BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

N ⁶-methyladenosine (m⁶A) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass and obesity-associated protein (FTO), the first identified m⁶A demethylase, is critical for cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, and bioassay. As a result, two FTO inhibitors namely 18077 and 18097 were identified, which can selectively inhibit demethylase activity of FTO. Specifically, 18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells. In addition, 18097 reprogrammed the epi-transcriptome of breast cancer cells, particularly for genes related to P53 pathway. 18097 increased the abundance of m⁶A modification of suppressor of cytokine signaling 1 (SOCS1) mRNA, which recruited IGF2BP1 to increase mRNA stability of SOCS1 and subsequently activated the P53 signaling pathway. Further, 18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and C/EBPβ. Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer cells. Collectively, we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer.

AIM: To compare the consistency and feasibility of objective ocular torsion measured with GMPE module-based optical coherence tomography(OCT)and fundus color photography(FCP).METHODS: Patients were enrolled in our strabismus clinic from December 2020 to March 2021, and the objective ocular torsion of the eyes was measured by both GMPE module-based OCT and FCP on the same day. FCP was used to measure the fovea-disc angle(FDA)manually by using the Adobe Photoshop software, while the GMPE module-based OCT software positioned automatically the macula and the center of the optic disc to measure the FDA.RESULTS: Fifty-five patients were included, the FDA measured by OCT was -6.6°±4.5° in the right eye and -8.8°±4.7° in the left eye, respectively; The FDA measured by FCP was -6.6°±4.7° in the right eye and -8.4°±4.1° in the left eye, respectively, with no statistically significant difference between the results of the two methods(Pright eye=0.90, Pleft eye=0.08). In patients with exotropia, the FDA measured by OCT was -5.8°±4.9° in the right eye and -9.1°±4.5° in the left eye, respectively, the FDA measured by FCP was -5.7°±5.0° in the right eye and -8.6°±4.3° in the left eye, respectively,(Pright eye=0.75, Pleft eye=0.15). Similarly, the patients with esotropia, the FDA measured by OCT was -9.0°±7.3° in the right eye and -11.3°±3.5° in the left eye, respectively, while the FDA measured by FCP was -10.0°±7.0° in the right and -10.1°±2.8° in the left eye(Pright eye=0.21, Pleft eye=0.10), respectively. There were no significant differences between the two methods in patients with esotropia or exotropia(P>0.05). The results of both Pearson test and Bland-Altman analysis were highly correlated(rright eye=0.93, rleft eye=0.94, P<0.01). CONCLUSION: GMPE module-based OCT can be used for objective ocular torsion measurement with high reliability and reproducibility, and is a promising clinical alternative to the fundus color photographic method.

AIM:To investigate the correlation between corneal biomechanical parameters measured by the corneal visualization Scheimpflug Technology(Corvis ST)and corneal high-order aberrations(HOAs)in children with mild to moderate myopia.METHODS:A cross-sectional study. A total of 255 pediatric patients with myopia enrolled from April to July 2021 in Tianjin Medical University Eye Hospital were continuously collected, and all the right eyes were taken for analysis. Corneal biomechanical parameters were obtained from Corvis ST. Pentacam three-dimensional anterior segment analyzer was used to measure total corneal higher-order aberrations(RMSh), third order aberrations(RMS3)and fourth order aberrations(RMS4).RESULTS:RMS3 was positively correlated with the second applanation time(A2T)(r=0.175, P=0.009)and negatively correlated with the axis length(AL)(r=-0.155, P=0.014). RMS4 was negatively correlated with the highest concavity radius(HCR)(r=-0.165, P=0.009). RMSh was negatively correlated with HCR and AL(r=-0.152, P=0.037; r=-0.175, P=0.005).CONCLUSION:There is a correlation between corneal biomechanical parameters and HOAs in children with myopia. Cornea with higher stiffness and stronger deformation resistance has smaller RMS3, RMS4 and RMSh.

