COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies

Objective To explore the association between arachidonic acid(AA)metabolism and cervical cancer(CC),to provide new ideas for metabolic therapies for CC.Methods The activity and migration ability of CC cells after AA intervention were detected by CCK-8 assay and cell scratch assay,respectively.Bioinformatics analysis was performed using GEPIA 2 and GSCA databases to study the correlation between key enzymes of AA metabolism(COX2,ALOX15)and the progression,prognosis,pathway activation,and tumor immunity of CC.The mRNA expression of inflammatory factors interleukin-6(IL-6),monocyte chemoattractant protein-1(MCP-1),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),cyclooxygenase 2(COX2),and arachidonic acid lipoxygenase 15(ALOX15)were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results A A at 5μmol/ml significantly promoted the growth of CC cells(t=7.672,P=0.0166)and increased the relative cell migration rate by 30％at the same concentration(t=6.672,P=0.0026).And the expression levels of inflammatory factors also showed significant differences(P＜0.05).Further bioinformatics analysis revealed that the expression levels of key enzymes of AA metabolism,COX2 and ALOX15,were significantly up-regulated in CC(P＜0.05),which also different in different stages and increased the risk of poor prognosis in patients.Among them,COX2 may accelerate the progression of CC by decreasing the level of tyrosine kinase metabolism and exacerbating DNA damage,and ALOX15 may form a tumor inflammatory environment by increasing the degree of infiltration of resting CD8+T cells and B lymphocytes.Conclusion AA metabolism promotes the proliferation and migration of CC cells and induces changes in the tumor inflam-matory microenvironment,in which its metabolic key enzymes,COX2 and ALOX15,may play an important role.

Objective:To assess the efficacy of neoadjuvant treatment with PD-1 (programmed cell death protein 1) inhibitors combined with paclitaxel (albumin-conjugated) and cisplatin (TP regimen) for locally advanced hypopharyngeal squamous cell carcinoma and laryngeal organ function preservation.Methods:Data of 53 patients, including 51 males and 2 females, aged 38-70 years old, who were diagnosed with locally advanced hypopharyngeal squamous carcinoma confirmed by histology and enhanced CT at the Cancer Prevention and Control Center of Sun Yat-sen University during the initial treatment from January 1, 2019 to January 15, 2023, were retrospectively analyzed. All patients received neoadjuvant therapy with PD-1 inhibitors combined with albumin-bound paclitaxel (260 mg/m 2) and cisplatin (60 mg/m 2) for 3 to 4 cycles. The main outcome measures were larynx dysfunction-free survival (LDFS), overall survival (OS), and progression-free survival (PFS). Survival curves were plotted using the Kaplan-Meier method, and Cox multifactorial analysis was further performed if Cox univariate analysis was statistically significant. Results:The overall efficiency was 90.6% (48/53). The 1-year and 2-year LDFS rates were 83.8% (95% CI: 74.0% to 94.8%) and 50.3% (95% CI: 22.1% to 91.6%), the 1-year and 2-year OS rates were 95.2% (95% CI: 88.9% to 100.0%) and 58.2% (95% CI: 25.6% to 81.8%), and the 1-year and 2-year PFS rates were 83.9% (95% CI: 74.2% to 94.9%) and 53.5% (95% CI: 32.1% to 89.1%). Adverse events associated with the neoadjuvant therapy were mainly myelosuppression (45.3%), gastrointestinal reactions (37.7%) and hypothyroidism (20.8%). Conclusion:The neoadjuvant treatment of locally advanced hypopharyngeal squamous cell carcinoma using PD-1 inhibitors combined with paclitaxel and cisplatin can provide with a higher survival rate with a improved laryngeal organ function preservation rate.

Objective To explore the association between arachidonic acid(AA)metabolism and cervical cancer(CC),to provide new ideas for metabolic therapies for CC.Methods The activity and migration ability of CC cells after AA intervention were detected by CCK-8 assay and cell scratch assay,respectively.Bioinformatics analysis was performed using GEPIA 2 and GSCA databases to study the correlation between key enzymes of AA metabolism(COX2,ALOX15)and the progression,prognosis,pathway activation,and tumor immunity of CC.The mRNA expression of inflammatory factors interleukin-6(IL-6),monocyte chemoattractant protein-1(MCP-1),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),cyclooxygenase 2(COX2),and arachidonic acid lipoxygenase 15(ALOX15)were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results A A at 5μmol/ml significantly promoted the growth of CC cells(t=7.672,P=0.0166)and increased the relative cell migration rate by 30％at the same concentration(t=6.672,P=0.0026).And the expression levels of inflammatory factors also showed significant differences(P＜0.05).Further bioinformatics analysis revealed that the expression levels of key enzymes of AA metabolism,COX2 and ALOX15,were significantly up-regulated in CC(P＜0.05),which also different in different stages and increased the risk of poor prognosis in patients.Among them,COX2 may accelerate the progression of CC by decreasing the level of tyrosine kinase metabolism and exacerbating DNA damage,and ALOX15 may form a tumor inflammatory environment by increasing the degree of infiltration of resting CD8+T cells and B lymphocytes.Conclusion AA metabolism promotes the proliferation and migration of CC cells and induces changes in the tumor inflam-matory microenvironment,in which its metabolic key enzymes,COX2 and ALOX15,may play an important role.

