Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

OBJECTIVE: Pneumoconiosis, a lung disease caused by irreversible fibrosis, represents a significant public health burden. This study investigates the causal relationships between gut microbiota, gene methylation, gene expression, protein levels, and pneumoconiosis using a multi-omics approach and Mendelian randomization (MR). METHODS: We analyzed gut microbiota data from MiBioGen and Esteban et al. to assess their potential causal effects on pneumoconiosis subtypes (asbestosis, silicosis, and inorganic pneumoconiosis) using conventional and summary-data-based MR (SMR). Gene methylation and expression data from Genotype-Tissue Expression and eQTLGen, along with protein level data from deCODE and UK Biobank Pharma Proteomics Project, were examined in relation to pneumoconiosis data from FinnGen. To validate our findings, we assessed self-measured gut flora from a pneumoconiosis cohort and performed fine mapping, drug prediction, molecular docking, and Phenome-Wide Association Studies to explore relevant phenotypes of key genes. RESULTS: Three core gut microorganisms were identified: Romboutsia ( OR = 0.249) as a protective factor against silicosis, Pasteurellaceae ( OR = 3.207) and Haemophilus parainfluenzae ( OR = 2.343) as risk factors for inorganic pneumoconiosis. Additionally, mapping and quantitative trait loci analyses revealed that the genes VIM, STX8, and MIF were significantly associated with pneumoconiosis risk. CONCLUSIONS This multi-omics study highlights the associations between gut microbiota and key genes ( VIM, STX8, MIF) with pneumoconiosis, offering insights into potential therapeutic targets and personalized treatment strategies.
Humans ; Male ; East Asian People/genetics* ; Europe ; Gastrointestinal Microbiome ; Lung ; Macrophage Migration-Inhibitory Factors/metabolism* ; Mendelian Randomization Analysis ; Multiomics ; Pneumoconiosis/microbiology* ; Intramolecular Oxidoreductases

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

Objective:To explore the value of pre-ablation stimulated thyroglobulin (psTg) before 131I treatment combined with lymph node ratio (LNR) in predicting 131I treatment response in patients with papillary thyroid cancer (PTC). Methods:From January 2016 to December 2018, 178 PTC patients (47 males, 131 females; age (43.2±12.6) years) treated with 131I in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. According to 131I treatment response, patients were divided into excellent response (ER) group and non-ER group. The clinical data of the two groups were compared by χ2 test, independent-sample t test and Mann-Whitney U test. The cut-off values and AUCs of psTg and LNR to predict treatment response were calculated according to the ROC curve. Factors affecting 131I treatment response were analyzed by logistic multivariate regression analysis. Results:There were 118 patients (66.3%, 118/178) in ER group and 60 patients (33.7%, 60/178) in non-ER group, and there were significant differences in N stage ( χ2=11.15, P=0.004), 131I treatment dose ( χ2=12.65, P<0.001), American Thyroid Association (ATA) initial risk stratification ( χ2=15.25, P<0.001), number of metastatic lymph nodes ( χ2=22.63, P<0.001), LNR ( U=1 506.00, P<0.001) and psTg ( U=919.00, P<0.001) between the two groups. The cut-off values of psTg and LNR predicting ER were 3.97 μg/L and 0.29, with the AUC of 0.870 and 0.787 respectively. PsTg (odds ratio ( OR)=10.88, 95% CI: 4.67-25.36, P<0.001) and LNR ( OR=5.30, 95% CI: 1.85-15.23, P=0.002) were independent factors to predict 131I treatment response in PTC patients. When psTg≥3.97 μg/L, LNR ( OR=9.40, 95% CI: 2.06-42.92, P=0.004) was an independent factor affecting 131I treatment response in PTC patients. Conclusions:PsTg and LNR are independent factors affecting 131I treatment response in PTC patients. When psTg≥3.97 μg/L, LNR can be used as a supplementary factor to predict 131I treatment response. The combination of psTg and LNR can better predict 131I treatment response in PTC patients.

