Effect of negative remodeling of the side branch ostium on the efficacy of a two-stent strategy for distal left main bifurcation lesions: an intravascular ultrasound study.

OBJECTIVES: To investigate whether negative remodeling (NR) detected by intravascular ultrasound (IVUS) of the side branch ostium (SBO) would affect in-stent neointimal hyperplasia (NIH) at the one-year follow-up and the clinical outcome of target lesion failure (TLF) at the long-term follow-up for patients with left main bifurcation (LMb) lesions treated with a two-stent strategy. METHODS: A total of 328 patients with de novo true complex LMb lesions who underwent a 2-stent strategy of percutaneous coronary intervention (PCI) treatment guided by IVUS were enrolled in this study. We divided the study into two phases. Of all the patients, 48 patients who had complete IVUS detection pre- and post-PCI and at the 1-year follow-up were enrolled in phase I analysis, which aimed to analyze the correlation between NR and in-stent NIH at SBO at the 1-year follow-up. If the correlation was confirmed, the cutoff value of the remodeling index (RI) for predicting NIH ≥ 50% was analyzed next. The phase II analysis focused on the incidence of TLF as the primary endpoint at the 1- to 5-year follow-up for all 328 patients by grouping based on the cutoff value of RI. RESULTS: In phase I: according to the results of a binary logistic regression analysis and receiver operating characteristic (ROC) analysis, the RI cutoff value predicting percent NIH ≥ 50% was 0.85 based on the ROC curve analysis, with a sensitivity of 85.7%, a specificity of 88.3%, and an AUC of 0.893 (0.778, 1.000), P = 0.002. In phase II: the TLR rate (35.8% vs. 5.3%, P < 0.0001) was significantly higher in the several NR (sNR, defined as RI ≤ 0.85) group than in the non-sNR group. CONCLUSION: The NR of LCxO is associated with more in-stent NIH post-PCI for distal LMb lesions with a 2-stent strategy, and NR with RI ≤ 0.85 is linked to percent NIH area ≥ 50% at the 1-year follow-up and more TLF at the 5-year follow-up.

PCSK9 Inhibitor Added to High-Intensity Statin Therapy to Prevent Cardiovascular Events in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Randomized, Double- Blind, Placebo-Controlled, Multicenter SHAWN Study.

BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at one-year follow-up between two groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.

Clinical Value of the Quantitative Flow Ratio to Predict Long-term Target Vessel Failure in Patients with In-stent Restenosis after Drug-coated Balloon Angioplasty.

OBJECTIVE: The study sought to investigate the clinical predictive value of quantitative flow ratio (QFR) for the long-term target vessel failure (TVF) outcome in patients with in-stent restenosis (ISR) by using drug-coated balloon (DCB) treatment after a long-term follow-up. METHODS: This was a retrospective study. A total of 186 patients who underwent DCB angioplasty for ISR in two hospitals from March 2014 to September 2019 were enrolled. The QFR of the entire target vessel was measured offline. The primary endpoint was TVF, including target vessel-cardiac death (TV-CD), target vessel-myocardial infarction (TV-MI), and clinically driven-target vessel revascularization (CD-TVR). RESULTS: The follow-up time was 3.09±1.53 years, and 50 patients had TVF. The QFR immediately after percutaneous coronary intervention (PCI) was significantly lower in the TVF group than in the no-TVF group. Multivariable Cox regression analysis indicated that the QFR immediately after PCI was an excellent predictor for TVF after the long-term follow-up [hazard ratio (HR): 5.15×10-5 (6.13×10-8-0.043); P<0.01]. Receiver-operating characteristic (ROC) curve analysis demonstrated that the optimal cut-off value of the QFR immediately after PCI for predicting the long-term TVF was 0.925 (area under the curve: 0.886, 95% confidence interval: 0.834-0.938; sensitivity: 83.40%, specificity: 88.00; P<0.01). In addition, QFR≤0.925 post-PCI was strongly correlated with the TVF, including TV-MI and CD-TVR (P<0.01). CONCLUSION: The QFR immediately after PCI showed a high predictive value of TVF after a long-term follow-up in ISR patients who underwent DCB angioplasty. A lower QFR immediately after PCI was associated with a worse TVF outcome.

