Combined application of arbuscular mycorrhizal fungi and selenium fertilizer increased wheat biomass under cadmium stress and shapes rhizosphere soil microbial communities.

BACKGROUND: Selenium (Se) fertilizer and arbuscular mycorrhizal fungi (AMF) are known to modulate cadmium (Cd) toxicity in plants. However, the effects of their co-application on wheat growth and soil microbial communities in Cd-contaminated soil are unclear. RESULTS: A pot experiment inoculation with two types of AMF and the application of Se fertilizer under Cd stress in wheat showed that inoculation AMF alone or combined with Se fertilizer significantly increased wheat biomass. Se and AMF alone or in combination significantly reduced available Cd concentration in wheat and soil, especially in the Se combined with Ri treatment. High throughput sequencing of soil samples indicated that Se and AMF application had stronger influence on bacterial community compared to fungal community and the bacterial network seemed to have more complex interconnections than the fungal network, and finally shaped the formation of specific microflora to affect Cd availability. CONCLUSION: These results indicate that the application of Se and AMF, particularly in combination, could successfully decrease soil Cd availability and relieve the harm of Cd in wheat by modifying rhizosphere soil microbial communities.

Dietary lauric acid promoted antioxidant and immune capacity by improving intestinal structure and microbial population of swimming crab (Portunus trituberculatus).

Lauric acid (LA), a saturated fatty acid with 12 carbon atoms, is widely regarded as a healthy fatty acid that plays an important role in disease resistance and improving immune physiological function. The objective of this study was to determine the effects of dietary lauric acid on the growth performance, antioxidant capacity, non-specific immunity and intestinal microbiology, and evaluate the potential of lauric acids an environmentally friendly additive in swimming crab (Portunus trituberculatus) culture. A total of 192 swimming crabs with an initial body weight of 11.68 ± 0.02 g were fed six different dietary lauric acid levels, the analytical values of lauric acid were 0.09, 0.44, 0.80, 1.00, 1.53, 2.91 mg/g, respectively. There were four replicates per treatment and 8 juvenile swimming crabs per replicate. The results indicated that final weight, percent weight gain, specific growth rate, survival and feed intake were not significantly affected by dietary lauric acid levels; however, crabs fed diets with 0.80 and 1.00 mg/g lauric acid showed the lowest feed efficiency among all treatments. Proximate composition in hepatopancreas and muscle were not significantly affected by dietary lauric acid levels. The highest activities of amylase and lipase in hepatopancreas and intestine were found at crabs fed diet with 0.80 mg/g lauric acid (P < 0.05), the activity of carnitine palmityl transferase (CPT) in hepatopancreas and intestine significantly decreased with dietary lauric acid levels increasing from 0.09 to 2.91 mg/g (P < 0.05). The lowest concentration of glucose and total protein and the activity of alkaline phosphatase in hemolymph were observed at crabs fed diets with 0.80 and 1.00 mg/g lauric acid among all treatments. The activity of GSH-Px in hepatopancreas significantly increased with dietary lauric acid increasing from 0.09 to 1.53 mg/g, MDA in hepatopancreas and hemolymph was not significantly influenced by dietary lauric acid levels. The highest expression of cat and gpx in hepatopancreas were exhibited in crabs fed diet with 1.00 mg/g lauric acid, however, the expression of genes related to the inflammatory signaling pathway (relish, myd88, traf6, nf-κB) were up-regulated in the hepatopancreas with dietary lauric acid levels increasing from 0.09 to 1.00 mg/g, moreover, the expression of genes related to intestinal inflammatory, immune and antioxidant were significantly affected by dietary lauric acid levels (P < 0.05). Crabs fed diet without lauric acid supplementation exhibited higher lipid drop area in hepatopancreas than those fed the other diets (P < 0.05). The expression of genes related to lipid catabolism was up-regulated, however, and the expression of genes related to lipid synthesis was down-regulated in the hepatopancreas of crabs fed with 0.80 mg/g lauric acid. Lauric acid improved hepatic tubular integrity, and enhanced intestinal barrier function by increasing peritrophic membrane (PM) thickness and upregulating the expression of structural factors (per44, zo-1) and intestinal immunity-related genes. In addition, dietary 1.00 mg/g lauric acid significantly improved the microbiota composition of the intestinal, increased the abundance of Actinobacteria and Rhodobacteraceae, and decreased the abundance of Vibrio, thus maintaining the microbiota balance of the intestine. The correlation analysis showed that there was a relationship between intestinal microbiota and immune-antioxidant function. In conclusion, the dietary 1.00 mg/g lauric acid is beneficial to improve the antioxidant capacity and intestinal health of swimming crab.

