Terahertz-triggered ultrafast nonlinear optical activities in two-dimensional centrosymmetric PtSe2.

The nonlinear mechanisms of polarization and optical fields can induce extensive responses in materials. In this study, we report on two kinds of nonlinear mechanisms in the topological semimetal PtSe2 crystal under the excitation of intense terahertz (THz) pulses, which are manipulated by the real and imaginary parts of the nonlinear susceptibility of PtSe2. Regarding the real part, the broken inversion symmetry of PtSe2 is achieved through a THz-electric-field polarization approach, which is characterized by second harmonic generation (SHG) measurements. The transient THz-laser-induced SHG signal occurs within 100 fs and recombines to the equilibrium state within 1 ps, along with a high signal-to-noise ratio (∼51 dB) and a high on/off ratio (∼102). Regarding the imaginary part, a nonlinear absorption change can be generated in the media. We reveal a THz-induced absorption enhancement in PtSe2 via nonlinear transmittance measurements, and the sheet conductivity can be modulated up to 42% by THz electric fields in our experiment. Therefore, the THz-induced ultrafast nonlinear photoresponse reveals the application potential of PtSe2 in photonic and optoelectronic devices in the THz technology.

Long-term prognosis analysis of surgical therapy for bilateral synchronous multiple primary lung cancer: a follow-up of 293 cases.

Background: Bilateral synchronous multiple primary lung cancer (BSMPLC) presents significant clinical challenges due to its unique characteristics and prognosis. Understanding the risk factors that influence overall survival (OS) and recurrence-free survival (RFS) is crucial for optimizing therapeutic strategies for BSMPLC patients. Methods: We retrospectively analyzed clinical characteristics and treatment outcomes of 293 patients with BSMPLC who underwent surgical treatment between January 2010 and July 2017. Results: The 10-year OS and RFS rates were 96.1% and 92.8%, respectively. Preoperative forced expiratory volume in 1 second (FEV1) ≥70% [hazard ratio (HR), 0.214; 95% confidence interval (CI): 0.053 to 0.857], identical pathology types (HR, 9.726; 95% CI: 1.886 to 50.151), largest pT1 (HR, 7.123; 95% CI: 2.663 to 19.055), and absence of lymphovascular invasion (LVI; HR, 7.021; 95% CI: 1.448 to 34.032) emerged as independent predictors of improved OS. Moreover, the sum of tumor sizes less than or equal to 3 cm (HR, 6.229; 95% CI: 1.411 to 27.502) and absence of pleural invasion (HR, 3.442; 95% CI: 1.352 to 8.759) were identified as independent predictors of enhanced RFS. The presence or absence of residual nodules after bilateral surgery did not influence patients' OS (P=0.987) and RFS (P=0.054). Conclusions: Patients with BSMPLC who underwent surgery generally had a favorable prognosis. Whether or not to remove all nodules bilaterally does not affect the patient's long-term prognosis, suggesting the need for an individualized surgical approach.

Hollow metal tubes for efficient electron manipulation using terahertz surface waves.

Compact electron sources have been instrumental in multidiscipline sciences including fundamental physics, oncology treatments, and advanced industries. Of particular interest is the terahertz-driven electron manipulation that holds great promise for an efficient high gradient of multi-GeV/m inside a regular dielectric-lined waveguide (DLW). The recent study relying on terahertz surface waves has demonstrated both high terahertz energy and improved coupling efficiency with the DLW. However, the large energy spread pertaining to the laser-induced electron pulse impedes the practical use of the system. Here, we propose a scheme for extending the idea of surface-wave-driven electron manipulation to mature electron sources such as commercial direct-current and radio-frequency electron guns. By using a simple hollow cylinder tube for electron transmission, we show that the electron energy modulation can reach up to 860 keV, or compress the electron pulse width to 15 fs using a 2.9 mJ single-cycle terahertz pulse. The trafficability of the hollow tube also allows for a cascade of the system, which is expected to pave the way for compact and highly efficient THz-driven electron sources.

