Immunotherapy combined with apatinib in the treatment of advanced or metastatic gastric/gastroesophageal tumors: a systematic review and meta-analysis.

BACKGROUND: Immunotherapy or apatinib alone has been used as third-line adjuvant therapy for advanced or metastatic gastric/gastroesophageal junction (G/GEJ) tumors, but the efficacy of combining them with each other for the treatment of patients with advanced or metastatic G/GEJ is unknown; therefore, we further evaluated the efficacy and safety of immunotherapy combined with apatinib in patients with advanced or metastatic G/GEJ. METHODS: The main search was conducted on published databases: Embase, Cochrane library, PubMed.The search was conducted from the establishment of the database to December 2023.Clinical trials with patients with advanced or metastatic G/GEJ and immunotherapy combined with apatinib as the study variable were collected. Review Manager 5.4 software as well as stata 15.0 software were used for meta-analysis. RESULTS: A total of 651 patients from 19 articles were included in this meta-analysis. In the included studies, immunotherapy combined with apatinib had a complete response (CR) of 0.03 (95% CI: 0.00 -0.06), partial response (PR) of 0.34 (95% CI: 0.19-0.49), stable disease (SD) of 0.43 (95% CI: 0.32-0.55), objective response rate (ORR) was 0.36 (95% CI: 0.23-0.48), disease control rate (DCR) was 0.80 (95% CI: 0.74-0.86), and median progression-free survival (PFS) was 4.29 (95% CI: 4.05-4.52), median Overall survival (OS) was 8.79 (95% CI: 7.92-9.66), and the incidence of grade ≥ 3 TRAEs was 0.34 (95% CI: 0:19-0.49). PR, ORR, DCR, median PFS and median OS were significantly higher in the immunotherapy and apatinib combination chemotherapy group (IAC) than in the immunotherapy combination apatinib group (IA). And the difference was not significant in the incidence of SD and grade ≥ 3 TRAEs. CONCLUSION: This meta-analysis shows that immunotherapy combined with apatinib is safe and effective in the treatment of advanced or metastatic G/GEJ, where IAC can be a recommended adjuvant treatment option for patients with advanced or metastatic G/GEJ. However, more large multicenter randomized studies are urgently needed to reveal the long-term outcomes of immunotherapy combined with apatinib treatment.

pDenoiser: A Personalized Speech Enhancement Neural Network for Pre-hospital Emergency Medical Services.

Pre-hospital emergency medical service (EMS) tasks often come with complex and diverse noise interferences, posing challenges in implementing ASR-based medical technologies and hindering efficient and accurate telephonic communication. Among the different types of noise distortion, interfering speech is especially annoying. To address these issues, our aim is to develop a technology capable of extracting the intended speech content of the target physician from noisy and mixed audio during EMS tasks. In this work, we propose a monoaural personalized speech enhancement (PSE) method called pDenoiser, which is a real-time neural network that operates in the time domain. By leveraging the prior vocalization cues of emergency physicians, pDenoiser selectively enhances target speech components while suppressing noise and nontarget speech components, thereby improving speech quality and speech recognition accuracy under noisy conditions. We demonstrate the potential value of our approach through evaluations on both public general-domain test sets and our self-collected real-world EMS test sets. The experimental results are promising, as our model effectively promotes both speech quality and ASR performance under various conditions and outperforms related methods across multiple evaluation metrics. Our methodology will hopefully elevate EMS efficiency and fortify security against nontarget speech during EMS tasks.

GhCLCc-1, a Chloride Channel Gene from Upland Cotton, Positively Regulates Salt Tolerance by Modulating the Accumulation of Chloride Ions.