Selenium uptake, translocation, subcellular distribution and speciation in winter wheat in response to phosphorus application combined with three types of selenium fertilizer.

BACKGROUND: Selenium (Se) deficiency causes a series of health disorders in humans, and Se concentrations in the edible parts of crops can be improved by altering exogenous Se species. However, the uptake, transport, subcellular distribution and metabolism of selenite, selenate and SeMet (selenomethionine) under the influence of phosphorus (P) has not been well characterized. RESULTS: The results showed that increasing the P application rate enhanced photosynthesis and then increased the dry matter weight of shoots with selenite and SeMet treatment, and an appropriate amount of P combined with selenite treatment increased the dry matter weight of roots by enhancing root growth. With selenite treatment, increasing the P application rate significantly decreased the concentration and accumulation of Se in roots and shoots. P1 decreased the Se migration coefficient, which could be attributed to the inhibited distribution of Se in the root cell wall, but increased distribution of Se in the root soluble fraction, as well as the promoted proportion of SeMet and MeSeCys (Se-methyl-selenocysteine) in roots. With selenate treatment, P0.1 and P1 significantly increased the Se concentration and distribution in shoots and the Se migration coefficient, which could be attributed to the enhanced proportion of Se (IV) in roots but decreased proportion of SeMet in roots. With SeMet treatment, increasing the P application rate significantly decreased the Se concentration in shoots and roots but increased the proportion of SeCys2 (selenocystine) in roots. CONCLUSION: Compared with selenate or SeMet treatment, treatment with an appropriate amount of P combined with selenite could promote plant growth, reduce Se uptake, alter Se subcellular distribution and speciation, and affect Se bioavailability in wheat.

Cathepsin S inhibition in dendritic cells prevents Th17 cell differentiation in perivascular adipose tissues following vascular injury in diabetic rats.

In the context of diabetes mellitus (DM), the circulating cathepsin S (CTSS) level is significantly higher in the cardiovascular disease group. Therefore, this study was designed to investigate the role of CTSS in restenosis following carotid injury in diabetic rats. To induce DM, 60 mg/kg of streptozotocin (STZ) in citrate buffer was injected intraperitoneally into Sprague-Dawley rats. After successful modeling of DM, wire injury of the rat carotid artery was performed, followed by adenovirus transduction. Levels of blood glucose and Th17 cell surface antigens including ROR-γt, IL-17A, IL-17F, IL-22, and IL-23 in perivascular adipose tissues (PVAT) were evaluated. For in vitro analysis, human dendritic cells (DCs) were treated with 5.6-25 mM glucose for 24 h. The morphology of DCs was observed using an optical microscope. CD4+ T cells derived from human peripheral blood mononuclear cells were cocultured with DCs for 5 days. Levels of IL-6, CTSS, ROR-γt, IL-17A, IL-17F, IL-22 and IL-23 were measured. Flow cytometry was conducted to detect DC surface biomarkers (CD1a, CD83, and CD86) and Th17 cell differentiation. The collected DCs presented a treelike shape and were positive for CD1a, CD83, and CD86. Glucose impaired DC viability at the dose of 35 mM. Glucose treatment led to an increase in CTSS and IL-6 expression in DCs. Glucose-treated DCs promoted the differentiation of Th17 cells. CTSS depletion downregulated IL-6 expression and inhibited Th17 cell differentiation in vitro and in vivo. CTSS inhibition in DCs inhibits Th17 cell differentiation in PVAT tissues from diabetic rats following vascular injury.

Establishment of a Risk Scoring Model for Perioperative Unex-Plained Shock during Percutaneous Coronary Intervention for the Treatment of Chronic Total Occlusion.

