Suppression of viral RNA polymerase activity is necessary for persistent infection during the transformation of measles virus into SSPE virus.

Subacute sclerosing panencephalitis (SSPE) is a fatal neurodegenerative disease caused by measles virus (MV), which typically develops 7 to 10 years after acute measles. During the incubation period, MV establishes a persistent infection in the brain and accumulates mutations that generate neuropathogenic SSPE virus. The neuropathogenicity is closely associated with enhanced propagation mediated by cell-to-cell fusion in the brain, which is principally regulated by hyperfusogenic mutations of the viral F protein. The molecular mechanisms underlying establishment and maintenance of persistent infection are unclear because it is impractical to isolate viruses before the appearance of clinical signs. In this study, we found that the L and P proteins, components of viral RNA-dependent RNA polymerase (RdRp), of an SSPE virus Kobe-1 strain did not promote but rather attenuated viral neuropathogenicity. Viral RdRp activity corresponded to F protein expression; the suppression of RdRp activity in the Kobe-1 strain because of mutations in the L and P proteins led to restriction of the F protein level, thereby reducing cell-to-cell fusion mediated propagation in neuronal cells and decreasing neuropathogenicity. Therefore, the L and P proteins of Kobe-1 did not contribute to progression of SSPE. Three mutations in the L protein strongly suppressed RdRp activity. Recombinant MV harboring the three mutations limited viral spread in neuronal cells while preventing the release of infectious progeny particles; these changes could support persistent infection by enabling host immune escape and preventing host cell lysis. Therefore, the suppression of RdRp activity is necessary for the persistent infection of the parental MV on the way to transform into Kobe-1 SSPE virus. Because mutations in the genome of an SSPE virus reflect the process of SSPE development, mutation analysis will provide insight into the mechanisms underlying persistent infection.

PTGR1-mediated immune evasion mechanisms in late-stage triple-negative breast cancer: mechanisms of M2 macrophage infiltration and CD8+ T cell suppression.

Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by metabolic dysregulation. Tumor cell immune escape plays an indispensable role in the development of TNBC tumors. Furthermore, in the abstract, we explicitly mention the techniques used and enhance the clarity and impact of our findings. "Based on bioinformatics analysis results, we utilized CRISPR/Cas9 technology to knockout the target gene and established a mouse model of breast cancer. Through experiments such as CCK8, scratch assay, and Transwell assay, we further investigated the impact of target gene knockout on the malignant behavior of tumor cells. Subsequently, we conducted immunohistochemistry and Western Blot experiments to study the expression of macrophage polarization and infiltration-related markers and evaluate the effect of the target gene on macrophage polarization. Next, through co-culture experiments, we simulated the tumor microenvironment and used immunohistochemistry staining to observe and analyze the distribution and activation status of M2 macrophages and CD8+ T cells in the co-culture system. We validated in vivo experiments the molecular mechanism by which the target gene regulates immune cell impact on TNBC progression.

Effects of volunteering over six months on loneliness, social and mental health outcomes among older adults: The HEAL-HOA Dual Randomized Controlled Trial.

OBJECTIVE: To determine the beneficial effects of volunteering as lay counselor via telephone on own loneliness, social network engagement, perceived social support, stress, anxiety, and depressive symptoms among Chinese older adults in Hong Kong during the COVID-19 pandemic. DESIGN, SETTING, INTERVENTION, AND PARTICIPANTS: "Helping Alleviate Loneliness in Hong Kong Older Adults" (HEAL-HOA), a dual randomized controlled trial, was implemented to test effects of telephone-based psychosocial interventions delivered by older-adult volunteers for low-income lonely older adults. To evaluate the effects of volunteering on loneliness, we randomized 375 individuals ages 50-70 into a volunteering condition versus an active control (psychoeducation with social gatherings). Following a 6-week training, participants in the volunteering condition, delivered tele-interventions to older intervention recipients. MEASUREMENT: The primary outcome was loneliness measured with the UCLA Loneliness Scale. Secondary outcomes were loneliness measured with the De Jong Gierveld Scale (DJG), social network engagement, perceived social support, perceived stress, anxiety, and depressive symptoms. Assessments were completed before training (baseline) and immediately after the 6-month volunteering period. RESULTS: Results from linear mixed models show significant positive effects of volunteering (significant interactions of condition × time) on both measures of loneliness (dppc2 = -0.41 ULCA Loneliness score, dppc2 = -0.70 total DJG score), social network engagement, stress and depressive symptoms as compared to control participants. CONCLUSIONS: The HEAL-HOA trial demonstrates beneficial effects of volunteer-delivered tele-interventions on decreasing loneliness on the volunteer interventionists themselves. Communicating these benefits for volunteers may attract more older adults into volunteering. This effective tele-based volunteer program is scalable for wider implementation. SUMMARY: This RCT tested effects of volunteering on loneliness in Hong Kong during the COVID-19-pandemic. Three hundred seventy-five individuals ages 50-70 were randomized into volunteering (delivering tele-interventions against loneliness) versus an active control condition. After 6 months, volunteers compared to controls, showed benefits on loneliness, social network engagement, stress and depressive symptoms. A program engaging lonely older adults in loneliness intervention delivery has beneficial effects on volunteers themselves and could be a scalable solution for our loneliness epidemic.

