RNA-binding protein AZGP1 inhibits epithelial cell proliferation by regulating the genes of alternative splicing in COPD.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by high morbidity, disability, and mortality rates worldwide. RNA-binding proteins (RBPs) might regulate genes involved in oxidative stress and inflammation in COPD patients. Single-cell transcriptome sequencing (scRNA-seq) offers an accurate tool for identifying intercellular heterogeneity and the diversity of immune cells. However, the role of RBPs in the regulation of various cells, especially AT2 cells, remains elusive. MATERIALS AND METHODS: A scRNA-seq dataset (GSE173896) and a bulk RNA-seq dataset acquired from airway tissues (GSE124180) were employed for data mining. Next, RNA-seq analysis was performed in both COPD and control patients. Differentially expressed genes (DEGs) were identified using criteria of fold change (FC ≥ 1.5 or ≤ 1.5) and P value ≤ 0.05. Lastly, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and alternative splicing identification analyses were carried out. RESULTS: RBP genes exhibited specific expression patterns across different cell groups and participated in cell proliferation and mitochondrial dysfunction in AT2 cells. As an RBP, AZGP1 expression was upregulated in both the scRNA-seq and RNA-seq datasets. It might potentially be a candidate immune biomarker that regulates COPD progression by modulating AT2 cell proliferation and adhesion by regulating the expression of SAMD5, DNER, DPYSL3, GBP5, GBP3, and KCNJ2. Moreover, AZGP1 regulated alternative splicing events in COPD, particularly DDAH1 and SFRP1, holding significant implications in COPD. CONCLUSION: RBP gene AZGP1 inhibits epithelial cell proliferation by regulating genes participating in alternative splicing in COPD.

Supplementation with stigma maydis polysaccharide attenuates autism-like behaviors and improves gut function in valproic acid-induced autism model male rats.

Stigma maydis polysaccharide (SMPS) has regulatory effect on the intestinal microflora and promotes gastrointestinal peristalsis. Children with autism spectrum disorder (ASD) often experience gastrointestinal problems and dysbiosis in their gut microbiota. Our previous study revealed that SMPS interventions had an impact on the gut microbiota of valproic acid (VPA)-induced autism model rats. However, the effects of SMPS on the behavior and gut function of autism model rats remain poorly understood. Therefore, we gave different doses of SMPS intervention in the early stage of autism model rats to observe their developmental conditions and behavior performances. Through histological evaluation and real-time polymerase chain reaction (PCR), integrity of the intestinal structure and the expression of tight junction-related gene Zo-1 and Occludin were detected. The results indicated that SMPS intervention improved the physical development, learning and memory impairment, and social performance of autism model rats. Meanwhile, SMPS promoted intestinal peristalsis and restored the integrity of the intestinal structure, reduced the number of inflammatory cells, and increased the expression of the Zo-1 and Occludin genes. Furthermore, the expression levels of neurotransmitters (substance P, enkephalin, vasoactive intestinal peptide, and 5-hydroxytryptamine) in the hippocampal tissues were altered after SMPS treatment. In conclusion, SMPS could ameliorate ASD-like phenotypes and gut problems in autism model rats. Collectively, these results provide new evidence for the relationship between the gut-brain axis and ASD and suggest a novel therapeutic target for ASD treatment.

Comparative dosimetric study of h-IMRT and VMAT plans for breast cancer after breast-conserving surgery.

AIM: To compare the dosimetric advantages and disadvantages between hybrid intensity-modulated radiation therapy (h-IMRT) and the volumetric modulated arc therapy (VMAT) technique in hypofractionated whole-breast irradiation (HF-WBI) for early-stage breast cancer (BC). METHODS: The dose distribution of h-IMRT and VMAT plans was compared in 20 breast cancer patients. This comparison included evaluation of dosimetric parameters using dose volume histograms (DVHs) for the planning target volume (PTV) and organs-at-risk (OARs). Additionally, the study examined the normal tissue complication probability (NTCP), the second cancer complication probability (SCCP) and the tumor control probability (TCP) based on different models. RESULTS: Significant differences were detected between the two plans, in terms of Machine units (MUs), the control points, 95 % volume (V95 %), dose homogeneity index (DHI) and conformity index (CI). The endpoint of grade II radiation pneumonitis and cardiac death due to ischemic heart disease were assessed. In h-IMRT plan, the NTCP values were marginally lower for radiation pneumonitis and slightly higher for cardiac death compared to VMAT plan, as determined by the Lyman-Kutcher-Burman model. The Schneider model was employed to predict the SCCP for both the bilateral lungs and contralateral breast, the results demonstrate that the h-IMRT plan outperforms the VMAT plan, with statistical significance. Additionally, the LQ-Poisson model was employed to forecast the TCP of the PTV, showing that the h-IMRT plan outperformed the VMAT plan (P > 0.05). CONCLUSION: The h-IMRT technique, offering superior dose coverage and better therapeutic efficacy with fewer side effects as calculated by models, is more suitable for HF-WBI compared to the VMAT technique.