Background: Several complications can contribute to the risk of shock during the chronic total occlusion (CTO) percutaneous coronary intervention (PCI) procedure. However, some patients that develop shock do not exhibit any apparent complications, and few studies to date have discussed the risk of unexplained perioperative shock in patients undergoing CTO PCI. Accordingly, this study was designed with the goal of defining perioperative risk factors linked to the odds of unexplained shock during CTO PCI. Methods: In total, this study analyzed data from 924 patients that underwent CTO PCI without any in-hospital complications from January 2016-August 2021. Cardiologists collected data pertaining to patient clinical characteristics, laboratory findings, angiographic findings, and procedural characteristics. Patients were separated into two groups based upon whether or not they experienced perioperative shock. The relationship between specific variables and perioperative shock incidence was assessed via a multivariable stepwise logistic regression approach. A risk-scoring nomogram was then designed for use as a tool to guide patient risk assessment efforts during PCI procedural planning. Results: Overall, 4.8% of these patients (44/924) experienced unexplained perioperative shock. Independent predictors associated with unexplained shock during CTO PCI included baseline systolic pressure (odds ratio (OR) 0.968, 95% confidence interval (CI): 0.945-0.991), baseline heart rate (OR 1.055, 95% CI: 1.020-1.091), baseline hemoglobin (OR 0.970, 95% CI: 0.947-0.994), procedure duration (OR 1.008, 95% CI: 1.002-1.015), J-CTO score (OR 1.521, 95% CI: 1.021-2.267), and use of a retrograde approach (OR 3.252, 95% CI: 1.426-7.415). The unbiased C-index estimate was 0.859, and this model exhibited excellent calibration. Conclusions: The risk of unexplained shock is an important consideration for clinicians performing the CTO PCI procedure. These analyses revealed unexplained shock risk to be independently related to lower baseline systolic pressure, higher baseline heart rate, lower baseline hemoglobin, more procedure time, higher J-CTO score, and more use of a retrograde approach.

Molecular characterization and expression analysis of galectins in Japanese pufferfish (Takifugu rubripes) in response to Vibrio harveyi infection.

Galectins are a family of proteins with conserved carbohydrate recognition domains (CRDs) that bind to specific glycans, including the glycans on the surface of pathogens, and therefore play a role in cytokine secretion, cell activation, migration, adhesion and apoptosis. Currently, galectins have been extensively studied in mammalian species but rarely studied in teleost fish species. In this study, a total of 12 galectin genes were characterized to understand the molecular mechanisms of galectin function in Japanese pufferfish (Takifugu rubripes). Phylogenetic analyses and syntenic analyses confirmed their correct annotation and suggested the strongest relationships to tetraodon. Furthermore, expression analyses were conducted in healthy tissues of Japanese pufferfish and after infection with Vibrio harveyi in the intestine, liver and spleen. The results showed that galectin genes were widely expressed in all examined tissues; however, most of the galectin genes were highly expressed in mucosal tissues (skin, gill and intestine). Moreover, majority of the galectin genes were significantly regulated after V. harveyi infection in the intestine, liver and spleen, suggesting that galectins were involved in the immune response to V. harveyi infection in Japanese pufferfish. This study established the foundation for future studies of galectin gene functions.

Comparative transcriptomic analysis reveals the gene expression profiles in the liver and spleen of Japanese pufferfish (Takifugu rubripes) in response to Vibrio harveyi infection.

Japanese pufferfish (Takifugu rubripes) is one of the main marine aquatic fish species cultured in Asia due to its high nutritional value. In recent years, disease caused by Vibrio harveyi infections have led to serious mortality in Japanese pufferfish industry. To understand the complex molecular mechanisms between V. harveyi and Japanese pufferfish, we performed a transcriptome analysis of liver and spleen samples from Japanese pufferfish at 1 and 2 day post-infection. Between-group comparisons revealed 922 genes that were significantly differentially expressed. The altered genes emphasized the function in several immune related pathways including MAPK signaling pathway, JAK-STAT signaling pathway, toll-like receptor signaling pathway, cytokine-cytokine receptor interaction and lysosomal pathway. The data generated in this study provided insight into the responses of Japanese pufferfish against V. harveyi at the transcriptome level, promoting our comprehensive understanding of immune responses for aquatic animal against V. harveyi.

[Impact of exogenous fibroblast growth factor 21 on atherosclerosis in apolipoprotein E deficient mice].

