Efficacy and Safety of Tirofiban Before Stenting for Symptomatic Intracranial Atherosclerotic Stenosis: A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Acute stent thrombosis (AST) is not uncommon and even catastrophic during intracranial stenting angioplasty in patients with symptomatic high-grade intracranial atherosclerotic stenosis (ICAS). The purpose of this study was to investigate whether adjuvant intravenous tirofiban before stenting could reduce the risk of AST and periprocedural ischemic stroke in patients receiving stent angioplasty for symptomatic ICAS. METHODS: A prospective, multicenter, open-label, randomized clinical trial was conducted from September 9, 2020, to February 18, 2022, at 10 medical centers in China. Patients intended to receive stent angioplasty for symptomatic high-grade ICAS were enrolled and randomly assigned to receive intravenous tirofiban or not before stenting in a 1:1 ratio. The primary outcomes included the incidence of AST within 30 minutes after stenting, periprocedural new-onset ischemic stroke, and symptomatic intracranial hemorrhage. The outcomes were analyzed using logistic regression analysis to obtain an odds ratio and 95% confidence interval. RESULTS: A total of 200 participants (122 men [61.0%]; median [interquartile ranges] age, 57 [52-66] years) were included in the analysis, with 100 participants randomly assigned to the tirofiban group and 100 participants to the control (no tirofiban) group. The AST incidence was lower in the tirofiban group than that in the control group (4.0% vs 14.0%; adjusted odds ratio, 0.25; 95% CI 0.08-0.82; p = 0.02). No significant difference was observed in the incidence of periprocedural ischemic stroke (7.0% vs 8.0%; p = 0.98) or symptomatic intracranial hemorrhage between the 2 groups. DISCUSSION: This study suggests that adjuvant intravenous tirofiban before stenting could lower the risk of AST during stent angioplasty in patients with symptomatic high-grade ICAS. TRIAL REGISTRATION INFORMATION: URL: chictr.org.cn; Unique identifier: ChiCTR2000031935. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with symptomatic high-grade ICAS, pretreatment with tirofiban decreases the incidence of acute stent thrombosis. This study is Class II due to the unequal distribution of involved arteries between the 2 groups.

Rreb1 is a key transcription factor in Sertoli cell maturation and function and spermatogenesis in mouse.

Spermatogenesis is a developmental process driven by interactions between germ cells and Sertoli cells. This process depends on appropriate gene expression, which might be regulated by transcription factors. This study focused on Rreb1, a zinc finger transcription factor, and explored its function and molecular mechanisms in spermatogenesis in a mouse model. Our results showed that RREB1 was predominantly expressed in the Sertoli cells of the testis. The decreased expression of RREB1 following injection of siRNA caused impaired Sertoli cell development, which was characterized using a defective blood-testis barrier structure and decreased expression of Sertoli cell functional maturity markers; its essential trigger might be SMAD3 destabilization. The decreased expression of RREB1 in mature Sertoli cells influenced the cell structure and function, which resulted in abnormal spermatogenesis, manifested as oligoasthenoteratozoospermia, and we believe RREB1 plays this role by regulating the transcription of Fshr and Wt1. RREB1 has been reported to activate Fshr transcription, and we demonstrated that the knockdown of Rreb1 caused a reduction in follicle-stimulating hormone receptor (FSHR) in the testis, which could be the cause of the increased sperm malformation. Furthermore, we confirmed that RREB1 directly activates Wt1 promoter activity, and RREB1 downregulation induced the decreased expression of Wt1 and its downstream polarity-associated genes Par6b and E-cadherin, which caused increased germ-cell death and reduced sperm number and motility. In conclusion, RREB1 is a key transcription factor essential for Sertoli cell development and function and is required for normal spermatogenesis.

LDLa containing C-type lectin mediates phagocytosis of V.anguillarum and regulates immune effector genes in shrimp.