Dapagliflozin: A sodium-glucose cotransporter 2 inhibitor, attenuates angiotensin II-induced atrial fibrillation by regulating atrial electrical and structural remodeling.

AIM: Atrial fibrillation (AF), the most common arrhythmia, is characterized by atrial electrical and structural remodeling. Previous studies have found that sodium-glucose cotransporter 2 inhibitor (SGLT2i) can protect myocardium in a glucose independent mechanism. But the role of SGLT2i in regulating AF remains largely unknown. This study, we aimed to investigate the effect of Dapagliflozin (DAPA) in reducing AF susceptibility via inhibiting electrical and structural remodeling. METHOD: The mouse model was established by Angiotensin II (2000 ng/kg/min) infusion for 3 weeks, and an in vitro model was generated by stimulating HL-1 and primary mouse fibroblast with Ang II (1 µM) for 24 h. Programmed electrical stimulation, ECG and whole-cell patch clamp were used to detect DAPA effect on atrial electrical remodeling induced by Ang II. To observe DAPA effect on atrial structural remodeling induced by Ang II, we used echocardiographic, H&E and Masson staining to evaluate atrial dilation. To further explore the protective mechanism of DAPA, we adopt in silico molecular docking approaches to investigate the binding affinity of Ang II and CaMKII at Met-281 site. Western blot was to detect expression level of CaMKII, ox-CaMKII, Nav1.5, Kv4.3, Kv4.2, Kchip2, Kir2.1 and Cx40. RESULTS: Ang II induced AF, atrial dilatation and fibrosis, led to atrial electrical and structural remodeling. However, these effects were markedly abrogated by DAPA treatment, a specific SGLT2i. Our observation of atrial electrical activity in mice revealed that DAPA could rescue the prolonged action potential duration (APD) and the abnormal currents of IK1, Ito and INaL triggered by Ang II infusion. DAPA could reduce the binding affinity of Ang II and CaMKII at Met-281 site, which indicated that DAPA may directly alleviate the activation of CaMKII caused by Ang II. DAPA could reduce the upregulation of ox-CaMKII caused by Ang II infusion in atrial tissues. Moreover, DAPA also ameliorated the aberrant expression levels of electrical activity related proteins (Nav1.5, Kv4.3, Kv4.2, Kchip2, Kir2.1 and Cx40) and fibrosis related signal pathways (TGF-ß1, p-smad/smad) caused by Ang II. Furthermore, we confirmed that DAPA, as well as other SGLT2i (EMPA, CANA), could reverse these abnormalities caused by Ang II incubation in HL-1 cells and primary mouse fibroblasts, respectively. CONCLUSION: Overall, our study identifies DAPA, a widely used SGLT2i, contributes to inhibiting Ang II-induced ox-CaMKII upregulation and electrical and structural remodeling to reduce AF susceptibility, suggesting that DAPA may be a potential therapy of treating AF.

Comparison of bio-beads combined with Pseudomonas edaphica and three phosphate materials for lead immobilization: Performance, mechanism and plant growth.