The ionic toxicity induced by salinization has adverse effects on the growth and development of crops. However, researches on ionic toxicity and salt tolerance in plants have focused primarily on cations such as sodium ions (Na+), with very limited studies on chloride ions (Cl-). Here, we cloned the homologous genes of Arabidopsis thaliana AtCLCc, GhCLCc-1A/D, from upland cotton (Gossypium hirsutum), which were significantly induced by NaCl or KCl treatments. Subcellular localization showed that GhCLCc-1A/D were both localized to the tonoplast. Complementation of Arabidopsis atclcc mutant with GhCLCc-1 rescued its salt-sensitive phenotype. In addition, the silencing of the GhCLCc-1 gene led to an increased accumulation of Cl- in the roots, stems, and leaves of cotton seedlings under salt treatments, resulting in compromised salt tolerance. And ectopic expression of the GhCLCc-1 gene in Arabidopsis reduced the accumulation of Cl- in transgenic lines under salt treatments, thereby enhancing salt tolerance. These findings elucidate that GhCLCc-1 positively regulates salt tolerance by modulating Cl- accumulation and could be a potential target gene for improving salt tolerance in plants.

Arsenic effectively improves the degradation of fluorene by Rhodococcus sp. 2021 under the combined pollution of arsenic and fluorene.

The performance of bacterial strains in executing degradative functions under the coexistence of heavy metals/heavy metal-like elements and organic contaminants is understudied. In this study, we isolated a fluorene-degrading bacterium, highly arsenic-resistant, designated as strain 2021, from contaminated soil at the abandoned site of an old coking plant. It was identified as a member of the genus Rhodococcus sp. strain 2021 exhibited efficient fluorene-degrading ability under optimal conditions of 400 mg/L fluorene, 30 °C, pH 7.0, and 250 mg/L trivalent arsenic. It was noted that the addition of arsenic could promote the growth of strain 2021 and improve the degradation of fluorene - a phenomenon that has not been described yet. The results further indicated that strain 2021 can oxidize As3+ to As5+; here, approximately 13.1% of As3+ was converted to As5+ after aerobic cultivation for 8 days at 30 °C. The addition of arsenic could greatly up-regulate the expression of arsR/A/B/C/D and pcaG/H gene clusters involved in arsenic resistance and aromatic hydrocarbon degradation; it also aided in maintaining the continuously high expression of cstA that codes for carbon starvation protein and prmA/B that codes for monooxygenase. These results suggest that strain 2021 holds great potential for the bioremediation of environments contaminated by a combination of arsenic and polycyclic aromatic hydrocarbons. This study provides new insights into the interactions among microbes, as well as inorganic and organic pollutants.

Evaluation of neoadjuvant immunotherapy in resectable gastric/gastroesophageal junction tumors: a meta-analysis and systematic review.

Background: Neoadjuvant therapy for resectable gastric cancer/gastroesophageal junction tumors is progressing slowly. Although immunotherapy for advanced gastric cancer/gastroesophageal junction tumors has made great progress, the efficacy and safety of neoadjuvant immunotherapy for locally resectable gastric cancer/gastroesophageal junction tumors have not been clearly demonstrated. Here, we conducted a systematic review and meta-analysis to assess the efficacy and safety of neoadjuvant immunotherapy and advance the current research. Methods: Original articles describing the safety and efficacy of neoadjuvant immunotherapy for resectable gastric cancer/gastroesophageal junction tumors published up until October 15, 2023 were retrieved from PubMed, Embase, the Cochrane Library, and other major databases. The odds ratios (OR) and 95% confidence intervals (CIs) were calculated for heterogeneity and subgroup analysis. Results: A total of 1074 patients from 33 studies were included. The effectiveness of neoadjuvant immunotherapy was mainly evaluated using pathological complete remission (PCR), major pathological remission (MPR), and tumor regression grade (TRG). Among the included patients, 1015 underwent surgical treatment and 847 achieved R0 resection. Of the patients treated with neoadjuvant immunotherapy, 24% (95% CI: 19%-28%) achieved PCR and 49% (95% CI: 38%-61%) achieved MPR. Safety was assessed by a surgical resection rate of 0.89 (95% CI: 85%-93%), incidence of ≥ 3 treatment-related adverse events (TRAEs) of 28% (95% CI: 17%-40%), and incidence of ≥ 3 immune-related adverse events (irAEs) of 19% (95% CI: 11%-27%). Conclusion: Neoadjuvant immunotherapy, especially neoadjuvant dual-immunotherapy combinations, is effective and safe for resectable gastric/gastroesophageal junction tumors in the short term. Nevertheless, further multicenter randomized trials are required to demonstrate which combination model is more beneficial. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=358752, identifier CRD42022358752.