Dynamic natural components and morphological changes in nonculprit subclinical atherosclerosis in patients with acute coronary syndrome and mild chronic kidney disease at the 1-year follow-up and clinical significance at the 5-year follow-up.

INTRODUCTION: The natural outcome of coronary plaque in acute coronary syndrome (ACS) patients with chronic kidney disease (CKD) is unique, which can be analyzed quantitatively by optical flow ratio (OFR) software. METHODS: A total of 184 ACS patients with at least one nonculprit subclinical atherosclerosis (NSA) detected by optical coherence tomography (OCT) at baseline and 1-year follow-up were divided into non-CKD group (n = 106, estimated glomerular filtration rate (eGFR)> 90 mL/(min×1.73 m2)) and mild CKD group (n = 78, 60≤eGFR<90 mL/(min×1.73 m2)). Changes of normalized total atheroma volume (TAVn) of NSA was the primary endpoint at the 1-year follow-up. RESULTS: Patients with mild CKD showed more TAVn progression of NSA than non-CKD (p = 0.019) from baseline to the 1-year follow-up, which was mainly due to an increase in calcium TAVn (p<0.001). The morphological change in the maximal calcification thickness (p = 0.026) was higher and the change in the distance from the calcified surface to the contralateral coronary media membrane (ΔC-to-M) at the maximal cross-sectional calcium area was lower (p<0.001) in mild CKD group than in non-CKD group. Mild CKD had more NSA related MACEs at the 5-year follow-up than non-CKD (30.8% vs. 5.8%, p = 0.045). CONCLUSIONS: Mild CKD patients had more plaque progression of NSA which showed the increase of calcium component with more protrusion into the lumen morphologically at the 1-year follow-up and a higher corresponding incidence of NSA-related MACEs at the 5-year follow-up. TRIAL REGISTRATION: Clinical Trial registration ClinicalTrials.gov. NCT02140801. https://classic.clinicaltrials.gov/ct2/show/NCT02140801.

Serum secreted phosphoprotein 1 level is associated with plaque vulnerability in patients with coronary artery disease.

Background: Vulnerable plaque was associated with recurrent cardiovascular events. This study was designed to explore predictive biomarkers of vulnerable plaque in patients with coronary artery disease. Methods: To reveal the phenotype-associated cell type in the development of vulnerable plaque and to identify hub gene for pathological process, we combined single-cell RNA and bulk RNA sequencing datasets of human atherosclerotic plaques using Single-Cell Identification of Subpopulations with Bulk Sample Phenotype Correlation (Scissor) and Weighted gene co-expression network analysis (WGCNA). We also validated our results in an independent cohort of patients by using intravascular ultrasound during coronary angiography. Results: Macrophages were found to be strongly correlated with plaque vulnerability while vascular smooth muscle cell (VSMC), fibrochondrocyte (FC) and intermediate cell state (ICS) clusters were negatively associated with unstable plaque. Weighted gene co-expression network analysis showed that Secreted Phosphoprotein 1 (SPP1) in the turquoise module was highly correlated with both the gene module and the clinical traits. In a total of 593 patients, serum levels of SPP1 were significantly higher in patients with vulnerable plaques than those with stable plaque (113.21 [73.65 - 147.70] ng/ml versus 71.08 [20.64 - 135.68] ng/ml; P < 0.001). Adjusted multivariate regression analysis revealed that serum SPP1 was an independent determinant of the presence of vulnerable plaque. Receiver operating characteristic curve analysis indicated that the area under the curve was 0.737 (95% CI 0.697 - 0.773; P < 0.001) for adding serum SPP1 in predicting of vulnerable plaques. Conclusion: Elevated serum SPP1 levels confer an increased risk for plaque vulnerability in patients with coronary artery disease.

Circulating secretoneurin level reflects angiographic coronary collateralization in stable angina patients with chronic total occlusion.