Phosphate materials (PMs) combine with phosphate solubilizing bacteria play an essential roles in lead (Pb) immobilization, but their resulting ability to reduce Pb bioavailability may vary depending on PMs used. In this study, Pseudomonas edaphica GAU-665 and three PMs: tricalcium phosphate, calcium phytate and nano-hydroxyapatite were respectively encapsulated into bio-beads by sodium alginate, which immobilization efficiency of Pb2+ were 99.11%, 97.76% and 99.02% at initial Pb2+ concentration of 200 mg L-1, respectively. The Pb2+ immobilization performance of bio-beads under different conditions and their organic acids secreted were examined. Most Pb2+ was immobilized by bio-beads through combined functions of adsorption, precipitation, ion exchange and biomineralization, accompanied by the formation of more stable compounds such as Pb3(PO4)2, Pb5(PO4)3OH and Pb5(PO4)3Cl. Meanwhile, pot experimental results indicated that the inoculation of CPhy (calcium phytate) bio-beads with PSB have highest biomass and root growth of oat (Avena sativa L.) in Pb-stressed compared with CK, which increased the content of chlorophyll b (167.51%) in shoot. In addition, the CPhy bio-beads enhance the peroxidase, catalase activities and reduce the malondialdehyde content to alleviating lead physiological toxicity in oat, which reductions the Pb accumulation in shoot (52.06%) and root (81.04%), and increased the residual fraction of Pb by 165.80% in soil. These findings suggest the bio-beads combined with P. edaphica GAU-665 and calcium phytate is an efficient Pb immobilization material and provided feasible way to improve safety agricultural production and Pb-contaminated soil remediation.

Kaempferol attenuates inflammation in lipopolysaccharide-induced gallbladder epithelial cells by inhibiting the MAPK/NF-κB signaling pathway.

Kaempferol (KPR), a flavonoid compound found in various plants and foods, has garnered attention for its anti-inflammatory, antioxidant, and anticancer properties. In preliminary studies, KPR can modulate several signaling pathways involved in inflammation, making it a candidate for treating cholecystitis. This study aimed to explore the effects and mechanisms of KPR on lipopolysaccharide (LPS)-induced human gallbladder epithelial cells (HGBECs). To assess the impact of KPR on HGBECs, the HGBECs were divided into control, KPR, LPS, LPS + KPR, and LPS + UDCA groups. Cell viability and cytotoxicity were evaluated by MTT assay and lactate dehydrogenase (LDH) assay, respectively, and concentrations of KPR (10-200 µM) were tested. LPS-induced inflammatory responses in HGBECs were to create an in vitro model of cholecystitis. The key inflammatory markers (IL-1ß, IL-6, and TNF-α) levels were quantified using ELISA, The modulation of the MAPK/NF-κB signaling pathway was measured by western blot using specific antibodies against pathway components (p-IκBα, IκBα, p-p65, p65, p-JNK, JNK, p-ERK, ERK, p-p38, and p38). The cell viability and LDH levels in HGBECs were not significantly affected by 50 µM KPR, thus it was selected as the optimal KPR intervention concentration. KPR increased the viability of LPS-induced HGBECs. Additionally, KPR inhibited the inflammatory factors level (IL-1ß, IL-6, and TNF-α) and protein expression (iNOS and COX-2) in LPS-induced HGBECs. Furthermore, KPR reversed LPS-induced elevation of p-IκBα/IκBα, p-p65/p65, p-JNK/JNK, p-ERK/ERK, and p-p38/p38 ratios. KPR attenuates the LPS-induced inflammatory response in HGBECs, possibly by inhibiting MAPK/NF-κB signaling.

Administration of USP7 inhibitor p22077 alleviates Angiotensin II (Ang II)-induced atrial fibrillation in Mice.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is an important contributor to mortality and morbidity. Ubquitin-specific protease 7 (USP7), one of the most abundant ubiquitin-specific proteases (USP), participated in many cellular events, such as cell proliferation, apoptosis, and tumourigenesis. However, its role in AF remains unknown. Here, the mice were treated with Ang II infusion to induce the AF model. Echocardiography was used to measure the atrial diameter. Electrical stimulation was programmed to measure the induction and duration of AF. The changes in atrial remodeling were measured using routine histologic analysis. Here, a significant increase in USP7 expression was observed in Ang II-stimulated atrial cardiomyocytes and atrial tissues, as well as in atrial tissues from patients with AF. The administration of p22077, the inhibitor of USP7, attenuated Ang II-induced inducibility and duration of AF, atrial dilatation, connexin dysfunction, atrial fibrosis, atrial inflammation, and atrial oxidase stress, and then inhibited the progression of AF. Mechanistically, the administration of p22077 alleviated Ang II-induced activation of TGF-ß/Smad2, NF-κB/NLRP3, NADPH oxidases (NOX2 and NOX4) signals, the up-regulation of CX43, ox-CaMKII, CaMKII, Kir2.1, and down-regulation of SERCA2a. Together, this study, for the first time, suggests that USP7 is a critical driver of AF and revealing USP7 may present a new target for atrial fibrillation therapeutic strategies.