Objective:To investigate the relationship of triglyceride (TG), fasting blood glucose (FPG) and triglyceride glucose product index (TyG) with the incidence of hypertension, and provide basic data for the prevention and treatment of hypertension in the population.Methods:A total of 23 581 individuals who met the research criteria in Jinchang cohort were selected as the research subjects, the Cox proportional hazard model was used to analyze the relationship of TG, FPG, and TyG with the risk of hypertension. A stratified analysis was conducted by sex.Results:After adjusting for confounding factors, compared with the normal TG group, the HR(95% CI) of the elevated TG margin group and the elevated group were 1.16 (1.01-1.34) and 1.49 (1.30-1.70), respectively in the total population. Among men, they were 1.13 (1.01-1.27) and 1.17 (1.06-1.30), and among women, they were 1.05 (0.88-1.26) and 1.06 (0.88-1.28). Compared with the normal FPG group, the HR (95% CI) of the FPG-impaired group were 1.29 (1.13-1.48) in the total population, 1.26 (1.08-1.48) in men and 1.59 (1.14-2.21) in women. Taking the lowest quartile array as a reference, the HR (95% CI) of the highest quartile array of TyG was 1.73 (1.45-2.07) in the total population, 1.32 (1.14-1.53) in men and 1.87 (1.37-2.54) in women. TG, FPG had a nonlinear dose-response relationship with the risk of hypertension, while TyG had a linear correlation with the risk of hypertension. Conclusions:Higher TG, FPG, and TyG levels are independent risk factors for the incidence of hypertension. People with higher TG, FPG and TyG are at high risk for hypertension, to which close attention should be paid in the prevention and treatment of hypertension.

Objective:To explore the relationship between lipid indicators and the incidence of diabetes, and to compare the diabetes prediction and identification power of traditional lipid combined lipid indicators, in order to explore the best alternative indicators for identifying and predicting diabetes.Methods:Based on the Jinchang cohort, a nested case-control study was conducted in 1 025 new cases of diabetes after excluding patients with malignant tumor and related endocrine, circulatory system disease, then an age (±2 years), gender matched 1∶1 control group of 1 025 cases was set to analyze the relationship between the incidence of diabetes and lipid parameters.Results:Among the traditional lipid parameters, the fourth quartile of TG, TC, and LDL-C indicated higher risks of developing diabetes, which was 14.00 times (95% CI: 9.73-20.15), 2.15 times (95% CI: 1.65-2.79) and 1.66 times (95% CI: 1.29-2.14) than that of the first quartile, respectively. The risk of developing diabetes indicated by the fourth quartile of HDL-C was 0.21 times than that indicated by the first quartile (95% CI: 0.15-0.28). In the combined lipid parameters, the fourth quartile of TG/HDL-C, TC/HDL-C, LDL-C/HDL-C and non-HDL-C indicated higher risks of developing diabetes, which was 14.86 times (95% CI: 10.35-21.34), 8.12 times (95% CI: 5.94-11.01), 5.85 times (95% CI:4.34-7.88) and 5.20 times (95% CI: 3.85-7.03) than that indicated by the first quartile, respectively. The areas under the ROC curve of TG, TC, HDL-C, LDL-C, TG/HDL-C, TC/HDL-C, LDL-C/HDL-C and non-HDL-C were 0.76 (95% CI: 0.74-0.78), 0.59 (95% CI: 0.57-0.61), 0.67 (95% CI: 0.65-0.69), 0.57 (95% CI: 0.55-0.59), 0.77 (95% CI: 0.75-0.78), 0.73 (95% CI: 0.71-0.75), 0.69 (95% CI: 0.67-0.71) and 0.66 (95% CI: 0.64-0.68), respectively. The optimal diabetes predicting point cuts of TG, TC, HDL-C, LDL-C, TG/HDL-C, TC/HDL-C, LDL-C/HDL-C and non-HDL-C were 1.40, 4.70, 1.28, 3.25, 1.17, 3.43, 2.46, and 3.58 mmol/L, respectively. Conclusions:Lipid metabolic disorder is a risk factor for diabetes. TG and TG/HDL-C are the good lipid metabolism indicators for the prediction of diabetic.