OBJECTIVE: To investigate the association between circulating secretoneurin (SN) and angiographic coronary collateralization in stable angina patients with chronic coronary total occlusion (CTO). METHODS: SN concentrations in serum were measured in 641 stable angina patients with CTO by radioimmunoassay. The status of coronary collaterals from the contra-lateral vessel was visually estimated using the Rentrop grading system, and was categorized into poor (grade 0 or 1) or good (grade 2 or 3) collateralization. RESULTS: Serum SN levels were significantly higher in patients with good coronary collaterals compared to those with poor collaterals (175.23 ± 52.09 pmol/L vs. 143.29 ± 42.01 pmol/L, P < 0.001). Serum SN increased stepwise across Rentrop score 0 to 3 (P < 0.001), and increasing SN tertiles were associated with higher proportion of good coronary collateralization (OR, 1.907; 95% CI, 1.558 ~ 2.335, P < 0.001). After adjustment for confounding variables, serum SN (per tertile) remained an independent factor for predicting good coronary collaterals (OR, 1.870; 95% CI, 1.515 ~ 2.309; P < 0.001). Moreover, the diagnostic value of serum SN (per tertile) was consistent after stratifying patients based on gender, age, body mass index, hypertension, diabetes, history of smoking, severity of coronary artery disease and kidney function (OR: 1.511 ~ 2.680, P interaction ≥ 0.327). CONCLUSION: Elevated circulating SN reflects good angiographic coronary collaterals in stable angina patients with CTO. The findings may provide insight into decision-making for these patients.

Morphologies and composition changes in nonculprit subclinical atherosclerosis in diabetic versus nondiabetic patients with acute coronary syndrome who underwent long-term statin therapy.

Although patients are undergoing similar lipid-lowering therapy (LLT) with statins, the outcomes of coronary plaque in diabetic mellitus (DM) and non-DM patients are different. Clinical data of 239 patients in this observational study with acute coronary syndrome was from our previous randomized trial were analyzed at 3 years, and 114 of them underwent OCT detection at baseline and the 1-year follow-up were re-anlayzed by a novel artificial intelligence imaging software for nonculprit subclinical atherosclerosis (nCSA). Normalized total atheroma volume changes (ΔTAVn) of nCSA were the primary endpoint. Plaque progression (PP) was defined as any increase in ΔTAVn. DM patients showed more PP in nCSA (ΔTAVn; 7.41 (- 2.82, 11.85) mm3 vs. - 1.12 (- 10.67, 9.15) mm3, p = 0.009) with similar reduction of low-density lipoprotein cholesterol (LDL-C) from baseline to 1-year. The main reason is that the lipid component in nCSA increases in DM patients and non-significantly decreases in non-DM patients, which leads to a significantly higher lipid TAVn (24.26 (15.05, 40.12) mm3 vs. 16.03 (6.98, 26.54) mm3, p = 0.004) in the DM group than in the non-DM group at the 1-year follow-up. DM was an independent predictor of PP in multivariate logistic regression analysis (OR = 2.731, 95% CI 1.160-6.428, p = 0.021). Major adverse cardiac events (MACEs) related to nCSA at 3 years were higher in the DM group than in the non-DM group (9.5% vs. 1.7%, p = 0.027). Despite a comparable reduction in LDL-C levels after LLT, more PP with an increase in the lipid component of nCSA and a higher incidence of MACEs at the 3-year follow-up was observed in DM patients.Trial registration: ClinicalTrials.gov. identifier: NCT02140801.

Preliminary study of the significance of reverberation by IVUS detection for patients with severe calcified lesions.

To explore the potential significance of the reverberation of calcification by comparing both intravascular ultrasound (IVUS) and optical coherence tomography (OCT) measurement post manual coregistration. The reverberation phenomenon is often detected by IVUS for severe calcified lesions post rotational atherectomy (RA), which is thought to be due to the glassy and smooth inner surfaces of calcifications. Because of the poor penetration of IVUS, it is impossible to measure the thickness of calcifications, and the relationship between multiple reverberations and the thickness of calcification lesions has not been reported before. A total of forty-nine patients with severe calcified coronary lesions that were detected by IVUS and OCT simultaneously were enrolled in our retrospective study. If reverberation phenomena were detected by IVUS, intravascular imaging (IVI) data (including distance between the IVUS catheter center and the inner surface of the reverberation signal, the intervals between all adjacent reverberation signals, the number of layers of reverberation in IVUS, and the thickness of the calcification in OCT) were measured at the same position and same direction (each cross-section had 4 mutually perpendicular directions) at 1-mm intervals. The correlation between each reverberation observational value and OCT data was the primary target in this retrospective study, and the correlation between reverberation and calcium crack post predilatation was analyzed in other 15 patients. Four hundred twenty-eight valid observational points were analyzed simultaneously by IVUS and OCT; among them, 300 points had a single layer of reverberation, 83 had double layers of reverberation and 42 had multiple layers (≥ 3 layers) of reverberation by IVUS detection post-RA. Multivariate logistic regression analysis showed that the number of layers of reverberation by IVUS was significantly related to the thickness of calcifications by OCT at the same point and in the same direction (p < 0.001). Single, double, and multiple layers of reverberation in IVUS correspond to median calcification thicknesses (interquartile ranges (IQRs)) of 0.620 mm (0.520-0.720), 0.950 mm (0.840-1.040) and 1.185 mm (1.068-1.373), respectively, by OCT detection. Another 100 points in other 15 patients with integrated IVUS data pre- and post-predilatation showed that only single layer of reverberation was related to calcium crack (p < 0.001). The number of layers of reverberation signal detected by IVUS is positively correlated with the thickness of calcifications measured by OCT post-RA and single layer of reverberation is correlated to calcium crack post-predilatation.