Towards an Environmentally Robust Speech Assistant System for Emergency Medical Services.

Automated speech recognition technology with robust performance in various environments is highly needed by emergency clinicians, but there are few successful cases. One main challenge is the wide variety of environmental interference involved during a typical prehospital care emergency service such as background noises and overlapping speech. To solve this problem, we try to establish an environmentally robust speech assistant system with the help of the proposed personalized speech enhancement (PSE) method, which utilizes the target physician's voiceprint feature to suppress non-target signal components. We demonstrate its potential value using both general public test set and our real EMS test set by evaluating the objective speech quality metrics, DNSMOS, and the recognition accuracy. Hopefully, the proposed method will raise EMS efficiency and security against non-target speech.

Clinical study of thoracoscopic assisted different surgical approaches for early thymoma: a meta-analysis.

OBJECTIVE: The efficacy and safety of subxiphoid thoracoscopic thymectomy (SVATS) for early thymoma are unknown. The purposes of this meta-analysis were to evaluate the effectiveness and safety of SVATS for early thymoma, to compare it with unilateral intercostal approach video thoracoscopic surgery (IVATS) thymectomy, and to investigate the clinical efficacy of modified subxiphoid thoracoscopic thymectomy (MSVATS) for early anterior mediastinal thymoma. METHODS: Original articles describing subxiphoid and unilateral intercostal approaches for thoracoscopic thymectomy to treat early thymoma published up to March 2023 were searched from PubMed, Embase, and the Cochrane Library. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated and analyzed for heterogeneity. Clinical data were retrospectively collected from all Masaoka stage I and II thymoma patients who underwent modified subxiphoid and unilateral intercostal approach thoracoscopic thymectomies between September 2020 and March 2023. The operative time, intraoperative bleeding, postoperative drainage, extubation time, postoperative hospital stay, postoperative visual analog pain score (VAS), and postoperative complications were compared, and the clinical advantages of the modified subxiphoid approach for early-stage anterior mediastinal thymoma were analyzed. RESULTS: A total of 1607 cases were included in the seven studies in this paper. Of these, 591 cases underwent SVATS thymectomies, and 1016 cases underwent IVATS thymectomies. SVATS thymectomy was compared with IVATS thymectomy in terms of age (SMD = - 0.09, 95% CI: -0.20 to - 0.03, I2 = 20%, p = 0.13), body mass index (BMI; SMD = - 0.10, 95% CI: -0.21 to - 0.01, I2 = 0%, p = 0.08), thymoma size (SMD = - 0.01, 95% CI: -0.01, I2 = 0%, p = 0.08), operative time (SMD = - 0.70, 95% CI: -1.43-0.03, I2 = 97%, p = 0.06), intraoperative bleeding (SMD = - 0.30. 95% CI: -0.66-0.06, I2 = 89%, p = 0.10), time to extubation (SMD = - 0.34, 95%CI: -0.73-0.05, I2 = 91%, p = 0.09), postoperative hospital stay (SMD = - 0.40, 95% CI: -0.93-0.12, I2 = 93%, p = 0.13), and postoperative complications (odds ratio [OR] = 0.94, 95% CI: 0.42-2.12, I2 = 57%, p = 0.88), which were not statistically significantly different between the SVATS and IVATS groups. However, the postoperative drainage in the SVATS group was less than that in the IVATS group (SMD = - 0.43, 95%CI: -0.84 to - 0.02, I2 = 88%, p = 0.04), and the difference was statistically significant. More importantly, the postoperative VAS was lower in the SVATS group on days 1 (SMD = - 1.73, 95%CI: -2.27 to - 1.19, I2 = 93%, p < 0.00001), 3 (SMD = - 1.88, 95%CI: -2.84 to - 0.81, I2 = 97%, p = 0.0005), and 7 (SMD = - 1.18, 95%CI: -2.28 to - 0.08, I2 = 97%, p = 0.04) than in the IVATS group, and these differences were statistically significant. A total of 117 patients undergoing thoracoscopic thymectomy for early thymoma in the Department of Thoracic Surgery of the Second Hospital of Jilin University were retrospectively collected and included in the analysis, for which a modified subxiphoid approach was used in 42 cases and a unilateral intercostal approach was used in 75 cases. The differences between the two groups (MSVATS vs. IVATS) in general clinical characteristics such as age, sex, tumor diameter, Masaoka stage, Word Health Organization (WHO) stage, and intraoperative and postoperative conditions, including operative time, postoperative drainage, extubation time, postoperative hospital stay, and postoperative complication rates, were not statistically significant (p > 0.05), while BMI, intraoperative bleeding, and VAS on postoperative days 1, 3, and 7 were all statistically significant (p < 0.05) in the MSVATS group compared with the IVATS group. CONCLUSION: The meta-analysis showed that the conventional subxiphoid approach was superior in terms of postoperative drainage and postoperative VAS pain scores compared with the unilateral intercostal approach. Moreover, the modified subxiphoid approach had significant advantages in intraoperative bleeding and postoperative VAS pain scores compared with the unilateral intercostal approach. These results indicate that MSVATS can provide more convenient operation conditions, a better pleural cavity view, and a more complete thymectomy in the treatment of early thymoma, indicating that is a safe and feasible minimally invasive surgical method.