Gigahertz electromagnetic pulse emission from femtosecond relativistic laser-irradiated solid targets.

The interactions between high-intensity laser and matter produce particle flux and electromagnetic radiation over a wide energy range. The generation of extremely intense transient fields in the radio frequency-microwave regime has been observed in femtosecond-to-nanosecond laser pulses with 1011-1020-W/cm2 intensity on both conductive and dielectric targets. These fields typically cause saturation and damage to electronic equipment inside and near an experimental chamber; nevertheless, they can also be effectively used as diagnostic tools. Accordingly, the characterization of electromagnetic pulses (EMPs) is extremely important and currently a popular topic for present and future laser facilities intended for laser-matter interaction. The picosecond and sub-picosecond laser pulses are considerably shorter than the characteristic electron discharge time (∼0.1 ns) and can be efficient in generating GHz EMPs. The EMP characterization study of femtosecond laser-driven solid targets is currently mainly in the order of 100 mJ laser energy, in this study, the EMP generated by intense (Joule class) femtosecond laser irradiation of solid targets has been measured as a function of laser energy, laser pulse duration, focal spot size, and target materials. And a maximum electric field of the EMP reaching up to 105 V/m was measured. Analyses of experimental results confirm a direct correlation between measured EMP energy and laser parameters in the ultrashort pulse duration regime. The EMP signals generated by femtosecond laser irradiation of solid targets mainly originate from the return current inside the target after hot electron excitation. Numerical simulations of EMP are performed according to the target charging model, which agree well with the experimental results.

Perioperative outcomes of bi-pigtail catheter drainage strategy versus conventional chest tube after uniportal video-assisted thoracic lung surgery.

OBJECTIVES: Chest tube (CT) drainage is a main cause of postoperative pain in lung surgery. Here, we introduced a novel drainage strategy with bi-pigtail catheters (PCs) and conducted a randomized controlled trial to compare with conventional CT drainage after uniportal video-assisted thoracic surgery lung surgery. METHODS: A single-centre, prospective, open-labelled, randomized controlled trial (ChiCTR2000035337) was conducted with a preplanned sample size of 396. The primary outcome was the numerical pain rating scale (NPRS) on the first postoperative day. Secondary outcomes included other indicators of postoperative pain, drainage volume, duration of drainage, postoperative hospital stay, incidence of postoperative complications, CT reinsertion and medical costs. RESULTS: A total number of 396 patients were randomized between August 2020 and January 2021, 387 of whom were included in the final analysis. The baseline and clinical characteristics of the patients were well balanced between 2 groups. The NPRS on the first postoperative day was significantly lower in the PC group than in the CT group (2.40 ± 1.27 vs 3.02 ± 1.39, p < 0.001), as well as the second/third-day NPRS, the incidence of sudden severe pain (9/192, 4.7% vs 34/195, 17.4%, P < 0.001) and pain requiring intervention (19/192, 9.9% vs 46/195, 23.6%, P < 0.001). In addition, the medical cost in the PC group was lower (US$7809 ± 1646 vs US$8205 ± 1815, P = 0.025). Univariable and multivariable analyses revealed that the drainage strategy was the only factor influencing the incidence of pain requiring intervention. CONCLUSIONS: The drainage strategy with bi-PCs in patients undergoing uniportal video-assisted thoracic surgery lung surgery alleviates postoperative pain with adequate safety and efficacy.

Potential Value of FAPI PET/CT in the Detection and Treatment of Fibrosing Mediastinitis: Preclinical and Pilot Clinical Investigation.