Clinical value of normal saline injection for expansion of the anterior perirectal space during prostate cryoablation.

BACKGROUND: The objective of this study is to describe the technique and evaluate the clinical value of normal saline (NS) injection for expanding the anterior perirectal space during prostate cryoablation for prostate cancer (PCa) patients. METHODS: PCa patients who received cryoablation between August 2014 and December 2019 were enrolled, and the technique of NS injection was adopted. The complications were evaluated. The prostate-specific antigen (PSA) nadir and biochemical progression-free survival (bPFS) were measured in localized PCa patients who received cryoablation as the primary treatment. RESULTS: A total of 159 PCa patients were included. Among 147 patients with the data of anterior perirectal space, the median (interquartile range [IQR]) distance of estimated iceball edge beyond the prostatic capsule was 8.3 (7.0-10.0) mm. No cases of urethrorectal fistula were reported; 29 patients developed urinary retention and 25 patients presented scrotal edema. All complications below Clavien-Dindo grade IIIb disappeared within 7 weeks after surgery. Urinary incontinence was reported in 6 patients. Among localized PCa patients, the median (IQR) follow-up time was 56.5 (36.0-73.5) months. The estimated 5-year bPFS was 82.3% overall, 82.8% for low-to intermediate-risk PCa patients, and 82.1% for high-risk PCa patients. For 52 patients received cryoablation alone, the median (IQR) PSA nadir was 0.147 (0.027-0.381) ng/mL. CONCLUSIONS: The technique of NS injection for expanding the anterior perirectal space during cryoablation surgery could avoid urethrorectal fistula and might benefit localized PCa patients with lower PSA nadir and longer bPFS.

First biological report on the genus Cantonius (Buprestidae, Agrilinae, Aphanisticini), with descriptions of two new species from China.

Background: The genus Cantonius Théry, 1929 is a small group with two subgenera and 12 species. However, the biology of this genus is still unknown. New information: In this paper, three species of the genus Cantonius Théry, 1929 were found on bamboo leaves, revealing for the first time that Cantonius species are also leaf-miners. Two new species were recorded from Jiangxi Province and are described here: Cantonius (Cantonius) anjiensis sp. n. (host plant: Pleioblastusamarus) and Cantonius (Procantonius) qiyunensis sp. n. (host plant: Bambusablumeana) followed by C. (P.) austrisinicus Kalashian, 2021 (host plant: Oligostachyumpaniculatum) recorded from Guangxi Province. Including habitats, photos of three species together with C. (P.) qiyunensis sp. n. pupa, host plants, and leaf mines of the three species are presented. Moreover, the bionomics and habits of the genus are discussed for the first time, and a hypothesis for the distribution of Cantonius is provided.

Danggui Sini decoction treatment of refractory allergic cutaneous vasculitis: A case report.

