Deciphering a global source of non-genetic heterogeneity in cancer cells.

Cell-to-cell variability within a clonal population, also known as non-genetic heterogeneity, has created significant challenges for intervening with diseases such as cancer. While non-genetic heterogeneity can arise from the variability in the expression of specific genes, it remains largely unclear whether and how clonal cells could be heterogeneous in the expression of the entire transcriptome. Here, we showed that gene transcriptional activity is globally modulated in individual cancer cells, leading to non-genetic heterogeneity in the global transcription rate. Such heterogeneity contributes to cell-to-cell variability in transcriptome size and displays both dynamic and static characteristics, with the global transcription rate temporally modulated in a cell-cycle-coupled manner and the time-averaged rate being distinct between cells and heritable across generations. Additional evidence indicated the role of ATP metabolism in this heterogeneity, and suggested its implication in intrinsic cancer drug tolerance. Collectively, our work shed light on the mode, mechanism, and implication of a global but often hidden source of non-genetic heterogeneity.

Meta-analysis of multi-modality therapies in sinonasal undifferentiated carcinoma-A timely update.

OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare but aggressive tumour with very poor prognosis. There are currently no well-established clinical trials to guide therapy and the impact of various treatment modalities on survival is not well defined. We aim to provide an updated systematic review on current treatment modalities on survival outcomes. DESIGN AND SETTING: Individual patient data were extracted, and survival data pooled in a one-stage meta-analysis. Descriptive statistics were analysed using the Kaplan-Meier method. Patient-level comparisons stratified by treatment modalities, adjusted for demographics, were conducted using shared-frailty Cox regression. PARTICIPANTS AND MAIN OUTCOME MEASURES: Participants include all patients diagnosed with SNUC based on histological evidence. We looked at the overall cumulative survival outcome for different treatment modalities and overall survival by treatment modality in low versus high stage SNUC patients. RESULTS AND CONCLUSION: Seventeen studies were identified, comprising 208 patients from 1993 to 2020. There was no significant difference in cumulative overall survival in low versus high stage patients, and no significant difference in outcomes by treatment modality. The overall cumulative survival of SNUC is 30% at 95 months. Among patients treated with various combinations of treatment modalities, patients with chemoradiotherapy had the highest cumulative survival of 42% at 40 months. Definitive chemoradiotherapy was associated with improved disease survival rate. Regardless of tumour stage, patients should be treated early and aggressively, with no superiority of one treatment regimen over another. Trimodality treatment does not confer survival advantage over bimodality treatment.

Prognostic value of cranial radiotherapy and optimal timing stratified by lung-molGPA for NSCLC patients with brain metastases.

PURPOSE: The updated Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (lung-molGPA) index provide more accurate survival prediction for patients diagnose with advanced non-small cell lung cancer (NSCLC) with brain metastases (BM). Given that the value of cranial radiotherapy (CRT) is still controversial for NSCLC patients with BM, this retrospective study aimed to evaluate the value of CRT and optimal timing in NSCLC patients with initial BM after stratified with lung-molGPA index. METHODS: This study screened NSCLC patients with initial BM in our cancer center from February 2012 to July 2018. The prognosis value of CRT and optimal timing was evaluated with Kaplan-Meier survival analysis and the patients were classified into lung-molGPA0-2 and lung-molGPA2.5-4 group. Upfront CRT was defined as received CRT within 3 months after initial diagnosis and without BM progression, other CRT was classified into deferred CRT. RESULTS: Overall, 288 patients were enrolled in our study, 156 patients received CRT. The median follow-up time was 47 months. In the entire cohort, the median PFS and OS were 9.2 and 17.0 months, respectively. In the lung-molGPA2.5-4 group, CRT can bring significantly overall survival benefit for NSCLC patients with initial BM (HR: 0.48, 95% CI: 0.34-0.68, P < 0.0001), and the upfront CRT can further expand this survival benefits compared with deferred CRT (HR: 0.49, 95% CI: 0.27-0.89, P = 0.0026). But this phenomenon was not observed in lung-molGPA0-2 group patients. CONCLUSION: Upfront CRT could bring significantly overall survival benefit for these patients with lung-molGPA2.5-4 but not for patients with lung-molGPA0-2.

Brain injury after cranial radiotherapy combined with immunotherapy for brain metastases in lung cancer: a retrospective study.