Comparing tocilizumab biosimilar BAT1806/BIIB800 with reference tocilizumab in patients with moderate-to-severe rheumatoid arthritis with an inadequate response to methotrexate: a phase 3, randomised, multicentre, double-blind, active-controlled clinical trial.

BACKGROUND: Biosimilars provide an opportunity to address unmet medical need by expanding access to biological treatments. This study aimed to show equivalent efficacy, and comparable safety, immunogenicity, and pharmacokinetic profiles of a proposed tocilizumab biosimilar BAT1806/BIIB800, to reference tocilizumab, in participants with rheumatoid arthritis with an inadequate response to methotrexate. METHODS: This phase 3, multicentre, randomised, double-blind, active-controlled, equivalence study comprised a 24-week initial treatment period (results reported here) and a 24-week secondary treatment period. Participants were recruited at 54 centres across five countries (China, Ukraine, Poland, Georgia, and Bulgaria). Patients with active rheumatoid arthritis with an inadequate response to methotrexate were randomly assigned (1:1:2) to receive reference tocilizumab up to week 48, or reference tocilizumab up to week 24 followed by BAT1806/BIIB800 up to week 48 (the two reference tocilizumab groups were analysed as a single group in this analysis), or BAT1806/BIIB800 up to week 48 (the BAT1806/BIIB800 group), administered by intravenous infusion once every 4 weeks at a starting dose of 8 mg/kg. The primary endpoint was the proportion of participants who had a 20% improvement in American College of Rheumatology criteria (ACR20) at week 12 (for the European Medicines Agency [EMA]) or week 24 (for the US Food and Drug Administration [FDA] and China National Medical Products Administration [NMPA]) using prespecified equivalence margins (95% CI -14·5 to +14·5 [EMA], 90% CI -12·0 to +15·0 [FDA], and 95% CI -13·6 to +13·6 [NMPA]). The International Council for Harmonisation E9(R1) estimand framework, with strategies for addressing intercurrent events, was implemented for the efficacy evaluations with expected differences as per the predefined equivalence margins. This trial is registered at ClinicalTrials.gov (NCT03830203) and EudraCT (2018-002202-31), and is closed to new participants. FINDINGS: Between Dec 19, 2018, and Jan 5, 2021, we randomly assigned 621 participants: 309 to the reference tocilizumab group and 312 to the BAT1806/BIIB800 group. The mean age was 50·5 years (SD 12·0), 534 (86%) were women, 87 (14%) were men, and 368 (59%) were White. For the primary estimands, estimated ACR20 response rates were 64·8% in the reference tocilizumab group and 69·0% in the BAT1806/BIIB800 group (treatment difference 4·1% [95% CI -3·6 to 11·9]) at week 12, and 67·9% in the reference tocilizumab group and 69·9% in the BAT1806/BIIB800 group (treatment difference 1·9% [90% CI -4·0 to 7·9; 95% CI -5·2 to 9·1]) at week 24. All confidence intervals were contained within the predefined equivalence margins. Comparable pharmacokinetic and immunogenicity profiles were observed for the reference tocilizumab and BAT1806/BIIB800 groups. Adverse events were reported by 201 (65%) participants in the reference tocilizumab group and 206 (66%) in the BAT1806/BIIB800 group; 196 (63%) participants in the reference tocilizumab group and 201 (64%) participants in the BAT1806/BIIB800 group reported a treatment-emergent adverse event. Five participants had a fatal event (reference tocilizumab n=1; BAT1806/BIIB800 n=4). INTERPRETATION: BAT1806/BIIB800 showed equivalent efficacy, and comparable safety, immunogenicity, and pharmacokinetic profiles as reference tocilizumab. FUNDING: Bio-Thera Solutions and Biogen.

Refining prediction of stroke in sinus node dysfunction patients without atrial fibrillation using a P-combined score: a multi-centre study.

