Objective To evaluate the dyssynchrony of left ventricle in patients with dilated cardiomyopathy by two-dimensional speckle-tracking strain (2DS) and tissue velocity imaging (TVI).Methods Study population consisted of 37 dilated cardiomyopathy patients. High frame rate two-dimensional images were recorded from the left ventricular short-axis views at the levels of mitral annulus,papillary muscles and apex, and the apical four-chamber view, two-chamber view and long-axis of the left ventricle. The time to peak myocardial longitudinal systolic velocity was measured by TVI, 2DS was acquired to measure the time to peak radial strain in the short axis and the time to peak longitudinal strain inthe long axis,left ventricular synchronization index (△T) was defined as the difference of the time to peak value between anterior septum and posterior wall. Results △T measured by 2DS on the long axis and the short axis increased significantly compared with TVI(P<0.01) in the basal segment; 2DS on the short axis had a more significantly increased △T than TVI(P<0.01) in the middle segment. △T measured by 2DS on the short axis significantly increased in the basal and middle segment compared with 2DS on the long axis(P<0.05). Dyssynchrony eases and the detection rate of dyssynchrony measured by 2DS on the long axis were significantly higher than 2DS on the short axis and TVI(P<0.01). Dyssynchrony cases and the detection rate measured by 2DS on the short axis were higher than those measured by TVI, but the difference had no statistical significance. Conclusions The dyssynchrony detection rate measured by longitudinal strain of 2DS is significantly higher than TVI and radial strain.

Objective: To explore the treatment technique, occurrence and development patterns of such radiation injuries as in a major radiological accident in which a victim suffered mild bone marrow radiation sickness combined grade degree Ⅲ acute radiation induced skin injury, based on his dose estimation, clinical manifestations and disease treatments. Methods: History inquiry in detail, earlier physical dose estimation and biological dose estimation were conducted in conjunction with analyzing the chromosome aberration of peripheral blood lymphocytes. The physical dose was estimated by Monte Carlo method.The systematic laboratory and imaging examination was performed to evaluate the condition. The comprehensive analysis was conducted to determine the diagnosis and treatment plan. Results: At 3d after the exposure, "Ren" felt mild pain and discomfortable on the skin of the right index finger. The body of the right hand index finger was covered with blister at 21 d after exposure.The estimation of biological dose was 0.43 Gy (95%CI: 0.31-0.58 Gy), and the physical dose was estimated to be 36-164 Gy for each part of the right hand finger. The hematopoietic system, immune system and endocrine system were normal. The liver function index value was transiently increased. The liver damage resulted from the use of antibiotic-induced combined with the patient′s past medical history and admission examination result, and the relevant antibiotics were discontinued. The liver function returned to normal after liver protection treatment. At 22 d after irradiation, a right finger incision and decompression surgery were performed. The stem cells were extracted and implanted into the right index finger. After 59 days of hospitalization, there was no obvious discomfort in the body, and the right index finger recovered well, as well as the pain significantly relieved, and the knuckle activity was basically normal. Conclusions The patient with excessive radiation and grade Ⅲ acute radiation skin injury was successfully treated, and local application of autologous adipose-derived stem cell transplantation achieved good result .

Objective:To investigate the protective effect of naringenin on acute lung injury related with sepsis; To discuss its possible mechanism.Methods:Totally 30 male SD rats were randomly divided into sham-operation group, model group, naringin low-, medium- and high-dosage groups, with 6 rats in each group. The sepsis-related acute lung injury model was established by cecal ligation and puncture in all groups except the sham-operation group. After modeling, naringin low-, medium- and high-dosage groups were given naringin 20 mg/kg, 40 mg/kg and 80 mg/kg, respectively for gavage, while the sham-operation group and the model group were given the same volume of distilled water by gavage, once a day, for 2 days. Pathological changes in lung tissue were observed using HE staining. The levels of 1L-1, IL-6 and IL-18 in bronchoalveolar lavage fluid (BALF) were measured by ELISA; the expression of TNF-α in lung tissue was detected by immunofluorescence histopathology; the expressions of TGF-β1, TGF-βR1 and Smad2 were detected by Western Blot. An agonist group and a naringin plus agonist group were set up, with 6 mice in each group, and the expressions of TGF-β1 and Smad2 protein in the lung tissue of each group were detected by immunohistochemical staining to verify the effect of naringin on the expressions of TGF-β1 and Smad2 protein.Results:Compared with the model group, the pathological injury of lung tissue in naringin groups were obviously alleviated, and the levels of IL-1β, IL-6 and IL-18 in BALF decreased ( P<0.01), the protein expressions of TNF-α, TGF-β1, TGF-βR1 and Smad2 in lung tissue decreased ( P<0.01 or P<0.05). Further verification found that the expressions of TGF-β1 and Smad2 in the agonist group increased ( P<0.01), while the expressions of TGF-β1 and Smad2 in the naringin agonist group decreased ( P<0.01). Conclusion:Naringin can reduce the inflammatory response in the lung of the rats to protect against sepsis-related acute lung injury, and its protective effect could be related to the inhibition of the TGF-β1/Smad2 signaling pathway.

Objective: To investigate the effect of long-term deep slow-wave sleep deprivation on the gonad axis, sperm abnormality rate, and structure of the testis in male rats and possible mechanisms. Methods: A total of 30 specific pathogen-free male Wistar rats aged 5 weeks were randomly divided into slow-wave sleep deprivation group 1 (SD1 group) , slow-wave sleep and sleep time deprivation group 2 (SD2 group) , and control group, with 10 rats in each group. The flower pot method was used to establish a model of sleep deprivation. In addition to 12-hour sleep deprivation at night, the rats in the SD1 group were given interference once every 24 minutes, and those in the SD2 group were deprived of sleep for 8 minutes every 24 minutes; the rats in the control group were given 12-hour light illumination and then placed in dark environment for 12 hours. All rats were sacrificed by exsanguination from the femoral artery, and the testis, the epididymis, and blood were collected for analysis. Sperm abnormality rate and sperm motility rate were measured, and cauda epididymal sperm counting was performed. ELISA was used to measure the serum levels of testosterone (T) , follicle-stimulating hormone (FSH) , and luteinizing hormone (LH) . Results: Compared with the control group, the SD2 group had a significant increase in organ coefficient of the epididymis (P<0.05) and a significant reduction in sperm motility rate (P<0.05) . There were significant differences between the SD1 group and the SD2 group in the increase in sperm abnormality rate (P<0.05) and the reduction in cauda epididymal sperm count (P<0.05) . The levels of FSH and T tended to increase, and the level of LH tended to decrease. Pathological examination showed degeneration and vacuolization of a small amount of spermatogenic cells in the SD1 group; in the SD2 group, there were significant degeneration, edema, and vacuolization of most spermatogenic cells, some spermatogenic cells were observed in the lumen, and there were no sperms in the lumen. Conclusion Long-term deep slow-wave sleep deprivation impairs the structure of the testis, affects sperm motility rate and sex hormones, and increases the risk of sperm abnormality.