Thermal Emission Manipulation Enabled by Nano-Kirigami Structures.

The nano-kirigami metasurfaces have controllable 3D geometric parameters and dynamic transformation functions and therefore provide a strong spectral regulation capability of thermal emission. Here, the authors propose and demonstrate a dynamic and multifunctional thermal emitter based on deformable nano-kirigami structures, which can be actuated by electronic bias or mechanical compression. Selective emittance and the variation of radiation intensity/wavelength are achieved by adjusting the geometric shape and the transformation of the structures. Particularly, a thermal management device based on a composite structure of nano-kirigami and polydimethylsiloxane (PDMS) thin film is developed, which can dynamically switch the state of cooling and heating by simply pressing the device. The proposed thermal emitter designs with strong regulation capability and multiple dynamic adjustment strategies are desirable for energy and sensing applications and inspire further development of infrared emitters.

An unmanned emergency blood dispatch system based on an early prediction and fast delivery strategy: Design and development study.

BACKGROUND AND OBJECTIVE: For severe trauma patients, hemorrhage is the most common cause of medically preventable deaths. Early transfusion is beneficial to major hemorrhagic patients. However, the early supply of emergency blood products for major hemorrhagic patients is still a major problem in many areas. The aim of this study was to design and develop an unmanned emergency blood dispatch system for the fast delivery of blood resources and rapid emergency response to trauma events, especially those with mass hemorrhagic trauma patients and those occurred in remote areas. METHODS: Based on the process of emergency medical services for trauma patients, we introduced unmanned aerial vehicle (UAV) and designed the main flowchart of the dispatch system, which combines an emergency transfusion prediction model and UAV-related dispatch algorithms to improve first aid efficiency and quality. The system identifies patients in need of emergency transfusion through a multidimensional prediction model. Then, by analyzing the blood center, hospitals and UAV stations nearby, the system recommends the patient's transfer destination for emergency transfusion and dispatch schemes of UAVs and trucks for a fast supply of blood products. Simulation experiments of urban and rural scenarios were conducted to evaluate the proposed system. RESULTS: The developed emergency transfusion prediction model of the proposed system achieves a higher AUROC value of 0.8453 than a classical transfusion prediction score. In the urban experiment, by adopting the proposed system, the average wait time per patient decreased from 32 to 18 min, and the total time decreased from 42 to 29 min. Owing to the combination of the prediction and the fast delivery function, the proposed system took 4 and 11 min less wait time than the strategy with only the prediction function and the strategy with only the fast delivery function, respectively. In the rural experiment, for trauma patients requiring an emergency transfusion at 4 locations, the wait time for transfusion under the proposed system was 16.54, 17.08, 38.70 and 46.00 min less than that under the conventional strategy. The health status-related score increased by 6.9%, 0.9%, 19.1% and 36.7%, respectively. CONCLUSIONS: Experimental results demonstrate that the proposed system works well with a faster blood supply speed for severe hemorrhagic patients and better health status. With the assistance of the system, emergency doctors at the scene of an injury are able to comprehensively analyze patients' status and the surrounding rescue conditions and then make decisions, especially when encountering mass casualties or casualties in remote areas.