C-type lectins (CTLs) function as pattern recognition receptors (PRRs) by recognizing invading microorganisms, thereby triggering downstream immune events against infected pathogens. In this study, a novel CTL containing a low-density lipoprotein receptor class A (LDLa) domain was obtained from Litopenaeus vannamei, designed as LvLDLalec. Stimulation by the bacterial pathogen Vibrio anguillarum (V. anguillarum) resulted in remarkable up-regulation of LvLDLalec, as well as release of LvLDLalec into hemolymph. The rLvLDLalec protein possessed broad-spectrum bacterial binding and agglutinating activities, as well as hemocyte attachment ability. Importantly, LvLDLalec facilitated the bacterial clearance in shrimp hemolymph and protected shrimp from bacterial infection. Further studies revealed that LvLDLalec promoted hemocytes phagocytosis against V. anguillarum and lysosomes were involved in the process. Meanwhile, LvLDLalec participated in humoral immunity through activating and inducing nuclear translocation of Dorsal to regulate phagocytosis-related genes and antimicrobial peptides (AMPs) genes, thereby accelerated the removal of invading pathogens in vivo and improved the survival rate of L. vannamei. These results unveil that LvLDLalec serves as a PRR participate in cellular and humoral immunity exerting opsonin activity to play vital roles in the immune regulatory system of L. vannamei.

Plaque features of the middle cerebral artery are associated with periprocedural complications of intracranial angioplasty and stenting.

PURPOSE: The identification of plaque features in the middle cerebral artery (MCA) may help minimize periprocedural complications and select patients suitable for percutaneous transluminal angioplasty and stenting (PTAS). However, relevant research is lacking. METHODS: We retrospectively included patients with symptomatic MCA stenosis who received PTAS. All patients underwent intracranial vessel wall MRI (VWMRI) before surgery. Periprocedural complications (PC) included ischemic and hemorrhagic stroke within 30 days. Stenosis location, MCA shape, plaque eccentricity and distribution, plaque thickness and length, and enhancement ratio were compared between patients with and without PC. RESULTS: Sixty-six patients were included in the study, of which 12.1% (8/66) had PC. Of the eight patients with PC, seven (87.5%) had superior wall plaques. In the non-PC group (n = 58), nine (17%) patients had superior wall plaques. Compared with patients without PC, those with PC had more frequent superior wall plaques (17% vs 87.5%, p < 0.001) and s-shaped MCAs (19% vs 50%, p = 0.071), different stenosis locations (p = 0.012), thicker plaques (1.58 [1.35, 2.00] vs 1.98 [1.73, 2.43], p = 0.038), and less frequent inferior wall plaques (79.2% vs 12.5%, p < 0.001). Multivariate analysis showed that only the presence of superior wall plaques (OR = 41.54 [2.31, 747.54]) was independently associated with PC. CONCLUSION: MCA plaque features were highly correlated with PC in patients with symptomatic MCA stenosis who underwent PTAS.

Efficacy, safety and dose selection of AZD3759 in patients with untreated EGFR-mutated non-small-cell lung cancer and central nervous system metastases in China (CTONG1702-Arm 8): a multi-center, single-arm, phase 2 trial.

Background: Central nervous system (CNS) metastases is inevitable for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). AZD3759 is a novel EGFR-TKI with impressive CNS penetration. Methods: We initiated a phase 2, multi-center, umbrella trial (CTONG1702, NCT03574402). The eighth arm assessed the efficacy and safety of AZD3759 in untreated EGFR-mutated NSCLC with CNS metastases. The primary objective was the objective response rate (ORR). Simon's minimax two-stage design was used to calculate the sample size. Dose optimal selection was performed using 200- and 300-mg bid cohorts. Findings: Between Oct 18, 2018 and Sep 14, 2020, 30 patients received AZD3759 at 200 mg (n = 15) or 300 mg (n = 15) bid. At data cutoff (Dec 31, 2022), median follow-up was 35.4 months. The primary endpoint was reached, with a confirmed ORR of 70% (21/30) (200 mg, 80%; 300 mg, 60%). The median progression-free survival was 12.9 months (200 mg, 15.8 months; 300 mg, 10.7 months). Grade 3 or 4 treatment-related adverse events occurred in 73% (22/30) of the patients (200 mg: 60%; 300 mg: 87%). 59% (10/17) of the patients developed a T790M mutation at disease progression. The median overall survival was 33.7 months, and 34.1 months and 25.3 months in patient treated with or without osimertinib in a later-line setting, respectively. Interpretation: AZD3759 showed promising efficacy and tolerable safety as a first-line therapy in EGFR-mutated NSCLC with CNS metastases. The 200-mg bid cohort had better clinical outcomes. Sequential use of AZD3759 and third-generation EGFR-TKIs represents a new option. Funding: Chinese Thoracic Oncology Group (CTONG).