AIMS: Isolated sinus node dysfunction (ISND) is a sinus node dysfunction without atrial fibrillation. A high risk of ischaemic stroke (IS) has been reported in ISND populations. However, current guidelines do not recommend anticoagulation in ISND management. P-wave indicates ISND-related atrial remodelling. P-wave indices and the CHA2DS2-VASc score may contribute to risk stratification for ISND-related IS. METHODS AND RESULTS: In this multi-centre longitudinal cohort, ISND patients were divided into development (n = 1185) and external validation (n = 988) cohorts. Ischaemic stroke prediction capacity of the P-combined score was assessed with regard to discrimination, calibration, and clinical effectiveness. The cut-off value of the score was confirmed by using a restricted cubic spline curve. One hundred and twenty-four (10.46%) ISND patients developed IS [1.63%/year; 95% confidence interval (CI): 1.49-1.78%/year] after a median 3.02-year follow-up in the development cohort. The P-wave terminal force in electrocardiogram-lead V1 (PTFV1) was the only significantly abnormal P-wave index (adjusted hazard ratio: 2.56; 95% CI: 1.72-3.80). Therefore, we incorporated the PTFV1 with the CHA2DS2-VASc score to generate a P-combined score. For a 5-year IS risk, the P-combined score improved Harrell's C-statistic (95% CI) from 0.678 (0.618-0.738) to 0.716 (0.657-0.774) and 0.747 (0.677-0.816) to 0.808 (0.747-0.868) in the development and validation cohorts, respectively, along with calibration and decision curve analyses. The cut-off value of the score was 3 in the development cohort and well-discriminated in the validation cohort. CONCLUSION: Chinese ISND patients have a higher IS risk than the general population. Compared with the CHA2DS2-VASc score, the PTFV1-combined CHA2DS2-VASc score shows a better risk-stratification capacity for ISND-related IS.

By screening the risk factors of ischaemic stroke for isolated sinus node dysfunction (sinus node dysfunction without atrial fibrillation), we developed and validated a new scoring system­P-combined score, which is a combination of an abnormal P-wave terminal force in electrocardiogram-lead V1 (PTFV1) and the CHA2DS2-VASc score. We constructed the P-combined score in the following way: abnormal PTFV1 (2 points), age (1 point for 65­74 years and 2 points for ≥75 years), sex (1 point for female), congestive heart failure (1 point), hypertension (1 point), diabetes mellitus (1 point), vascular disease (1 point), and thrombotic event (2 points). Based on our analysis, we found that the P-combined score showed a strong performance (with a C-statistic of 0.716 for 5 years), which was better than the CHA2DS2-VASc score (C-statistic of 0.678 for 5 years). We also found that the performance of the P-combined score was rigorous in an independent cohort from two external centres (with a C-statistic of 0.808 for 5 years) and outperformed the CHA2DS2-VASc score (C-statistic of 0.747 for 5 years).

Patterns of Anticoagulation Use and All-Cause of Mortality in Cancer Patients with Atrial Fibrillation.

BACKGROUND: There is uncertainty regarding the clinical benefit of anticoagulant (AC) treatment in patients with cancer with atrial fibrillation (AF). We aimed to evaluate the distribution and patterns of AC use and its impact on all-cause mortality in cancer patients with AF. METHODS: A total of 1,653 patients with cancer diagnosed with AF were included in this retrospective cohort analysis. Multivariable logistic regression was applied to identify the clinical predictors of anticoagulant prescription. Kaplan-Meier curve with a log-rank test was used to compare the probability of survival between the AC and non-AC groups. Multivariate Cox proportional hazard regression models were implemented to evaluate the influences of various variables on all-cause death. RESULTS: Of 1,653 patients with cancer with AF, 971 (58.7%) did not receive a prescription for AC. Among patients with CHA2DS2-VASC ≥2 in men or ≥3 in women and HAS-BLED <3, 56.5% were not prescribed AC. Rivaroxaban and warfarin are more frequently used than dabigatran, mainly in patients with lung and breast cancer. Over a median follow-up of 36 months, 776 deaths were identified. The Kaplan-Meier curve suggested that patients with AC prescriptions had better clinical outcomes. On multivariate Cox proportional risk regression analysis, AC prescription was significantly associated with a lower risk of all-cause mortality (hazard ratio, 0.78; 95% confidence interval, 0.66-0.91; P = 0.002). CONCLUSIONS: The prescription of anticoagulants in patients with cancer with AF was suboptimal. AC prescription at discharge was associated with a decreased risk of all-cause mortality. IMPACT: This study highlights the importance of AC prescriptions in patients with cancer with AF.

Sinus node dysfunction and stroke risk: a systematic review and meta-analysis.