OBJECTIVE: To explore the effects and related mechanisms of exogenous fibroblast growth factor (FGF) 21 on atherosclerosis in apolipoprotein E deficient (apoE-/-) mice. METHODS: Male 17-week-old C57BL/6J mice and apoE-/- mice were randomly divided into three groups (n = 12 each): blank control group (C vehicle), atherosclerosis group without FGF21 (apoE-/- vehicle) and apoE-/- plus FGF21 (100 µg × kg⁻¹ × d⁻¹ subcutaneously treatment) . All mice were fed with high-fat diet for 4 weeks. After 4 weeks treatments, atherosclerotic lesions in aortic arch and inner diameter of abdominal aorta were measured by ultrasonography. Plasma lipid profiles, CRP and TNFα were measured. The whole aorta and aortic root were prepared for HE and oil red O staining to analyze lesion areas. RESULTS: There was no evident plaque in C vehicle group. TC/HDL-C, LDL-C/HDL-C, non-HDL-C, expression of CRP and TNFα were significantly higher in apoE-/- vehicle group than in C vehicle group (all P < 0.05). IMT of aorta [(156.4 ± 17.6)µm vs. (57.8 ± 7.4)µm] were significantly higher in apoE-/- vehicle group than in C vehicle group (all P < 0.05). While FGF21 significantly reduced the lesion area in aorta arch [(1.42 ± 0.16) mm² vs. (2.30 ± 0.10) mm², P < 0.05] and the inner diameter of abdominal aorta [(0.97 ± 0.03) mm vs. (0.75 ± 0.18) mm, P < 0.05] compared to apoE-/- vehicle group. Similarly, TC/HDL-C(5.11 ± 0.70), LDL-C/HDL-C(3.90 ± 0.76), non-HDL-C[(6.33 ± 1.22)mmol/L], plasma CRP[(4.20 ± 1.03)mmol/L] and plasma TNFα[(1.29 ± 0.47)mmol/L] were also reduced by FGF21( all P < 0.05 vs. apoE-/- vehicle). Moreover, FGF21 decreased the IMT[(107.2 ± 33.5)µm vs. (156.4 ± 17.6)µm], lesion area of aorta [(14.26 ± 3.5)%] vs. [(23.06 ± 4.16)%] and plaque size of aorta root [(21.75 ± 7.14)% vs. (38.03 ± 5.76)%] (all P < 0.05 vs. apoE-/- vehicle). CONCLUSIONS: FGF21 can protect apoE-/- mice from atherosclerosis by modifying lipid profiles and downregulating CRP and TNFα expressions.

Dietary Astaxanthin Can Promote the Growth and Motivate Lipid Metabolism by Improving Antioxidant Properties for Swimming Crab, Portunus trituberculatus.

This study aimed to assess the influence of varying dietary levels of astaxanthin (AST) on the growth, antioxidant capacity and lipid metabolism of juvenile swimming crabs. Six diets were formulated to contain different AST levels, and the analyzed concentration of AST in experimental diets were 0, 24.2, 45.8, 72.4, 94.2 and 195.0 mg kg-1, respectively. Juvenile swimming crabs (initial weight 8.20 ± 0.01 g) were fed these experimental diets for 56 days. The findings indicated that the color of the live crab shells and the cooked crab shells gradually became red with the increase of dietary AST levels. Dietary 24.2 mg kg-1 astaxanthin significantly improved the growth performance of swimming crab. the lowest activities of glutathione (GSH), total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and peroxidase (POD) were found in crabs fed without AST supplementation diet. Crabs fed diet without AST supplementation showed lower lipid content and the activity of fatty acid synthetase (FAS) in hepatopancreas than those fed diets with AST supplementation, however, lipid content in muscle and the activity of carnitine palmitoyl transferase (CPT) in hepatopancreas were not significantly affected by dietary AST levels. And it can be found in oil red O staining that dietary 24.2 and 45.8 mg kg-1 astaxanthin significantly promoted the lipid accumulation of hepatopancreas. Crabs fed diet with 195.0 mg kg-1 AST exhibited lower expression of ampk, foxo, pi3k, akt and nadph in hepatopancreas than those fed the other diets, however, the expression of genes related to antioxidant such as cMn-sod, gsh-px, cat, trx and gst in hepatopancreas significantly down-regulated with the increase of dietary AST levels. In conclusion, dietary 24.2 and 45.8 mg kg-1 astaxanthin significantly promoted the lipid accumulation of hepatopancreas and im-proved the antioxidant and immune capacity of hemolymph.

Multiparametric immune profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: an exploratory study of the CLAP trial.

PURPOSE: Checkpoint immunotherapy is a promising treatment option for advanced cervical cancer. To aid in selecting patients for this treatment, we identified potential predictors of the response to anti-PD-1 combination therapy. METHODS: We simultaneously characterized CD8+, FoxP3+, PD-L1+, CD68+, CD31+, PANCK+, and PANCK-PD-L1+ cells at the invasive margin (IM) of tumor by multispectral imaging of tissue sections from 37 patients with advanced cervical cancer in our previous trial cohort. The densities of each cell and cell-to-cell topography were compared between the responder and non-responder groups and evaluated for their predictive value in clinical response and survival. RESULTS: CD8+ T cells, PD-L1+ cells, and PANCK-PD-L1+ immune cells showed higher densities at the IM in the responders than in the non-responders (P = 0.022, 0.0094, and 0.049, respectively). A higher density of CD8+ T cells at the IM was related to prolonged progression-free survival (PFS; P = 0.031). A higher ratio of CD68+/CD8+ cells was found in the non-responder group (P = 0.003) and related to poor PFS (P = 0.016). A higher density of PANCK-PD-L1+ immune cells within 20, 30, and 45 µm of PANCK+ tumor cells was correlated with better clinical response (P = 0.017, 0.017, and 0.02, respectively). CONCLUSIONS: Multiparametric immune profiling of CD8+ T cells, PD-L1+ cells, CD68+ macrophages and PANCK-PD-L1+ immune cells at the invasive margin may help identify patients with cervical cancer who may benefit from anti-PD-1 combination therapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials. gov identifier: NCT03816553, January 25, 2019.