OBJECTIVES: Intracerebral hemorrhage (ICH) has the highest mortality and disability rates among various subtypes of stroke. Previous studies have shown that the gut microbiome (GM) is closely related to the risk factors and pathological basis of ICH. This study aims to explore the causal effect of GM on ICH and the potential mechanisms. METHODS: Genome wide association study (GWAS) data on GM and ICH were obtained from Microbiome Genome and International Stroke Genetics Consortium. Based on the GWAS data, we first performed Mendelian randomization (MR) analysis to evaluate the causal association between GM and ICH. Then, a conditional false discovery rate (cFDR) method was conducted to identify the pleiotropic variants. RESULTS: MR analysis showed that Pasteurellales, Pasteurellaceae, and Haemophilus were negatively correlated with the risk of ICH, whileVerrucomicrobiae, Verrucomicrobiales, Verrucomicrobiaceae, Akkermansia, Holdemanella, and LachnospiraceaeUCG010 were positively correlated with ICH. By applying the cFDR method, 3 pleiotropic loci (rs331083, rs4315115, and rs12553325) were found to be associated with both GM and ICH. CONCLUSIONS There is a causal association and pleiotropic variants between GM and ICH.
Humans ; Genome-Wide Association Study ; Gastrointestinal Microbiome/genetics* ; Genetic Predisposition to Disease ; Cerebral Hemorrhage/genetics* ; Stroke

As the focus of public health work in the world, diabetic foot disease has aroused high public concern. This paper introduces the application of the diabetic foot wearable monitoring equipment types, including plantar pressure monitoring, temperature monitoring, monitoring of the biomechanics and multimode monitoring, and wearable devices application status in patients with diabetes, puts forward the existing problems and prospect, in order to carry out domestic related to diabetic foot wearable monitoring equipment research to provide the reference.

Objective To evaluate therapeutic effects of dihydrotanshinone Ⅰ on hepatic fibrosis based on liver metabolomics method. Methods 28 rats were randomly divided into four groups including control group, hepatic fibrosis model group and dihydrotanshinone Ⅰ low dose group and dihydrotanshinone Ⅰ high dose group. The dihydrotanshinone Ⅰ treated groups received dihydrotanshinone Ⅰ for 28 days. The rat liver samples were collected and analyzed by liquid chromatography-mass spectrometer (LC-MS). The OPLS-DA pattern recognition analysis of metabolomics differences among the groups and therapeutic effects of dihydrotanshinone Ⅰ on hepatic fibrosis were evaluated. Results 38 metabolites were identified through liver metabolomics analysis. The possible mechanism of hepatic fibrosis was mainly involved glutathione metabolism, melatonin metabolism, amino acid metabolism, lipid metabolism and TCA cycle. The hepatic fibrosis induced by TAA was reversed by dihydrotanshinone Ⅰ. Conclusion Dihydrotanshinone Ⅰ provided satisfactory therapeutical effects on hepatic fibrosis through partially regulating the perturbed glutathione metabolism, melatonin metabolism, amino acid metabolism, lipid metabolism, TCA cycle.

Objective:To investigate the prognostic significance of D-dimer level in patients with diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 70 newly diagnosed DLBCL patients who were admitted to Tianjin People's Hospital from January 2015 to June 2019 were retrospectively analyzed. The optimal cut-off value of D-dimer for survival was determined according to the receiver operating characteristic (ROC) curve, and the patients were grouped. The differences of coagulation related indexes and clinicopathological features between patients with different D-dimer levels were compared. Kaplan-Meier method was used for univariate analysis of overall survival (OS), and Cox regression model was used for multivariate analysis of OS.Results:According to ROC curve, the best cut-off value of D-dimer for survival was 0.75 mg/L. The proportion of patients with different clinical staging, international prognostic index score, lactate dehydrogenase level had statistically significant differences between the D-dimer ≥0.75 mg/L group (36 cases) and <0.75 mg/L group (34 cases) (all P < 0.05). The prothrombin time of D-dimer ≥ 0.75 mg/L group and < 0.75 mg/L group were (13.5±0.9) s and (13.0±0.8) s, respectively, and the activated partial thromboplastin time were (37±5) s and (34±6) s, respectively,and the differences were statistically significant (all P < 0.05). Univariate analysis showed that the 5-year OS rates of DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ, international prognostic index score > 2, lactate dehydrogenase level > 240 U/L, B symptoms, D-dimer level ≥0.75 mg/L were decreased (all P < 0.05). Multivariate Cox regression analysis showed that D-dimer ≥0.75 mg/L was an independent risk factor for OS of DLBCL patients ( HR=0.368, 95% CI 0.144-0.944, P= 0.038). Conclusion:The level of D-dimer can be used as a clinical indicator to judge the prognosis of DLBCL patients, and the prognosis of patients with high D-dimer level is poor.

Objective To identify the blood components of Fuzheng Huayu capsule by ultra performance liquid chromatography-high resolution time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Methods ACQUITY UPLCHSS T3 (2.1 mm × 100 mm, 1.8 μm) was used to chromatographic separation; mobile phase was 0.1% formic acid aqueous solution (A) −0.1% formic acid acetonitrile solution (B). The gradient elution conditions included: 0−3 min, 2% B; 3−18 min, 2%−50% B; 18−22 min, 50%−95% B; 22−25 min, 95% B. The equilibration time was 10 min, the flow rate was 0.40 ml/min, and the analysis time was 25 min. The mass spectrometry was characterized by electrospray ionization by a positive-negative ion mode scan with a range of 100-1 100 m/z. Results 49 components were identified in the serum samples at one time, of which 4 were positive and negative ion modes. Conclusion The blood components of Fuzheng Huayu capsule were clarified by this method, which enriched the scientific connotation of Fuzheng Huayu capsule, and laid the foundation for the in-depth study of the compound.