Effects of Wisdom-Enhancement Narrative-Therapy and Empathy-Focused interventions on loneliness over 4 weeks among older adults: A Randomized Controlled Trial.

OBJECTIVE: In this three-armed RCT, we tested the effects of a telephone-delivered wisdom enhancement narrative therapy-based intervention (Tele-NT) and a telephone-delivered empathy-focused intervention (Tele-EP) in reducing loneliness against an active control group that received regular call (ACG) at the 4-week follow-up assessment. DESIGN, SETTING, INTERVENTION, AND PARTICIPANTS: To evaluate the effects of the interventions on loneliness, we randomized 287 older adults based in Hong Kong, ages 65 to 90, into Tele-NT (N = 97), Tele-EP (N = 95), or ACG (N = 95). MEASUREMENT: The primary outcome was loneliness, calculated using the De Jong Gierveld Scale and the UCLA Loneliness Scale. Secondary outcomes were sleep quality, depressive symptoms, social network engagement, and perceived social support. Assessments were done before training and 4 weeks after the intervention period. RESULTS: Results from linear mixed models showed significant positive effects of Tele-NT on loneliness measured by the De Jong Gierveld Loneliness Scale compared to ACG. Compared to the ACG, the Tele-NT group significantly reduced loneliness at the 4-week follow-up (mean difference = -0.51, p = 0.019, Cohen's d = 0.60). However, the difference between Tele-EP and the ACG at the 4-week follow-up was not significant (MD = -0.34, p = 0.179, Cohen's d = 0.49). Tele-NT and Tele-EP did not show significant effects on the secondary outcomes, compared to the ACG. CONCLUSIONS: In this randomized clinical trial, we found that a 4-week wisdom enhancement narrative therapy program significantly reduced feelings of loneliness. This effective telephone-based, lay-therapist-delivered program is scalable for broader implementation.

Cells in the liver microenvironment regulate the process of liver metastasis.

The research of liver metastasis is a developing field. The ability of tumor cells to invade the liver depends on the complicated interactions between metastatic cells and local subpopulations in the liver (including Kupffer cells, hepatic stellate cells, liver sinusoidal endothelial cells, and immune-related cells). These interactions are mainly mediated by intercellular adhesion and the release of cytokines. Cell populations in the liver microenvironment can play a dual role in the progression of liver metastasis through different mechanisms. At the same time, we can see the participation of liver parenchymal cells and nonparenchymal cells in the process of liver metastasis of different tumors. Therefore, the purpose of this article is to summarize the relationship between cellular components of liver microenvironment and metastasis and emphasize the importance of different cells in the occurrence or potential regression of liver metastasis.

Misremembering Solitude: The Role of Personality and Cultural Self-Concepts in Shaping Discrepancies Between Recalled and Concurrent Affect in Solitude.