Objective: To quantitatively assess the pulmonary vasculature using non-contrast computed tomography (CT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) pre- and post-treatment and correlate CT-based parameters with right heart catheterization (RHC) hemodynamic and clinical parameters. Materials and Methods: A total of 30 patients with CTEPH (mean age, 57.9 years; 53% female) who received multimodal treatment, including riociguat for ≥ 16 weeks with or without balloon pulmonary angioplasty and underwent both noncontrast CT for pulmonary vasculature analysis and RHC pre- and post-treatment were included. The radiographic analysis included subpleural perfusion parameters, including blood volume in small vessels with a cross-sectional area ≤ 5 mm 2 (BV5) and total blood vessel volume (TBV) in the lungs. The RHC parameters included mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac index (CI). Clinical parameters included the World Health Organization (WHO) functional class and 6-minute walking distance (6MWD). Results: The number, area, and density of the subpleural small vessels increased after treatment by 35.7% (P < 0.001), 13.3% (P = 0.028), and 39.3% (P < 0.001), respectively. The blood volume shifted from larger to smaller vessels, as indicated by an 11.3% increase in the BV5/TBV ratio (P = 0.042). The BV5/TBV ratio was negatively correlated with PVR (r = -0.26; P = 0.035) and positively correlated with CI (r = 0.33; P = 0.009). The percent change across treatment in the BV5/TBV ratio correlated with the percent change in mPAP (r = -0.56; P = 0.001), PVR (r = -0.64; P < 0.001), and CI (r = 0.28; P = 0.049).Furthermore, the BV5/TBV ratio was inversely associated with the WHO functional classes I–IV (P = 0.004) and positively associated with 6MWD (P = 0.013). Conclusion Non-contrast CT measures could quantitatively assess changes in the pulmonary vasculature in response to treatment and were correlated with hemodynamic and clinical parameters.

Objective To design a mobile intelligent inventory system for medical equipment to solve the problems of medical equipment management in efficiency and accuracy due to manual inventory.Methods A mobile intelligent inventory system for medical equipment was designed with radio frequency identification(RFID)technology,optical character recognition technology and wireless network technology,which was composed of a photo acquisition device,an inventory workstation,a wireless router,a mobile cart,a RFID barcode printer and a mobile power source.The photo acquisition device realized equipment image collection with a photography App in the cell phone or tablet computer;the inventory workstation consisted of an offline inventory system and an equipment nameplate recognition system,which built inventory tasks with Tomcat Web service and identified equipment nameplate information through feature-based learning algorithms;the RFID barcode printer controlled label printing by an offline inventory system embedded into its driver.Results The system developed executed medical equipment inventory and labeling simultaneously,which established electronic file for each piece of equipment to realize accounts corresponding to the equipment accurately.Conclusion The inventory system developed enhances the efficiency of medical equipment inventory,standardizes the flow of medical equipment ledger management and provides support for life-cycle management of medical equipment.[Chinese Medical Equipment Journal,2023,44(11):45-49]

Dexmedetomidine is an α2 adrenoceptor agonist and has cardioprotective effect,the mechanism of which is being studied.Increasing studies have proved the clinical value of dexmedetomidine in reducing postoperative complications and improving the prognosis of patients.Therefore,this review summarizes the cardiac protection mechanism of dexmedetomidine based on the existing studies and expounds the application of dexmedetomidine in the perioperative period of cardiovascular surgery.
Dexmedetomidine/therapeutic use* ; Heart ; Humans