Fibrosing mediastinitis (FM) is a rare proliferative disease within the mediastinum that leads to pulmonary hypertension, which has been regarded as a major cause of death. This study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-PET/CT in the integration of diagnosis and treatment of FM through targeting FAPI in fibrosis rats and provide a theoretical basis for clinical management of FM patients. By performing a 18F-FAPI PET/CT scan, the presence of FAPI-avid in the fibrotic lesion was determined. Through a fibrosis rat model, 18F-FAPI-74 was used for lesion imaging and 177Lu-FAPI-46 was utilized to investigate the potential therapeutic effect on FM in vivo. In addition, biodistribution analysis and radiation dosimetry were carried out. With the 177Lu-FAPI-46 pharmacokinetic data of rats as the input, the estimated dose for female adults was computed, which can provide some useful information for the safe application of radiolabeled FAPI in the detection and treatment of FM in patients. Then, major findings on the use of FAPI PET/CT and SPECT/CT in FM were presented. 18F-FAPI-74 showed a high-level uptake in FM lesions of patients (SUVmax 7.94 ± 0.26), which was also observed in fibrosis rats (SUVmax 2.11 ± 0.23). Consistently, SPECT/CT imaging of fibrosis rats also revealed that 177Lu-FAPI-46-avid was active for up to 60 h in fibrotic lesions. In addition to this robust diagnostic performance, a possible therapeutic impact was evaluated as well. It turned out that no spontaneous healing of lesions was observed in the control group, whereas there was complete healing on day 9, day 11, and day 14 in the 30, 100, and 300 MBq groups, respectively. With a significant difference in the free of event rate in the Kaplan-Meier curve among four groups (P < 0.001), a dose of 300 MBq displayed the best therapeutic effect, and no obvious damage was observed in the kidney. Furthermore, organ-absorbed doses and an effective dose (0.4320 mSv/MBq) of 177Lu-FAPI-46 presumed for patients were assumed to give a preliminary indication of its safe use in clinical practice. In conclusion, 18F-FAPI-46 PET/CT can be a potentially valuable tool for the diagnosis of FM. Of note, 177Lu-FAPI-46 may be a novel and safe radiolabeled reagent for the integration of diagnosis and treatment of FM.

Generation and characterization of intense terahertz pulses from DSTMS crystal.

Matter manipulation in terahertz range calls for a strong-field broadband light source. Here, we present a scheme for intense terahertz generation from DSTMS crystal driven by a high power optical parametric chirped pulse amplifier. The generated terahertz energy is up to 175 µJ with a peak electric field of 17 MV/cm. The relationship between terahertz energy, conversion efficiency, and pump fluence is demonstrated. This study provides a powerful driving light source for strong-field terahertz pump-probe experimentation.

Comparative study of the quantitative accuracy of oncological PET imaging based on deep learning methods.

Background: [18F] Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is an important tool for tumor assessment. Shortening scanning time and reducing the amount of radioactive tracer remain the most difficult challenges. Deep learning methods have provided powerful solutions, thus making it important to choose an appropriate neural network architecture. Methods: A total of 311 tumor patients who underwent 18F-FDG PET/CT were retrospectively collected. The PET collection time was 3 min/bed. The first 15 and 30 s of each bed collection time were selected to simulate low-dose collection, and the pre-90s was used as the clinical standard protocol. Low-dose PET was used as input, convolutional neural network (CNN, 3D Unet as representative) and generative adversarial network (GAN, P2P as representative) were used to predict the full-dose images. The image visual scores, noise levels and quantitative parameters of tumor tissue were compared. Results: There was high consistency in image quality scores among all groups [Kappa =0.719, 95% confidence interval (CI): 0.697-0.741, P<0.001]. There were 264 cases (3D Unet-15s), 311 cases (3D Unet-30s), 89 cases (P2P-15s) and 247 cases (P2P-30s) with image quality score ≥3, respectively. There was significant difference in the score composition among all groups (χ2=1,325.46, P<0.001). Both deep learning models reduced the standard deviation (SD) of background, and increased the signal-to-noise ratio (SNR). When 8%PET images were used as input, P2P and 3D Unet had similar enhancement effect on SNR of tumor lesions, but 3D Unet could significantly improve the contrast-noise ratio (CNR) (P<0.05). There was no significant difference in SUVmean of tumor lesions compared with s-PET group (P>0.05). When 17%PET image was used as input, SNR, CNR and SUVmax of tumor lesion of 3D Unet group had no statistical difference with those of s-PET group (P>0.05). Conclusions: Both GAN and CNN can suppress image noise to varying degrees and improve image quality. However, when 3D Unet reduces the noise of tumor lesions, it can improve the CNR of tumor lesions. Moreover, quantitative parameters of tumor tissue are similar to those under the standard acquisition protocol, which can meet the needs of clinical diagnosis.