BACKGROUND: Allergic cutaneous vasculitis (ACV) is a difficult disease to treat. At present, there is no effective treatment for this condition. Traditionally, immunosuppressants and hormones have been primarily used in its management, but the treatment effect is suboptimal, and it has several side effects. CASE SUMMARY: We present the case of a 19-year-old woman who presented at our hospital with a four-year history of symmetric skin lesions mainly affecting her lower extremities. She had previously undergone treatment with prednisolone acetate, cetirizine hydrochloride, and loratadine tablets but had not experienced any relief in her condition. Thereafter, she was treated with oral traditional Chinese medicine. Her skin damage gradually improved within two months of treatment initiation. After six months, the skin ulcers had completely subsided. No evidence of skin ulcer recurrence was observed during the subsequent follow-up. This report presents the first case of a female patient who received oral Danggui Sini decoction for the treatment of ACV. CONCLUSION: Danggui Sini decoction may be a promising oral treatment for ACV patients.

SerpinG1: A Novel Biomarker Associated With Poor Coronary Collateral in Patients With Stable Coronary Disease and Chronic Total Occlusion.

Background This study aimed to explore predictive biomarkers of coronary collateralization in patients with chronic total occlusion. Methods and Results By using a microarray expression profiling program downloaded from the Gene Expression Omnibus database, weighted gene coexpression network analysis was constructed to analyze the relationship between potential modules and coronary collateralization and screen out the hub genes. Then, the hub gene was identified and validated in an independent cohort of patients (including 299 patients with good arteriogenic responders and 223 patients with poor arteriogenic responders). Weighted gene coexpression network analysis showed that SERPING1 in the light-cyan module was the only gene that was highly correlated with both the gene module and the clinical traits. Serum levels of serpinG1 were significantly higher in patients with bad arteriogenic responders than in patients with good arteriogenic responders (472.53±197.16 versus 314.80±208.92 µg/mL; P<0.001) and were negatively associated with the Rentrop score (Spearman r=-0.50; P<0.001). Receiver operating characteristic curve analysis indicated that the area under the curve was 0.77 (95% CI, 0.72-0.81; P<0.001) for serum serpinG1 in prediction of bad arteriogenic responders. After adjusting for traditional cardiovascular risk factors, serum serpinG1 levels (per SD) remained an independent risk factor for bad arteriogenic responders (odds ratio, 2.20 [95% CI, 1.76-2.74]; P<0.001). Conclusions Our findings illustrate that SERPING1 screened by weighted gene coexpression network analysis was associated with poor collateralization in patients with chronic total occlusion.

Fine-scale genetic structure and wolbachia infection of aedes albopictus (Diptera: Culicidae) in Nanjing city, China.

Background: Aedes albopictus is an indigenous primary vector of dengue and Zika viruses in China. Wolbachia is a gram-negative and common intracellular bacteria, which is maternally inherited endosymbionts and could expand their propagation in host populations by means of various manipulations. Compared with research on the dispersion of Ae. albopictus at the macrospatial level (mainly at the country or continent level), little is known about its variation and Wolbachia infection at the microspatial level, which is essential for its management. Meanwhile, no local cases of dengue fever have been recorded in the history of Nanjing, which implies that few adulticides have been applied in the city. Thus, the present study examines how the Ae. albopictus population varies and the Wolbachia infection status of each population among microspatial regions of Nanjing City. Methods: The genetic structure of 17 Aedes albopictus populations collected from urban, urban fringe, and rural regions of Nanjing City was investigated based on 9 microsatellite loci and the mitochondrial coxI gene. The Wolbachia infection status of each population was also assessed with Wolbachia A- and Wolbachia B-specific primers. Results: Nine out of 58 tested pairs of microsatellite markers were highly polymorphic, with a mean PIC value of 0.560, and these markers were therefore chosen for microsatellite genotyping analysis. The Na value of each Ae. albopictus population was very high, and the urban area populations (7.353 ± 4.975) showed a lower mean value than the urban fringe region populations (7.866 ± 5.010). A total of 19 coxI haplotypes were observed among 329 Ae. albopictus individuals via haplotype genotyping, with the highest diversity observed among the urban fringe Ae. albopictus populations (Hd = 0.456) and the lowest among the urban populations (Hd = 0.277). Each Ae. albopictus population showed significant departure from HWE, and significant population expansion was observed in only three populations from the urban (ZSL), urban fringe (HAJY), and rural areas (HSZY) (p < 0.05). Combined with DAPC analysis, all the Ae. albopictus populations were adequately allocated to two clades with significant genetic differences according to population structure analysis, and the best K value was equal to two. AMOVA results showed that most (96.18%) of the genetic variation detected in Ae. albopictus occurred within individuals (FIT = 0.22238, p < 0.0001), while no significant positive correlation was observed via isolation by distance (IBD) analysis (R 2 = 0.03262, p = 0.584). The TCS network of all haplotypes showed that haplotype 1 (H1) and haplotype 4 (H4) were the most frequent haplotypes among all populations, and the haplotype frequency significantly increased from urban regions (36.84%) to rural regions (68.42%). Frequent migration was observed among Ae. albopictus populations from rural to urban regions via the urban fringe region, with four direct migration routes between rural and urban regions. Furthermore, Wolbachia genotyping results showed that most of the individuals of each population were coinfected with Wolbachia A and Wolbachia B. The independent infection rate of Wolbachia A was slightly higher than that of Wolbachia B, and no significant differences were observed among different regions. Conclusion: In the microspatial environment of Nanjing City, the urban fringe region is an important region for the dispersion of Ae. albopictus populations between rural and urban areas, and Wolbachia A and Wolbachia B coinfection is the most common Wolbachia infection status in all Ae. albopictus populations among different regions.