Objective:To explore the relationship of body mass index and blood pressure with the incidence of diabetes in Jinchang cohort.Methods:We designed a nested case-control study, a total of 29 572 workers who had no history of diabetes in baseline survey in Jinchang cohort were selected as the study cohort from June 2011 to December 2013. After 2 year follow-up, 1 021 workers with first diagnosed diabetes were selected as the case group, after 1∶1 matching according to the same gender and age ±2 years among those without diabetes, circulatory system, or endocrine system diseases during the same follow-up period, 1 021 controls was selected and 2 042 subjects were finally included. We used multivariate conditional logistic regression model, additive interaction model and multiplicative interaction model to explore the relationship of body mass index and blood pressure with the incidence of diabetes.Results:After adjusting for factors such as occupation, alcohol use, family history of diabetes, hyperuricemia, hypercholesterolemia, hypertriglyceridemia, low-HDL cholesterolemia and high-LDL cholesterolemia, multivariate conditional logistic regression analysis showed that the risk of diabetes increased with body mass index and blood pressure. Hypertension and overweight/obesity had a multiplicative interaction on the incidence of diabetes. The risks of diabetes in men and women with hypertension and overweight/obese were 2.04 times (95% CI: 1.54-2.69) and 3.88 times (95% CI: 2.55-5.91) higher than those in men and women with normal body weight and blood pressure, respectively. In the combination of BMI and blood pressure, obese individuals with SBP≥160 mmHg were 4.57 times (95% CI: 2.50-8.34) more likely to have diabetes than those with normal BMI and SBP, obese individuals with DBP≥90 mmHg were 3.40 times (95% CI: 2.19-5.28) more likely to have diabetes than those with normal BMI and DBP. Conclusions:Overweight/obesity and hypertension can increase the risk of diabetes. Health education about body weight and blood pressure controls should be strengthened to reduce the risk of diabetes.

Emergencies refer to those events that cause serious social harm, including natural disasters and public health events, and require emergency response. Medical rescue team is the main emergency rescue team. While carrying out the rescue mission, they are under great pressure both physically and mentally due to the unadaptability of the rescue environment, the lack of protective materials, overwork and other reasons, often resulting in fear, tension, anxiety, pessimism, self-blame and even acute stress disorder. Without timely and effective psychological support, long-term psychological problems such as post-traumatic stress disorder will remain after the event. Comprehensive psychological support includes psychological measurement of the whole rescue process, team formation before rescue and detailed psychological support intervention training, self-relaxation during rescue, basic life and safety guarantee, drug treatment, online psychological assistance, withdrawal of stressors after rescue and lifestyle reconstruction.

By using multivariate statistical analysis to evaluate essential quality, and provide scientific basis for their comprehensive utilization, we established an UHPLC-QTRAP-MS/MS method for the fast, precise, efficient determination of 21 kinds of amino acids and 10 kinds of nucleosides in different species of Dendrobium. The analysis was performed on a Waters XBridge Amide column(2.1 mm×100 mm,3.5 μm) with elution by mobile phase of 0.2% formic acid in water-0.2% formic acid in acetonitrile at a flow rate of 0.2 mL·min~(-1) with the column temperature at 30 ℃. The target compounds were analyzed by the positive ion multiple reaction monitoring(MRM) mode. The comprehensive evaluation of different species of Dendrobium was carried out by PCA and TOPSIS analysis. All 21 kinds of amino acids and 10 nucleosides showed good linearity among certain concentration range(r>0.999), the RSDs of the stability, precision, and repeatability tests were less than 3.0%. The recovery rate was in the range from 93.31% to 107.5%, and RSD was in the range of 1.1%-3.7%. The comprehensive evaluation index obtained with PCA showed that D. huoshanense was significantly higher than others regarding amino acids and D. officinale has higher nucleosides than other species. The biggest C_i difference of TOPSIS was 68.7%, and comprehensive evaluation showed that D. huoshanense produced the highest comprehensive quality. The method is precise, fast and efficient and can provide reliable basis for further researches and intrinsic quality control of Dendrobium.
Amino Acids ; Chromatography, High Pressure Liquid ; Dendrobium ; Nucleosides ; Tandem Mass Spectrometry