Highly stable, flexible delivery of microjoule-level ultrafast pulses in vacuumized anti-resonant hollow-core fibers for active synchronization.

We demonstrate the stable and flexible light delivery of multi-microjoule, sub-200-fs pulses over a ∼10-m-long vacuumized anti-resonant hollow-core fiber (AR-HCF), which was successfully used for high-performance pulse synchronization. Compared with the pulse train launched into the AR-HCF, the transmitted pulse train out of the fiber exhibits excellent stabilities in pulse power and spectrum, with pointing stability largely improved. The walk-off between the fiber-delivery and the other free-space-propagation pulse trains, in an open loop, was measured to be <6 fs root mean square (rms) over 90 minutes, corresponding to a relative optical-path variation of <2 × 10-7. This walk-off can be further suppressed to ∼2 fs rms simply by using an active control loop, highlighting the great application potentials of this AR-HCF setup in large-scale laser and accelerator facilities.

The incremental significance of heart rate recovery as a predictor during exercise-stress myocardial perfusion SPECT imaging in individuals with suspected coronary artery disease.

Background: Major adverse cardiac events (MACE) are more likely to occur when abnormal heart rate recovery (HRR). This study aimed to assess the incremental predictive significance of HRR over exercise stress myocardial perfusion single-photon emission computed tomography (MPS) results for MACE in individuals with suspected coronary artery disease (CAD). Methods: Between January 2014 and December 2017, we continually gathered data on 595 patients with suspected CAD who received cycling exercise stress MPS. HRR at 1, 2, 3, and 4 min were used as study variables to obtain the optimal cut-off values of HRR for MACE. The difference between the peak heart rate achieved during exercise and the heart rate at 1, 2, 3, and 4 min was used to calculate the HRR, as shown in HRR3. Heart rate variations between two locations in time, such as HRR2 min-1 min, were used to establish the slope of HRR. All patients were followed for a minimum of 4 years, with MACE as the follow-up goal. The associations between HRR and MACE were assessed using Cox proportional hazards analyses. Results: Patients with MACE were older (P = 0.001), and they also had higher rates of hypertension, dyslipidemia, diabetes, abnormal MPS findings (SSS ≥ 5%), medication history (all P < 0.001), and lower HRR values (all P < 0.01). Patients with and without MACE did not significantly vary in their HRR4 min-3 min. The optimal cut-off of HRR1, 2, and 3 combined with SSS can stratify the risk of MACE in people with suspected CAD (all P < 0.001). HRR 1, 2, and 3 and its slope were linked to MACE in multivariate analysis, where HRR3 was the most significant risk predictor. With a global X2 increase from 101 to 126 (P < 0.0001), HRR3 demonstrated the greatest improvement in the model's predictive capacity, incorporating clinical data and MPS outcomes. Conclusions: HRR at 3 min has a more excellent incremental prognostic value for predicting MACE in patients with suspected CAD following cycling exercise stress MPS. Therefore, incorporating HRR at 3 min into known predictive models may further improve the risk stratification of the patients.

Design of Wideband High-Gain Patch Antenna Array for High-Temperature Applications.