Serum cytokine levels and other associated factors as possible immunotherapeutic targets and prognostic indicators for lung cancer.

Lung cancer is one of the most prevalent cancer types and the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all cancer incidences. Lung cancer therapy and prognosis largely depend on the disease's degree at the diagnosis time. Cytokines are soluble polypeptides that contribute to cell-to-cell communication, acting paracrine or autocrine on neighboring or distant cells. Cytokines are essential for developing neoplastic growth, but they are also known to operate as biological inducers following cancer therapy. Early indications are that inflammatory cytokines such as IL-6 and IL-8 play a predictive role in lung cancer. Nevertheless, the biological significance of cytokine levels in lung cancer has not yet been investigated. This review aimed to assess the existing literature on serum cytokine levels and additional factors as potential immunotherapeutic targets and lung cancer prognostic indicators. Changes in serum cytokine levels have been identified as immunological biomarkers for lung cancer and predict the effectiveness of targeted immunotherapy.

Efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced esophageal cancer: A meta-analysis.

Objective: The progress of neoadjuvant therapy for resectable locally advanced esophageal cancer has been stagnant. There has been much progress in immunotherapy for advanced esophageal cancer, but the efficacy and safety of neoadjuvant immunotherapy for resectable locally advanced esophageal cancer have not yet been definitively demonstrated. Methods: Original articles describing the safety and efficacy of neoadjuvant immunotherapy in resectable locally advanced esophagus published until July 2022 were retrieved from PubMed, Embase, and the Cochrane Library. The ratio (OR) and 95% confidence interval (CI) were calculated to conduct heterogeneity and subgroup analysis. Results: In total, 759 patients from 21 studies were enrolled. The effectiveness of neoadjuvant immunotherapy in combination with chemotherapy was evaluated using the major pathologic response (MPR) and pathologic complete response (PCR). In the enrolled patients, 677 were treated surgically and 664 achieved R0 resection. Major pathological remission was achieved in 52.0% (95% CI: 0.44-0.57) of patients on neoadjuvant immunotherapy combined with chemotherapy and complete pathological remission in 29.5% (95% CI: 0.25-0.32) of patients. The safety was primarily assessed by the incidence of treatment-related adverse events (TRAEs) and surgical resection rates. The incidence of TRAEs and the surgical resection rate combined ORs were 0.15 (95% CI: 0.09-0.22) and 0.86 (95% CI: 0.83-0.89), respectively. Conclusion: Neoadjuvant immunotherapy combined with chemotherapy in locally advanced resectable esophageal cancer is effective and safe.

Modified subcostal arch xiphoid thoracoscopic expanded thymectomy for thymic carcinoma: a case report and review of literature.