BACKGROUND: Affect recall is key to psychological assessment and decision-making. However, self-concepts (self-beliefs) may bias retrospective affect reports such that they deviate from lived experiences. Does this experience-memory gap apply to solitude experiences? We hypothesized that individuals misremember how they feel overall and when in solitude, in line with self-concepts of introversion, self-determined/not-self-determined solitude motivations, and independent/interdependent self-construal. A pilot study comparing retrospective to daily affect reports captured over 2 weeks (N = 104 UK university students) provided preliminary evidence of introversion and not-self-determined solitude shaping affect recall. METHODS: In the main pre-registered study, participants aged 18-49 in the UK (N = 160) and Hong Kong (N = 159) reported their momentary affective states and social situations 5 times per day over 7 days, then recalled how they felt over the week. RESULTS AND DISCUSSION: Individuals higher in self-determined solitude were more prone to retrospectively overestimate their high- and low-arousal positive affect in solitude and showed less overestimation/more underestimation of negative affect in solitude. Higher not-self-determined solitude was associated with overestimating loneliness, and higher interdependent self-construal with overestimating loneliness and energy levels, in solitude. Comparisons based on residence/ethnicity suggest culture influences solitude-seeking and affective memory. Implications for well-being and affect measurement are discussed.

Reducing discrepancies between actual and ideal affect across adulthood: the roles of activity flow conduciveness, pleasantness, and familiarity.

Previous findings demonstrate that people often do not feel how they want to feel, supporting the distinction between "actual affect" and "ideal affect." But are there certain activities that reduce the discrepancy between actual and ideal affect? Based on flow theory and socioemotional selectivity theory, we examined whether the discrepancy between people's actual and ideal positive affect would be smaller during activities that were more conducive to flow (a state of intense absorption and concentration), pleasant, and familiar. In Study 1, U.S. participants aged 17-79 (N = 393) reported their ideal affect and how they felt during activities with varying degrees of challenges and skills. For both low-arousal positive affect (LAP) and high-arousal positive affect (HAP), participants reported smaller actual-ideal affect discrepancies during flow-conducive activities (when skills matched challenges). Study 2 was a 14-day experience sampling study, in which Hong Kong participants aged 18-83 (Nindividual = 109) reported their momentary actual and ideal affect, and how pleasant and familiar their activities were (Nexperience = 3,815). Greater activity familiarity was associated with smaller discrepancies in actual-ideal LAP, while greater activity pleasantness was associated with smaller discrepancies in actual-ideal HAP. These findings provide insights on the activities that help people achieve their ideal affect more easily.

[Medicinal plant biodiversity in Jilin province based on big data of the fourth national survey of traditional Chinese medicine resources].

Using Origin2022Pro, PAST4.09, GraphPad, and ArcGIS, this study analyzed the big data of the fourth national survey of traditional Chinese medicine resources in Jilin province from five dimensions: differences in resource quantity, taxonomic group, family, and genus, regional distribution, and spatiotemporal distribution, aiming to fully elucidate the biodiversity of medicinal plants in Jilin province. The results indicated that 2 241 species of medicinal plants existed in Jilin province, belonging to 881 genera of 243 families, with 20 dominant families and 3 dominant genera. There were 1 901 species of medicinal plants(belonging to 778 genera of 227 families) in the eastern mountainous region, 1 503 species(belonging to 690 genera of 225 families) in the mid-mountainous areas of the central mountainous region, and 811 species(belonging to 436 genera of 136 families) in the western plain region. The biodiversity of medicinal plants in Jilin province was high and presented a trend of high in the east and low in the west. The medicinal plant resources were mainly concentrated in the eastern mountainous region, and the number of medicinal plant groups had significant diffe-rences between regions, following the trend of western region > central region > eastern region. The species richness was in the order of eastern region > western region > central region. The species diversity structure in the central region was similar to that in the eastern and western regions, while it was significantly different between the western and eastern regions. Compared with the third national survey of traditional Chinese medicine resources, the fourth survey showed an increase of 1 417 species, a decrease of 580 species, and 824 common species, indicating significant changes in the biodiversity of medicinal plants in Jilin province. The reasons for these changes need to be further explored. This article elucidates the background and biodiversity changes of medicinal plant resources in Jilin province, laying a foundation for the protection, utilization, and industrial development of traditional Chinese medicine resources in Jilin province.

Safety and efficacy of apatinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma after the failure of two or more lines of chemotherapy (AHEAD): a prospective, single-arm, multicenter, phase IV study.