A low-profile, wideband, and high-gain antenna array, based on a novel double-H-shaped slot microstrip patch radiating element and robust against high temperature variations, is proposed in this work. The antenna element was designed to operate in the frequency range between 12 GHz and 18.25 GHz, with a 41.3% fractional bandwidth (FBW) and an obtained peak gain equal to 10.2 dBi. The planar array, characterized by a feed network with a flexible 1 to 16 power divider, comprised 4 × 4 antenna elements and generated a pattern with a peak gain of 19.1 dBi at 15.5 GHz. An antenna array prototype was fabricated, and the measurements showed good agreement with the numerical simulations as the manufactured antenna operated in the range of 11.4-17 GHz, with a 39.4% FBW, and the peak gain at 15.5 GHz was 18.7 dBi. The high-temperature simulated and experimental results, performed in a temperature chamber, demonstrated that the array performance was stable in a wide temperature range, from -50 °C to 150 °C.

Generation of 13.9-mJ Terahertz Radiation from Lithium Niobate Materials.

Extremely strong-field terahertz (THz) radiation in free space has compelling applications in nonequilibrium condensed matter state regulation, all-optical THz electron acceleration and manipulation, THz biological effects, etc. However, these practical applications are constrained by the absence of high-intensity, high-efficiency, high-beam-quality, and stable solid-state THz light sources. Here, the generation of single-cycle 13.9-mJ extreme THz pulses from cryogenically cooled lithium niobate crystals and a 1.2% energy conversion efficiency from 800 nm to THz are demonstrated experimentally using the tilted pulse-front technique driven by a home-built 30-fs, 1.2-Joule Ti:sapphire laser amplifier. The focused peak electric field strength is estimated to be 7.5 MV cm-1 . A record of 1.1-mJ THz single-pulse energy at a 450 mJ pump at room temperature is produced and observed that the self-phase modulation of the optical pump can induce THz saturation behavior from the crystals in the substantially nonlinear pump regime. This study lays the foundation for the generation of sub-Joule THz radiation from lithium niobate crystals and will inspire more innovations in extreme THz science and applications.

An alarm device for mechanical compression device displacement at femoral artery puncture sites.

OBJECTIVE: To develop an alarm device for the mechanical compression device displacement (MCD), and further evaluate its effectiveness in clinical use. MATERIAL AND METHODS: The alarm device is mainly composed of buzzer, indicator light, magnetic sheet. This is a prospective randomized and controlled study. Four hundred patients who met the inclusion/exclusion criteria were included and randomly assigned to two groups (MCD group vs alarm + MCD group). The primary outcome measures were the sensitivity and specificity of the alarm device to detect MCD displacement, time to hemostasis (TTH), time to ambulation (TTA), time to hospital discharge (TTHD), hospital costs (HC), complication rates, and patient satisfaction. RESULTS: The sensitivity and specificity of the alarm device in detecting MCD displacement were 94.44% and 88.46%, respectively. The study group achieved shorter TTH (p = .034), shorter TTA (p = .021), lower complication rates (p = .025), and better patients' satisfaction (p < .001) compared to the control group. However, no significant difference was observed in TTHD (p = .361) and HC (p = .583). CONCLUSION: The alarm device is highly sensitive in detecting MCD displacement, while achieving better clinical outcomes compared with artificial monitoring.

Overcoming AZD9291 Resistance and Metastasis of NSCLC via Ferroptosis and Multitarget Interference by Nanocatalytic Sensitizer Plus AHP-DRI-12.

