is associated with case fatality within 1 year after severe acute ischemic stroke. Materials and Methods: We included severe ischemic stroke patients (defined as National Institutes of Health Stroke Scale ≥15 score) within 24 hours from symptom onset admitted to the Department of Neurology, West China Hospital between January 2017 and June 2019. Admission plasma osmolality was calculated using the equation 1.86 * (sodium+potassium)+1.15 * glucose+urea+14. Elevated plasma osmolality was defined as plasma osmolality >296 mOsm/kg, indicating a state of dehydration. Study outcomes included 3-month and 1-year case fatalities. Multivariable logistic regression was performed to determine independent associations between plasma osmolality and case fatalities at different time points. Results: A total of 265 patients with severe acute ischemic stroke were included. The mean age was 71.2±13.1 years, with 51.3% being males. Among the included patients, case fatalities were recorded for 31.7% (84/265) at 3 months and 39.6% (105/265) at 1 year. Elevated plasma osmolality (dehydration) was associated with 3-month case fatality [odds ratio (OR) 1.98, 95% confidence interval (CI) 1.07–3.66, p=0.029], but not 1-year case fatality (OR 1.51, 95% CI 0.84–2.72, p=0.165), after full adjustment for confounding factors. Conclusion Elevated plasma osmolality was independently associated with 3-month case fatality, but not 1-year case fatality, for severe acute ischemic stroke.

Purpose: Plasma osmolality, a marker of dehydration, is associated with cardiovascular mortality. We aimed to investigate whether elevated plasma osmolality is associated with case fatality within 1 year after severe acute ischemic stroke. Materials and Methods: We included severe ischemic stroke patients (defined as National Institutes of Health Stroke Scale ≥15 score) within 24 hours from symptom onset admitted to the Department of Neurology, West China Hospital between January 2017 and June 2019. Admission plasma osmolality was calculated using the equation 1.86 * (sodium+potassium)+1.15 * glucose+urea+14. Elevated plasma osmolality was defined as plasma osmolality >296 mOsm/kg, indicating a state of dehydration. Study outcomes included 3-month and 1-year case fatalities. Multivariable logistic regression was performed to determine independent associations between plasma osmolality and case fatalities at different time points. Results: A total of 265 patients with severe acute ischemic stroke were included. The mean age was 71.2±13.1 years, with 51.3% being males. Among the included patients, case fatalities were recorded for 31.7% (84/265) at 3 months and 39.6% (105/265) at 1 year. Elevated plasma osmolality (dehydration) was associated with 3-month case fatality [odds ratio (OR) 1.98, 95% confidence interval (CI) 1.07–3.66, p=0.029], but not 1-year case fatality (OR 1.51, 95% CI 0.84–2.72, p=0.165), after full adjustment for confounding factors. Conclusion Elevated plasma osmolality was independently associated with 3-month case fatality, but not 1-year case fatality, for severe acute ischemic stroke.

Objective : To investigate the effects of N-cadherin silencing on the proliferation and migration of human dental pulp stem cells (DPSCs) and to provide experimental evidence for DPSCs-based dental pulp regeneration. Methods: DPSCs were transfected with N-cadherin shRNA lentivirus, and the knockdown efficiency of N-cadherin at both the mRNA and protein levels was confirmed by qRT-PCR and Western blot. The experiment included a negative control group (shRNA -NC) and an N-cadherin shRNA silencing group. Cell proliferation was detected by the CCK-8 method. Cell cycle and apoptosis were assessed by flow cytometry, and cell migration was detected using the Transwell method. Results: N-cadherin shRNA significantly reduced the expression levels of N-cadherin mRNA and protein in DPSCs (P<0.001). The proliferation activity of the N-cadherin shRNA group was significantly greater than that of the shRNA-NC group on the 3rd and 4th days after cell inoculation and lower than that of the shRNA-NC group from the 6th to 8th days (P<0.05). On the 3rd day after cell inoculation, the proportion of cells in S phase and G2 phase in the N-cadherin shRNA group was greater than that in the shRNA-NC group (P<0.05). On the 6th day after cell inoculation, the proportion of cells in S phase and G2 phase in the N-cadherin shRNA group was lower than that in the shRNA-NC group (P<0.05), and the proportion of apoptotic cells in the N-cadherin shRNA group was greater than that in the shRNA-NC group (P<0.01). Low densities cells and high densities cells were inoculated into Transwell upper chamber for 20 h, the number of cells passing through the membrane pores of upper chamber in the N-cadherin shRNA group was greater than that in the shRNA-NC group (P<0.001). Conclusion Silencing N-cadherin expression can promote the early proliferation and migration of DPSCs.

Male ; Humans ; Aged ; Sleep Duration ; Aging ; Testosterone ; China ; Sleep

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*