Promotion Effect of Catalpol on Angiogenesis and Potential Mechanisms: A Research Based on Network Pharmacology.

Catalpol, a natural iridoid glycoside, has potential therapeutic benefits, including anti-inflammatory and neuroprotective effects. Investigating catalpol's role in angiogenesis is critical for understanding its potential therapeutic applications, particularly in diseases where modulating angiogenesis is beneficial. This study investigates catalpol's influence on angiogenesis and its mechanisms, combining network pharmacology and in vitro experiments. The target genes corresponding to the catalpol were analyzed by SwissTargetPrediction. Then angiogenesis-related targets were acquired from databases like GeneCards. Subsequently, the Database for Annotation, Visualization and Integrated Discovery was employed for Gene Ontology and pathway analysis, while Cytoscape visualized protein interactions. The effect of catalpol on viability and angiogenesis of HUVECs was further examined using Cell Counting Kit-8 and angiogenesis assays. RT-qPCR and western blot were applied to check the expression of angiogenesis-related proteins. Totally, 312 target genes of catalpol and 823 angiogenesis-related targets were obtained with 56 common targets leading to PPI network analysis, highlighting hub genes (AKT1, EGFR, STAT3, MAPK3, and CASP3). These hub genes were mainly enriched in lipid and atherosclerosis pathway and EGFR-related pathway. The in vitro experimental results showed that catalpol achieved a concentration-dependent increase in HUVECs viability. Catalpol also promoted the migration and angiogenesis of HUVECs and up-regulated the expression of EGFR. EGFR knockdown inhibited the effect of catalpol on HUVECs. Catalpol promotes angiogenesis in HUVECs by upregulating EGFR and angiogenesis-related proteins, indicating its potential therapeutic application in vascular-related diseases.

Effect of rTMS combined with CBT on alcohol craving and cognitive function in patients with alcohol dependence / 中华行为医学与脑科学杂志

Objective:To explore the effect of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive behavioral therapies (CBT) on the cognitive function and alcohol craving in patients with alcohol dependence.Methods:From March 2019 to September 2021, a total of 150 patients with alcohol dependence were enrolled and randomly divided into rTMS treatment group (rTMS+ sham CBT, n=41), CBT treatment group (CBT+ sham rTMS, n=34), rTMS+ CBT treatment group( n=36) and control group (sham rTMS+ sham CBT, n=39). At baseline (before treatment), 2nd week, 8th week, 12th week and 24th week, alcohol dependence scale (ADS) was used to evaluate the degree of alcohol dependence, the obsessive compulsive drinking scale (OCDS) was used to assess patients' drinking craving, and Montreal cognitive assessment scale (MoCA) was used to assess the overall cognitive level of patients.SPSS 23.0 statistical software was used to compare the differences of ADS, OCDS and MoCA scale scores of the four groups by repeated measure ANOVA and simple effect analysis. Results:(1)The patients in the four groups were evaluated with ADS scale at baseline, 12th week and 24th week respectively.The interaction of group×time( F=1.279, P=0.279) and the main effect of group were not significant ( F=0.882, P=0.454), and the main effect of time was significant ( F=12.925, P<0.001) .Further simple effect analysis showed that the ADS score of rTMS+ CBT group was lower than that of baseline(14.48±5.70, 10.00±6.51) ( P=0.01) at 24th week.(2)Patients in the four groups were assessed with OCDs scale at baseline, 2nd week, 8th week, 12th week and 24th week, and the interaction of group×time was significant ( F=2.015, P=0.042). Further simple effect analysis showed that the OCDs scores of rTMS group and rTMS+ CBT group at each follow-up time node were lower than those at baseline period (all P<0.05). (3)Patients in the four groups were assessed with MoCA scale at baseline, 8th week, 12th week and 24th week, and the interaction of group×time was not significant ( F=1.660, P=0.106), and the main effect of group and the main effect of time were significant ( F=2.964, P=0.038; F=14.239, P<0.001). Further simple effect analysis showed that the score of MoCA scale in CBT group at the 24th week was higher than that at baseline (21.73±5.81, 24.60±3.98)( P=0.029), the score of MoCA scale in rTMS+ CBT group at the 24th week was higher than that at the 8th week (23.50±6.01, 25.95±2.87) ( P=0.006), and the score of MoCA scale in rTMS group at the 12th week was higher than that in control group (22.08±6.64, 26.64±2.46)( P=0.009). Conclusion:rTMS combined with CBT can be effective in improving alcohol craving and cognitive function in patients with alcohol dependence, and has a good long-term effect.