The acquired resistance to Osimertinib (AZD9291) greatly limits the clinical benefit of patients with non-small cell lung cancer (NSCLC), whereas AZD9291-resistant NSCLCs are prone to metastasis. It's challenging to overcome AZD9291 resistance and suppress metastasis of NSCLC simultaneously. Here, a nanocatalytic sensitizer (VF/S/A@CaP) is proposed to deliver Vitamin c (Vc)-Fe(II), si-OTUB2, ASO-MALAT1, resulting in efficient inhibition of tumor growth and metastasis of NSCLC by synergizing with AHP-DRI-12, an anti-hematogenous metastasis inhibitor by blocking the amyloid precursor protein (APP)/death receptor 6 (DR6) interaction designed by our lab. Fe2+ released from Vc-Fe(II) generates cytotoxic hydroxyl radicals (•OH) through Fenton reaction. Subsequently, glutathione peroxidase 4 (GPX4) is consumed to sensitize AZD9291-resistant NSCLCs with high mesenchymal state to ferroptosis due to the glutathione (GSH) depletion caused by Vc/dehydroascorbic acid (DHA) conversion. By screening NSCLC patients' samples, metastasis-related targets (OTUB2, LncRNA MALAT1) are confirmed. Accordingly, the dual-target knockdown plus AHP-DRI-12 significantly suppresses the metastasis of AZD9291-resistant NSCLC. Such modality leads to 91.39% tumor inhibition rate in patient-derived xenograft (PDX) models. Collectively, this study highlights the vulnerability to ferroptosis of AZD9291-resistant tumors and confirms the potential of this nanocatalytic-medicine-based modality to overcome critical AZD9291 resistance and inhibit metastasis of NSCLC simultaneously.

Performance of Chouioia cunea reared from a coleopteran alternative host as a biocontrol agent against the invasive lepidopteran pest, Hyphantria cunea.

BACKGROUND: Chouioia cunea is a generalist pupal endoparasitoid. Native to Eurasia, the parasitoid has been mass-reared on an alternative lepidopteran host (Antheraea pernyi) to successfully control the exotic invasive lepidopteran pest Hyphantria cunea in China. To solicit more accessible hosts, this study evaluated the potential of an easily cultured coleopteran beetle (Tenebrio molitor) as a substitute for rearing C. cunea through comparing the relative performance of the parasitoids reared from both alternative hosts on H. cunea. RESULTS: Compared with those reared from A. pernyi, the parasitoids reared from T. molitor (i.e., T. molitor vs. A. pernyi groups) performed equally well in terms of parasitism rate (94.4 vs. 88.9%), number of offspring produced per parasitized host (278 vs. 286), and female body length (1.334 vs. 1.351 mm), hind-tibia length (0.322 vs. 0.324 mm) and number of mature oocytes in the ovarioles (171 vs. 187), or even better based on offspring pre-emergence time (16.0 vs 16.9 days) and percentages of emerged offspring (99.8 vs. 99.1%) and female offspring (97.1 vs. 91.3%). Flight performance testing indicated that young C. cunea adults emerged from T. molitor had a similar percentage of actively flying wasps (76.9 vs. 72.9%) and a lower percentage of inactive wasps (2.3 vs. 10.6%) when compared to those reared from A. pernyi. CONCLUSION: Given the remarkable adaptability of C. cunea and the vast availability of T. molitor as a common resource insect worldwide, this indigenous parasitoid could be mass-reared on T. molitor to improve the prospect of biological control of H. cunea in its invaded regions. © 2022 Society of Chemical Industry.

Nuclear translocation of Gasdermin D sensitizes colorectal cancer to chemotherapy in a pyroptosis-independent manner.

Gasdermin D (GSDMD) has recently been identified as a cytoplasmic effector protein that plays a central role in pyroptosis of immune cells. However, GSDMD is a universally expressed protein, and its function beyond pyroptosis, especially in cancer cells, has not been well characterized. Here, we report that predominant localization of GSDMD in the nucleoplasm in vivo indicates favorable clinical outcomes in colorectal cancer, while a lack of nuclear localization of GSDMD is associated with poor outcomes. Nuclear GSDMD, rather than cytoplasmic GSDMD, inhibits cell growth and promotes apoptosis in colorectal cancer. Hypoxia in the tumor microenvironment accounts for mild or moderate nuclear translocation of GSDMD in vivo. Under the stimulation of chemotherapy drugs, nuclear GSDMD promotes apoptosis via regulation of its subcellular distribution rather than pyroptosis-related cleavage. After nuclear translocation, GSDMD interacts with PARP-1 to dramatically inhibit its DNA damage repair-related function by functioning like the PARP inhibitor olaparib, thus forming a "hypoxia/chemotherapy-GSDMD nuclear translocation-PARP-1 blockade-DNA damage and apoptosis" axis. This study redefines the pyroptosis-independent function of GSDMD and suggests that the subcellular localization of GSDMD may serve as a molecular indicator of clinical outcomes and a promising therapeutic target in colorectal cancer.