OBJECTIVES: The role of cardiac arrhythmia in ischaemic stroke is widely studied, but the size of the stroke risk in patients with sinus node dysfunction (SND) with and without atrial fibrillation (AF) is unclear. This systematic review and meta-analysis aimed to compare the risk of stroke and its associated factors in patients with SND with and without AF. DESIGN: A systematic review and meta-analysis was conducted based on the Grading of Recommendations, Assessment, Development and Evaluation approach. DATA SOURCES: PubMed, EMBASE and Cochrane Database were searched until December 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies that investigate stroke in patients with SND diagnosed with or without AF/atrial flutter. DATA EXTRACTION AND SYNTHESIS: Two independent authors screened studies for inclusion and extracted data. Literature quality assessment was performed using the Newcastle-Ottawa Scale and the Cochrane Collaboration Tool. The overall risk of stroke was estimated using the random-effects model. The generic inverse variance method was used to calculate the pooled estimates of stroke-associated factors. We performed a sensitivity analysis using a fixed-effects model. RESULTS: Of the 929 records retrieved, 6 papers (106 163 patients) met the inclusion criteria. The average yearly stroke incidence in patients with SND was 1.542% (95% CI: 1.334% to 1.749%). The stroke incidence was similar between the isolated SND (1.587%; 95% CI: 1.510% to 1.664%) and non-isolated (SND+AF) (1.660%; 95% CI: 0.705% to 2.615%) groups. AF (HR, 95% CI: 1.53 (1.01 to 2.33)), stroke/transient ischaemia attack/other thrombotic events (HR, 95% CI: 2.54 (1.14 to 5.69)), hypertension (HR, 95% CI: 1.51 (1.11 to 2.07)) and heart failure (HR, 95% CI: 1.41 (1.01 to 1.97)) were associated with stroke in the SND population. CONCLUSION: Our findings suggest that patients with SND carry a similar risk of stroke to those with combined SND and AF. Future studies are needed to investigate whether interventions targeting stroke prevention, such as anticoagulation therapy, can help to prevent stroke in patients with SND. PROSPERO REGISTRATION NUMBER: CRD42023408436.

Effect of Astragali radix extract on pharmacokinetic behavior of dapagliflozin in healthy and type 2 diabetic rats.

Objective: This study aimed to investigate effect of antidiabetic herb Astragali Radix (AR) on pharmacokinetic behavior of dapagliflozin (DAPA) in healthy rats and type 2 diabetes mellitus (T2DM) rats. Methods: The T2DM rats were induced by high-fat diet (HFD) and intraperitoneal injection of streptozotocin (STZ). Concentrations of DAPA in healthy and T2DM rat plasma were determined by UPLC-MS/MS method. Effect of AR extract (ARE) on pharmacokinetic behavior of DAPA in healthy and T2DM rats was evaluated, respectively. Results: The diabetes status and co-administrated with ARE significantly affected pharmacokinetic behaviors of DAPA in the rats. Compared to that in healthy rats, t max of DAPA significantly shortened, its C max significantly increased in T2DM rats, and its t 1/2, V, AUC, CL and MRT kept unchanged. When ARE was co-administrated with DAPA, C max of DAPA significantly increased, its t max and MRT significantly decreased, and its t 1/2, V, AUC and CL kept unchanged in healthy rats. t max and C max of DAPA significantly decreased, its t 1/2 and V significantly increased, and its AUC, CL and MRT were unchanged in T2DM rats when ARE was co-administrated with DAPA. Co-administration of DAPA and ARE promoted absorptive rate of DAPA, increased its extravascular tissue distribution, and prolonged its duration of action. ARE did not cause accumulation of DAPA in vivo. Conclusion: Both disease status of T2DM and co-administration of ARE affect pharmacokinetic behavior of DAPA in vivo. Potential pharmacokinetic interactions may occur in vivo when herbs and drugs are co-administrated, which may affect efficacy and safety of drugs.

Enhanced Goos-Hänchen shift in a defective Pell quasiperiodic photonic crystal with monolayer MoS2.

