Objective To compare the clinical outcomes of segmental pulmonary veins isolation (SPVI) and circumferential pulmonary veins ablation (CPVA) for patients with paroxysmal atrial fibrillation. Methods Sixty-eight patients with paroxysmal atrial fibrillation from January 2004 to April 2008 were divided into SPVI group (30 cases) and CPVA group (38 cases).The mean procedure time,the mean fluoroscopy time and relapse rate were compared. Results The mean procedure time in CPVA and SPVI group had no significant difference [(171.0 ± 25.8) min vs (168.2 ± 21.7) min, P = 0.579], but the mean fluoroscopy time in CPVA group [(38.5 ± 8.4) min]was less than that in SPVI group [(45.8 ± 16.1) min (P= 0.019). Mean term of the follow up was (17.1 ± 7.8) months. Relapse rate in CPVA group was less than that in SPVI group (5.3% vs 23.3%, P= 0.029). Both groups had no severe complications. Conclusion In patients with paroxysmal atrial fibrillation, CPVA strategy provides a more favourable clinical outcomes and less fluoroscopy time.

Objective:To investigate the short-term prognosis of patients with acute ischemic stroke after thrombolysis with alteplase and the relationship between TOAST and OCSP classification and prognosis of patients with acute ischemic stroke.Methods:A retrospective analysis was conducted in 193 patients with acute ischemic stroke in the Emergency Department of our hospital from January 2019 to June 2020, including 158 males and 85 females, aged 69.46±13.02 years. Among them, 66 patients were treated with alteplase thrombolysis and 127 patients were not treated with thrombolysis. The short-term prognosis of thrombolytic patients and non-thrombolytic patients were compared; the influence of TOAST classification and OCSP classification on the prognosis of acute ischemic stroke was analyzed.Results:There was no significant difference in the length of hospital stay between the thrombolytic group and the non-thrombolytic group ( P>0.05), while the improvement rate of NIHSS score, GCS score, and mRS score were significantly different at admission and discharge ( P<0.05). According to TOAST classification, 78 cases (40.41%) were LAA, 100 cases (51.81%) were SAO, 9 cases (4.66%) were CE, 3 cases (1.55%) were SOE, and 3 cases (1.55%) were SUE; SAO type accounted for the highest proportion (51.81%), the improvement rate of NIHSS score at admission and discharge was significantly different from that of the LAA patients ( P<0.05), and the short-term prognosis was the best. According to OCSP classification, 39 cases (20.21%) were LACI, 64 cases (33.16%) were PACI, 55 cases (28.50%) were POCI, 35 cases (18.13%) were TACI, among which the PACI patients had the highest proportion, while the improvement rate of NIHSS score in the LACI patients was significantly different at admission and discharge compared with other types of patietns ( P<0.05), and the short-term prognosis was good. Conclusions:The short-term prognosis and symptom improvement of patients with acute ischemic stroke after alteplase thrombolytic therapy are obvious. TOAST classification and OCSP classification have certain prediction effects and play clinical reference roles on the short-term prognosis of patients with acute ischemic stroke.

Objective:To investigate the effect of venous blood carbon dioxide binding capacity (CO 2-CP) on the short-term prognosis of patients with acute ischemic stroke (AIS) after thrombolytic therapy. Methods:A total of 86 AIS inpatients who received thrombolytic therapy in the emergency department of Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University from April 2019 to May 2021 were analyzed retrospectively. According to the venous blood CO 2-CP levels at admission, the patients were divided into two groups: low CO 2-CP group (CO 2-CP < 23 mmol/L, n = 52) and high CO 2-CP group (CO 2-CP ≥ 23 mmol/L, n = 34). The CO 2-CP levels and changes between the two groups before and after thrombolytic therapy were compared. The National Institutes of Health Stroke scale (NIHSS) score was used to evaluate the improvement rate of patients after thrombolytic therapy [NIHSS score at admission-NIHSS score at discharge)/NIHSS score at admission ×100%] and in-hospital death was also recorded. The correlation between CO 2-CP levels and prognosis of patients with AIS during emergency visit was analyzed, the receiver operator characteristic curve (ROC curve) was drawn and the area under the ROC curve (AUC) was calculated to evaluate the predictive value of CO 2-CP in the prognosis of AIS patients. Results:The CO 2-CP levels of low CO 2-CP group and high CO 2-CP group after thrombolytic therapy were significantly higher than those before treatment (mmol/L: 23.08±2.34 vs. 20.46±1.51, 25.24±2.16 vs. 23.94±1.07, both P < 0.05). The differences of CO 2-CP before and after treatment in low CO 2-CP group were significantly higher than those in high CO 2-CP group (mmol/L: 2.62±0.83 vs. 1.30±1.09, P < 0.05). The improvement rate of CO 2-CP levels in the high CO 2-CP group (NIHSS improvement rate > 45%) was significantly higher than that in the low CO 2-CP group [85.29% (29/34) vs. 23.08% (12/52)], while the mortality in the low CO 2-CP group was significantly higher than that in the high CO 2-CP group [11.54% (6/52) vs. 0% (0/34), P < 0.05]. The AUC of CO 2-CP for the prognosis of patients with AIS thrombolysis was 0.820, the 95% confidence interval (95% CI) was 0.727-0.924, P = 0.000 1. Conclusion:AIS patients with CO 2-CP levels less than 23 mmol/L have a poor short-term prognosis, which has certain predictive and clinical reference value for choosing thrombolytic time in emergency stroke patients.

Sulfonylureas are widely used oral anti-diabetic drugs. However, its long-term usage effects on patients' lifespan remain controversial, with no reports of influence on animal longevity. Hence, the anti-aging effects of chlorpropamide along with glimepiride, glibenclamide, and tolbutamide were studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K⁺ (mitoK-ATP) channels and mitochondrial complex II. Chlorpropamide delayed aging in Caenorhabditis elegans, human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and mice. In addition, the mitochondrial membrane potential and ATP levels were significantly increased in chlorpropamide-treated worms, which is consistent with the function of its reported targets, mitoK-ATP channels. Increased levels of mitochondrial reactive oxygen species (mtROS) were observed in chlorpropamide-treated worms. Moreover, the lifespan extension by chlorpropamide required complex II and increased mtROS levels, indicating that chlorpropamide acts on complex II directly or indirectly via mitoK-ATP to increase the production of mtROS as a pro-longevity signal. This study provides mechanistic insight into the anti-aging effects of sulfonylureas in C. elegans.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reapproved for heart failure (HF) therapy in patients with and without diabetes. However, the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice. A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect. To address this issue, we conducted structural repurposing of EMPA, a representative SGLT2 inhibitor, to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2. Compared to EMPA, the optimal derivative JX01, which was produced by methylation of C2-OH of the glucose ring, exhibited weaker SGLT2-inhibitory activity (IC₅₀ > 100 nmol/L), and lower glycosuria and glucose-lowering side-effect, better NHE1-inhibitory activity and cardioprotective effect in HF mice. Furthermore, JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity, and good pharmacokinetic properties in both mouse and rat species. Collectively, the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs, and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.