Prognostic Significance of Percutaneous Coronary Intervention for First Acute Myocardial Infarction with Heart Failure: Five-Year Follow-Up Results.

Objective: The study aimed to investigate the incidence and influencing factors of heart failure after 5 years of percutaneous coronary intervention (PCI) for first acute myocardial infarction. Methods: A total of 1235 patients, diagnosed as acute myocardial infarction and treated with PCI in Beijing Anzhen Hospital, Capital Medical University, from January 1, 2014, to December 31, 2014, were enrolled. Based on the exclusion criteria, 671 patients were followed up to obtain echocardiographic results 5 years after the onset of myocardial infarction (from January 1, 2019, to December 31, 2019). Of 671 patients, 62 were lost to follow-up. Finally, 609 patients were recruited in this study. According to the results of the echocardiographic examination, patients were divided into a heart failure group (n = 97) (LVEF < 50%) and a nonheart failure group (n = 512) (LVEF ≥ 50%). The clinical characteristics were compared between the two groups, and the influencing factors of heart failure after 5 years of PCI in patients with acute myocardial infarction were analyzed using logistic regression and receiver-operating characteristic (ROC) analyses. Results: Of 609 patients, 97 had heart failure within 5 years after PCI for first myocardial infarction, with an incidence of 15.9%. Multivariate regression analysis finally examined the predictors related to the occurrence of heart failure, including age (aOR, 1.008; 95% confidence interval (CI), 1.054-1.123; P ≤ 0.001), peak troponin I level (aOR, 1.020; 95% CI, 1.006-1.034; P = 0.004), left ventricular ejection fraction (LVEF) (during admission) (aOR, 0.908; 95% CI, 0.862-0.956; P ≤ 0.001), and left ventricular end-diastolic dimension (LVEDD) (at admission) (aOR, 1.136; 95% CI, 1.016-1.271; P = 0.025). Conclusion: In this study, the incidence of heart failure (LVEF < 50%) in patients with acute myocardial infarction who underwent PCI was 15.9% at a five-year follow up. Age, peak troponin I level, and LVEDD (at admission) were risk factors for heart failure, while LVEF (at admission) of patients during hospitalization was a protective factor for heart failure.

Predicting the Success Rate of Elective Percutaneous Coronary Intervention for Prior Failed Chronic Total Occlusion: a Novel Scoring System.

To investigate a scoring system for predicting the risk of successful percutaneous coronary intervention (PCI) after prior failed chronic total occlusion (CTO). Patients with previously attempted CTO-PCI were enrolled in our study retrospectively from January 2016 to December 2019. All clinical and procedural data were collected and analyzed. Univariate and multivariate logistic regression was performed to investigate the predictors of technical success. A total of 194 patients/CTO lesions were studied. The multivariate logistic regression showed that occlusion length < 20 mm (odds ratio (OR) = 2.94, score = 1), non-calcification (OR = 2.93, score = 1), adequate distal landing zone (OR = 4.46, score = 1), Rentrop grade ≥ 2 (OR = 5.98, score = 1), and retrograde approach as the initial strategy (OR = 10.28, score = 2) were predictors of the success of re-attempt PCI. The technical success rate for scores from 0 to ≥ 4 were 0%, 17.9%, 46.2%, 77.8%, and 93.3% respectively. Our scoring system can be used to predict the success rate of re-attempt CTO-PCI.

Role of Lymphadenectomy During Interval Debulking Surgery Performed After Neoadjuvant Chemotherapy in Patients With Advanced Ovarian Cancer.