An esterase-activatable prodrug formulated liposome strategy: potentiating the anticancer therapeutic efficacy and drug safety.

Liposomal nanomedicine represents a common and versatile carrier for the delivery of both lipophilic and hydrophilic drugs. However, the direct formulation of many chemotherapeutics into a liposomal system remains an enormous challenge. Using the topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin (SN38) as a model drug, we combined lipophilic prodrug construction with subsequent integration into an exogenous liposomal scaffold to assemble a prodrug-formulated liposome for systemic administration. Reconstructing SN38 with lipid cholesterol via the esterase-activatable bond endows the resulting prodrug with elevated miscibility with liposomal compositions and esterase-responsive drug release in cancerous cells. The systemic administration of the prodrug-based nanoassemblies (Chol-SN38@LP) exhibited preferential accumulation of therapeutic payloads in tumor lesions. Compared to the SN38 clinical counterpart irinotecan, our prodrug-based nanoassemblies with adaptive features showed elevated therapeutic efficacy (∼1.5 times increase of tumor inhibition) in a preclinical A549 lung carcinoma cell-derived mouse model and improved drug tolerability (i.e., alleviated bloody diarrhea and liver damage) in multiple mice models. These results may be ascribed to extended systemic circulation and preferential tumor accumulation of our nanodrugs. Hence, our findings demonstrate that rational engineering of therapeutic nanomedicine is a promising approach for effective and safe delivery of antitumor chemotherapeutics, especially to rescue drug candidates that have failed in clinical trials owing to poor PK properties or severe toxicity in patients.

Development and validation of a prognostic predictive model of pulmonary spindle cell carcinoma from the surveillance, epidemiology and end results database.

Background: Pulmonary spindle cell carcinoma (PSCC) is a rare type of non-small cell lung cancer (NSCLC). The prognostic influent factors and therapeutic methods of PSCC are unclear, for there are only some case reports or small samples' analysis. This study aims to find prognosis related factors of PSCC, develop and validate a nomogram to predict their survival probability. Methods: The Surveillance, Epidemiology, and End Results (SEER) 18 Registries database (2000-2018) was searched to study PSCC. According to diagnosed time, data was divided into primary cohort (2000-2015) and validation cohort (2016-2018), both followed until December 31 2018. Chosen by Least Absolute Shrinkage and Selection Operator (LASSO) regression, age, sex, stage, surgery, chemotherapy, N, size and history of malignancy were taken out as predictive variables. The primary cohort was used to develop a nomogram to predict 1-, 3- and 5-year overall survival (OS) probability, and be validated by the validation cohort using concordance index (C-index) and calibration curves. Both cohorts were used to conduct a Cox regression to find the influential factors on OS of PSCC. Results: The nomogram shows a good concordance and discrimination on the prediction of OS, both internal (n=457 and C-index is 0.79) and external validation (n=100 and C-index is 0.76). The median survival time of PSCC is 4 months, with 20.1% OS possibility in 5 years. Multivariate analysis identified patients of older age [hazard ratio (HR), 1.02; 95% confidence interval (CI): 1.01-1.04], larger size of neoplasm (HR, 1.01; 95% CI: 1.01-1.01), M1 (HR, 2.96; 95% CI: 2.17-4.04), N2 (HR, 2.55; 95% CI: 1.81-3.59) or N3 (HR, 2.99; 95% CI: 1.58-5.66), regional stages (HR, 2.11; 95% CI: 1.29-3.44) and distant stages (HR, 6.17; 95% CI: 3.83-9.94) had a lower OS possibility, while surgery (HR, 0.39; 95% CI: 0.28-0.53) and history of malignancy (HR, 0.68; 95% CI: 0.48-0.98) was protective factors for PSCC. PSCC survived longer with surgery performed instead of chemotherapy or radiotherapy. Conclusions: Patients of PSCC have a poor prognosis, and using the nomogram developed by this study can predict their 1-, 3- and 5-year OS probability. Surgery is a better choice for PSCC and more studies are necessary to find potential treatment like targeted therapy, programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1).