Ticagrelor versus clopidogrel after intracranial stent angioplasty: a real-world study.

Objective: It was unknown whether a regimen of aspirin plus ticagrelor (aspirin-ticagrelor) attenuates ischemic vascular events without increasing bleeding risk in patients who had undergone intracranial stenting compared with an aspirin plus clopidogrel (aspirin-clopidogrel) regimen. This article compares the efficacy and safety outcomes of the two double antibody regimens in patients undergoing intracranial stent and investigates whether aspirin-ticagrelor could be an alternative antiplatelet agent without increasing the risk of bleeding. Methods: We conducted a retrospective analysis of our database for patients who had undergone intracranial stenting. From January 2017 to May 2021, consecutive patients treated with endovascular stenting were identified and dichotomized by whether aspirin-ticagrelor or aspirin-clopidogrel were used. The outcomes were compared by propensity score matching. Results: A total of 340 patients treated with intracranial stent were included. Of all, 132 patients were matched. At 180 days, ischemic vascular events occurred in one patient (1.5%) in the aspirin-ticagrelor group and in six patients (9.1%) in the aspirin-clopidogrel group. Although the absolute incidence of ischemic vascular events [1.5% (1/66) vs. 9.1% (6/66), p = 0.125] was lower in the aspirin-ticagrelor group than in the aspirin-clopidogrel group, there were no statistical differences. There were no statistical differences in ischemic vascular events, ischemic stroke, or death up to 180 days between the two groups. In addition, the incidence of bleeding did not differ. No intracranial hemorrhage or mild bleeding occurred. No statistically significant difference was noted in restenosis and symptomatic restenosis at follow-up. Conclusion: In our study involving patients with acute ischemic stroke who had undergone intracranial stenting, aspirin-ticagrelor was not found to be superior to aspirin-clopidogrel in reducing the rate of ischemic vascular events. The risk of bleeding did not differ between the two groups. Aspirin-ticagrelor does not lower total restenosis and symptomatic restenosis risk at follow-up.

Safety and efficacy of endovascular recanalization for symptomatic non-acute atherosclerotic intracranial large artery occlusion.

Background and objective: The optimal treatment for patients with symptomatic non-acute atherosclerotic intracranial large artery occlusion (ILAO) despite medical treatment is not well established. We aimed to assess the safety, efficacy, and feasibility of angioplasty and stenting for these patients. Methods: A total of 251 consecutive patients with symptomatic non-acute atherosclerotic ILAO treated with interventional recanalization were retrospectively collected in our center from March 2015 to August 2021. The rate of successful recanalization, perioperative complications, and follow-up outcomes were evaluated. Results: Successful recanalization was achieved in 88.4% (222/251) of the patients. A total of 24 (24/251, 9.6%) symptomatic complications occurred among 251 procedures. In the 193 patients with clinical follow-up during 19.0 ± 14.7 months, 11 (11/193, 5.7%) patients developed ischemic stroke and four (4/193, 2.1%) patients developed transient ischemic attack (TIA). In the 106 patients with vascular imaging follow-up during 6.8 ± 6.6 months, seven (7/106, 6.6%) patients had restenosis and 10 (10/106, 9.4%) patients had reocclusion. Conclusion: This study suggests that interventional recanalization may be a feasible, basically safe, and an effective alternative in carefully selected patients with symptomatic non-acute atherosclerotic ILAO who have failed medical management.

Genomic and immune characteristics of HER2-mutated non-small-cell lung cancer and response to immune checkpoint inhibitor-based therapy.