OBJECTIVE: The role of lymphadenectomy in interval debulking surgery (IDS) performed after neoadjuvant chemotherapy (NACT) in advanced ovarian cancer remains unclear. We aimed to investigate the clinical significance of lymphadenectomy in IDS. METHODS: We retrospectively reviewed and analyzed the data of patients with advanced ovarian cancer who underwent NACT followed by IDS. RESULTS: In 303 patients receiving NACT-IDS, lymphadenectomy was performed in 127 (41.9%) patients. One hundred and sixty-three (53.8%) patients achieved no gross residual disease (NGRD), and 69 (22.8%) had residual disease < 1 cm, whereas 71 (23.4%) had residual disease ≥ 1cm. No significant difference in progression-free survival (PFS) and overall survival (OS) was observed between the lymphadenectomy group and the no lymphadenectomy group in patients with NGRD, residual disease < 1 cm, and residual disease ≥ 1 cm, respectively. The proportions of pelvic, para-aortic and distant lymph node recurrence were 7.9% (10/127), 4.7% (6/127) and 5.5% (7/127) in the lymphadenectomy group, compared with 5.7% (10/176, P = 0.448), 4.5% (8/176, P = 0.942) and 5.1% (9/176, P = 0.878), respectively, in no lymphadenectomy group. Multivariate analysis identified residual disease ≥ 1 cm [hazard ratios (HR), 4.094; P = 0.008] and elevated CA125 levels after 3 cycles of adjuvant chemotherapy (HR, 2.883; P = 0.004) were negative predictors for OS. CONCLUSION: Lymphadenectomy may have no therapeutic value in patients with advanced ovarian cancer underwent NACT-IDS. Our findings may help to better the therapeutic strategy for advanced ovarian cancer. More clinical trials are warranted to further clarify the real role of lymphadenectomy in IDS.

The impact of dissection and re-entry versus wire escalation techniques on long-term clinical outcomes in patients with chronic total occlusion lesions following percutaneous coronary intervention: An updated meta-analysis.

BACKGROUND: The meta-analysis was performed to evaluate the effect of dissection and re-entry (DR) vs. wire escalation (WE) techniques on long-term clinical outcomes in patients with chronic total occlusion (CTO) lesions undergoing percutaneous coronary intervention. METHODS: Studies were searched in electronic databases from inception to September, 2019. Results were pooled using random effects model and fixed effects model and are presented as risk ratios (RR) with 95% confidence intervals (CI). RESULTS: Pooled analyses revealed that patients with DR techniques had overall higher complexity CTO lesions than patients with WE techniques and required a greater number of stents and a greater mean stent length. The "extensive" DR techniques may have a higher incidence of target vessel revascularization (TVR) (RR = 2.30, 95% CI: 1.77-2.98), in-stent restenosis (RR = 1.71, 95% CI: 1.30-2.23), in-stent reocclusion (RR = 1.86, 95% CI: 1.03-3.3) and death/myocardial infarction/TVR (RR = 2.10, 95% CI: 1.71-2.58), when compared with WE techniques, during the long-term follow-up. However, "limited" DR techniques result in more promising outcomes, and are comparable to conventional WE techniques. CONCLUSIONS: Dissection and re-entry techniques were associated with increased risk of long-term negative clinical events, especially "extensive" DR techniques. However, "limited" DR techniques resulted in good long-term outcomes, comparable to WE techniques.

Predictors and complications of side branch occlusion after recanalization of chronic total occlusions complicated with bifurcation lesions.

Data on risk factors and periprocedural complications associated with side branch (SB) occlusion after chronic coronary total occlusion (CTO) recanalization are limited. The aims of this study were to identify independent predictors of side branch (SB) occlusion after chronic total occlusion (CTO) recanalization and assess the relationship between SB occlusion and perioperative complications. 245 patients with CTO bifurcation lesions (BFLs) who underwent successful CTO recanalization were included in the study. In the occlusion group, most of the SB occlusions were observed after the implantation of the stents and lack of SB protection was more common. However, there was no significant between-group difference in the angles between the main vessel (MV) and SB. SB occlusion was associated with a higher risk of periprocedural myocardial infarction and a higher composite periprocedural complication rate. Identified as predictors of SB occlusion were no SB protection, use of a dissection-reentry strategy, ostial SB stenosis, and proximal MV stenosis of 50% or more.

Genomic profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: a secondary analysis of the CLAP trial.