Dynamic natural morphologies and component changes in nonculprit subclinical atherosclerosis in patients with acute coronary syndrome at 1-year follow-up and clinical significance at 3-year follow-up.

BACKGROUND AND AIMS: We aimed to explore the dynamic natural morphologies and main components of nonculprit subclinical atherosclerotic changes underlying lesion regression (LR) or lesion progression (LP) in patients with acute coronary syndrome. METHODS: The primary endpoints were changes in percent atheroma volume (ΔPAV), normalized total atheroma volume (ΔTAVn) and each component in nonculprit subclinical atherosclerosis from baseline to 1 year measured by optical flow ratio (OFR) software. LR or LP was defined by an increase or decrease in PAV. Secondary endpoints included the correlation between changes in the lipid profile and ΔPAV/ΔTAVn and major adverse cardiac events (MACEs) related to nonculprit subclinical atherosclerosis at 3 years. RESULTS: This was a subgroup analysis of our previous randomized trial with a total of 161 nonculprit lesions analysed. In the LR (approximately 55.3% of the lesions) group, ΔTAVn was positively correlated only with lipid ΔTAVn (r = 0.482, p < 0.001) but not fibrous and calcium ΔTAVn, and ΔPAV was positively correlated with lipid ΔPAV (r = 0.315, p = 0.003) but not fibrous and calcium ΔPAV. The percent reduction in low-density lipoprotein cholesterol (LDL-C) was an independent predictor of LR in multivariate logistic regression analysis (OR = 3.574, 95% CI: 1.125-11.347, p = 0.031). The incidence of MACEs related to nonculprit lesions at 3 years was higher in the LP group than the LR group (9.9% vs. 2.2%, p = 0.040). CONCLUSIONS: LR of nonculprit subclinical atherosclerosis at 1-year follow-up was mainly caused by regression of the lipid component, which was correlated with the degree of LDL-C reduction and fewer MACEs at 3-year follow-up.

Survival Analysis and Prediction Model of ASCP Based on SEER Database.

Background: This study aims to compare the incidence and clinical and survival characteristics of adenosquamous carcinoma of the pancreas (ASCP) and adenomatous carcinoma of the pancreas (ACP), analyze the survival factors of ASCP and construct a prognostic model. Method: Patients diagnosed with pancreatic cancer from 2000 to 2018 are selected from the SEER database. ASCP and ACP are compared in terms of epidemiology, clinical characteristics and prognosis. Cases are matched in a 1:2 ratio, and survival analysis is performed. The Cox proportional hazard model is used to determine covariates related to overall survival (OS), and an ASCP prognosis nomogram is constructed and verified by consistency index (C-index), calibration chart and decision curve analysis (DCA). The accuracy of the model is compared with that of AJCC.Stage and SEER.Stage to obtain the area under the receiver operating characteristic (ROC) curve. Results: the age-adjusted incidence of ACP increased significantly over time from 2000 to 2008 and from 2008 to 2018 (P < 0.05). APC was 2.01% (95% CI: 1.95-2.21) and 1.08% (95% CI: 0.93-1.25) respectively. The age-adjusted incidence of ASCP increased with time from 2000 to 2018 (P < 0.05) and APC was 3.64% (95% CI: 3.25-4.01).After propensity score matching (PSM), the OS and cancer-specific survival (CSS) of ACP are better than those of ASCP. The survival time of ASCP is significantly improved by the combined treatment of surgery + chemotherapy + radiotherapy, with a median OS of 31 months. Cox proportional hazard regression analysis shows that age, race, surgery, radiotherapy, chemotherapy and tumor size are independent factors affecting the prognosis. DCA and area under the curve (AUC) value shows that the model has good discrimination ability. Conclusion: The OS prognosis of ASCP is worse than that of ACP, and the nomogram has high accuracy for the prognosis prediction of ASCP.