Monolayer M o S 2 has attracted wide attention because of its finite bandgap, and it has become a potential candidate for the investigation of the Goos-Hänchen (GH) shift. However, the magnitude of the GH shift in free-standing monolayer M o S 2 is small, which greatly hinders its possible applications in the photoelectric sensors and detectors. We have theoretically designed a defective quasiperiodic photonic crystal and investigated its GH shift, where monolayer M o S 2 is sandwiched between two quasiperiodic photonic crystals arranged by the Pell sequence. By optimizing the thicknesses of all the components and the period number of the Pell quasiperiodic photonic crystal, we find that the GH shift of the designed structure is significantly enhanced at the specific working wavelength. In addition, we discuss the influence of the thicknesses of the dielectric components on the GH shift. Our work confirms that the quasiperiodic photonic crystal structure has the ability to enhance the GH shift of monolayer transition metal dichalcogenides, which provides a new platform for the GH investigations and greatly promotes the applications of this defective structure in optoelectric devices.

Arterial stiffness is associated with cancer mortality: Insight from Kailuan study.

BACKGROUND: There is limited evidence on the association between arterial stenosis and the risk of all-cause mortality in cancer patients (ACMC). This study investigated whether the status of arterial function and structure measured by brachial-ankle pulse wave velocity (baPWV) is associated with ACMC. METHODS: A total of 43,943 Chinese adults underwent a baPWV examination. Cox proportional hazards model was used to assess the association between the baPWV values and ACMC. RESULTS: During a total follow-up duration of 3.81 ± 2.50 years, there were 157 deaths among 553 cancer cases diagnosed during the follow-up. Patients with baPWV ≥18 m/s showed an increased risk of ACMC compared to patients with ideal vascular function. In the multivariate-adjusted model, we observed a significant association between arterial stiffness severity and ACMC with a hazard ratio (HR) 2.72 (95% confidence interval [CI]: 1.55-4.80; p < 0.001) in those with baPWV ≥18 m/s. With a 1-SD increase in baPWV, the HR (95% CI) for ACMC in the entire cohort, men, and patients ≤60 years old were 1.20 (95% CI: 1.03-1.41; p < 0.05), 1.20 (95% CI: 1.01-1.43; p < 0.05), and 1.44 (95% CI: 1.10-1.44; p = 0.008), respectively. CONCLUSIONS: Increased arterial stiffness measured by baPWV is associated with ACMC. The association between high baPWV (≥18 m/s) and risk of all-cause mortality was prominent in men and those ≤60 years of age.

The relationship between circadian rhythm of blood pressure and vascular dysfunction in essential hypertension.

OBJECTIVE: This study aimed to explore whether circadian rhythm of blood pressure is associated with brachial-ankle pulse wave velocity (baPWV) and brachial artery flow-mediated dilation (FMD) in patients with essential hypertension. METHOD: This cross-sectional study included 4,217 patients with essential hypertension who completed 24-hour ambulatory blood pressure monitoring, baPWV, and FMD. BaPWV and FMD were measured to evaluate arterial stiffness and endothelial dysfunction. Participants were divided into dipper, non-dipper, and reverse dipping groups according to the nocturnal systolic blood pressure dipping percentage. RESULTS: In this study, baPWV was highest in the reverse dipping groups, followed by non-dipper and dipper groups (1667.11 ± 327.90 vs. 1613.88 ± 325.11 vs. 1577.45 ± 306.15 cm/s, P < .001) and FMD gradually increased (4.41 ± 2.87 vs. 4.70 ± 2.84 vs. 4.92 ± 2.79%, P = .001). baPWV and FMD were significantly associated with declining nocturnal systolic blood pressure (SBP). Interestingly, FMD (ß = 0.042, P = .014) was only positively associated with a drop in nocturnal SBP decline in patients <65 years of age. Whereas baPWV was consistently negatively associated with nocturnal SBP decline regardless of age (ß = -0.065, P < .001, age <65 years; ß = -0.149, P = .002, age ≥ 65). Receiver operating characteristics (ROC) curves analysis showed areas under the curve (AUC) of baPWV/FMD for predicting circadian rhythm of blood pressure are 0.562/0.554 with a sensitivity of 51.7%/53.9% and specificity of 56.4%/53.4. CONCLUSION: Impairment of baPWV and FMD were correlated with abnormal circadian rhythm of blood pressure in essential hypertension, suggesting a decrease in nighttime SBP may associate with endothelial function and arterial stiffness.

Early atrial remodeling predicts the risk of cardiovascular events in patients with metabolic syndrome: a retrospective cohort study.