Thymic neoplasms are a relatively uncommon tumor, with the anterior mediastinum being the most common. Median sternotomy is the procedure of choice for the treatment of thymomas. With the advent of thoracoscopy, an increasing number of countries are adopting the right thoracic approach for the treatment of thymomas, but there are still no clear surgical standards or modalities to treat thymic carcinoma. We propose a modified subxiphoid subcostal arch thoracoscopic enlarged thymectomy to treat thymic carcinoma based on various reviews. We have also reviewed the relevant literature on the subject of evidence-based medicine. The evaluation of CD70 in combination with CD5 and CD117 or preferentially expressed antigen in melanoma in combination with CD5 and CD117 may help to diagnose thymic squamous cell carcinoma (TSCC) more accurately. The modified thoracoscopic expanded thymic resection under the costal arch of the xiphoid process is not only suitable for TSCC but also for thymic cyst, thymoma, locally invasive thymoma, and thymic carcinoma.

[Advances in bioremediation of polycyclic aromatic hydrocarbons contaminated soil].

Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent pollutants that are widely distributed in the environment. Due to their stable structure and poor degradability, PAHs exhibit carcinogenic, teratogenic, and mutagenic toxicity to the ecological environment and organisms, thus increasing attentions have been paid to their removals and remediation. Green, safe and economical technologies are widely used in the bioremediation of PAHs-contaminated soil. This article summarizes the present status of PAHs pollution in soil of China from the aspects of origin, migration, fate, and pollution level. Meanwhile, the types of microorganisms and plants capable of degrading PAHs, as well as the underlying mechanisms, are summarized. The features of three major bioremediation technologies, i.e., microbial remediation, phytoremediation, and joint remediation, are compared. Analysis of the interaction mechanisms between plants and microorganisms, selection and cultivation of stress-resistant strains and plants, as well as safety and efficacy evaluation of practical applications, are expected to become future directions in this field.

Degradation and regeneration of Fe-N x active sites for the oxygen reduction reaction: the role of surface oxidation, Fe demetallation and local carbon microporosity.

The severe degradation of Fe-N-C electrocatalysts during a long-term oxygen reduction reaction (ORR) has become a major obstacle for application in proton-exchange membrane fuel cells. Understanding the degradation mechanism and regeneration of aged Fe-N-C catalysts would be of particular interest for extending their service life. Herein, we show that the by-product hydrogen peroxide during the ORR not only results in the oxidation of the carbon surface but also causes the demetallation of Fe active sites. Quantitative analysis reveals that the Fe demetallation constitutes the main reason for catalyst degradation, while previously reported carbon surface oxidation plays a minor role. We further reveal that post thermal annealing of the aged catalysts can transform the oxygen functional groups on the carbon surface into micropores. These newly formed micropores not only help to increase the active-site density but also the intrinsic ORR activity of the neighbouring Fe-N4 sites, both contributing to complete activity recovery of aged Fe-N-C catalysts.

Protective effect of anisodamine on bleomycin-induced acute lung injury in immature rats via modulating oxidative stress, inflammation, and cell apoptosis by inhibiting the JAK2/STAT3 pathway.

BACKGROUND: Pediatric acute lung injury (ALI) is one of the most common causes of infant mortality. Although lung-protective strategies have developed in recent years, no ALI treatment is currently available. Anisodamine (Ani) is a common drug used to treat gastrointestinal smooth muscle spasm. The protective effects of Ani against acute kidney injury and myocardial injury have been reported. However, the efficacy of Ani on bleomycin (BLM)-induced ALI has not been examined previously. In the present study, we aimed to examine the effects of Ani on bleomycin (BLM)-induced ALI on immature rats. METHODS: The ALI rat model was established by intratracheally administration of BLM. Ani treatment was performed by an intravenous injection at different concentrations. The lung function of each rat was measured, and then lung tissue structures, apoptosis, and collagen deposition were observed by hematoxylin-eosin staining, terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling assay, and Masson's staining, respectively. Enzyme-linked immunosorbent assay was used to detect the levels of inflammatory cytokines. The expression of apoptosis-related proteins and fibrosis-related markers was determined by reverse transcription-polymerase chain reaction and/or Western blot analysis. Finally, the expression levels of Janus tyrosine kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were determined. RESULTS: Our findings indicated that lung function was remarkably decreased in BLM-induced rats, which could be reversed by Ani. Ani treatment increased the levels of antioxidant enzymes, decreased the apoptotic rate and apoptosis-related proteins, and downregulated the expression of fibrosis-related markers. Additionally, Ani treatment also attenuated inflammatory response and suppressed the activation of the JAK2/STAT3 pathway. CONCLUSIONS: Our results demonstrated that Ani had potent activity against BLM-induced ALI in immature rats through inhibiting the JAK2/STAT3 signaling pathway. Our findings provide supporting evidence to further investigate the therapeutic effect of Ani against ALI in children.