BACKGROUND: The Camrelizumab Plus Apatinib in Patients with Advanced Cervical Cancer trial was a single-arm, phase II study that showed promising activity of the programmed death-1 (PD-1) inhibitor camrelizumab plus the vascular endothelial growth factor receptor-2 inhibitor apatinib in patients with advanced cervical cancer. However, the predictive biomarkers for treatment outcomes are unknown. In this study, we aimed to identify potential predictors of treatment response in PD-1 inhibitor combination therapy. METHODS: Genomic profiling was performed on patients with available biopsy or surgical samples by targeted next-generation sequencing of 425 cancer-related genes in this preplanned, secondary analysis. Somatic alterations, including all non-synonymous mutations, and tumor mutational burden (TMB) were assessed for their predictive values in objective response rate, progression-free survival (PFS), and overall survival (OS). RESULTS: A subset of 32 patients was included in this analysis. Top altered genes included PIK3CA (43.8%), STK11 (25%), FBXW7 (15.6%), and PTEN (15.6%). The PI3K/AKT pathway was among the most frequently dysregulated pathways, and its genetic alterations were identified in 68.8% of patients. PIK3CA (PFS HR 0.33, p=0.05; OS HR 0.23, p=0.04) and PTEN (PFS HR 3.71e-09, p=0.05; OS HR 3.64e-09, p=0.08) alterations were associated with improved outcomes. PI3K/AKT pathway genetic alterations showed improved predictive power compared with either PIK3CA or PTEN alterations alone (PFS HR 0.33, p=0.03; OS HR 0.25, p=0.02), while ERBB3 mutations (PFS HR 34.9, p<0.001; OS HR 19.8, p<0.001) correlated with poor survival. TMB-high (≥5 mut/Mb) was associated with prolonged PFS (HR 0.26, p<0.01) and OS (HR 0.31, p=0.05). Multivariate analysis showed ERBB3 mutations (PFS p=0.01, OS p<0.001), PD-L1 positive (PFS p=0.01, OS p=0.05), and high TMB (PFS p=0.01, OS p=0.05) remained significantly associated with survival. CONCLUSIONS: We uncovered that genetic alterations in PIK3CA, PTEN, ERBB3, and PI3K/AKT pathway, as well as TMB, could be novel predictive biomarkers in patients with cervical cancer treated with PD-1 inhibitor combination therapy. TRIAL REGISTRATION NUMBER: NCT03816553.

Angiographic Scoring System for Predicting Successful Percutaneous Coronary Intervention of In-Stent Chronic Total Occlusion.

The purpose of this study was to develop a scoring model to predict the technical success of recanalizing via antegrade approach in-stent chronic total occlusion (IS-CTO) by percutaneous coronary intervention (PCI). We retrospectively collected data from 474 patients who underwent an uneasy IS-CTO PCI via antegrade approach from January 2015 to December 2018, consecutively. We selected clinical and angiographic factors and utilized a derivation and validation cohort (4:1 sampling ratio) analysis. Factors with strong correlations with technical failure, according to multivariable analysis, were assigned 1 point, and a scoring system with a 4-point maximum was established. The model was then validated with a validation cohort. The overall procedural success rate was 77.4%. On multivariable analysis, the factors that correlated with technical failure were proximal bending (beta coefficient [ß] = 2.142), tortuosity (ß = 2.622), stent under expansion (ß = 3.052), and poor distal landing zone (ß = 2.004). The IS-CTO score demonstrated good calibration and excellent predicting capacity in the derivation (receiver-operator characteristic [ROC] area = 0.973 and Hosmer-Lemeshow chi-squared = 5.252; p = 0.072) and validation (ROC area = 0.976 and Hosmer-Lemeshow chi-squared = 0.916; p = 0.632) cohorts. In the validation subset, the IS-CTO score demonstrated superior performance to the Japanese chronic total occlusion score (J-CTO) and PROGRESS CTO scores for predicting technical success (area under the a curve [AUC] 0.976 vs. 0.642 vs. 0.579, respectively; difference in AUC between the IS-CTO score and J-CTO score = 0.334, p < 0.01; difference in AUC between the IS-CTO score and PROGRESS score = 0.397, p < 0.01). Our results suggest that the IS-CTO score system is a helpful tool to predict the technical success of IS-CTO PCI via antegrade approach in china. Graphical Abstract.

Clinical analysis of acute coronary syndrome patients with Qi-blood syndromes: establishment of a diagnostic prediction model for syndrome differentiation.