The efficacy of immunotherapy in advanced HER2-mutated non-small-cell lung cancer (NSCLC) remains incomprehensively studied. A total of 107 NSCLC patients with de novo HER2 mutations were retrospectively studied at Guangdong Lung Cancer Institute [GLCI cohort, exon 20 insertions (ex20ins): 71.0%] to compare clinical/molecular features and immune checkpoint inhibitor (ICI)-based therapy efficacy between patients with ex20ins and non-ex20ins. Two external cohorts (TCGA, n = 21; META-ICI, n = 30) were used for validation. In the GLCI cohort, 68.2% of patients displayed programmed death-ligand 1 (PD-L1) expression < 1%. Compared with ex20ins patients, non-ex20ins patients had more concurrent mutations in the GLCI cohort (P < 0.01) and a higher tumour mutation burden in the TCGA cohort (P = 0.03). Under ICI-based therapy, advanced NSCLC patients with non-ex20ins had potentially superior progression-free survival [median: 13.0 vs. 3.6 months, adjusted hazard ratio (HR): 0.31, 95% confidence interval (CI): 0.11-0.83] and overall survival (median: 27.5 vs. 8.1 months, adjusted HR: 0.39, 95% CI: 0.13-1.18) to ex20ins patients, consistent with findings in the META-ICI cohort. ICI-based therapy may serve as an option for advanced HER2-mutated NSCLC, with potentially better efficacy in non-ex20ins patients. Further investigations are warranted in clinical practice.

Emerging evidence and treatment paradigm of non-small cell lung cancer.

Research on biomarker-driven therapy and immune check-point blockade in non-small cell lung cancer (NSCLC) is rapidly evolving. The width and depth of clinical trials have also dramatically improved in an unprecedented speed. The personalized treatment paradigm evolved every year. In this review, we summarize the promising agents that have shifted the treatment paradigm for NSCLC patients across all stages, including targeted therapy and immunotherapy using checkpoint inhibitors. Based on recent evidence, we propose treatment algorithms for NSCLC and propose several unsolved clinical issues, which are being explored in ongoing clinical trials. The results of these trials are likely to impact future clinical practice.

Longitudinal Plasma Proteomics-Derived Biomarkers Predict Response to MET Inhibitors for MET-Dysregulated NSCLC.

MET inhibitors have shown promising efficacy for MET-dysregulated non-small cell lung cancer (NSCLC). However, quite a few patients cannot benefit from it due to the lack of powerful biomarkers. This study aims to explore the potential role of plasma proteomics-derived biomarkers for patients treated with MET inhibitors using mass spectrometry. We analyzed the plasma proteomics from patients with MET dysregulation (including MET amplification and MET overexpression) treated with MET inhibitors. Thirty-three MET-dysregulated NSCLC patients with longitudinal 89 plasma samples were included. We classified patients into the PD group and non-PD group based on clinical response. The baseline proteomic profiles of patients in the PD group were distinct from those in the non-PD group. Through protein screening, we found that a four-protein signature (MYH9, GNB1, ALOX12B, HSD17B4) could predict the efficacy of patients treated with MET inhibitors, with an area under the curve (AUC) of 0.93, better than conventional fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) tests. In addition, combining the four-protein signature with FISH or IHC test could also reach higher predictive performance. Further, the combined signature could predict progression-free survival for MET-dysregulated NSCLC (p < 0.001). We also validated the performance of the four-protein signature in another cohort of plasma using an enzyme-linked immunosorbent assay. In conclusion, the four plasma protein signature (MYH9, GNB1, ALOX12B, and HSD17B4 proteins) might play a substitutable or complementary role to conventional MET FISH or IHC tests. This exploration will help select patients who may benefit from MET inhibitors.

Sourcing decisions with loss aversion under yield and demand randomness.

Yield and demand randomness are common in the industry, and loss aversion has been regarded as an inherent behavior for decision-makers. We combine these two factors and investigate a retailer's ordering decisions under both yield and demand randomness with loss aversion. Before the selling season, the demand is unknown and the loss-averse retailer places an order from an unreliable supplier with an uncertain yield rate. After the demand and supply from the unreliable supplier are known, the retailer can carry out emergency replenishment from a spot market during the selling season. We characterize the retailer's optimal ordering decisions in three scenarios: (1) the retailer is risk-neutral; (2) the retailer is loss-averse and has a zero reference profit; (3) the retailer is loss-averse and has a nonzero fixed reference profit (FRP). We compare the retailer's order quantities in the three scenarios and find that the order quantity of the loss-averse retailer with a zero reference profit is always lower than that of the risk-neutral retailer. However, the order quantity of the loss-averse retailer with a nonzero fixed reference profit is higher than that of the risk-neutral retailer when the salvage value is sufficiently large. Interestingly, we find that the loss-averse retailer's optimal order quantity decreases with the reference profit and increases with the loss-averse degree and the maximum fulfillment rate from the unreliable supplier under some conditions. We investigate these conditions under a uniform demand distribution. We further study the ordering quantity of the retailer with a prospect-dependent reference point (PRP) and compare the results under FRP and PRP.