Aim: To explore whether immune checkpoint inhibitors (ICIs) increase the incidence of radiation-induced brain injury in lung cancer patients with brain metastases. Methods: According to whether they received ICIs within 6 months before and after cranial radiotherapy (CRT), all patients were divided into two groups: ICIs + CRT group and CRT + non-ICIs group. Results: The incidence of radiation necrosis (RN) in the CRT + ICIs group was 14.3%, while that in the CRT + non-ICIs group was 5.8% (p = 0.090). If ICIs were used within 3 months of CRT, there was statistical significance. A maximum diameter of brain metastasis >3.3 cm and cumulative radiation dose of metastatic lesions >75.7 Gy were risk factors for RN. Conclusion: ICIs could increase the risk of RN, especially when used within 3 months of CRT.

Effect of mindfulness-based stress reduction in patients with acute myocardial infarction after successful primary percutaneous coronary intervention: a retrospective study.

OBJECTIVE: This study aimed to examine the effects of mindfulness-based stress reduction (MBSR) in patients with acute myocardial infarction (AMI) after primary percutaneous coronary intervention (PPCI). METHODS: A retrospective study was conducted with data collected from AMI patients who underwent successful PPCI. The study included 61 cases that received 8-week MBSR intervention (MBSR group) and 61 cases that received weekly health education (control group) over the same period. Outcome measures, including hemodynamic parameters, psychosocial characteristics [Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS), Perceived Social Support Scale (PSSS)], health-related quality of life [HRQoL, 7-item Seattle Angina Questionnaire (SAQ-7)], and major adverse cardiovascular events (MACE), were assessed at baseline (T1), post-intervention (T2), 1 month after the post-intervention (T3) and 3 months after the post-intervention (T4). RESULTS: Compared to the control group, the MBSR group showed improvements in blood pressure, specifically in systolic blood pressure (SBP) at T4, and diastolic blood pressure (DBP) at T3 and T4, and mean arterial blood pressure (MABP) at T3 and T4. Additionally, the MBSR group had lower scores of anxiety and perceived stress (HADS, PSS) and higher scores of perceived social support (PSSS) after the intervention. Furthermore, the MBSR group had higher scores on the SAQ-7 at all measurement points. The control group had a significantly higher total MACE rate compared to the MBSR group (26.23% vs. 9.84%). CONCLUSIONS: This study provides support for the potential benefits of MBSR as an adjunctive treatment for AMI patients undergoing PPCI.

The encoding of race during face processing, an event-related potential study.

It is well known that adults spontaneously classify people into social categories and this categorization in turn guides their cognition and behavior. A wealth of research has examined how people perceive race and investigated the effect of race on social behavior. But what about race encoding? Although considerable behavioral research has investigated the encoding of race, that is, the social categorization by race, the neural underpinning of it is largely underexplored. To investigate the time course of race encoding, the current study employed a modified category verification task and a multivariate analyzing approach. We found that racial information became decodable from event-related potential topographies as early as about 200 ms after stimulus onset. At this stage, the brain can differentiate different races in a task-relevant manner. Nonetheless, it is not until 100 ms later that racial information is encoded in a socially relevant manner (own- versus other-race). Importantly, perceptual differentiation not only occurs before the encoding of the race but actually influences it: the faces that are more easily perceptually categorized are actually encoded more readily. Together, we posit that the detection and the encoding of race are decoupled although they are not completely independent. Our results provide powerful constraints toward the theory-building of race.

Genetic and genomic analysis of the seed-filling process in maize based on a logistic model.

Seed filling is a dynamic process that determines seed size and nutritional quality. This time-dependent trait follows a logistic (S-shaped) growth curve that can be described by a logistic function, with parameters of biological relevance. When compared between genotypes, the filling dynamics variations are explained by the differences of parameter values; as such, the parameter estimates can be considered as "traits" for genetic analysis to identify loci that are associated with the seed-filling process. We carried out genetic and genomic analysis of the seed-filling process in maize, using a recombinant inbred line (RIL) population derived from the two inbred lines with contrasting seed-filling dynamics. We recorded seed dry weight at 14 time points after pollination, spanning the early filling phases to the late maturation stages. Fitting these data to a logistic model allowed for estimating 12 characteristic parameters that can be used to meaningfully describe the seed-filling process. Quantitative trait locus (QTL) mapping of these parameters identified a total of 90 nonredundant loci. Using bulked segregant RNA-sequencing (BSR-seq) analysis, we identified eight genes that showed differential gene expression patterns at multiple time points between the extreme pools, and these genes co-localize with the mapped QTL regions. Two of the eight genes, GRMZM2G391936 and GRMZM2G008263, are implicated in starch and sucrose metabolism, and biosynthesis of secondary metabolites that are well known for playing a vital role in seed filling. This study suggests that the logistic model-based approach can efficiently identify genetic loci that regulate dynamic developing traits.