Predictive value of serum bone sialoprotein and prostate-specific antigen doubling time in patients with bone metastasis of prostate cancer / 华中科技大学学报（医学）（英德文版）

This study aimed to evaluate the diagnostic and prognostic significance of serum bone sialoprotein (BSP) and prostate-specific antigen doubling time (PSADT) in patients with bone metastasis (BM) from prostate cancer (PC). A total of 116 patients with PC, 120 patients with benign prostatic hyperplasia (BPH) and 120 healthy controls were enrolled in this study. PC patients were divided into bone metastasis (BM) group (n=56) and non-bone metastasis (NBM) group (n=60). Serum BSP was detected by Sandwich ELISA. Severity of bone pain was evaluated using visual analogue score (VAS). Serum f-PSA and t-PSA levels were measured by using electrochemiluminescence immunoassay (ECLIA). PSADT was calculated according to the formula: PSADT=lg(2)/[log(PSA2)-log(PSA1)]. The mean serum BSP level in PC patients with BM was significantly higher than in PC patients without BM, BPH patients and controls (P<0.001 for all). Pearson's analysis showed that serum BSP level was positively correlated with VAS in PC patients with BM (P<0.05). Receiver operating characteristics (ROC) analysis demonstrated that BSP discriminated patients with BM from those without BM at the cutoff value of 33.26 ng/mL. The sensitivity and specificity were 78.21% and 79.28%, respectively. The optimal cutoff value of PSADT was 131 days, with sensitivity of 85.69% and specificity of 85.36%. Kaplan-Meier analysis revealed that subjects with higher BSP levels/shorter PSADT had a shorter BM-free period than those with lower BSP levels/longer PSADT. Serum BSP and PSADT are useful biomarkers for the diagnosis of BM from PC, and can be regarded as independent factors for predicting the prognosis of BM from PC. Combined determination of BSP and PSADT can improve accuracy and positive rate of BM from PC significantly.

Predictive value of serum bone sialoprotein and prostate-specific antigen doubling time in patients with bone metastasis of prostate cancer / 华中科技大学学报（医学）（英德文版）

This study aimed to evaluate the diagnostic and prognostic significance of serum bone sialoprotein (BSP) and prostate-specific antigen doubling time (PSADT) in patients with bone metastasis (BM) from prostate cancer (PC). A total of 116 patients with PC, 120 patients with benign prostatic hyperplasia (BPH) and 120 healthy controls were enrolled in this study. PC patients were divided into bone metastasis (BM) group (n=56) and non-bone metastasis (NBM) group (n=60). Serum BSP was detected by Sandwich ELISA. Severity of bone pain was evaluated using visual analogue score (VAS). Serum f-PSA and t-PSA levels were measured by using electrochemiluminescence immunoassay (ECLIA). PSADT was calculated according to the formula: PSADT=lg(2)/[log(PSA2)-log(PSA1)]. The mean serum BSP level in PC patients with BM was significantly higher than in PC patients without BM, BPH patients and controls (P<0.001 for all). Pearson's analysis showed that serum BSP level was positively correlated with VAS in PC patients with BM (P<0.05). Receiver operating characteristics (ROC) analysis demonstrated that BSP discriminated patients with BM from those without BM at the cutoff value of 33.26 ng/mL. The sensitivity and specificity were 78.21% and 79.28%, respectively. The optimal cutoff value of PSADT was 131 days, with sensitivity of 85.69% and specificity of 85.36%. Kaplan-Meier analysis revealed that subjects with higher BSP levels/shorter PSADT had a shorter BM-free period than those with lower BSP levels/longer PSADT. Serum BSP and PSADT are useful biomarkers for the diagnosis of BM from PC, and can be regarded as independent factors for predicting the prognosis of BM from PC. Combined determination of BSP and PSADT can improve accuracy and positive rate of BM from PC significantly.

Effects of acute cerebral ischemia on cerebral perfusion: quantitative evaluation by contrast-enhanced ultrasound in dogs / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the changes of cerebral blood flow (CBF) with real-time contrast-enhanced ultrasound (CEU) in a canine model of acute cerebral ischemia.</p><p><b>METHODS</b>Cerebral perfusion was assessed in 6 dogs subjected to craniotomy with CEU at the time of 0, 30, 60, 90 and 120 min after occlusion of the left common carotid artery (LCCA). The microvascular volume (A) and blood flow velocity (beta) in the brain were measured from the time-versus-acoustic intensity plots, and the value of Axbeta were calculated. 99mTc-ECD brain single photon emission computed tomography (SPECT) was performed on the day before the experiment and at 120 min after LCCA occlusion. The radioactive counts on both sides of the cerebral cortex were calculated.</p><p><b>RESULTS</b>A significant correlation was found between Axbeta from CEU and volume of the blood flow of the CCA from Doppler flowmetry. A, beta and Axbeta values varied significantly between the different time points (P>0.001). The ipsilateral hemisphere showed a low-perfusion state while the contralateral hemisphere showed a high-perfusion state immediately after the occlusion.</p><p><b>CONCLUSIONS</b>The changes of beta is the main regulation mechanism during acute cerebral ischemia in dogs.</p>