Drug-Coated Balloon Treatment for Delayed Recanalization of Symptomatic Intracranial Artery Occlusion.

Patients with medically refractory non-acute intracranial artery occlusion (ICAO) are difficult to treat. The optimal intervention for these patients is not known. We evaluated the feasibility and safety of drug-coated balloon (DCB) treatment for non-acute ICAO. Consecutive patients with symptomatic medically refractory atherosclerotic non-acute ICAO from January 2015 to July 2021 who underwent DCB treatment were retrospectively analyzed. The rates of stroke, transient ischemic attack, and death within 30 days and the follow-up results were evaluated. A total of 148 patients were enrolled in this study. The 30-day rate of stroke, transient ischemic attack, and death was 8.8%. During the 25.8 ± 15.8-month clinical follow-up period, the rate of outcome beyond 30 days was 4.7%. In the 66 patients with vessel imaging follow-up, 13.6% (9/66) had restenosis. The present study suggests that DCB dilatation is a feasible and effective alternative in carefully selected patients with symptomatic non-acute ICAO.

Plaque modification and stabilization after drug-coated balloon angioplasty for intracranial atherosclerotic lesions.

OBJECTIVES: A drug-coated balloon (DCB) has potential applications in the treatment of intracranial atherosclerotic disease (ICAD). We aimed to evaluate changes of vessel wall features of ICAD lesions after DCB treatment by using vessel wall MRI (VWMRI). METHODS: We retrospectively included patients with symptomatic ICAD who underwent DCB angioplasty alone. The incidences of stenosis of the lumen area, vessel wall thickening, hyperintense plaques, and prominent wall enhancement were compared between the baseline and follow-up VWMRI. RESULTS: There were 29 ICAD lesions from 29 patients, of which 22 were stenosis and 7 were occlusion. The median interval between DCB treatment and follow-up VWMRI was 4.1 [3.3, 6.7] months. After DCB treatment, follow-up VWMRI showed a significant decrease in the stenosis degree of the lumen area (83% [71%, 96%] vs 15% [3%, 41%], p < 0.001). Thirty-eight percent (11/29) of the patients observed normal appearance of the target vessel wall on follow-up VWMRI. In the stenosis group, the prevalence of hyperintense plaques decreased from 66.7% (14/21) at baseline to 23.8% (5/21) at follow-up, and prominent wall enhancement decreased from 66.7% (14/21) at baseline to 19.0%(4/21) at follow-up. The incidence of hyperintense plaques (p = 0.028) and vessel wall thickening (p = 0.018) tended to decrease with follow-up time. Although not significant (p = 0.106), a similar trend was observed between the incidence of prominent wall enhancement and follow-up time. CONCLUSION: Vascular healing with plaque modification and stabilization occurred following DCB treatment of ICAD lesions. KEY POINTS: • A drug-coated balloon (DCB) has potential applications in the treatment of intracranial atherosclerotic disease (ICAD). • Vascular healing with plaque modification and stabilization occurred following DCB treatment of ICAD lesions.

Subsequent treatments beyond progression on osimertinib in EGFR-mutated NSCLC and leptomeningeal metastases.