BACKGROUND: Apatinib, a highly selective VEGFR2 inhibitor, significantly improved efficacy versus placebo as a third- and later-line treatment for advanced gastric cancer in phase 2 and 3 trials. This prospective, single-arm, multicenter phase IV AHEAD study was conducted to verify the safety and efficacy of apatinib in patients with advanced or metastatic gastric or gastroesophageal adenocarcinoma after at least two lines of systematic therapy in clinical practice settings. METHODS: Patients with advanced gastric cancer who had previously failed at least two lines of chemotherapy received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Adverse events were summarized by the incidence rate. Median OS and PFS were estimated using the Kaplan-Meier method. ORR, DCR, OS at 3 and 6 months, and PFS at 3 and 6 months were calculated, and their 95% CIs were estimated according to the Clopper-Pearson method. RESULTS: Between May 2015 and November 2019, a total of 2004 patients were enrolled, and 1999 patients who received at least one dose of apatinib were assessed for safety. In the safety population, 87.9% of patients experienced treatment-related adverse events (TRAEs), with the most common hypertension (45.2%), proteinuria (26.5%), and white blood cell count decreased (25.3%). Additionally, 51% of patients experienced grade ≥ 3 TRAEs. Fatal TRAEs occurred in 57 (2.9%) patients. No new safety concerns were reported. Among the 2004 patients included in the intention-to-treat population, the ORR was 4.4% (95% CI, 3.6-5.4%), and DCR was 35.8% (95% CI, 33.7-38.0%). The median PFS was 2.7 months (95% CI 2.2-2.8), and the median OS was 5.8 months (95% CI 5.4-6.1). CONCLUSIONS: The findings in the AHEAD study confirmed the acceptable and manageable safety profile and clinical benefit of apatinib in patients with advanced gastric cancer as a third- or later-line of treatment. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov NCT02426034. Registration date was April 24, 2015.

Safety, efficacy and pharmacokinetics of BPI-9016M in c-MET overexpression or MET exon 14 skipping mutation patients with locally advanced or metastatic non-small-cell lung cancer: a phase Ib study.

BACKGROUND: As a potential target receptor tyrosine kinase, mesenchymal-epithelial transition factor (MET) exhibits high aberrant expression across various tumors. This study aimed to evaluated the safety, tolerability, efficacy and pharmacokinetics (PK) of BPI-9016M, a novel tyrosine kinase inhibitor (TKI) targeting c-MET, in c-MET overexpression or MET exon 14 skipping mutation patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). METHODS/DESIGN: In this two-part multicenter phase Ib study, eligible patients with locally advanced or metastatic NSCLC harboring c-MET overexpression or MET exon 14 skipping mutation were enrolled into Part A (tested positive for c-MET overexpression [immunohistochemical staining score ≥ 2+]; 300 mg quaque die [QD], 450 mg QD and 600 mg QD cohorts) or Part B (tested positive for MET exon 14 skipping mutation; 400 mg bis in die [BID] cohort), respectively. The primary endpoints were safety, objective response rate (ORR) and disease control rate (DCR), the second endpoints were PK parameters, progression-free survival (PFS) and overall survival (OS). RESULTS: Between March 15, 2017 and September 18, 2021, 38 patients were enrolled (Part A, n = 34; Part B, n = 4). Of 38 patients, 32 (84.2%) patients completed the treatment protocol. As of the data cut-off date on January 27, 2022, all patients reported at least one treatment-emergent adverse event (TEAE). Ninety-two point one percent (35/38) of patients experienced treatment-related adverse events (TRAEs), and grade ≥ 3 TRAEs were observed in 11 (28.9%) patients. The most common TRAEs were elevated alanine aminotransferase (ALT, 14/38, 36.8%) and elevated aspartate aminotransferase (AST, 11/38, 28.9%). Only one (2.6%) patient had treatment-related serious adverse event (SAE) in 600 mg QD cohort due to thrombocytopenia. PK analysis showed BPI-9016M and its main metabolites (M1 and M2-2) reached steady state after seven days of continuous administration. At the dose of 300 mg QD and 450 mg QD, the exposure of BPI-9016M increased with increasing dose. Exposure of BPI-9016M was similar at 450 mg QD and 600 mg QD, which may exhibit a saturation trend. In all patients, ORR and DCR were 2.6% (1/38, 95% confidence interval [CI] 0.1-13.8%) and 42.1% (16/38, 95% CI 26.3-59.2%), respectively. Only one partial response (PR) patient was observed at a dose of 600 mg QD in Part A. In Part B, DCR was 75.0% (3/4, 95% CI 19.4-99.4%). The median PFS and OS in all 38 patients were 1.9 months (95% CI 1.9-3.7) and 10.3 months (95% CI 7.3-not evaluable [NE]), respectively. CONCLUSION: BPI-9016M showed manageable safety profile in c-MET overexpression or MET exon 14 skipping mutation patients with locally advanced or metastatic NSCLC, but showed limited efficacy. TRIAL REGISTRATION: Clinicaltrials.gov NCT02929290 (11/10/2016).