Plasmodium falciparum multidrug resistance protein 1 (pfmrp1) gene and its association with in vitro drug susceptibility of parasite isolates from north-east Myanmar.

OBJECTIVES: Plasmodium falciparum multidrug resistance protein 1 (pfmrp1) has recently emerged as an important determinant of drug resistance and mutations in the gene have been associated with several drugs. The aim of this study was to understand the level of genetic diversity in pfmrp1 and to determine the association of different mutations with altered drug susceptibilities of P. falciparum. METHODS: We analysed 193 sequences of pfmrp1 from South-East Asia, west Asia, Africa, Oceania and South America. We measured the level of genetic diversity and determined signatures of selection on the gene. In vitro susceptibilities of 28 P. falciparum isolates from north-east Myanmar to a panel of seven commonly used antimalarials were determined. Statistical analysis was performed to determine the association of different mutations with in vitro drug susceptibilities. RESULTS: A total of 28 single nucleotide polymorphisms were identified in 193 sequences, of which 22 were non-synonymous. Whereas mutations in the pfmrp1 gene were conserved among different countries within a continent, they were different between continents. Seven non-synonymous mutations were identified in the north-east Myanmar isolates; all were relatively frequent in this region as well as in other neighbouring countries. Molecular evolutionary analysis detected signatures of positive selection on the gene. Moreover, some mutations in this gene were found to be associated with reduced susceptibilities to chloroquine, mefloquine, pyronaridine and lumefantrine. CONCLUSIONS: Evidence of the positive selection of pmfrp1 and its association with the susceptibilities of parasites to multiple drugs signifies its potential as an important candidate for monitoring drug resistance.

Ten-year prescription trends of asthma medications in the management of childhood wheeze.

Asthma is the most common chronic disorder of childhood. The aim of this study was to assess prescription trends of asthma medications to provide a measure to evaluate treatment practices and compliance with established international practice guidelines. A retrospective study of data obtained from outpatient prescription databases (2001-2010) of the University Children's Medical Institute for children aged 0-18 years was performed. The following drugs were included: short-acting beta-agonists (SABAs), long-acting beta-agonists in combination with inhaled corticosteroids (LABA-ICSs), ICS, and leukotriene receptor antagonists. Statistical analysis of prescription trends was performed with linear regression to determine the trends in prescription of controller medications. From 2001 to 2010, the number of patients who were prescribed SABA increased significantly by 72% (p = 0.016). The increases in ICS patient numbers and ICS/SABA drug unit ratios were significant only in the school-going (>5 years) age group. There was a trend away from the use of nebulized SABA and ICS, although this was statistically insignificant. LABA-ICS patient numbers decreased significantly by 32.4% (p = 0.003), especially in preschoolers (1-5 years). There was a corresponding rise in montelukast patient numbers by 194.6% (p = 0.009) and montelukast/SABA ratio by 345.3% (p = 0.032) in preschoolers (aged 1-5 years). Montelukast patient numbers, but not the montelukast/SABA ratio, increased in school-going children. The move away from LABA-ICS combination especially in younger children and a tendency toward more montelukast usage is a reflection of practice preferences in accordance with current international guidelines in young children.

[Pathogenesis and Therapeutic Prospects of Chronic Graft-Versus-Host Disease --Review].

Chronic graft-versus-host disease (cGVHD) is one of a major complication that affecting the long-term survival and living quality of patients after allogeneic hematopoietic stem cell transplantation, with the incidence of 30%-70%. Unlike acute GVHD, cGVHD involves a large number of immune cells and cytokines in addition to T cell, which is activated abnormally by the donor, and cytokine storms, which characterized by infiltration of donor lymphocytes and damage to host target organ. Recent studies have further made progress in targeting related immune cells and cytokines. In this review, the pathogenesis and therapeutic prospects of cGVHD were summarized from the perspectives of classical innate and adaptive immunity.

