ObjectiveAs a second messenger in intracellular signal transduction, Ca²⁺ plays an important role in cell migration. Previous studies have demonstrated that extracellular Ca²⁺ influx can promote electric field-guided cell migration, known as electrotaxis. However, the effect of intracellular Ca²⁺ flow on electrotaxis is unclear. Therefore, in this study, we investigate the effect of Ca²⁺ flux on the electrotaxis of Dictyostelium discoideum. MethodsThe electrotaxis of Dictyostelium discoideum was investigated by applying a direct current (DC) electric field. Cell migration was recorded using a real-time imaging system. Calcium channel inhibitors, the extracellular Ca²⁺ chelator EGTA, Ca²⁺-free DB buffer, and caffeine were applied to investigate the impact of intra- and extracellular Ca²⁺ flow on electrotaxis. The involvement of G proteins and ERK2 in directed cell migration mediated by endoplasmic reticulum Ca²⁺ release was explored using mutants. ResultsDictyostelium discoideum migrated toward the cathode in the electric field in a voltage-dependent manner. The intracellular Ca²⁺ concentration of the cells was significantly increased in the electric field. Inhibition of both extracellular Ca²⁺ influx and intracellular Ca²⁺ release suppressed cell electrotaxis migration. Inhibition of endoplasmic reticulum Ca²⁺ release induced by caffeine significantly impaired the electrotaxis of Dictyostelium discoideum. Deletion of Gα2, Gβ, Gγ, and Erk2 notably reduced the electrotaxis of the cells. Enhancing Ca²⁺ release mediated by caffeine restored the electrotaxis of the Gα2^-, Gβ ^-, and Erk2^- mutant cells partially or completely, but did not restore electrotaxis in the Gγ^- mutant cells. ConclusionCa²⁺ release from the endoplasmic reticulum regulates electrotaxis migration in Dictyostelium discoideum and is involved in the regulation of cell electrotaxis by G proteins and ERK2.

ObjectiveTo explore the pathological mechanism-syndrome-treatment patterns of approved Chinese patent medicines （CPMs） that treat collateral disorders， providing a reference for the principle of "treating different diseases with the same therapy" in collateral pathology. MethodsCPMs that apply treatment strategies based on collateral disorders were identified from the Pharmacodia database by extracting information from the "efficacy" or "indications" sections of drug package inserts. A database was established to extract the names and compositions of the CPMs， as well as their indications， related traditional Chinese medicine （TCM） symptoms， disease locations （affected areas）， and pathological factors. Frequency statistics were performed. Using the Apriori algorithm， an association rule analysis was conducted on CPMs and disease-location combinations related to the top three most frequent pathological factor combinations. Core formulas for these combinations were identified and analyzed through drug network analysis and MCODE module clustering. ResultsA total of 660 CPMs targeting collateral disorders were retrieved， involving 299 indications， 323 TCM symptoms， 21 disease locations， 19 pathological factors， and 124 pathological factor combinations. The most frequent pathological factor combinations were blood stasis （involved in 109 CPMs， 16.52%）， exogenous wind （外风） -cold-dampness （involved in 43 CPMs， 6.52%）， and qi deficiency-blood stasis （involved in 42 CPMs， 6.36%）. Analysis of the core formulas for these combinations revealed common ingredients such as Honghua （Carthami Flos）， Chuanxiong （Chuanxiong Rhizoma）， Danggui （Angelicae Sinensis Radix）， and Dilong （Pheretima）. ConclusionCollateral disorders involve a wide range of pathogenesis and represent a fundamental mechanism in the onset and development of various diseases， characterized by obstruction and stagnation. The primary therapeutic principle is unblocking of the collaterals. Blood stasis obstructing the collaterals is the core pathological basis， and the strategy of activating blood circulation and resolving stasis to unblock the collaterals should be central to the treatment. The core medication pattern involves combining blood-activating and stasis-resolving herbs with insect-derived medicinals that unblock collaterals. Exogenous wind is often the initiating patholo-gical factor in colla-teral disorders， and the appropriate addition of wind-dispelling herbs can enrich the treatment strategies for such conditions.