Nitration of Pyrrolo[2,1-a]isoquinolines.

We have successfully modified a series of pyrrolo[2,1-a]isoquinolines via direct nitration under mild reaction conditions. Easily accessible nitrates including CAN, Cu(NO3)2·H2O, and Fe(NO3)3·9H2O all can serve as effective nitrating reagents for functionalizing pyrrolo[2,1-a]isoquinolines. Various nitro-bearing pyrrolo[2,1-a]isoquinolines have been efficiently prepared in acceptable to good yields.

Recent progress in the oxidative bromination of arenes and heteroarenes.

Oxidative bromination has been serving as a powerful tool for the synthesis of bromo-containing molecules, as this bromination strategy features environmental friendliness, high flexibility in reaction system design and wide abundance of bromide sources and oxidants. The past decade has witnessed a large number of efficient oxidative bromination reaction systems and novel brominated aromatics. This review summarizes recent developments in the field of oxidative preparation of bromoarenes and bromoheteroarenes covering from 2012 to 2022.

An Integrated Autonomous Dynamic Navigation Approach toward a Composite Air-Ground Risk Construction Scenario.

Unmanned transportation in construction scenarios presents a significant challenge due to the presence of complex dynamic on-ground obstacles and potential airborne falling objects. Consequently, the typical methodology for composite air-ground risk avoidance in construction scenarios holds enormous importance. In this paper, an integrated potential-field-based risk assessment approach is proposed to evaluate the threat severity of the environmental obstacles. Meanwhile, the self-adaptive dynamic window approach is suggested to manage the real-time motion planning solution for air-ground risks. By designing the multi-objective velocity sample window, we constrain the vehicle's speed planning instructions within reasonable limits. Combined with a hierarchical decision-making mechanism, this approach achieves effective obstacle avoidance with multiple drive modes. Simulation results demonstrate that, in comparison with the traditional dynamic window approach, the proposed method offers enhanced stability and efficiency in risk avoidance, underlining its notable safety and effectiveness.

Serplulimab, a novel anti-PD-1 antibody, in patients with microsatellite instability-high solid tumours: an open-label, single-arm, multicentre, phase II trial.

BACKGROUND: Microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) tumours have a high response rate to immunotherapy. Antitumour activity and safety of serplulimab, a novel humanised anti-PD-1 monoclonal antibody, were evaluated in this phase II study. METHODS: In this ongoing, single-arm, open-label, phase II trial, patients with previously treated unresectable or metastatic MSI-H/dMMR solid tumours received intravenous serplulimab 3 mg/kg every 2 weeks for up to 52 cycles. The primary endpoint was objective response rate (ORR) assessed by an independent radiological review committee per Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included additional efficacy measures, safety, and tolerability. RESULTS: As of 9 January 2021, 108 patients were enrolled, and 68 patients with confirmed MSI-H solid tumours were included in the main efficacy analysis population (MEAP). The median follow-up duration in the MEAP was 7.7 months, with an ORR of 38.2% (95% confidence interval, 26.7-50.8). Of the 108 patients, grade ≥3 treatment-emergent adverse events were reported in 53 (49.1%) patients; immune-related adverse events occurred in 52 (48.1%) patients. CONCLUSIONS: Serplulimab demonstrates a durable antitumour effect and a manageable safety profile in previously treated patients with MSI-H solid tumours. Serplulimab is a promising tissue-agnostic treatment for previously treated MSI-H solid tumours. TRIAL REGISTRATION: NCT03941574.

Phase Ia/Ib Study of the Selective MET Inhibitor, Savolitinib, in Patients with Advanced Solid Tumors: Safety, Efficacy, and Biomarkers.