Background: This study aims to assess the prevalence of atrial cardiomyopathy (ACM) in patients with new-onset metabolic syndrome (MetS) and investigate whether ACM could be a predictor of hospital admission for cardiovascular (CV) events. Methods: Patients with MetS who were free of clinically proven atrial fibrillation and other CV diseases (CVDs) at baseline were included in the present study. The prevalence of ACM was compared between MetS patients with and without left ventricular hypertrophy (LVH). The time to first hospital admission for a CV event between subgroups was assessed using the Cox proportional hazard model. Results: A total of 15,528 MetS patients were included in the final analysis. Overall, LVH patients accounted for 25.6% of all newly diagnosed MetS patients. ACM occurred in 52.9% of the cohort and involved 74.8% of LVH patients. Interestingly, a significant percentage of ACM patients (45.4%) experienced MetS without LVH. After 33.2 ± 20.6 months of follow-up, 7,468 (48.1%) patients had a history of readmission due to CV events. Multivariable Cox regression analysis revealed that ACM was associated with an increased risk of admission for CVDs in the MetS patients with LVH [hazard ratio (HR), 1.29; 95% confidence interval (CI), 1.142-1.458; P < 0.001]. Likewise, ACM was found to be independently associated with hospital readmission due to CVD-related events in MetS patients without LVH (HR, 1.175; 95% CI, 1.105-1.250; P < 0.001). Conclusion: ACM is a marker of early myocardial remodeling and predicts hospitalization for CV events in patients with MetS.

The association between arterial stiffness and cancer occurrence: Data from Kailuan cohort study.

Background: This study aimed to investigate whether increased arterial stiffness, measured by brachial-ankle pulse wave velocity (baPWV) is associated with cancer. Materials and methods: A total of 45,627 Chinese adults underwent a baPWV examination. The participants were followed up from 1st January 2012 to 31st December 2018. Cox proportional hazards model was used to assess the association between the baPWV values and cancer. Results: During a total follow-up duration of 172,775.69 person-years, there were 553 new cases of cancer. The subjects in the highest baPWV group showed an increased risk of cancer when compared with the lowest baPWV group as confirmed by multivariate-adjusted hazard ratios (HR = 1.51, 95% CI = 1.14∼2.00) in the entire cohort. Compared with participants in the lowest baPWV group, the HRs (95% CI) for digestive cancer in the second and third groups were 1.55 (1.00∼2.40) and 1.99 (1.19∼3.33), respectively. The Kaplan-Meier analysis demonstrated a significant increase in cancer in participants with a baPWV ≥ 18 m/s (P < 0.001). Compared with the lowest baPWV group, the highest baPWV group showed an increased risk of cancer in men (HR = 1.72, 95% CI = 1.22∼2.43) and those < 60 years (HR = 1.75, 95% CI = 1.20∼2.55), respectively. Conclusion: Increased arterial stiffness measured by baPWV is associated with cancer occurrence, especially digestive cancer occurrence. Clinical trial registration: ClinicalTrials.gov, identifier ChiCTR-TNRC-11001489.

Corrigendum: In-depth characterization of phytase-producing plant growth promotion bacteria isolated in alpine grassland of Qinghai-Tibetan Plateau.

[This corrects the article DOI: 10.3389/fmicb.2022.1019383.].

Treatment of Calcific Insertional Achilles Tendinopathy: Knotless Internal Brace versus Knot-Tying Suture Bridge.

BACKGROUND: This study aimed to compare the knotless internal brace technique and the knot-tying suture bridge technique via the medial approach in the treatment of calcific Achilles tendinopathy. METHODS: The clinical data of 25 cases of calcific Achilles tendinopathy in which nonoperative treatments had failed were retrospectively collected. All the patients received Achilles tendon debridement and Haglund deformity excision through a medial approach, followed by repair using the knotless internal brace technique or the knot-tying suture bridge technique. Pain was evaluated by using the visual analog scale (VAS). The American Orthopedic Foot and Ankle Score (AOFAS) questionnaire was administered preoperatively and postoperatively. RESULTS: The mean follow-up time was 2.6 (range 2-3.5) years. There were no wound complications and no Achilles tendon ruptures. At 1 year postoperatively, the internal brace group was superior to the suture bridge group in terms of the VAS scores (p = 0.003). However, no differences were noticed between the two groups in either the VAS or the AOFAS scores at 2 years postoperatively. CONCLUSIONS: The medial approach in combination with the suture bridge technique was effective in treating calcific Achilles tendinopathy. The knotless internal brace technique involved less pain compared to the knot-tying suture bridge technique only at the early postoperative stage.