Exploring the association between cardiovascular health and bowel health.

Chronic constipation, diarrhea, and fecal incontinence have high incidence, potential disability, and socioeconomic impact, imposing a heavy burden on the quality of life. We aim to explore the association between cardiovascular health (CVH) and bowel health from National Health and Nutrition Survey 2005-2010. CVH is assessed using Life's Essential 8 (LE8). Chronic constipation, chronic diarrhea, and fecal incontinence are assessed based on Bristol Stool Form Scale classification, bowel movements, and bowel leakage. Better health behaviors (odds ratio [OR]: 0.71, 95% confidence interval [CI] 0.53-0.94, p = 0.02) and worse health factors (OR: 1.45, CI 1.03-2.04, p = 0.04) were associated with less chronic constipation. Less chronic diarrhea is correlated with better CVH (OR: 0.53, 95% CI 0.35-0.79, p = 0.003) and health factors (OR: 0.61, CI 0.46-0.81, p = 0.001). Meanwhile, the proportion of chronic diarrhea significantly decreases when the health behaviors score exceeds 59.42. Lower fecal incontinence was associated with better health behaviors (OR: 0.63, CI 0.44-0.90, p = 0.01) CVH. Better CVH and health behaviors are both linked to lower all-cause mortality in participants with chronic constipation and chronic diarrhea. A higher health behaviors score is also associated with less all-cause mortality in patients with fecal incontinence. Maintaining CVH at the population level contributes to intestinal health, achieving the dual management of both while saving on healthcare costs. However, further prospective research is needed to confirm these associations.

Assess the Outcomes of Transcatheter Aortic Valve Replacement in Bicuspid Valve with Mixed Disease versus Predominant Aortic Stenosis.

Purpose: In mixed aortic valve disease (MAVD), the results of transcatheter aortic valve replacement (TAVR) are conflicting. There is limited data on the outcomes of TAVR in patients with bicuspid aortic valve (BAV) and MAVD. The objective of this study is to compare outcomes after TAVR in BAV patients with MAVD and predominant aortic stenosis (PAS). Patients and Methods: Patients with BAV who underwent TAVR between January 2016 and April 2023 were included. The primary outcome was device success. The secondary endpoints were periprocedural mortality and other complications as defined by the Valve Academic Research Consortium-3 (VARC-3). Propensity score matching was used to minimize potential confounding. Results: A total of 262 patients were included in this study, 83 of whom had MAVD. The median age was 72 years, and 55.7% were male. The baseline comorbidity risk files were comparable between the two groups. Patients with MAVD had more mitral regurgitation, tricuspid regurgitation and pulmonary hypertension, larger annular and left ventricular outflow tract dimensions, and more severe calcification than PAS. In the unmatched population, MAVD patients had similar device success rate (69.9% vs 79.9%, P=0.075) and 30-day mortality (3.6% vs 3.4%, P=1) compared to PAS. Propensity score matching resulted in 66 patient pairs. Device success rate were still comparable in the matched population. Other clinical outcomes, including stroke, bleeding (type 2-4), major vascular complications, acute kidney injury (stage 2-4) and permanent pacemaker implantation, were comparable between the two groups. Multivariable logistic regression analysis did not show MAVD to be an independent negative predictor of device success. At one year, survival was similar between patients with MAVD and those with PAS. Conclusion: For the bicuspid valve, patients with MAVD had a more challenging anatomy. MAVD patients associated with comparable 30-day clinical outcomes after TAVR compared to PAS patients in patients with BAV.

Fragility index analysis for randomized controlled trials of approved biologicals and small molecule drugs in inflammatory bowel diseases.