BACKGROUND: Savolitinib has shown good tolerability and preliminary efficacy, but efficacy biomarkers require investigation. The main purpose of this study was to confirm in Chinese patients the recommended phase II dose (RP2D) of savolitinib and to explore overall benefit in tumors bearing c-Met aberration. METHODS: This was an open-label, multi-center, 2-part phase I study. A starting dose of 600 mg QD was initiated in the escalation phase, utilizing a 3+3 design with repeated QD and BID dosing. In the dose expansion phase, we enrolled patients with gastric cancer and non-small cell lung cancer (NSCLC) with documented c-met aberration into 5 cohorts to further explore biomarkers. c-Met overexpression and amplification were assessed by immunohistochemistry and FISH, respectively. RESULTS: The safety analysis set included 85 patients. Only one dose-limiting toxicity (grade 3 fatigue) was reported in the 600 mg BID dosing group. The most frequent treatment-related adverse events were nausea (29.4%), vomiting (27.1%), and peripheral edema (21.2%). Notably, in gastric cancer, response was only observed in patients with MET amplification (copy number 9.7-18.4), with an objective response rate of 35.7% and a disease control rate of 64.3%. For patients with NSCLC bearing a MET exon 14 skipping mutation, obvious target lesion shrinkage was observed in 2 of 4 patients, although PR was not achieved. CONCLUSION: The RP2D of savolitinib was established as 600 mg QD or 500 mg BID in Chinese patients. The promising response observed in patients with gastric cancer with c-met amplification and NSCLC with MET exon 14 skipping mutation warrants further investigation. CLINICALTRIALS.GOV IDENTIFIER: NCT0198555.

BRD4 inhibition exerts anti-viral activity through DNA damage-dependent innate immune responses.

Chromatin dynamics regulated by epigenetic modification is crucial in genome stability and gene expression. Various epigenetic mechanisms have been identified in the pathogenesis of human diseases. Here, we examined the effects of ten epigenetic agents on pseudorabies virus (PRV) infection by using GFP-reporter assays. Inhibitors of bromodomain protein 4 (BRD4), which receives much more attention in cancer than viral infection, was found to exhibit substantial anti-viral activity against PRV as well as a range of DNA and RNA viruses. We further demonstrated that BRD4 inhibition boosted a robust innate immune response. BRD4 inhibition also de-compacted chromatin structure and induced the DNA damage response, thereby triggering the activation of cGAS-mediated innate immunity and increasing host resistance to viral infection both in vitro and in vivo. Mechanistically, the inhibitory effect of BRD4 inhibition on viral infection was mainly attributed to the attenuation of viral attachment. Our findings reveal a unique mechanism through which BRD4 inhibition restrains viral infection and points to its potent therapeutic value for viral infectious diseases.

Perioperative Aspirin Use Is Associated with Bleeding Complications during Robotic Partial Nephrectomy.

PURPOSE: Daily aspirin use following cardiovascular intervention is commonplace and creates concern regarding bleeding risk in patients undergoing surgery. Despite its cardio-protective role, aspirin is often discontinued 5-7 days prior to major surgery due to bleeding concerns. Single institution studies have investigated perioperative outcomes of aspirin use in robotic partial nephrectomy (RPN). We sought to evaluate the outcomes of perioperative aspirin (pASA) use during RPN in a multicenter setting. MATERIALS AND METHODS: We performed a retrospective evaluation of patients undergoing RPN at 5 high volume RPN institutions. We compared perioperative outcomes of patients taking pASA (81 mg) to those not on aspirin. We analyzed the association between pASA use and perioperative transfusion. RESULTS: Of 1,565 patients undergoing RPN, 228 (14.5%) patients continued pASA and were older (62.8 vs 56.8 years, p <0.001) with higher Charlson scores (mean 3 vs 2, p <0.001). pASA was associated with increased perioperative blood transfusions (11% vs 4%, p <0.001) and major complications (10% vs 3%, p <0.001). On multivariable analysis, pASA was associated with increased transfusion risk (OR 1.94, 1.10-3.45, 95% CI). CONCLUSIONS: In experienced hands, perioperative aspirin 81 mg use during RPN is reasonable and safe; however, there is a higher risk of blood transfusions and major complications. Future studies are needed to clarify the role of antiplatelet therapy in RPN patients requiring pASA for primary or secondary prevention of cardiovascular events.

A data-driven method to learn a jump diffusion process from aggregate biological gene expression data.