BACKGROUND: Despite the reported efficacy of osimertinib, central nervous system (CNS) progression is still frequent in EGFR-mutated NSCLC. This study aimed to reveal site-specific resistant mechanisms to osimertinib and investigate subsequent treatments for leptomeningeal metastases (LM). METHODS: EGFR-mutated NSCLC with LM who progressed on osimertinib were included. Molecular analysis of cerebrospinal fluid (CSF) at osimertinib progression was performed. Subsequent treatments of LM were collected and analyzed. RESULTS: A total of 246 patients were identified. Only those with LM as a progression site on osimertinib were included (n=81). In 58 CSF-plasma pairs, more alterations were uniquely detected in CSF (77%) than in plasma (7%). These mechanisms led to 22 patients receiving matched targeted therapy. Among them, 16 (72.7%) had a clinical response. The median overall survival was 7.2 months. For non-matched therapy (n=59), the osimertinib combination had a longer median overall survival than the regimen switch in CNS-only progression (15.3 vs. 7 months, p=0.03). Finally, serial monitoring by CSF revealed the potential evolution of LM. CONCLUSIONS: Private resistant mechanisms in CSF might match osimertinib-resistant LM for targeted therapy. Besides, continuing osimertinib with intensification strategy might prolong survival, especially for those with CNS-only progression. Prospective  exploration is needed.

TMPRSS12 Functions in Meiosis and Spermiogenesis and Is Required for Male Fertility in Mice.

Serine proteases are involved in many physiological activities as initiators of proteolytic cascades, and some members have been reported to play roles in male reproduction. Transmembrane serine protease 12 (TMPRSS12) has been shown to regulate sperm motility and uterotubal junction migration in mice, but its role in the testis remains unknown. In this study, we verified that TMPRSS12 was expressed in the spermatocytes and spermatids of testis and the acrosome of sperm. Mice deficient in Tmprss12 exhibited male sterility. In meiosis, TMPRSS12 was demonstrated to regulate synapsis and double-strand break repair; spermatocytes of Tmprss12 -/- mice underwent impaired meiosis and subsequent apoptosis, resulting in reduced sperm counts. During spermiogenesis, TMPRSS12 was found to function in the development of mitochondria; abnormal mitochondrial structure in Tmprss12 -/- sperm led to reduced availability of ATP, impacting sperm motility. The differential protein expression profiles of testes in Tmprss12 -/- and wild-type mice and further molecule identification revealed potential targets of TMPRSS12 related to meiosis and mitochondrial function. Besides, TMPRSS12 was also found to be involved in a series of sperm functions, including capacitation, acrosome reaction and sperm-egg interaction. These data imply that TMPRSS12 plays a role in multiple aspects of male reproduction.

Drug-Coated Balloon for the Treatment of Nonacute Symptomatic Intracranial Carotid Artery Terminus Occlusion: Initial Experience and Follow-Up Outcome.

BACKGROUND: Studies on the recanalization for occlusion of the internal carotid artery terminus are scattered. Recently, drug-coated balloon (DCB) has been increasingly applied in the intracranial artery occlusion and achieved encouraging results. However, there seems no convincing data for the nonacute symptomatic internal carotid artery terminus occlusion (sICATO). OBJECTIVE: To assess the feasibility and effectiveness (safety) of DCB for patients with nonacute sICATO refractory to medical therapy. APPROACH: This study included 30 patients with nonacute sICATO treated with DCBs and/or remedial stenting. The rate of successful recanalization, periprocedural complications, and clinical and vascular imaging follow-up outcomes were retrospectively analyzed. RESULTS: Drug-coated balloon (DCB) dilatation of nonacute sICATO gives a 100% rate of successful recanalization, with a low complication rate (10.00%), good clinical outcomes (86.20%), low restenosis/reocclusion rate (3.45%), and one asymptomatic ipsilateral infarction (3.45%). CONCLUSION: Drug-coated balloon dilation seems to be the promising treatment option for nonacute sICATO considering its safety and feasibility.

Investigating the influencing factors of incentive-based household waste recycling using structural equation modelling.