Effect of obstructive sleep apnea syndrome on blood lipid and blood glucose in elderly hypertensive patients / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of obstructive sleep apnea syndrome (OSAS) on blood lipid and blood glucose in elderly hypertensive patients.</p><p><b>METHOD</b>a One hundred and seven elderly hypertensive patients received examinations by polysomnography and according to the apnea-hypopnea index (AHI), the patients were divided into four groups, namely uncomplicated hypertension group (n=23) and 3 hypertension groups with mild (n=31), moderate (n=29) and severe (n=24) OSAS. The fasting and 2-hour postprandial plasma glucose, glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), Apo-A, and Apo-B of these patients were measured.</p><p><b>RESULTS</b>aCompared with the non-OSAS patients, all the OSAS patients showed increased fasting and 2-hour postprandial plasma glucose, HbA1c, TC, TG, LDL and TC/HDL, and the increments were statistically significant in severe OSAS patients (P<0.05). The level of HDL was lowered in the OSAS groups, showing significant difference between severe OSAS group and the non-OSAS group (P<0.05). Apo-A level was lowered and Apo-B increased in the OSAS groups, but the differences were not statistically significant (P>0.05).</p><p><b>CONCLUSIONS</b>OSAS may produce harmful affect on the blood glucose and blood lipids in elderly hypertensive patients.</p>

Relationship between chronic congestive heart failure and sleep-disordered breathing in elderly patients / 南方医科大学学报

<p><b>OBJECTIVE</b>To determine the prevalence of sleep disordered breathing (SDB) in elderly patients with chronic congestive heart failure (CHF) and explore the relations between SDB and left ventricular function.</p><p><b>METHODS</b>By means of polysomnography, 56 elderly patients with CHF were divided into non-SDB, mild SDB, moderate SDB, and severe SDB groups, and the left ventricular ejection fraction (LVEF) was measure by (99)Tc equilibrium radionuclide angiography.</p><p><b>RESULTS</b>In the 56 elderly patients with CHF, 38 (67.9%) had SDB, including 12 (21.4%) mild SDB, 14 (25.0%) moderate SDB, and 12 (21.4%) severe SDB patients. Thirty (53.6%) of the 56 patients with CHF had obstructive sleep apnea (OSA), 4 (7.1%) had central sleep apnea and 22 (39.2%) had mixed sleep apnea. The moderate and severe SDB groups had lower minimum arterial oxyhemoglobin saturation during sleep than the non-SDB groups, and the apnea-hyponea index was closely related to LVEF (r=-0.74, P<0.01).</p><p><b>CONCLUSION</b>The prevalence of SDB, predominantly OSA, is high in elderly patients with CHF. Moderate and severe SDB might affect the left ventricular function in these patients, who require polysomnography monitoring.</p>

In vitro study of combination rhOPG-Fc and alendronate on inhibition osteoclast / 中华外科杂志

<p><b>OBJECTIVE</b>To study the effect of combination rhOPG-Fc and alendronate on mature osteoclasts.</p><p><b>METHODS</b>Recombinant human osteoprotegerin secretory expression in P. pastoris was performed. Osteoblasts were got from new born mouse skeletal bone and proved by ALP staining and incubated together with osteoclasts precursor cell line Raw 264.7 in 96 well plate. After 9 d, 10 micromol/L ALN, 10(-5) g/L rhOPG-Fc, 10 micromol/L ALN + 10(-5) g/L rhOPG-Fc, 5 micromol/L ALN + 5 x 10(-6) g/L rhOPG-Fc were added to these coculture systems. Osteoblasts cultured without the drugs mentioned above served as controls. TRAP stain positive cells counting and cortical bone pit formation counting were preformed in the following the 3rd and 7th d.</p><p><b>RESULTS</b>SDS-PAGE and Western blot showed that molecular weight of the expressed protein was about 55 KD, and it could reach specifically with anti-IgG antibody. Many multi-nuclear TRAP stain positive cells were found in the coculture control group after 9 d incubation, and proved to be mature osteoclasts by TRAP stain. In the 3rd and 7th d after the addition of rhOPG-Fc, ALN or both, TRAP stain positive cells counting and cortical bone pit formation counting decreased significantly in the rhOPG-Fc, ALN or both groups than in the control group, and the combine group (10(-5) g/L rhOPG-Fc + 10 micromol/L ALN) decreased most significantly when compared with rhopG-FC or ALN single.</p><p><b>CONCLUSIONS</b>rhOPG-Fc can decrease the number of osteoclasts and inhibit their function. The combination of both rhOPG-Fc and ALN shows the significant inhibition effect on mature osteoclasts.</p>