The influencing factors of college students' legal emotion and the mechanism of its effect on aggressive behavior.

Current research has increasingly focused on the preventive role of individual legal socialization in crime. The socialization of legal emotions is an important part of legal socialization. Building upon existing literature, this study, conducted through two sub-studies, investigated the influencing factors of legal emotions in N mainland Chinese university students and the mechanisms through which legal emotions impact aggressive behavior. In study 1, the results indicated that mother-child attachment, innovation spirit, and positive emotional expression positively predicted positive legal emotion, while mother-child attachment, dependency dimension in adult attachment, and positive emotional expression negatively predicted negative legal emotions. The anxiety dimension in adult attachment and negative emotional expression positively predicted negative legal emotions. In study 2, Positive legal emotion among university students could directly negatively predict aggressive behavior or exert influence through social alienation. Negative legal emotions could not only directly positively predict aggressive behavior but also partly affect it through social alienation. In summary, our study not only identified factors that influence legal emotions, but also found that legal emotions have an impact on aggressive behavior directly or indirectly through social alienation. Our research findings have significant implications for cultivating positive legal emotion in university students and curbing aggressive behavior. This can be achieved by promoting the legal socialization of university students and ultimately contributing to crime prevention.

Regulations of m6A and other RNA modifications and their roles in cancer.

RNA modification is an essential component of the epitranscriptome, regulating RNA metabolism and cellular functions. Several types of RNA modifications have been identified to date; they include N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), N6,2'-O-dimethyladenosine (m6Am), N4-acetylcytidine (ac4C), etc. RNA modifications, mediated by regulators including writers, erasers, and readers, are associated with carcinogenesis, tumor microenvironment, metabolic reprogramming, immunosuppression, immunotherapy, chemotherapy, etc. A novel perspective indicates that regulatory subunits and post-translational modifications (PTMs) are involved in the regulation of writer, eraser, and reader functions in mediating RNA modifications, tumorigenesis, and anticancer therapy. In this review, we summarize the advances made in the knowledge of different RNA modifications (especially m6A) and focus on RNA modification regulators with functions modulated by a series of factors in cancer, including regulatory subunits (proteins, noncoding RNA or peptides encoded by long noncoding RNA) and PTMs (acetylation, SUMOylation, lactylation, phosphorylation, etc.). We also delineate the relationship between RNA modification regulator functions and carcinogenesis or cancer progression. Additionally, inhibitors that target RNA modification regulators for anticancer therapy and their synergistic effect combined with immunotherapy or chemotherapy are discussed.

Nomogram for Predicting the Risk of Complications in Hospitalized Children With Peripheral Intravenous Catheters.

OBJECTIVE: The aim of the study is to identify the hospitalized children at risk of peripheral intravenous catheter (PIVC) complications by severity prediction. METHODS: The study included the data of 301 hospitalized children with PIVC complications in 2 tertiary teaching hospitals. A researcher-designed tool was used to collect risk factors associated with PIVC complications. Predictors of PIVC complications at univariate analysis and multivariable logistic regression analysis by backward stepwise. A nomogram was constructed based on the results of the final multivariable model, making it possible to estimate the probability of developing complications. RESULTS: A total of 182 participants (60.5%) had a moderate injury from PIVC complications. Multivariable logistic regression analysis indicated that the vascular condition, limb immobilization, needle adjustment in venipuncture, infusion length, infusion speed, and insertion site were independent predictors. The nomogram for assessing the severity of PIVC complications indicated good predictive accuracy (area under the curve = 0.79) and good discrimination (concordance index = 0.779). Decision curve analysis demonstrated that the nomogram was a good clinical value with a wide range of threshold probabilities (4%-100%). CONCLUSIONS: The risk prediction model has good predictive performance, and the nomogram provides an easy-to-use visualization to identify the severity of PIVC complications and guide timely nursing care management.

In vitro sensitivities of Plasmodium falciparum isolates from the China-Myanmar border to piperaquine and association with polymorphisms in candidate genes.

