NQO1 targeting prodrug triggers innate sensing to overcome checkpoint blockade resistance

Lack of proper innate sensing inside tumor microenvironment (TME) limits T cell-targeted immunotherapy. NAD(P)H:quinone oxidoreductase 1 (NQO1) is highly enriched in multiple tumor types and has emerged as a promising target for direct tumor-killing. Here, we demonstrate that NQO1-targeting prodrug β-lapachone triggers tumor-selective innate sensing leading to T cell-dependent tumor control. β-Lapachone is catalyzed and bioactivated by NQO1 to generate ROS in NQO1high tumor cells triggering oxidative stress and release of the damage signals for innate sensing. β-Lapachone-induced high mobility group box 1 (HMGB1) release activates the host TLR4/MyD88/type I interferon pathway and Batf3 dendritic cell-dependent cross-priming to bridge innate and adaptive immune responses against the tumor. Furthermore, targeting NQO1 is very potent to trigger innate sensing for T cell re-activation to overcome checkpoint blockade resistance in well-established tumors. Our study reveals that targeting NQO1 potently triggers innate sensing within TME that synergizes with immunotherapy to overcome adaptive resistance

Integrating microfluidics and biosensing on a single flexible acoustic device using hybrid modes

Integration of microfluidics and biosensing functionalities on a single device holds promise in continuous health monitoring and disease diagnosis for point-of-care applications. However, the required functions of fluid handling and biomolecular sensing usually arise from different actuation mechanisms. In this work, we demonstrate that a single acoustofluidic device, based on a flexible thin film platform, is able to generate hybrid waves modes, which can be used for fluidic actuation (Lamb waves) and biosensing (thickness shear waves). On this integrated platform, we show multiple and sequential functions of mixing, transport and disposal of liquid volumes using Lamb waves, whilst the thickness bulk shear waves allow us to sense the chemotherapeutic Imatinib, using an aptamer-based strategy, as would be required for therapy monitoring. Upon binding, the conformation of the aptamer results in a change in coupled mass, which has been detected. This platform architecture has the potential to generate a wide range of simple sample-to-answer biosensing acoustofluidic devices

Economic Burden for Lung Cancer Survivors in Urban China.

BackgroundWith the rapid increase in the incidence and mortality of lung cancer, a growing number of lung cancer patients and their families are faced with a tremendous economic burden because of the high cost of treatment in China. This study was conducted to estimate the economic burden and patient responsibility of lung cancer patients and the impact of this burden on family income.MethodsThis study uses data from a retrospective questionnaire survey conducted in 10 communities in urban China and includes 195 surviving lung cancer patients diagnosed over the previous five years. The calculation of direct economic burden included both direct medical and direct nonmedical costs. Indirect costs were calculated using the human capital approach, which measures the productivity lost for both patients and family caregivers. The price index was applied for the cost calculation.ResultsThe average economic burden from lung cancer was $43,336 per patient, of which the direct cost per capita was$42,540 (98.16%) and the indirect cost per capita was $795 (1.84$30,277 per capita, which accounted for 171% of the household annual income, a percentage that fell to 107% after subtracting the compensation from medical insurance.ConclusionsThe economic burden for lung cancer patients is substantial in the urban areas of China, and an effective control strategy to lower the cost is urgently needed

Alcohol-induced severe acute pancreatitis followed by hemolytic uremic syndrome managed with continuous renal replacement therapy

BACKGROUND: Acute kidney injury in patients with acute pancreatitis carries a poor prognosis. Hemolytic uremic syndrome (HUS) is characterized by non-immune hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney, and though rare in adults it is associated with high mortality and a high rate of chronic renal failure. CASE PRESENTATION: Herein, we report a case of alcohol-induced acute pancreatitis in a 38-year-old Chinese female complicated by HUS. Her renal function progressively deteriorated in 2 days, and daily continuous renal replacement therapy (CRRT) was thus performed for a total of 13 treatments. She also received intermittent transfusions of fresh frozen plasma. Her renal failure was successfully managed, with subsequent return of normal renal function. She was discharged 1 month after admission and follow-up at 3 months revealed normal urea and creatinine. CONCLUSION: CRRT was shown to be useful for the treatment of HUS following acute pancreatitis. Prior case reports and our case should remind clinicians that HUS is a possible complication of acute pancreatitis. This study highlights the importance of early diagnosis and prompt initiation of CRRT to prevent mortality and improve outcomes

miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy.

MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis