Incidence of suboptimal response to tumor necrosis factor antagonist therapy in inflammatory bowel disease in newly industrialised countries: The EXPLORE study

Abstract Background Incidence of inflammatory bowel disease (IBD) is increasing in newly industrialised countries (NICs); however, data on suboptimal response to anti-tumor necrosis factor (anti-TNF) agents are limited. Objectives To assess incidence and indicators of suboptimal response to first anti-TNF therapy in IBD patients in NICs. Methods A chart review was conducted in ten countries from Asia-Pacific (APAC), Latin America (LatAm), and Russia and the Middle East (RME) regions among patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD), initiating anti-TNF therapy in 2010–2015. The cumulative incidence of suboptimal response to anti-TNF therapy was assessed using the following indicators: dose escalation or discontinuation, augmentation with non-biologic therapy, IBD-related hospitalization, or surgery. Results The study included 1,674 patients (570 UC; 1,104 CD). At 24 months, 32.9% of UC (APAC: 45.1%; LatAm: 38.2%; RME: 23.8%) and 41.2% of CD patients (APAC: 54.1%; LatAm: 42.5%; RME: 29.5%) had experienced suboptimal response. The most frequent first indicator was non-biologic therapy augmentation in LatAm (41.7%), IBD-related hospitalization in RME (UC: 50.7%; CD:37.3%) and in APAC for CD (39.1%), and anti-TNF discontinuation in APAC for UC (38.3%). Conclusion Suboptimal response to anti-TNF agents is common in IBD patients in NICs. Observed regional differences in the incidence and indicators may reflect local practice and anti-TNF restrictions in IBD management. NCT Registration Number NCT03090139

“Seminal testosterone”, rising viewpoint of local spermatogenesis in nonobstructive azoospermia: One center long-term bidirectional cohort study

ObjectiveReproductive hormones are a traditional good method to evaluate spermatogenesis but might not accurately represent local spermatogenesis. To find a more accurate method, seminal reproductive hormones were studied.MethodsA bidirectional cohort study was performed. A total of 126 infertile men from 2018 to 2019 were retrospectively analyzed. They were divided into nonobstructive azoospermia (NOA), oligozoospermia (OLZ) and normal (NOR) groups. A prospective study was conducted on patients in the NOA and OLZ groups for 2 years. Microscopic testicular sperm extraction was performed for NOA patients, who were divided into a focal spermatogenesis group (FS) and an idiopathic azoospermia group (IA). Drug treatment was for OLZ patients, who were divided into a valid group (VA) and an invalid group (IN). The differences in sperm parameters and reproductive hormones were compared. ANOSIM analysis was used between and within groups. Pearson correlation analysis, CO inertia analysis and Proctor’s analysis were for relationships. ROC curve for the specificity and sensitivity. Time series analysis was for the trends between hormones and time.ResultsThe b-FSH, b-LH, s-T and ΔT in the NOA group were significantly higher than those in the OLZ and NOR groups. However, the s-FSH, s-E2, s-P, ΔFSH, ΔLH, ΔP and ΔE2 were lower. Thirty-one NOA patients underwent MTSE, of whom 12 had sperm (FS) and 19 had no sperm (IA). The s-FSH and s-E2 of the FS group were higher than those of the IA group. Twenty-six OLZ patients completed 30 days of treatment, of which 11 had an improved sperm count (VA) and 15 had no (IN). The ΔT of the VA group was higher than that of the IN group. After follow-up for 2 years, 18 patients’ results showed that b-FSH, b-LH and s-T were different over time, with delays of 19, 3 and -19 days. SC is closely related to pH, s-FSH, s-LH, s-E2, s-P, s-T, b-FSH, b-LH, ΔFSH, ΔLH, ΔP, ΔE2 and ΔT. There were complex common trends and relationships between different kinds of hormones. s-FSH, s-LH, s-E2, s-P, s-T, b-FSH and b-LH were useful to judge spermatogenesis, of which s-T, b-FSH and b-LH were more sensitive. If s-T, b-FSH and b-LH reached 64.4, 9.4 and 4.7, respectively, their prediction performance was the strongest.ConclusionSeminal testosterone is sensitive for judging local spermatogenesis in nonobstructive azoospermia patients, which may be the direction of local spermatogenesis in nonobstructive azoospermia.Clinical trial registrationhttp://www.chictr.org.cn/index.aspx, identifier ChiCTR2200060463

Advanced lung cancer inflammation index is associated with long-term cardiovascular death in hypertensive patients: national health and nutrition examination study, 1999–2018

Background: Hypertension is one of the main causes of cardiovascular death. Inflammation was considered influential factors of cardiovascular (CVD) death in patients with hypertension. Advanced lung cancer inflammation index (ALI) is an index to assess inflammation, few studies have investigated the relationship between advanced lung cancer inflammation index and cardiovascular death in hypertensive patients.Objective: The aim of this study was to investigate the association between advanced lung cancer inflammation index and long-term cardiovascular death in hypertensive patients.Method: Data from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 with mortality follow-up through 31 December 2019 were analyzed. Advanced lung cancer inflammation index was calculated as BMI (kg/㎡) × serum albumin level (g/dL)/neutrophil to lymphocyte ratio (NLR). A total of 20,517 participants were evaluated. Patients were divided into three groups based on tertiles of advanced lung cancer inflammation index as follows: T1 (n = 6,839), T2 (n = 6,839), and T3 (n = 6,839) groups. The relationship between advanced lung cancer inflammation index and long-term cardiovascular death was assessed by survival curves and Cox regression analysis based on the NHANES recommended weights.Results: The median advanced lung cancer inflammation index value in this study was 61.9 [44.4, 84.6]. After full adjustment, the T2 group (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.50–0.69; p < 0.001) and T3 group (HR: 0.48, 95% CI: 0.39–0.58; p < 0.001) were found to have a significantly lower risk of cardiovascular death compared to the T1 group.Conclusion: High levels of advanced lung cancer inflammation index were associated with reduced risk of cardiovascular death in hypertensive patients