Gender Differences in Depression: Evidence From Genetics.

Compared with men, female accounts for a larger proportion of patients with depression. Behavioral genetics researches find gender differences in genetic underpinnings of depression. We found that gender differences exist in heritability and the gene associated with depression after reviewing relevant research. Both genes and gene-environment interactions contribute to the risk of depression in a gender-specific manner. We detailed the relationships between serotonin transporter gene-linked promoter region (5-HTTLPR) and depression. However, the results of these studies are very different. We explored the reasons for the contradictory conclusions and provided some suggestions for future research on the gender differences in genetic underpinnings of depression.

MiR-1471 protects the aggravation of non-small-cell lung carcinoma by targeting FOXL1.

This study detected the expression pattern of miR-1471 in non-small-cell lung cancer (NSCLC) tissues, and analyzed the prognostic significance of miR-1471 in NSCLC. Subsequently, potential targets of miR-1471 were screened for assessing the potential molecular mechanism in NSCLC. A total of 47 primary NSCLC cases treated by radical resection and systematic lymphadenectomy in the department of thoracic surgery were collected, as well as their clinical data. MiR-1471 levels in NSCLC tissues were detected by quantitative real-time polymerase chain reaction. The prognostic potential of miR-1471 in NSCLC was assessed by Kaplan-Meier method, followed by log-rank test. Potential target genes of miR-1471 and the binding sites were predicted by bioinformatics analysis, and screened for the optimal one. The binding relationship between miR-1471 and the target FOXL1 was examined by dual-luciferase reporter assay. Subsequently, biological functions of miR-1471 and FOXL1 in NSCLC cell functions were explored by cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) assay and flow cytometry. MiR-1471 was downregulated in NSCLC tissues and its level was correlated to TNM staging in NSCLC patients. Overall survival was poor in NSCLC patients expressing low level of miR-1471. Overexpression of miR-1471 attenuated proliferative ability and arrested cell cycle progression in G1/S phase. FOXL1 was confirmed to be the target gene binding miR-1471. Its expression pattern and biological functions in NSCLC cells were contrary to those of miR-1471. MiR-1471 is downregulated in NSCLC samples, which is related to TNM staging and prognosis in NSCLC patients. Therefore, miR-1471 suppresses the malignant aggravation of NSCLC via inhibiting the translation of FOXL1 mRNA. In addition, it could be used as an effective biomarker for predicting the prognosis in NSCLC.

Fast Time Synchronization on Tens of Picoseconds Level Using Uncombined GNSS Carrier Phase of Zero/Short Baseline.

Since the observation precision of the Global Navigation Satellite System (GNSS) carrier phase is on the order of millimeters, if the phase ambiguity is correctly solved, while calibrating the receiver inter-frequency bias, time synchronization on the order of tens of picoseconds is expected. In this contribution, a method that considers the prior constraints of the between-receiver inter-frequency bias (IFB) and its random variation characteristics is proposed for the estimation of the between-receiver clock difference, based on the uncombined GNSS carrier phase and pseudorange observations of the zero and short baselines. The proposed method can rapidly achieve the single-difference ambiguity resolution of the zero and short baselines, and then obtain the high-precision relative clock offset, by using only the carrier phase observations, along with the between-receiver IFBs being simultaneously determined. Our numerical tests, carried out using GNSS observations sampled every 30 s by a dedicatedly selected set of zero and short baselines, show that the method can fix the between-receiver single-difference ambiguity successfully within an average of fewer than 2 epochs (interval 30 s). Then, a clock difference between two receivers with millimeter precision is obtained, achieving time synchronization on tens of picoseconds level, and deriving a frequency stability of 5 × 10-14 for averaging times of 30,000 s. Furthermore, the proposed approach is compared with the precise point positioning (PPP) time transfer method. The results show that, for different types of receivers, the agreement between the two methods is between -6.7 ns and 0.2 ns.