BACKGROUND: It has been proven that blood stasis plays an important role in the occurrence and development of acute coronary syndrome (ACS) due to Qi-stagnation or Qi-deficiency in traditional Chinese medicine (TCM). However, the diagnosis of Qi-stagnation and blood stasis (QSBS) and Qi-deficiency and blood stasis (QDBS) syndromes mainly depends on the subjective signs or symptoms in clinical practice. Using a combination of TCM and modern medicine, this study aimed to investigate the clinical characteristics of patients with QSBS or QDBS syndromes and to establish a diagnostic prediction model for Qi-blood syndrome differentiation in clinical practice. METHODS: Patients with ACS who were diagnosed with QSBS syndrome or QDBS syndrome and met the inclusion criteria were enrolled. Clinical characteristics, laboratory evaluation, and angiographic characteristics of the two syndrome groups were compared and analyzed. Potential predictive factors associated with QSBS and QDBS syndromes were explored to establish a diagnostic model for syndrome differentiation. RESULTS: A total of 216 participants with ACS, including 108 patients with QSBS syndrome and 108 patients with QDBS syndrome, were enrolled from Beijing Anzhen Hospital Affiliated to Capital Medical University from April 2018 to July 2019. We found that patients with QSBS syndrome were more likely to be males, and have of triple-vessel lesions, relatively high blood stasis syndrome score, normal ejection fraction, and a relatively low-density lipoprotein cholesterol (LDL-C) level. Meanwhile, patients with QDBS syndrome were more likely to have low ejection fraction, high LDL-C level, left main non-triple-vessel lesions, and a relatively low blood stasis syndrome score. The receiver operating characteristic curve and Hosmer-Leme show tests confirmed the discrimination power and reliability of the logistic regression model. CONCLUSIONS: The present study suggested that male sex, the level of LDL-C, ejection fraction, left main lesions, triple-vessel disease, and the score of blood stasis syndrome were the independent predictive factors of Qi-blood syndromes. A good discrimination power of clinical diagnostic prediction model was established using a combination of TCM and modern medicine, and could assist in the differentiation of QSBS syndrome and QDBS syndrome in clinical practice.

Procedural outcomes of chronic total occlusion percutaneous coronary intervention in patients with dissection and reentry versus wire escalation techniques: a meta-analysis.

BACKGROUND: The procedural safety of dissection and reentry (DR) techniques in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) remains controversial, when compared with conventional wire escalation (WE) techniques. The meta-analysis was performed to evaluate the impact of DR techniques vs. WE techniques on periprocedural outcomes in patients with CTO undergoing PCI. METHODS: Studies were searched in electronic database from inception to December 2018. Results were pooled using random effects model and fixed effects model. RESULTS: The pooled analyses revealed that DR techniques increased risks of periprocedural complications in patients with CTO PCI, including higher coronary perforation rate [risk ratio (RR) = 2.10, 95% confidence interval (CI) 1.24-3.55], periprocedural myocardial infarction (RR = 1.85, 95% CI 1.23-2.78), branch occlusion (RR = 2.69; 95% CI 1.92-3.77) and coronary hematoma (RR = 3.06; 95% CI 2.45-3.82) detected by intravascular ultrasound, when compared to those with WE techniques. However, DR techniques were more applied in patients with higher complexity CTO lesions, which was evidenced by higher J-CTO score [standard mean differences (SMD) = 0.71, 95% CI 0.51-0.91] and longer fluoroscopy time (SMD = 0.93, 95% CI 0.70-1.16), that may explain the higher complications rates in the DR techniques group as compared with WE techniques. CONCLUSION: The present meta-analysis suggests that the DR technique is relatively frequently used during contemporary CTO PCI, especially for challenging more complex CTO lesions. However, it is associated with higher, yet acceptable, rates of periprocedural adverse events as compared with a conventional WE strategy. Further refinement of DR techniques and evidence from large RCTs is needed to define the optimal role of DR in hybrid CTO PCI.

Development of elastic artificial vessels with a digital pulse flow system to investigate the risk of restenosis and vasospasm.

The postoperative risk of stenosis is a complex issue, with risk factors including the status of human umbilical vein endothelial cells, the shear stress of dynamic blood flow, and blood physiology. Current research would benefit from in vitro models that can mimic the microenvironment of living vessels, to study the response of endothelial cells to stent placement. In this study, we constructed a digital pulse flow system based on a group of programmable solenoid valves, to mimic dynamic blood flows in the left coronary artery. Elastic artificial vessels, with internally cultured endothelial cells, were used to simulate vessel function and physiology. Based on this novel platform, we systematically explored cell proliferation and function in artificial vessels implanted with bare metal stents or drug-eluting stents, using unstented vessels as controls, under static and pulse flow conditions. The results indicate that the natural shear stresses of dynamic blood flow actually benefit endothelial cell attachment and proliferation. And drug-eluting stents showed stronger inhibition of cell proliferation than bare metal stents, but had a more negative effect on the synthesis of nitric oxide synthase (NOS), suggesting that drug elution might reduce the postoperative risk of restenosis, while increasing the risk of vasospasm. The results suggest that stent evaluation should include both the risk of restenosis and the effect on endothelial cells. Our simulation establishes a realistic in vitro model for pathological studies of restenosis and vasospasm, shows potential for evaluation of new stent designs, and could help develop individualised therapies for patients with atherosclerosis.