Engineered nanovesicles from stromal vascular fraction promote angiogenesis and adipogenesis inside decellularized adipose tissue through encapsulating growth factors

Abstract Acellular matrix is a commonly used biomaterial in the field of biomedical engineering and revascularization is the key process to affect the effect of acellular matrix on tissue regeneration. The application of bioactive factors related to angiogenesis has been popular in the regulation of revascularization, but the immune system clearance, uncontrollable systemic reactions, and other factors make this method face challenges. Recent reports showed that engineered cells into nanovesicles can reorganize cell membranes and encapsulate cellular active factors, extending the in vitro preservation of cytokines. However, the problems of exogenous biological contamination and tumorigenicity restricted the clinical transformation and wide application of this method. Here, we for the first time engineer stromal vascular fraction (SVF) which is extracted from fat into nanovesicles (SVF-EVs) for angiogenesis in the acellular matrix. SVF-EVs not only promote the migration of vascular endothelial cells in vitro, but also facilitate the lipogenic differentiation of mesenchymal stem cells. In vivo, SVF-EVs enhanced the retention of decellularized adipose tissue after transplanting to the subcutaneous area of nude mice. Immunofluorescence staining further showed that SVF-EVs promoted the formation of vascular networks with large lumen diameter in the grafted acellular matrix, accompanied by adipocyte regeneration peripherally. These findings reveal that SVF-EVs can be a viable method for accelerating revascularization in acellular matrix, and this process of squeezing tissue into nanovesicles shows the potential for rapid clinical transformation

Study of natural aging behavior of Al-0.4Mg-1.0Si alloy with the addition of Sn at different solution heat treatment temperatures

In this paper, the combined effect of Sn addition and solution treatment temperature on natural aging (NA) hardness behavior and microstructure of Al-0.4Mg-1.0Si alloy were investigated by hardness test, scanning electron microscope (SEM) and scanning transmission electron microscope (STEM). The evolutions of clusters characterized by three-dimensional atom probe (3DAP) during initials stages of NA are also investigated based on the slow in formation of clusters due to Sn addition. The results shown that a Sn-rich particles with round shape retained in Al matrix after quenching treatment when the added Sn content exceeds it limit solubility, which will reduce the Mg content of the designed alloy. The suppression of NA can be enhanced with the increase in the adding Sn content and solution treatment temperature, which is strongly related to the delay of the segregation of Mg and Si to form clusters due to more trapping vacancies by Sn atoms. The addition of Sn also revealed that the segregation of Si during NA is earlier than that of Mg atoms. The Si-rich clusters are formed preferentially during initial stage of NA, and Mg–Si co-clusters are formed after long period of NA. The Mg/Si ratio and average size of Sn-containing clusters in the 0.04%Sn and 0.1%Sn alloy are obviously higher than that of Sn-free clusters regardless of the 1 day NA or 14 days NA as more Mg atoms are dragged into Sn-containing clusters due to strong interaction between Sn and Mg atoms

Effect of temperature and pre-annealing on the potential-induced degradation of silicon heterojunction photovoltaic modules

We investigate the effect of temperature and pre-annealing on the potential-induced degradation (PID) of silicon heterojunction (SHJ) photovoltaic (PV) modules. SHJ PV modules show a faster decrease in short-circuit current density (Jsc) at higher temperatures during PID tests. We also observe a complex relationship between the degree of the Jsc decrease and temperature during the PID tests. Pre-annealing before the PID tests at sufficiently high temperatures leads to the complete suppression of the PID of SHJ PV modules. The decrease in Jsc is known to be due to the chemical reduction of indium (In) in transparent conductive oxide (TCO) films in SHJ cells, in which water (H_2O) in SHJ modules is involved. These indicate that H_2O may out-diffuse from the SHJ PV modules during a PID test or pre-annealing at sufficiently high temperatures, by which the chemical reduction of indium in TCO into metallic In is suppressed

Near-Wall Settling Behavior of a Particle in Stratified Fluids

The phenomenon of near-wall particle settling in a stratified fluid is an emerging topic in the field of multiphase flow, and it is also widely found in nature and engineering applications. In stratified fluids, particle settling characteristics are affected by the physical and chemical properties of the upper and lower fluids, the particle size, the particle density, and the initial sedimentation conditions. In this study, the main objective is to determine the effect of liquid viscosity and particle density on the detaching process, and the trajectory and velocity of near-wall settling particles in stratified fluids. The inertia and velocity of the particle had a greater impact on the tail pinch-off model in low-viscosity lower fluids; that is, the lower the inertia and velocity, the more apparent the order between deep and shallow seal pinch-off. In comparison, in high-viscosity lower fluids, the tail pinch-off models of different inertia and velocity particles were similar. In terms of particle trajectory, the transverse motion of the particle in the low-viscosity lower fluid exhibited abrupt changes; that is, the particles moved away from the wall suddenly, whereas in the high-viscosity lower fluid, the transverse movement was gradual. Due to the existence of the wall, the transverse motion direction of the free settling particles in the stratified fluid, which is determined by the rotation direction of the particles, changed to a direction away from the wall regardless of the particle rotation direction. This transverse movement also caused the particle settling velocity to drop suddenly or its rising rate to decrease, this is because part of the energy was used for transverse motion and to increase the transverse velocity. In our study, the near-wall settling of particles in a stratified fluid mainly affected the particle trajectory; that is, forced movement away from the wall, thus changing the particle velocity. This characteristic provides a new approach to manipulate particles away from the wall