Dynamic models of gene expression are urgently required. In this paper, we describe the time evolution of gene expression by learning a jump diffusion process to model the biological process directly. Our algorithm needs aggregate gene expression data as input and outputs the parameters of the jump diffusion process. The learned jump diffusion process can predict population distributions of gene expression at any developmental stage, obtain long-time trajectories for individual cells, and offer a novel approach to computing RNA velocity. Moreover, it studies biological systems from a stochastic dynamic perspective. Gene expression data at a time point, which is a snapshot of a cellular process, is treated as an empirical marginal distribution of a stochastic process. The Wasserstein distance between the empirical distribution and predicted distribution by the jump diffusion process is minimized to learn the dynamics. For the learned jump diffusion process, its trajectories correspond to the development process of cells, the stochasticity determines the heterogeneity of cells, its instantaneous rate of state change can be taken as "RNA velocity", and the changes in scales and orientations of clusters can be noticed too. We demonstrate that our method can recover the underlying nonlinear dynamics better compared to previous parametric models and the diffusion processes driven by Brownian motion for both synthetic and real world datasets. Our method is also robust to perturbations of data because the computation involves only population expectations.

Correlations of Triglyceride with Type, Severity and Clinical Prognosis of Acute Pancreatitis.

BACKGROUND: The aim of this study was to explore the correlations of triglyceride (TG) with type, severity, and prognosis of acute pancreatitis (AP). METHODS: A total of 184 AP patients treated from January 2017 to June 2019 were selected. The severity and prognosis were assessed through modified computed tomography severity index (MCTSI) score and sequential organ failure assessment (SOFA) score, respectively. They were divided into biliary AP (BAP) and hyperlipidemic AP (HLAP) groups, and their blood lipid levels were compared. According to TG level, they were divided into normal and elevation groups (> 1.70 mmol/L), and the general data, severity, and prognosis were compared. The elevation group was further divided into mild, moderate, and severe elevation groups, and severity and prognosis were compared. Logistic regression analysis was performed with presence or absence of severe AP (SAP) and systemic inflammatory response syndrome (SIRS) as dependent variables. RESULTS: The levels of TG, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (Apo-A1), and Apo-B in the HLAP group were significantly higher than those in the BAP group (p < 0.05). Age, gender ratio, and body mass index had significant differences between normal and elevation groups (p < 0.05). Compared with the normal group, the numbers of cases of SAP, SIRS and pleural effusion, MCTSI score and SOFA score significantly rose, and the relief time of abdominal pain and length of hospital stay were significantly prolonged in the elevation group (p < 0.05). The number of cases of SAP, SIRS, and pleural effusion was significantly greater in the severe elevation group than that in the other three groups (p < 0.05), and the number of SIRS cases was significantly greater in the mild and moderate elevation groups than that in the normal group (p < 0.05). TG was an independent risk factor for SAP and SIRS (p < 0.05). CONCLUSIONS: Patients with TG elevation mostly suffer from HLAP. Higher TG level meant higher tendency of SAP, higher incidence rate of SIRS and worse prognosis of AP patients.

Novel mutation signatures in the prognosis of EGFR-TKIs targeted therapy for non-small cell lung cancer patients based on the 1000-gene panel sequencing.

The application of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) may be affected by somatic mutations. The purpose of this study was to explore the effect of mutations on the prognosis and tumor markers of NSCLC patients treated with EGFR-TKIs. 21 NSCLC patients treated with EGFR-TKIs were selected, and the targeted sequencing of the tumor tissues or whole blood samples with the 1000-gene panel was conducted to screen mutations. Afterward, functional enrichment analysis was performed based on mutant genes. Subsequently, the correlation between mutations and clinical indicators, prognosis, and tumor markers were analyzed. Finally, the prognosis after taking osimertinib was compared between NSCLC patients with EGFR p.T790M positive and negative mutations, and the EGFR p.T790M concomitant and uncommon mutations were screened. A total of 485 mutations in 251 genes were identified, in which MTOR, AXIN2, AR, EGFR, NOTCH1, and HRAS mutations were significantly correlated with PFS and/or tumor markers. There was no significant difference in PFS, therapeutic effect, and prognosis between EGFR p.T790M positive and negative patients who received osimertinib treatment. Besides, we also found 80 concomitant mutations and 54 uncommon mutations of EGFR p.T790M. AR, HRAS, EGFR, AXIN2, NOTCH1, and MTOR might be key genes to the prognosis of NSCLC treated with EGFR-TKIs. Osimertinib has certain efficacy in EGFR p.T790M negative NSCLC patients.