Icariin represses the inflammatory responses and survival of rheumatoid arthritis fibroblast-like synoviocytes by regulating the TRIB1/TLR2/NF-kB pathway.

BACKGROUND: Effective treatment methods for rheumatoid arthritis (RA) are still lacking. Previous studies have shown that icariin exerts a significant therapeutic effect on RA; however, the molecular mechanism requires further analysis. METHODS: qRT-PCR and western blot were performed to examine the gene or protein levels, respecctively. The proinflammatory cytokine levels were determined utilizing ELISA and western blot assays. Cell proliferation and apoptosis were quantified using CCK-8, EdU and flow cytometry assays, respectively. A RA mouse model was established to observe histopathological changes. RESULTS: Both icariin treatment and TRIB1 overexpression inhibited proliferation and inflammatory responses but promoted the apoptosis of TNF-α-treated RA-FLSs. Icariin treatment increased TRIB1 expression by promoting Nrf2 expression, thus blocking TLR2/NF-κB signalling. In addition, functional rescue experiments suggested that TRIB1 knockdown strikingly restrained the biological effects of icariin on TNF-α-treated RA-FLSs. Moreover, in vivo experimental results revealed that icariin restored inflammation and deterioration in RA mice by upregulating TRIB1. CONCLUSIONS: Based on these results, icariin repressed TNF-α-induced inflammatory responses and survival in RA-FLSs by regulating the TRIB1/TLR2/NF-kB pathway, implying that icariin may be a promising candidate drug for RA treatment.

High serum levels of N-epsilon-carboxymethyllysine are associated with poor coronary collateralization in type 2 diabetic patients with chronic total occlusion of coronary artery.

BACKGROUND: The formation of advanced glycation end-products (AGEs) is a crucial risk factor for the pathogenesis of cardiovascular diseases in diabetes. We investigated whether N-epsilon-carboxymethyllysine (CML), a major form of AGEs in vivo, was associated with poor coronary collateral vessel (CCV) formation in patients with type 2 diabetes mellitus (T2DM) and chronic total occlusion (CTO) of coronary artery. METHODS: This study consisted of 242 T2DM patients with coronary angiographically documented CTO. Blood samples were obtained and demographic/clinical characteristics were documented. The coronary collateralization of these patients was defined according to Rentrop or Werner classification. Serum CML levels were evaluated using ELISA assay. Receiver operating characteristic curve and multivariable regression analysis were performed. RESULTS: 242 patients were categorized into poor CCV group or good CCV group (107 vs. 135 by the Rentrop classification or 193 vs. 49 by the Werner classification, respectively). Serum CML levels were significantly higher in poor CCV group than in good CCV group (110.0 ± 83.35 vs. 62.95 ± 58.83 ng/ml by the Rentrop classification and 94.75 ± 78.29 ng/ml vs. 40.37 ± 28.69 ng/ml by Werner classification, both P < 0.001). Moreover, these CML levels were also significantly different across the Rentrop and Werner classification subgroups (P < 0.001). In multivariable logistic regression, CML levels (P < 0.001) remained independent determinants of poor CCV according to the Rentrop or Werner classification after adjustment of traditional risk factors. CONCLUSIONS: This study suggests that higher serum CML level is associated with poor collateralization in T2DM patients with CTO.

The receptor kinase OsWAK11 monitors cell wall pectin changes to fine-tune brassinosteroid signaling and regulate cell elongation in rice.