INTRODUCTION: Biologics and small molecules have been increasingly applied in Crohn's disease (CD) and ulcerative colitis (UC). But the robustness of their trials has not been evaluated. METHODS: We initially collected all the approved biologics or small molecules for CD or UC up to December 1, 2022. Databases were then queried by keywords in chemical name and CD or UC. Randomized controlled trials (RCTs) in the two-arm, 1:1 design were included. Fragility index (FI) and fragility quotient (FQ) were subsequently calculated. RESULTS: We included twenty-eight RCTs, including nine pivotal trials listed in approval labels, nineteen non-pivotal trials not included in the labels. The median sample size was 99 [IQR, 60-262] and the median number of loss-of-follow-up (LFU) was 14 [IQR, 8-43]. Pivotal trials in the labels had the median FI of 8 [IQR, 4-14, n = 6] that was marginally higher than non-pivotal trials (3 [IQR, 2-4], p = 0.08). The median FQ was 0.0330 [IQR, 0.1220-0.0466] and 0.0310 [IQR, 0.0129-0.0540] for pivotal and non-pivotal trials, respectively (p = 1.0). The sample size and FI were significantly correlated (Spearman correlation coefficient [r] = 0.56, 95 %CI 0.21-0.78, p = 0.003). The number of total events was also significantly correlated with FI (r = 0.53, 95 %CI 0.17-0.77, p = 0.006). Study p-values were significantly associated with FI (p = 0.01): trials with p-values < 0.001 had the highest median FI of 10 [IQR, 6-17]. No factor was found strongly correlated with FQ. CONCLUSION: Results from trials assessing administration-approved biologics or small molecules for treating CD or UC were vulnerable to small changes by measuring FI or FQ. Pivotal studies contributing to regulatory approvals exhibited a relatively higher degree of resilience compared to non-pivotal trials.

Comparative effectiveness and safety of ustekinumab at different intervals of maintenance phase in inflammatory bowel disease: a systematic review and meta-analysis.

Ustekinumab has two alternative drug maintenance intervals for inflammatory bowel disease (IBD), every 8 weeks (Q8W) and every 12 weeks (Q12W). The current study aimed at evaluating the comparative efficacy and safety of the two maintenance intervals in patients with IBD. A systematic search on PubMed, Web of Science, Cochrane Library, and EMBASE was carried out. The relative risk (RR) was pooled for efficacy and safety outcomes between the two intervals at various follow-up time points, categorized as short term (less than 44 weeks), medium term (about 92 weeks), and long term (about 152 weeks). A total of 14 studies with 1448 patients were included. Q8W didn't result in a remarkably higher proportion of clinical remission compared to Q12W at short term (RR, 0.99; 95% CI, 0.83-1.16), medium term (RR, 1.05; 95% CI, 0.91-1.20), and long term (RR, 1.07; 95% CI, 0.91-1.26). Similarly, no substantial differences exist at short term in clinical response (RR, 1.00; 95% CI, 0.85-1.17), endoscopic remission (RR, 0.97; 95% CI, 0.26-3.69), and histologic improvement (RR, 1.13; 95% CI, 0.93-1.36) between the two intervals. For safety outcomes, the RR values for any adverse events in the short, medium, and long term were 1.10 (95% CI, 1.00-1.21), 1.14 (95% CI, 1.08-1.20), and 1.12 (95% CI, 1.07-1.17) for Q8W versus Q12W. Finally, we conclude that ustekinumab maintenance therapy administered every 8 and 12 weeks showed similar effectiveness in achieving efficacy outcomes in IBD patients, and most safety outcomes were significantly better for Q12W during the maintenance phase.

The combined effect of cohesion and finite size on the collapse of wet granular columns.

The collapse of low-saturation liquid-containing granular materials is prevalent in nature and industrial processes, and understanding the associated transient dynamics is extremely important for exploring such complex flow processes. In this paper, the collapse of a finite-size wet granular column is systematically studied and the determinants affecting its dynamics are analyzed based on the discrete element model for wet particles and the corresponding small-scale experiments. With the aid of parametric analysis, the dimensionless cohesion parameter containing the system size and grain-scale bond number is proposed, and its relevance in characterizing column stability and collapse dynamics of wet granular materials is further confirmed. For the collapse of wet granular columns with a fixed aspect ratio, the initial height contained in the cohesion parameter is verified to be a manifestation of the finite size effect, which is present in a wet granular collapse and is coupled with the cohesive effect. Such a coupling effect is taken into account in our proposed scaling laws that can be applied to uniformly describe the deposit morphology of wet granular columns after collapse.

Transcatheter aortic valve replacement with the VenusA-Pro and VenusA-Plus systems: preliminary experience in China.