Objective:To explore the predictive value of preablative stimulated thyroglobulin (psTg) level before 131I treatment on the excellent response (ER) to 131I treatment in patients with functional residual lymph node metastasis without distant metastasis after papillary thyroid carcinoma (PTC) surgery. Methods:From March 2011 to June 2015, 72 patients (22 males, 50 females, age: 14-76 (46.5±14.4) years) who were diagnosed with functional lymph node metastasis without distant metastasis at the time of their first 131I treatment after total thyroid bilobectomy + lymph node dissection performed in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively included, and their serum thyroglobulin antibody (TgAb) levels were normal. Patients were divided into ER group and non-ER group according to the treatment response assessment system. Independent sample t test, χ2 test, and Mann-Whitney U test were used to compare the basic clinical characteristics between the two groups, and then multivariate logistic regression was performed. The ROC curve was employed to evaluate the predictive value of psTg and lymph node size in 131I treatment response. Results:The treatment responses of 44 patients were ER, and those of 28 were non-ER. The differences in gender, age, clinical stage, number and location of postoperative metastatic lymph nodes between ER and non-ER groups were not statistically significant ( t=0.82, χ2 values: 0.16-2.60, all P>0.05), while there were significant differences in American Thyroid Association (ATA) initial risk stratification ( χ2=33.38), lymph node size ( U=296.50) and psTg ( U=111.00, all P<0.001). PsTg (odds ratio ( OR)=0.047, 95% CI: 0.004-0.500, P=0.011) and lymph node size ( OR=0.146, 95% CI: 0.032-0.666, P=0.013) were independent factors affecting ER, whereas ATA initial risk stratification was not an independent factor ( OR=0.266, 95% CI: 0.051-1.390, P=0.116). AUCs for psTg and lymph node size were 0.904 and 0.873, respectively. The cut-off value of psTg was 20.05 μg/L with the sensitivity and specificity of 96.4%(27/28) and 75.0%(33/44) respectively, and lymph node size was 0.75 cm with the sensitivity and specificity of 78.6% (22/28) and 81.8% (36/44) respectively. Conclusion:PsTg can be used to predict 131I outcomes in patients with functional lymph node metastases after PTC, and lymph node size also has effect on ER.

Objective: To evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) with the novel Prizvalve^® system in treating severe aortic stenosis. Methods: This is a single-center, prospective, single-arm, observational study. A total of 11 patients with severe aortic stenosis with high risk or inappropriate for conventional surgical aortic valve replacement (SAVR) were included, and TAVI was achieved with the Prizvalve^® system between March 2021 and May 2021 in West China Hospital. Transthoracic echocardiography (TTE) was performed immediately after prosthesis implantation to evaluate mean transaortic gradient and maximal transaortic velocity. The device success rate was calculated, which was defined as (1) the device being delivered via the access, deployed, implanted and withdrawn, (2) mean transaortic gradient<20 mmHg (1 mmHg=0.133 kPa) or a maximal transaortic velocity<3 m/s post TAVI, and without severe aortic regurgitation or paravalvular leak post TAVI. TTE was performed at 30 days after the surgery, and all-cause mortality as well as the major cardiovascular adverse events (including acute myocardial infarction, disabling hemorrhagic or ischemic stroke) up to 30 days post TAVI were analyzed. Results: The age of 11 included patients were (78.1±6.3) years, with 8 males. A total of 10 patients were with NYHA functional class Ⅲ or Ⅳ. Devices were delivered via the access, deployed, implanted and withdrawn successfully in all patients. Post-implant mean transaortic gradient was (7.55±4.08) mmHg and maximal transaortic velocity was (1.78±0.44) m/s, and both decreased significantly as compared to baseline levels (both P<0.05). No severe aortic regurgitation or paravalvular leak was observed post TAVI. Device success was achieved in all the 11 patients. No patient died or experienced major cardiovascular adverse events up to 30 days post TAVI. Mean transaortic gradient was (9.45±5.07) mmHg and maximal transaortic velocity was (2.05±0.42) m/s at 30 days post TAVI, which were similar as the values measured immediately post TAVI (both P>0.05). Conclusions: TAVI with the Prizvalve^® system is a feasible and relatively safe procedure for patients with severe aortic stenosis and at high risk or inappropriate for SAVR. Further clinical studies could be launched to obtain more clinical experience with Prizvalve^® system.
Aged ; Aged, 80 and over ; Aortic Valve ; Aortic Valve Stenosis/surgery* ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation ; Humans ; Male ; Prospective Studies ; Transcatheter Aortic Valve Replacement/methods* ; Treatment Outcome

Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; Humans ; Transcatheter Aortic Valve Replacement