The recent reports of resistance in Plasmodium falciparum to artemisinin derivatives and their partner drugs demand intensive studies toward understanding the molecular mechanisms of resistance. In this study, we examined the in vitro susceptibility of 63 P. falciparum field isolates collected from the China-Myanmar border area to chloroquine (CQ) and piperaquine (PPQ). Parasite isolates remained highly resistant to CQ, with the geometric mean 50% inhibitory concentration (IC50) of 252.7 nM and a range of 51.9 to 1,052.0 nM. In comparison, these parasites had a geometric mean IC50 of 28.4 nM for PPQ, with a fairly wide range of 5.3 to 132.0 nM, suggesting that certain parasite isolates displayed relatively high levels of resistance to PPQ. Interestingly, within the 4 years of study, the parasites exhibited a continuous decline in susceptibilities to both CQ and PPQ, and there was a significant correlation between responses to CQ and PPQ (Pearson correlation coefficient = 0.79, P < 0.0001). Consistent with the CQ-resistant phenotype, all parasites carried the pfcrt K76T mutation, and most parasites had the CVIET type that is prevalent in Southeast Asia. In contrast, pfmdr1 mutations were relatively rare, and no gene amplification was detected. Only the pfmdr1 N1042D mutation was associated with resistance to CQ. For the pfmrp1 gene, four substitutions reached relatively high prevalence of >22%, and the I876V mutation was associated with reduced sensitivity to CQ. However, we could not establish a link between PPQ responses and the polymorphisms in the three genes associated with quinoline drug resistance.

Formation mechanism and prediction model of juvenile delinquency.

Exploring the formation mechanism of juvenile delinquency is of great significance to prevent juvenile delinquency. The present study examined relations and interactions among juvenile delinquents' self-consciousness, family factors, social relationships, belief in a just world, and legal consciousness, and then developed a predictive model to distinguish between juvenile delinquents and non-delinquents. The results showed that family factors have a significant influence on the formation of juvenile delinquents' self-consciousness and there are notable differences in family environment and self-consciousness between delinquent and non-delinquent adolescents. Due to the complex interactions among juvenile delinquency's self-consciousness, family factors, social relationships, belief in a just world and legal consciousness, adolescents' self- consciousness and social relationships can be utilized to predict and classify the groups of delinquent and non-delinquent adolescents effectively. Therefore, the key to preventing juvenile delinquency is to improve their self-consciousness and develop their prosocial relationships.

Pre-immunotherapy radiotherapy enhanced the efficacy of multi-line sintilimab in unresectable advanced esophageal squamous cell carcinoma.

Background: The use of immunotherapy for the treatment of esophageal squamous cell carcinoma (ESCC) is gradually increasing. In this retrospective study, we evaluated the efficacy and explored potential factors of prognosis in multi-line sintilimab for unresectable advanced ESCC. Methods: All pathological specimens were available from our Department of Pathology. We performed PD-L1 immunohistochemical staining of surgical or puncture specimens from 133 patients. We evaluated the efficacy of multi-line sintilimab and found potential factors according to multivariate analysis. We assessed the relationship between radiotherapy and immunotherapy, and according to whether patients had received radiotherapy within 3 months prior to immunotherapy, we attempted to analyze differences in progression-free survival (PFS) and overall survival (OS). Results: A total of 133 patients were enrolled in this retrospective study between January 2019 and December 2021. The median follow-up was 16.1 months. All patients were treated with at least two cycles of sintilimab. Of all patients, a total of 74 experienced disease progression, with a median progression-free survival of 9.0 months (95% CI 7.701-10.299). We found that pre-immunotherapy radiotherapy was a possible predictor that affected the prognosis of multi-line sintilimab and that 3 months was a significant cutoff. A total of 128 patients (96.2%) had received radiotherapy prior to immunotherapy. Of those patients, 89 (66.9%) had received radiation therapy within 3 months prior to immunotherapy. PFS was considerably longer in patients who were treated within 3 months of radiotherapy than in patients who did not receive radiation therapy within 3 months of radiation therapy prior to immunotherapy (median progression-free survival 10.0 months [95% CI 8.030-11.970] vs. 5.0 months [95% CI 2.755-7.245]). Among all patients, the median overall survival was 14.9 months (95% CI 12.558-17.242). Overall survival was significantly longer in patients who had previously received radiotherapy within 3 months prior to immunotherapy than in those who had not (median overall survival 15.3 months [95% CI 13.724-16.876] vs. 12.2 months [10.001-14.399]. Conclusion: Based on this retrospective study, sintilimab is a significant option for patients with unresectable advanced ESCC who have been previously treated, and pre-immunotherapy radiotherapy within 3 months enhanced the efficacy.