Background: The outcomes of transcatheter aortic valve replacement (TAVR) employing the second-generation retrievable VenusA-Pro and VenusA-Plus delivery systems with the self-expanding VenusA-Valve have not been described yet. This study aims to report the outcomes of these two second-generation delivery systems. Methods: From January 2022 to April 2023, we prospectively enrolled patients with severe aortic stenosis undergoing TAVR with VenusA-Pro from three centers across China in this first-in-man study and retrospectively identified those undergoing TAVR with VenusA-Plus. All outcomes were reported according to the Valve Academic Research Consortium 3 definition. The primary outcome was 30-day all-cause mortality. Results: A total of 156 patients were included, of which 46 underwent TAVR with VenusA-Pro and 110 underwent TAVR with VenusA-Plus. The Society of Thoracic Surgeons median score was 2.1%, bicuspid anatomy prevalence rate was 55.1%, and the mean aortic root calcification volume was 693 mm3. The technical success rate was 91.7%, comparable between the VenusA-Pro and VenusA-Plus groups (87.0% vs. 93.6%, P = 0.169). The 30-day all-cause mortality was 2.6%, similar between the VenusA-Pro and VenusA-Plus groups (2.2% vs. 2.7%, P = 0.842). No myocardial infarction occurred. The incidences of stroke (0.6%), major bleeding (3.8%), major vascular complications (5.1%), acute kidney injury (9.0%), permanent pacemaker implantation (5.1%), new-onset atrial fibrillation (5.8%), and moderate-to-severe paravalvular aortic regurgitation (6.0%) were favorable and comparable between the two groups. The clinical outcomes were similar between the patients with bicuspid and tricuspid aortic valve, except that the incidence of permanent pacemaker implantation was lower in patients with bicuspid anatomy (1.2% vs. 10.6%, P = 0.010). Conclusions: The 30-day outcomes of TAVR with VenusA-Pro and VenusA-Plus were favorable and comparable.

Abnormal structural alterations and disrupted functional connectivity in behavioral addiction: A meta-analysis of VBM and fMRI studies.

Background: Altered large-scale brain systems, including structural alterations and resting-state functional connectivity (rs-FC) changes, have been demonstrated as effective system-level biomarkers for revealing potential neural mechanism of multiple brain disorders. However, identifying consistent abnormalities of large-scale brain systems in behavioral addictions (BA) is challenging due to varying methods and inconsistent results. Therefore, the aim of this study was to identify the significantly abnormal large-scale brain systems in BA. Method: PubMed, OVID Embase, OVID Medline, and Web of Science were searched with relevant keywords to identify potential studies. A total of 52 studies including 35 rs-FC studies and 17 structural studies were examined by extracting the coordinates of seeds and target brain regions. The seeds were then categorized into predefined seven networks by their locations based on previous parcellations in rs-FC studies, followed by pooling the results in those networks. Results: The rs-FC findings illustrated that BA were characterized as abnormal networks in response to inhibition, salience attribution, self-referential mental process, and reward-driven behaviors. Meanwhile, meta-analysis of structural studies showed decreased gray matter volume in the anterior cingulate cortex, extending to the middle cingulate cortex and the superior frontal gyrus. Importantly, overlapping regions in the cingulate cortex and anterior thalamus projections extending to caudate regions exhibited both dysfunctions in structure and rs-FC. Conclusions: This study highlighted substantial dysconnectivity in BA, which might result in impaired response to inhibition and salience attribution. Therefore, this study might provide novel insights of neural biomarkers for clinical diagnoses and treatment targets for BA.

Do the policy burdens of state-owned enterprises affect the efficiency of resource allocation of tax incentives?

State-owned enterprises (SOEs) bear a significant policy burden in promoting economic development and enjoy preferential government resources such as tax breaks. This study investigates the effect of the policy burden of China's SOEs on tax incentive resources and allocation efficiency using ordinary least squares regressions for state-owned listed companies from 2007 to 2021. This study found that the heavier the policy burden borne by the SOEs, the more tax incentives they receive. Moreover, SOEs become more likely to invest inefficiently after receiving tax incentives. These negative effects are more significant for local SOEs, those in poor business environments, and those with low information transparency. This study not only expands the research framework of the resource allocation efficiency of tax incentives but also provides direct empirical evidence to reduce the policy burden of SOEs. Therefore, our findings can be used to promote SOE reforms.

Prognostic factors for the efficacy of infliximab in patients with luminal fistulizing Crohn's disease.