Objective:To investigate the regulatory effect of transient receptor potential cation channel subfamily C member 3 (TRPC3) on the retina in oxygen-induced retinopathy (OIR) mice and biological behavior of human retinal vascular endothelial cells (HREC).Methods:A total of 32 healthy SPF grade 7-day-old C57BL/6 mice were selected and randomly divided into a control group and an OIR group by the random number table method, with 16 mice in each group.The control group received no special treatment, and the OIR model was established in the OIR group.On postnatal day 17 (PN17), the success of the model establishment was verified by immunofluorescence staining of the retinal patch.The in vitro cultured HREC were divided into a normal control group, a transfection reagent group, and a si-TRPC3 group.The normal control group received no special treatment, while the transfection reagent group and the si-TRPC3 group were transfected with transfection reagent or transfection reagent + si-TRPC3.The relative expression of TRPC3 mRNA was detected by real-time quantitative fluorescence PCR.The relative expressions of TRPC3, transcription factor NF-E2 related factor (Nrf2), and superoxide dismutase (SOD) proteins were determined by Western blot.HREC were further divided into a normal control group, a vascular endothelial growth factor (VEGF) group, a si-TRPC3 group, and a Pyr3 (TRPC3 channel inhibitor) group, which were cultured in complete medium, medium containing 20 ng/ml VEGF recombinant protein, medium containing 20 ng/ml VEGF recombinant protein (si-TRPC3 transfection for 72 hours), and medium containing 20 ng/ml VEGF recombinant protein+ 1 μmol/L Pyr3 for 48 hours, respectively.The proliferation ability of HREC was detected using cell counting kit 8 (CCK-8). The horizontal and vertical migration ability of cells were detected by cell scratch assay and transwell assay, respectively.This study followed the 3R principles of animal welfare and was approved by the Ethics Committee of Hebei Eye Hospital (No.2023LW04). Results:Pathological neovascular clusters with strong fluorescent staining appeared in the retina of OIR mice on PN17.The relative expressions of TRPC3 mRNA and protein in the retina of OIR mice were 2.057±0.244 and 1.517±0.290, respectively, significantly higher than 0.983±0.033 and 0.874±0.052 of control group ( t=6.165, 3.094; both at P<0.05). The relative expression levels of TRPC3 mRNA and protein were significantly lower, and the relative expression levels of Nrf2 and SOD proteins were higher in the si-TRPC3 group than in the normal control and transfection reagent groups, and the differences were statistically significant (all at P<0.05). The CCK-8 experiment results showed that the cell absorbance value was higher in the VEGF group than in the normal control group, and lower in the si-TRPC3 and Pyr3 groups than in the VEGF group, with statistically significant differences (all at P<0.05). The results of the cell scratch experiment showed that the lateral migration rate of VEGF group cells was higher than that of normal control group, while the lateral migration rate of si-TRPC3 group and Pyr3 group cells was lower than that of VEGF group, and the differences were statistically significant (all at P<0.05). The transwell experiment results showed that the number of stained cells in the VEGF group was higher than that in the normal control group, and the number of stained cells in the si-TRPC3 group and Pyr3 group was lower than that in the VEGF group, with statistically significant differences (all at P<0.05). Conclusions:Hypoxia induces increased TRPC3 expression in OIR mouse retina, and downregulation of TRPC3 inhibits HREC proliferation and migration.The mechanism is related to the activation of the Nrf2-related oxidative stress pathway.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