Soluble programmed cell death-ligand 1 as a new potential biomarker associated with acute coronary syndrome.

Background: Soluble programmed cell death-ligand 1 (sPD-L1) has been well documented to activate immunosuppression and is considered an essential predictor of negative clinical outcomes for several malignances and inflammatory conditions. However, the clinical significance of sPD-L1 in the peripheral blood of patients with coronary artery disease (CAD) remains unclear. The aim of this study was to assess the correlations of sPD-L1 with clinical features in CAD patients and evaluate the diagnostic value of this protein in CAD. Methods: A total of 111 CAD patients and 97 healthy volunteers who served as healthy controls (HCs) were consecutively enrolled. Plasma levels of sPD-L1 were measured with an amplified enzyme-linked immunosorbent assay (ELISA), and hs-CRP was measured with a C-reactive protein assay kit. The levels of other inflammatory cytokines were assessed in 88 CAD patients and 47 HCs by a multiparameter immunoluminescence flow cytometry detection technique. A logistic regression model was used to assess the independent association of sPD-L1 with acute coronary syndrome (ACS). The correlation between sPD-L1 and inflammatory cytokines in ACS was also assessed. Results: Plasma levels of sPD-L1 were significantly increased in CAD patients, especially those with ACS. Univariate logistic regression analysis revealed that sPD-L1 (OR: 3.382, 95% CI: 2.249-5.084, p < 0.001), BMI, hypertension, diabetes, dyslipidemia, previous MI, and the levels of HDL-C, LDL-C and hs-CRP were significantly associated with ACS. sPD-L1 (OR: 3.336, 95% CI: 1.084-6.167, p = 0.001) was found to be independently and significantly associated with ACS in the subsequent multivariable logistic regression analysis. Additionally, elevated plasma sPD-L1 levels were associated with increased interleukin-6 and interleukin-8 levels in ACS patients. Receiver operating characteristic (ROC) analysis showed that the AUC of sPD-L1 for diagnosing ACS was 0.778, with a sensitivity of 73.9% and a specificity of 73.4%, which was comparable with that of the inflammatory biomarker hs-CRP. Conclusion: The plasma sPD-L1 level reflects the severity of CAD, is associated with inflammatory responses and is a potential new biomarker for the diagnosis of ACS.

Long-Read Sequencing Annotation of the Transcriptome in DNA-PK Inactivated Cells.

The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) with a Ku70/Ku80 heterodimer constitutes the intact DNA-PK kinase, which is an upstream component of the DNA repair machinery that signals the DNA damage, orchestrates the DNA repair, and serves to maintain genome integrity. Beyond its role in DNA damage repair, the DNA-PK kinase is also implicated in transcriptional regulation and RNA metabolism, with an illuminated impact on tumor progression and therapeutic responses. However, the efforts to identify DNA-PK regulated transcriptomes are limited by short-read sequencing to resolve the full complexity of the transcriptome. Therefore, we leveraged the PacBio Single Molecule, Real-Time (SMRT) Sequencing platform to study the transcriptome after DNA-PK inactivation to further underscore the importance of its role in diseases. Our analysis revealed additional novel transcriptome and complex gene structures in the DNA-PK inactivated cells, identifying 8,355 high-confidence new isoforms from 3,197 annotated genes and 523 novel genes. Among them, 380 lncRNAs were identified. We validated these findings using computational approaches and confirmatory transcript quantification with short-read sequencing. Several novel isoforms representing distinct splicing events have been validated through PCR experiments. Our analyses provide novel insights into DNA-PK function in transcriptome regulation and RNA metabolism.