BACKGROUND: Enteric fistula is one of the penetrating features in Crohn's disease (CD). This study aimed to clarify the prognostic factors for the efficacy of infliximab (IFX) treatment in luminal fistulizing CD patients. METHODS: We retrospectively included 26 cases diagnosed with luminal fistulizing CD hospitalized in our medical center from 2013 to 2021. The primary outcome of our research was defined as death from all causes and undergoing of any relevant abdominal surgery. Kaplan-Meier survival curves were used to describe overall survival. Univariate and multivariate analyses were used to identify prognostic factors. A predictive model was constructed using Cox proportional hazard model. RESULTS: The median follow-up time was 17.5 months (range 6-124 months). The 1- and 2-year surgery-free survival rates were 68.1% and 63.2%, respectively. In the univariate analysis, the efficacy of IFX treatment at 6 months after initiation (P < 0.001, HR 0.23, 95% CI 0.01-0.72) and the existence of complex fistula (P = 0.047, HR 4.11, 95% CI 1.01-16.71) was found significantly related to the overall surgery-free survival, while disease activity at baseline (P = 0.099) also showed predictive potential. The multivariate analysis showed that efficacy at 6 months (P = 0.010) was an independent prognostic factor. The C-index of the model for surgery-free survival was 0.923 (P < 0.001), indicating an acceptable predictive effect. CONCLUSION: Prognostic model including the existence of complex fistula, disease activity at baseline and efficacy of IFX at 6 months may be useful to predict long-term outcome of luminal fistulizing CD patients.

Long non-coding RNA ENST00000503625 is a potential prognostic biomarker and metastasis suppressor gene in prostate cancer.

BACKGROUND: Dysregulation of Long Non-coding RNAs (lncRNAs) emerges to be a hallmark of cancers. Metastatic prostate cancer and localized disease that recurs after treatment are clinical challenges, it remains unclear how lncRNA plays a role in those processes. METHODS: From previous RNA-Seq data on 65 prostate cancer and adjacent normal tissues. We identified a novel lncRNA ENST00000503625 down-regulated in prostate cancer and correlated with tumor progression characteristics. Public datasets were examined for associations between ENST00000503625 expression and clinical parameters and prognoses. Subsequently, we constructed and externally validated a nomogram for predicting biochemical recurrence (BCR). Finally, in vitro experiments were carried out to determine how ENST00000503625 functions biologically in prostate cancer. RESULTS: Low ENST00000503625 in tumor was associated with poor clinical features and prognoses. TCGA pan-cancer analysis found that ENST00000503625 was deregulated in a variety of tumors and correlated with overall survival, disease-specific survival, and progression-free survival. The nomogram for predicting BCR was constructed using TCGA data, which exhibited excellent accuracy in external validation with Chinese Prostate Cancer Genome and Epigenome Atlas data. Gene Ontology and KEGG pathway analysis found that genes related to ENST00000503625 were enriched in multiple tumor progression related pathways. When ENST00000503625 was knocked down in vitro, the epithelial-mesenchymal transition was induced, by which cancer cells migrated and invaded more readily. CONCLUSION: Our data suggested that ENST00000503625 may serve as a potential prognostic marker or a therapeutic target for prostate cancer metastases.

Multifaceted Protective Effects of Hesperidin by Aromatic Hydrocarbon Receptor in Endothelial Cell Injury Induced by Benzo[a]Pyrene.

Benzo[a]pyrene (BaP) causes atherosclerosis by activating the aromatic hydrocarbon receptor (AHR) signaling pathway to trigger lipid peroxidation and inflammation, thereby promoting the development of atherosclerosis. Hesperidin (Hsd), one of the 60 flavonoids of citrus, exhibits therapeutic effects on atherosclerosis. However, its antagonistic function for BaP remains unclear. In this study, the EA.hy926 cell model was used to systematically examine the antagonistic effect of Hsd with BaP, especially in low-density lipoprotein (LDL) oxidation and transport. Results showed that Hsd could reduce BaP-induced AHR activation in mRNA and protein expression level, and reduce LDL accumulation by decreasing the BaP-induced expression of advanced glycation end products and enhancing the BaP-inhibited Adenosine Triphosphate-binding cassette transporter A1 (ABCA1) protein and mRNA expression in EA.hy926 cells. In addition, Hsd could antagonize BaP-induced interaction of reactive oxygen species and the subsequent generation of oxidized LDL and malondialdehyde. Finally, Hsd could alleviate BaP-induced inflammatory response by decreasing IL-1ß and TNF-α expression. All these results suggest that Hsd suppresses LDL accumulation, oxidation, and inflammatory response, and thus strongly impedes the AHR pathway activated by BaP.