OBJECTIVE: To investigate the inhibitory effect of epidermal growth factor receptor tyrosine kinase inhibitor (EGFRTKI) HS-10296 on the proliferation of triple-negative breast cancer (TNBC) MDA-MB-231 cells and explore the possible molecular mechanism. METHODS: MDA-MB-231 cells were treated with HS-10296 for 24, 48, or 72 h, and CCK-8 assay was used to assess the changes in the cell viability. The inhibitory effect of HS-10296 on cell proliferation was determined by clonogenic assay. JC-1 and flow cytometry were employed for analyzing the cell apoptosis, and the ultrastructure of the cells was observed under electron microscope. After pretreatment with autophagy inhibitor chloroquine (CQ), MDA-MB-231 cells were divided into control group, CQ treatment group, HS-10296 (4 and 6 μmol/L) treatment groups and combined treatment groups, and the sensitivity of the treated cells to HS-10296 was determined using CCK-8 assay. The effects of HS-10296 on EGFR pathway and apoptosis- and autophagy-related proteins in MDA-MB-231 cells were investigated using Western blotting. RESULTS: HS-10296 significantly inhibited the proliferation of MDA-MB-231 cells with IC values at 24, 48 and 72 h of 8.393, 2.777 and 2.016 μmol/L, respectively. JC-1 and flow cytometry showed that HS-10296 induced obvious apoptosis of MDA-MB-231 cells, which showed an apoptosis rate of (21.63 ± 2.97)% following treatment with 8 μmol/L HS-10296. Autophagy vesicles were observed in the cells treated with HS-10296 under electron microscope. In MDA-MB-231 cells pretreated with CQ, inhibition of autophagy significantly enhanced HS-10296-induced cell death. Western blotting showed that the apoptosis-related protein caspase-3 was activated after HS-10296 treatment to cut its substrate PARP. The expression of autophagy-related protein light chain 3B (LC3B) was significantly enhanced after HS-10296 treatment ( < 0.01), which also resulted in inhibited phosphorylation of EGFR and AKT proteins in the cells. CONCLUSIONS HS-10296 can inhibit the proliferation and induce autophagy and apoptosis of MDA-MB-231 cells by inhibiting the EGFR/PI3K/AKT signaling pathway.
Apoptosis ; Autophagy ; Breast Neoplasms ; Cell Line, Tumor ; Cell Proliferation ; ErbB Receptors ; Humans ; Phosphatidylinositol 3-Kinases ; Protein Kinase Inhibitors

OBJECTIVE: To investigate the inhibitory effect of epidermal growth factor receptor tyrosine kinase inhibitor (EGFRTKI) HS-10296 on the proliferation of triple-negative breast cancer (TNBC) MDA-MB-231 cells and explore the possible molecular mechanism. METHODS: MDA-MB-231 cells were treated with HS-10296 for 24, 48, or 72 h, and CCK-8 assay was used to assess the changes in the cell viability. The inhibitory effect of HS-10296 on cell proliferation was determined by clonogenic assay. JC-1 and flow cytometry were employed for analyzing the cell apoptosis, and the ultrastructure of the cells was observed under electron microscope. After pretreatment with autophagy inhibitor chloroquine (CQ), MDA-MB-231 cells were divided into control group, CQ treatment group, HS-10296 (4 and 6 μmol/L) treatment groups and combined treatment groups, and the sensitivity of the treated cells to HS-10296 was determined using CCK-8 assay. The effects of HS-10296 on EGFR pathway and apoptosis- and autophagy-related proteins in MDA-MB-231 cells were investigated using Western blotting. RESULTS: HS-10296 significantly inhibited the proliferation of MDA-MB-231 cells with IC values at 24, 48 and 72 h of 8.393, 2.777 and 2.016 μmol/L, respectively. JC-1 and flow cytometry showed that HS-10296 induced obvious apoptosis of MDA-MB-231 cells, which showed an apoptosis rate of (21.63 ± 2.97)% following treatment with 8 μmol/L HS-10296. Autophagy vesicles were observed in the cells treated with HS-10296 under electron microscope. In MDA-MB-231 cells pretreated with CQ, inhibition of autophagy significantly enhanced HS-10296-induced cell death. Western blotting showed that the apoptosis-related protein caspase-3 was activated after HS-10296 treatment to cut its substrate PARP. The expression of autophagy-related protein light chain 3B (LC3B) was significantly enhanced after HS-10296 treatment ( < 0.01), which also resulted in inhibited phosphorylation of EGFR and AKT proteins in the cells. CONCLUSIONS HS-10296 can inhibit the proliferation and induce autophagy and apoptosis of MDA-MB-231 cells by inhibiting the EGFR/PI3K/AKT signaling pathway.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Autophagy ; drug effects ; Breast Neoplasms ; drug therapy ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; ErbB Receptors ; metabolism ; Humans ; Protein Kinase Inhibitors ; pharmacology ; Signal Transduction ; drug effects