This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

Objective: There is controversy among different guidelines regarding the use of thermal ablation to treat clinical T1a renal cell carcinomas with tumor sizes ranging from 3.1–4 cm. Therefore, we compared oncological outcomes between heat-based thermal ablation (hTA) and cryoablation (CA) in patients with solid T1a renal cell carcinomas, including those with a tumor size ≤3 cm and a tumor size of 3.1–4 cm. Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2000–2019), we identified patients with clinical T1a renal cell carcinomas that were histologically confirmed and treated with hTA or CA. After propensity score matching using a 1:1 ratio, the overall survival (OS) and cancer-specific survival (CSS) were estimated and compared between the two methods. Cancer-specific mortality (CSM) was also analyzed, considering other-cause mortality as a competing risk. Results: Of the 3513 assessable patients, 1426 (40.6%) and 2087 (59.4%) were treated with hTA and CA, respectively. After propensity score matching, the hTA and CA groups included 1393 and 1393 patients, respectively. hTA was associated with shorter OS than CA with a hazard ratio of 1.17 (95% confidence interval, 1.04–1.32; P = 0.010). The hTA and CA groups did not reveal statistically significant differences in CSS with a hazard ratio of 1.07 (95% confidence interval, 0.76–1.50; P = 0.706). The hTA and CA groups did not show statistically significant differences in CSM (P = 0.849). However, the hTA group showed a significantly higher other-cause mortality (P = 0.011). Conclusion In patients with clinical stage T1a renal cell carcinomas, hTA was comparable to CA in terms of CSS and CSM.However, hTA resulted in a slightly shorter OS than CA. Large-scale randomized clinical trials are required to obtain more robust evidence.

Objective: There is controversy among different guidelines regarding the use of thermal ablation to treat clinical T1a renal cell carcinomas with tumor sizes ranging from 3.1–4 cm. Therefore, we compared oncological outcomes between heat-based thermal ablation (hTA) and cryoablation (CA) in patients with solid T1a renal cell carcinomas, including those with a tumor size ≤3 cm and a tumor size of 3.1–4 cm. Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2000–2019), we identified patients with clinical T1a renal cell carcinomas that were histologically confirmed and treated with hTA or CA. After propensity score matching using a 1:1 ratio, the overall survival (OS) and cancer-specific survival (CSS) were estimated and compared between the two methods. Cancer-specific mortality (CSM) was also analyzed, considering other-cause mortality as a competing risk. Results: Of the 3513 assessable patients, 1426 (40.6%) and 2087 (59.4%) were treated with hTA and CA, respectively. After propensity score matching, the hTA and CA groups included 1393 and 1393 patients, respectively. hTA was associated with shorter OS than CA with a hazard ratio of 1.17 (95% confidence interval, 1.04–1.32; P = 0.010). The hTA and CA groups did not reveal statistically significant differences in CSS with a hazard ratio of 1.07 (95% confidence interval, 0.76–1.50; P = 0.706). The hTA and CA groups did not show statistically significant differences in CSM (P = 0.849). However, the hTA group showed a significantly higher other-cause mortality (P = 0.011). Conclusion In patients with clinical stage T1a renal cell carcinomas, hTA was comparable to CA in terms of CSS and CSM.However, hTA resulted in a slightly shorter OS than CA. Large-scale randomized clinical trials are required to obtain more robust evidence.

Objective: There is controversy among different guidelines regarding the use of thermal ablation to treat clinical T1a renal cell carcinomas with tumor sizes ranging from 3.1–4 cm. Therefore, we compared oncological outcomes between heat-based thermal ablation (hTA) and cryoablation (CA) in patients with solid T1a renal cell carcinomas, including those with a tumor size ≤3 cm and a tumor size of 3.1–4 cm. Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2000–2019), we identified patients with clinical T1a renal cell carcinomas that were histologically confirmed and treated with hTA or CA. After propensity score matching using a 1:1 ratio, the overall survival (OS) and cancer-specific survival (CSS) were estimated and compared between the two methods. Cancer-specific mortality (CSM) was also analyzed, considering other-cause mortality as a competing risk. Results: Of the 3513 assessable patients, 1426 (40.6%) and 2087 (59.4%) were treated with hTA and CA, respectively. After propensity score matching, the hTA and CA groups included 1393 and 1393 patients, respectively. hTA was associated with shorter OS than CA with a hazard ratio of 1.17 (95% confidence interval, 1.04–1.32; P = 0.010). The hTA and CA groups did not reveal statistically significant differences in CSS with a hazard ratio of 1.07 (95% confidence interval, 0.76–1.50; P = 0.706). The hTA and CA groups did not show statistically significant differences in CSM (P = 0.849). However, the hTA group showed a significantly higher other-cause mortality (P = 0.011). Conclusion In patients with clinical stage T1a renal cell carcinomas, hTA was comparable to CA in terms of CSS and CSM.However, hTA resulted in a slightly shorter OS than CA. Large-scale randomized clinical trials are required to obtain more robust evidence.