Household waste recycling management is one of the primary challenges of urban development. Incentive-based recycling systems have been used worldwide to increase the willingness of residents to take part in waste recycling. However, the factors that influence the amount of recyclables collected under the current incentive-based recycling systems have not been investigated thoroughly. In this study, the relationships between influencing factors and recycling behaviour were analysed using partial least squares structural equation modelling under a proposed analysis framework. A real-world case study in Shanghai of China was employed to demonstrate the framework's effectiveness. Six major observations were uncovered based on the studied communities: (1) The amount of recyclables collected increased by 190.9% during the pilot period of the new incentive-based recycling policy. (2) The recycling promotion effect of the new policy reached a peak after approximately three months during the pilot period. (3) Recycling motivation and publicity efforts improved recycling behaviour significantly, but the sense of community belonging and exogenous factors like rainy days and holidays did not necessarily have direct impacts on recycling behaviour. (4) Recycling motivation significantly mediated the relationship between the sense of community belonging and waste recycling behaviour. (5) Although publicity efforts in the studied communities did not necessarily enhance recycling motivation, publicity efforts promoted recycling behaviour significantly in the incentive-based recycling system in Shanghai. (6) Although the studied recycling company has made substantial efforts to formulate attractive recycling prices, its current pricing mechanism still has much room for improvement. This analysis framework and our observations offer insights for government authorities to move towards an enhanced incentive-based recycling system.

MET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors.

BACKGROUND: MET amplification plays an important role in the development of non-small-cell lung cancer (NSCLC) either de novo or in resistance to epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI) settings. Fluorescence in situ hybridization (FISH) is the standard method for MET amplification. With more and more discoveries of oncogenic driver genes, next-generation sequencing (NGS) plays a significant role in precision oncology. Meanwhile, the role of NGS in MET amplification remains uncertain. METHODS: Forty patients diagnosed with advanced NSCLC were included. FISH and NGS were conducted prior to MET inhibitors treatment. MET amplification by FISH was defined as a MET/CEP7 ratio of > 2.0 and/or copy number (CN) > 5. MET amplification by NGS was defined as gene copy number (GCN) ≥ 5. RESULTS: The concordance rate among FISH and NGS was 62.5% (25/40). MET amplification identified by FISH showed the optimal predictive value. The partial response (PR) rate was 68.0% (17/25 with MET amplification) vs. 6.7% (1/15 without MET amplification); the median progression-free survival (PFS) was 5.4 months versus 1.0 months (P < 0.001). MET amplification identified by NGS failed to distinguish significant clinical outcomes. The PR rate was 60.0% (6/10, with MET GCN ≥ 5) vs. 40.0% (12/30, with MET GCN < 5); the median PFS was 4.8 months vs. 2.2 months (P = 0.357). The PR rate was 68.8% (11/16) and the median PFS was 4.8 months in patients with focal amplification by NGS. CONCLUSIONS: MET amplification identified by FISH remains the optimal biomarker to identify suitable candidates for MET-TKI therapy. In comparison, amplification identified by NGS seems not as robust to be effective predictive biomarker. Further exploration is needed regarding the focal amplification by NGS in predicting the efficacy.

Safety and efficacy of prophylactic tirofiban infusion for acute intracranial intraprocedural stent thrombosis.

Periprocedural antithrombotic management with glycoprotein IIb/IIIa inhibitors (GPI) for intracranial artery stenting is still controversial. We sought to assess the safety and efficacy of prophylactic tirofiban infusion for acute intracranial intraprocedural stent thrombosis in routine clinical practice. From January 2013 to December 2019, consecutive patients treated with endovascular stenting for symptomatic intracranial atherosclerotic stenosis (ICAS) were identified and dichotomized by whether tirofiban was used. The efficacy and safety outcomes were compared by propensity score matching. A total of 160 consecutive patients in the tirofiban group and 177 patients in the non-tirofiban group were enrolled. Propensity score matching analysis selected 236 matched patients. One acute intraprocedural stent thrombosis (AIST) occurred in patients receiving prophylactic tirofiban, while 8 in the non-tirofiban group. The incidence of AIST in the tirofiban group was significantly lower than that in the non-tirofiban group (0.8% vs 6.8%, P = 0.039). The periprocedural ischemic events (8.5% vs 5.1%, P = 0.424), periprocedural intracranial hemorrhage (4.2% vs 0.8%, P = 0.219) and 30-day total mortality (3.4% vs 0%, P = 0.125) were not statistically different between the two groups. Compared with conventional stenting angioplasty without tirofiban, tirofiban prophylactic infusion can lower the incidence of AIST, without increasing the risk of periprocedural intracranial hemorrhage and 30-day total mortality. However, there is no superiority in reducing periprocedural ischemic events. The current study adds more important insights to the available clinical evidence on the use of tirofiban during stenting of ICAS.