The characteristics and risk factors of healthcare-seeking men with lower urinary tract symptoms in China: Initial report from the POInT group.

AIMS: To investigate the clinical characteristics of health care-seeking men presenting with lower urinary tract symptoms (LUTS) in China and to reveal risk factors for symptom severity. METHODS: This multicenter, hospital-based, cross-sectional study recruited 1477 eligible male subjects, who were at least 45 years, seeking health care at 9 participating hospitals across the mainland China. The general medical information and subjective symptoms were recorded, followed by the measurement of prostate volume, urodynamic indices, and laboratory tests for kidney function, plus glucose/lipid metabolism. Univariate and multivariate linear regression were employed for the detection of risk factors for symptom severity. RESULTS: The proportion of mild, moderate, and severe LUTS was 14.6%, 32.6%, and 52.8%, respectively, with 62.2% reporting the triple combination of storage, voiding, and postmicturition symptoms. Median prostate volume was 44.6 ml, and 71.1% were experiencing comorbidities. Thirteen independent risk factors for LUTS severity were identified, namely, nocturnal voiding episodes and the presence of straining and weak steam; the triple combination of symptom subtypes; general and nocturia quality of life; Qmax and bladder outlet obstruction index; and numbers of comorbidities, hypertension, estimated glomerular filtration rate, and cholesterol and glycosylated hemoglobin. CONCLUSIONS: The majority of health care-seeking LUTS men present with moderate-to-severe and overlapping symptoms, with a high prevalence of both lower urinary tract dysfunction and systemic comorbidities. The evidence from both urological and nonurological independent risk factors demonstrate the multifactorial nature of LUTS, for which a multidisciplinary management is essential.

Anatomical Predictors of Valve Malposition During Self-Expandable Transcatheter Aortic Valve Replacement.

Background: The consequence of valve malposition (VM) during transcatheter aortic valve replacement (TAVR) can be severe, but the determinants of VM with self-expandable TAVR have not been thoroughly evaluated. We aimed to investigate the anatomical predictors of VM during self-expandable TAVR. Methods: In this multicenter retrospective study, TAVR was performed using the Venus A-Valve. The baseline, computed tomography, and procedural characteristics along with clinical outcomes were collected. Multivariate logistic regression model and receiver operating characteristic (ROC) curve analyses were performed. Results: A total of 84 consecutive patients (23 with VM) were included. Stepwise regression showed that annulus perimeter/left ventricular outflow tract perimeter (AL ratio) and sinotubular junction (STJ) height were predictors of VM. The ROC curve indicated a moderate strength of AL ratio [area under the curve (AUC) 0.71, cutoff 0.96] and a weak strength of STJ height (AUC 0.69, cutoff 23.8 mm) to predict VM. The combination of both predictors revealed a higher predictive value of VM (AUC 0.77). In multivariate analysis, AL ratio <0.96 [odds ratio (OR) 3.98, p = 0.015] and STJ height ≥23.8 mm (OR 4.63, p = 0.008) were strong independent predictors of VM. The presence of both predictors was associated with a very high risk of VM (OR 10.67, p = 0.002). The rate of moderate-to-severe paravalvular regurgitation was higher in patients with VM at 30 days (26.1 vs. 4.9%, p = 0.011). Conclusions: A conical left ventricular outflow tract and tall aortic sinuses were strong anatomical predictors of VM during self-expandable TAVR.

Sustainable functional urethral reconstruction: Maximizing early continence recovery in robotic-assisted radical prostatectomy.