Rates of plant cell elongation change with day-night alternation, reflecting differences in metabolism related to cell wall remodeling. Information from cell wall surveillance pathways must be integrated with growth regulation pathways to provide feedback regulation of cell wall modification; such feedback regulation is important to ensure sufficient strength and prevent rupture of the cell wall during growth. Several lines of evidence suggest that cell wall perturbations often influence phytohormone signaling, but the identity of the nexus between these two processes remained elusive. Here, we show that wall-associated kinase11 (OsWAK11) acts as a linker connecting cell wall pectin methyl-esterification changes and brassinosteroid (BR) signaling in rice. Our data show that OsWAK11 controls several important agronomical traits by regulating cell elongation in rice. OsWAK11 directly binds and phosphorylates the BR receptor OsBRI1 at residue Thr752, within a motif conserved across most monocot graminaceous crops, thus hindering OsBRI1 interaction with its co-receptor OsSERK1/OsBAK1 and inhibiting BR signaling. The extracellular domain of OsWAK11 shows a much stronger interaction toward methyl-esterified pectin as compared with de-methyl-esterified pectin. OsWAK11 is stabilized in light but is degraded in darkness, in a process triggered by changes in the ratio of methyl-esterified to de-methyl-esterified pectin, creating fluctuations in plant BR signaling in response to day and night alternation. We conclude that OsWAK11 is a cell wall monitor that regulates cell elongation rates to adapt to the environment from the outside in, which complements the well-established inside-out signaling pathway affecting cell elongation in plants.

Overexpression of Lectin Receptor-Like Kinase 1 in Tomato Confers Resistance to Fusarium oxysporum f. sp. Radicis-Lycopersici.

The disease Fusarium crown and root rot (FCRR), caused mainly by Fusarium oxysporum f. sp. radicis-lycopersici (FORL), seriously affects commercial tomato [Solanum lycopersicum (Sl)] yields. However, the genes that offer resistance to FORL are limited and the mechanism of resistance to FCRR is poorly understood. Lectin receptor-like kinases (LecRKs) play critical roles in defensive responses and immunity in many plant species; however, whether specific LecRKs are involved in the response of tomato plants to FORL is unclear. Here, we report that the expression of SlLecRK1/Solyc09g011070.1 was obviously induced by the infection of FORL. Biochemical and cell biological data revealed that SlLecRK1 is an active kinase that is located at the cell membrane, while real-time quantitative PCR data suggested that SlLecRK1 is mainly expressed in stems and roots. Genetic studies showed that overexpression of SlLecRK1 significantly improved the resistance of tomato plants to FORL but did not cause visible changes in plant growth and development compared with wild-type control plants. RNA-Seq data suggested that the positive effects of SlLecRK1 on the resistance of tomato plants to FORL occur mainly by triggering the expression of ethylene-responsive transcription factor (ERF) genes. Together, our findings not only identify a new target for the development of FCRR-resistant tomato varieties, they also demonstrate a molecular mechanism linking SlLecRK1 and ERFs in regulating the immune responses of tomato plants to FORL.

Safety and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older: two single-center, randomised, double-blind, placebo-controlled, phase 1 and phase 2 trials.

COVID-19 vaccines from multiple manufacturers are needed to cope with the problem of insufficient supply. We did two single-center, randomised, double-blind, placebo-controlled phase 1 and phase 2 trials to assess the safety, tolerability and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older in China. Eligible participants were enrolled, the ratio of candidate vaccine and placebo within each dose group was 3:1 (phase 1) or 5:1 (phase 2). From August 28, 2020, 168 participants were sequentially enrolled and randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 28 days or 0, 14, 28 days in phase 1 trial. From November 18, 2020, 960 participants were randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 21 days or 0, 14, 28 days in phase 2 trial. The most common solicited injection site adverse reaction within 7 days in both trials was pain. The most common solicited systematic adverse reactions within 7 days were fatigue, cough, sore throat, fever and headache. ELISA antibodies and neutralising antibodies increased at 14 days, and peaked at 28 days (phase 1) or 30 days (phase 2) after the last dose vaccination. The GMTs of neutralising antibody against live SARS-CoV-2 at 28 days or 30 days after the last dose vaccination were highest in the adult high dose group (0, 14, 28 days), with 102.9 (95% CI 61.9-171.2) and 102.6 (95% CI 75.2-140.1) in phase 1 and phase 2 trials, respectively. Specific T-cell response peaked at 14 days after the last dose vaccination in phase 1 trial. This vaccine is safe, and induced significant immune responses after three doses of vaccination.