A COVID-19 Risk Assessment Decision Support System for General Practitioners: Design and Development Study.

BACKGROUND: The coronavirus disease (COVID-19) has become an urgent and serious global public health crisis. Community engagement is the first line of defense in the fight against infectious diseases, and general practitioners (GPs) play an important role in it. GPs are facing unique challenges from disasters and pandemics in delivering health care. However, there is still no suitable mobile management system that can help GPs collect data, dynamically assess risks, and effectively triage or follow-up with patients with COVID-19. OBJECTIVE: The aim of this study is to design, develop, and deploy a mobile-based decision support system for COVID-19 (DDC19) to assist GPs in collecting data, assessing risk, triaging, managing, and following up with patients during the COVID-19 outbreak. METHODS: Based on the actual scenarios and the process of patients using health care, we analyzed the key issues that need to be solved and designed the main business flowchart of DDC19. We then constructed a COVID-19 dynamic risk stratification model with high recall and clinical interpretability, which was based on a multiclass logistic regression algorithm. Finally, through a 10-fold cross-validation to quantitatively evaluate the risk stratification ability of the model, a total of 2243 clinical data consisting of 36 dimension clinical features from fever clinics were used for training and evaluation of the model. RESULTS: DDC19 is composed of three parts: mobile terminal apps for the patient-end and GP-end, and the database system. All mobile terminal devices were wirelessly connected to the back end data center to implement request sending and data transmission. We used low risk, moderate risk, and high risk as labels, and adopted a 10-fold cross-validation method to evaluate and test the COVID-19 dynamic risk stratification model in different scenarios (different dimensions of personal clinical data accessible at an earlier stage). The data set dimensions were (2243, 15) when only using the data of patients' demographic information, clinical symptoms, and contact history; (2243, 35) when the results of blood tests were added; and (2243, 36) after obtaining the computed tomography imaging results of the patient. The average value of the three classification results of the macro-area under the curve were all above 0.71 in each scenario. CONCLUSIONS: DCC19 is a mobile decision support system designed and developed to assist GPs in providing dynamic risk assessments for patients with suspected COVID-19 during the outbreak, and the model had a good ability to predict risk levels in any scenario it covered.

Curcumin inhibits cell viability, migration, and invasion of thymic carcinoma cells via downregulation of microRNA-27a.

Curcumin (CUR) is a kind of polyphenolic compound and widely used in the treatment of diseases. However, the involvement of CUR in thymic carcinoma remains unknown. The object of our research is to clarify the role of CUR and related regulatory mechanism in thymic carcinoma cells. After treatment with CUR for 24 hr, cell viability, apoptosis, migration, and invasion of TC1889 cells were measured. Real-time polymerase chain reaction was executed to examine the expression of microRNA-27a (miR-27a) in thymic carcinoma tissues and TC1889 cells. After miR-27a mimic transfection, whether miR-27a is involved in CUR-modulated cell behaviors was measured. Finally, western blot was utilized to detect mTOR and Notch 1 pathways-linked proteins. CUR restrained cell viability and increased cell apoptosis of TC1889 cells. In addition, cell migration and invasion were restrained by CUR. Meanwhile, miR-27a expression was positively regulated in thymic carcinoma tissues and downregulated by CUR in TC1889 cells. Overexpressed miR-27a reversed the CUR-induced reduction of growth, migration, and invasion in TC1889 cells. Furthermore, CUR blocked mTOR and Notch 1 pathways via downregulating miR-27a. We demonstrated that CUR blocked mTOR and Notch 1 pathways via downregulating miR-27a, thereby suppressing cell growth, migration, and invasion of thymic carcinoma cells.