Objective: There is controversy among different guidelines regarding the use of thermal ablation to treat clinical T1a renal cell carcinomas with tumor sizes ranging from 3.1–4 cm. Therefore, we compared oncological outcomes between heat-based thermal ablation (hTA) and cryoablation (CA) in patients with solid T1a renal cell carcinomas, including those with a tumor size ≤3 cm and a tumor size of 3.1–4 cm. Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2000–2019), we identified patients with clinical T1a renal cell carcinomas that were histologically confirmed and treated with hTA or CA. After propensity score matching using a 1:1 ratio, the overall survival (OS) and cancer-specific survival (CSS) were estimated and compared between the two methods. Cancer-specific mortality (CSM) was also analyzed, considering other-cause mortality as a competing risk. Results: Of the 3513 assessable patients, 1426 (40.6%) and 2087 (59.4%) were treated with hTA and CA, respectively. After propensity score matching, the hTA and CA groups included 1393 and 1393 patients, respectively. hTA was associated with shorter OS than CA with a hazard ratio of 1.17 (95% confidence interval, 1.04–1.32; P = 0.010). The hTA and CA groups did not reveal statistically significant differences in CSS with a hazard ratio of 1.07 (95% confidence interval, 0.76–1.50; P = 0.706). The hTA and CA groups did not show statistically significant differences in CSM (P = 0.849). However, the hTA group showed a significantly higher other-cause mortality (P = 0.011). Conclusion In patients with clinical stage T1a renal cell carcinomas, hTA was comparable to CA in terms of CSS and CSM.However, hTA resulted in a slightly shorter OS than CA. Large-scale randomized clinical trials are required to obtain more robust evidence.

Objective: There is controversy among different guidelines regarding the use of thermal ablation to treat clinical T1a renal cell carcinomas with tumor sizes ranging from 3.1–4 cm. Therefore, we compared oncological outcomes between heat-based thermal ablation (hTA) and cryoablation (CA) in patients with solid T1a renal cell carcinomas, including those with a tumor size ≤3 cm and a tumor size of 3.1–4 cm. Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2000–2019), we identified patients with clinical T1a renal cell carcinomas that were histologically confirmed and treated with hTA or CA. After propensity score matching using a 1:1 ratio, the overall survival (OS) and cancer-specific survival (CSS) were estimated and compared between the two methods. Cancer-specific mortality (CSM) was also analyzed, considering other-cause mortality as a competing risk. Results: Of the 3513 assessable patients, 1426 (40.6%) and 2087 (59.4%) were treated with hTA and CA, respectively. After propensity score matching, the hTA and CA groups included 1393 and 1393 patients, respectively. hTA was associated with shorter OS than CA with a hazard ratio of 1.17 (95% confidence interval, 1.04–1.32; P = 0.010). The hTA and CA groups did not reveal statistically significant differences in CSS with a hazard ratio of 1.07 (95% confidence interval, 0.76–1.50; P = 0.706). The hTA and CA groups did not show statistically significant differences in CSM (P = 0.849). However, the hTA group showed a significantly higher other-cause mortality (P = 0.011). Conclusion In patients with clinical stage T1a renal cell carcinomas, hTA was comparable to CA in terms of CSS and CSM.However, hTA resulted in a slightly shorter OS than CA. Large-scale randomized clinical trials are required to obtain more robust evidence.

OBJECTIVE: To investigate the optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) requiring complex percutaneous coronary intervention (PCI). METHODS: A total of 2403 patients with DM who underwent complex PCI from January to December 2013 were consecutively enrolled in this observational cohort study and divided according to DAPT duration into a standard group (11-13 months, n = 689) and two prolonged groups (13-24 months, n = 1133; > 24 months, n = 581). RESULTS: Baseline characteristics, angiographic findings, and complexity of PCI were comparable regardless of DAPT duration. The incidence of major adverse cardiac and cerebrovascular event was lower when DAPT was 13-24 months than when it was 11-13 months or > 24 months (4.6% vs. 8.1% vs. 6.0%, P = 0.008), as was the incidence of all-cause death (1.9% vs. 4.6% vs. 2.2%, P = 0.002) and cardiac death (1.0% vs. 3.0% vs. 1.2%, P = 0.002). After adjustment for confounders, DAPT for 13-24 months was associated with a lower risk of major adverse cardiac and cerebrovascular event [hazard ratio (HR) = 0.544, 95% CI: 0.373-0.795] and all-cause death (HR = 0.605, 95% CI: 0.387-0.944). DAPT for > 24 months was associated with a lower risk of all-cause death (HR = 0.681, 95% CI: 0.493-0.942) and cardiac death (HR = 0.620, 95% CI: 0.403-0.952). The risk of major bleeding was not increased by prolonging DAPT to 13-24 months (HR = 1.356, 95% CI: 0.766-2.401) or > 24 months (HR = 0.967, 95% CI: 0.682-1.371). CONCLUSIONS For patients with DM undergoing complex PCI, prolonging DAPT might improve the long-term prognosis by reducing the risk of adverse ischemic events without increasing the bleeding risk.