OBJECTIVE: To evaluate the safety profile and short-term functional outcome of sustainable functional urethral reconstruction (SFUR) in robotic-assisted radical prostatectomy (RARP). METHODS: One hundred and sixty-two consecutive prostate cancer patients who underwent RARP were retrospectively analyzed, in which 53 had undergone SFUR while the other 109 had undergone conventional RARP procedures. Immediate, 2-week, 1-month and 3-month continence recovery and other perioperative data were compared to evaluate short-term surgical and functional outcome. RESULTS: The median age was 68 and 67 years in the experimental group and control group, respectively (p=0.206), with a median prostate-specific antigen (PSA) of 13.6 ng/mL (interquartile range [IQR], 8.46-27.32 ng/mL) in the experimental group and 13.84 ng/mL (IQR, 9.12-26.80 ng/mL) in control group (p=0.846). Immediate, 2-week, 1-month and 3-month continence recovery rates between the groups were 34.0% vs. 3.7%, 50.9% vs. 14.7%, 62.3% vs. 27.5%, and 79.2% vs. 63.3% (all p<0.05). The morphological changes made by the new reconstruction technique were maintained on magnetic resonance imaging (MRI) 3 months postoperatively. Nerve-sparing procedures and adoption of the new reconstruction technique were significantly relevant to continence recovery on logistics regression model (p<0.001). CONCLUSIONS: SFUR is a safe and easy-to-handle modification that may contribute to early continence return for RARP. Long-term follow-up and prospective studies are required to further evaluate its value in postoperative quality-of-life improvement.

Whole-body MRI-based multivariate prediction model in the assessment of bone metastasis in prostate cancer.

PURPOSE: A whole-body MRI (WB-MRI) including T1, short time inversion recovery (STIR), diffusion-weighted imaging (high b value) was applied in our center for the detection of bone metastasis in prostate cancer (PCa) patients. We intended to assess the diagnostic performance of this examination. METHODS: 547 cases of PCa patients with higher risk of metastasis were referred to bone scintigraphy with SPECT/CT (BS + SPECT/CT) and whole-body MRI in Shanghai Changhai Hospital. Best valuable comparator (BVC) was applied for the final diagnosis of metastasis. A panel of radiologists interpreted the results. Decision curve analysis (DCA) and receiver operating characteristic curve (ROC) analysis were applied. RESULTS: Bone metastasis was diagnosed in 110 cases, and others were non-metastatic by BVC. The area under the receiver operating characteristic curve (AUC) was higher in WB-MRI (0.778) than BS + SPECT/CT (0.634, p < 0.001). A WB-MRI-based prediction model was established with AUC of 0.877. Internal validation showed that the predictive model was well-calibrated. The DCA demonstrated that the model had higher net benefit than the BS + SPECT/CT-based model. CONCLUSION: WB-MRI is more effective in identifying metastasis in PCa patients than BS + SPECT/CT. The prediction model combined WB-MRI with clinical parameters may be a promising approach to the assessment of metastasis.

Radium-223 in Asian patients with castration-resistant prostate cancer with symptomatic bone metastases: A single-arm phase 3 study.

AIM: Radium-223, a targeted alpha therapy, is approved widely for the treatment of patients with metastatic castrate-resistant prostate cancer, based on a pivotal phase 3 study in predominantly white patients. We investigated the efficacy and safety of radium-223 in Asian patients with castrate-resistant prostate cancer and metastatic bone disease. METHODS: This multicenter, prospective, single-arm, open-label phase 3 trial evaluated the efficacy and safety of the standard radium-223 regimen (55 kBq/kg every 4 weeks for six cycles) in patients from Asian countries. The primary endpoints were the safety and overall survival. RESULTS: A total of 226 patients were enrolled and received at least one dose of radium-223. Median overall survival was 14.0 months (95% confidence interval [CI], 11.2-17.4). Median time to total alkaline phosphatase and prostate-specific antigen progression were 7.5 (95% CI, 6.8-7.7) and 3.6 (95% CI, 3.1-3.7) months, respectively. Median skeletal-related event-free survival was 26.0 months (95% CI, 12.6-not reached). Grade ≥3 treatment-emergent adverse events were reported in 103 (46%) of 226 patients, with anemia being the most common event (34 [15%] patients). Grade ≥3 drug-related treatment-emergent adverse events occurred in 39 (17%) of 226 patients. Serious treatment-emergent adverse events were reported in 65 (29%) of 226 patients. Seven (3%) patients had an adverse event leading to death; none were considered to be related to radium-223. CONCLUSION: The results of this study support the use of the standard radium-223 regimen for the treatment of Asian patients with castrate-resistant prostate cancer and symptomatic bone metastases.