Remote cardiac rehabilitation program during the COVID-19 pandemic for patients with stable coronary artery disease after percutaneous coronary intervention: a prospective cohort study.

OBJECTIVE: The coronavirus disease-19 (COVID-19) pandemic restricts rapid implementation of in-person delivery of cardiac rehabilitation (CR) at the center for coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI), thus enabling a cohort comparison of in-person vs. remote CR program. This study aims to investigate outcomes of exercise capacity, health-related quality of life (HRQL), mental health, and family burden of stable CAD patients undergoing PCI in low-to-moderate risk after different delivery models of CR program. METHODS: The study included a cohort of stable CAD patients undergoing PCI who had experienced two naturally occurring modes of CR program after hospital discharge at two time periods, January 2019 to December 2019 (in-person CR program) and May 2020 to May 2021 (remote CR program). The exercise capacity was assessed by means of 6-min walk test (6MWT), maximal oxygen uptake (VO2max) and the respiratory anaerobic threshold (VO2AT) before discharge, at the end of the 8-week and 12-week in-person or remote CR program after discharge. RESULTS: No adverse events occurred during the CR period. CAD patients had a longer distance walked in 6 min with a higher VO2max after 8-week and 12-week CR program whether in-person or remote model (p < 0.05). The distance walked in 6 min was longer and the maximal oxygen uptake (VO2max) was higher at the end of the 12-week in-person or remote CR program than 8-week in-person or remote CR program (p < 0.05). The respiratory anaerobic threshold (VO2AT) of CAD patients was decreased after 8-week CR program whether in-person or remote model (p < 0.05). CAD patients receiving remote CR program exhibited higher HRQL scores in domains of vitality (p = 0.048), role emotional (p = 0.039), mental health (p = 0.014), and the summary score of the mental composite (p = 0.048) compared to in-person CR program after 8 weeks. The anxiety and depression scores of CAD patients undergoing PCI were decreased after 8-week CR program whether in-person or remote model (p < 0.05). The CAD patients receiving remote delivery showed lower anxiety and depression scores compared to those receiving in-person delivery at the end of the 8-week CR program (p < 0.05). It was found that the family burden scores of CAD patients undergoing PCI were reduced after 8-week and 12-week CR program whether in-person or remote model (p < 0.05). The CAD patients receiving remote CR program showed lower family burden scores than those receiving in-person CR program after whether 8 weeks or 12 weeks (p < 0.05). CONCLUSION: These data indicate that a properly designed and monitored remote delivery represents a feasible and safe model for low-to-moderate-risk, stable CAD patients undergoing PCI inaccessible to in-person CR during the COVID-19 pandemic.

Incongruent gestures slow the processing of facial expressions in university students with social anxiety.

In recent years, an increasing number of studies have examined the mechanisms underlying nonverbal emotional information processing in people with high social anxiety (HSA). However, most of these studies have focused on the processing of facial expressions, and there has been scarce research on gesture or even face-gesture combined processing in HSA individuals. The present study explored the processing characteristics and mechanism of the interaction between gestures and facial expressions in people with HSA and low social anxiety (LSA). The present study recruited university students as participants and used the Liebowitz Social Anxiety Scale scores to distinguish the HSA and LSA groups. We used a 2 (group: HSA and LSA) × 2 (emotion valence: positive, negative) × 2 (task: face, gesture) multifactor mixed design, and videos of a single face or gesture and combined face-gesture cues were used as stimuli. We found that (1) there is a distinction in the processing of faces and gestures, with individuals recognizing gestures faster than faces; (2) there is an attentional enhancement in the processing of gestures, particularly for negative gestures; and (3) when the emotional valence of faces and gestures align, it facilitates the recognition of both. However, incongruent gestures have a stronger impact on the processing of facial expressions compared to facial expressions themselves, suggesting that the processing of facial emotions is more influenced by environmental cues provided by gestures. These findings indicated that gestures played an important role in emotional processing, and facial emotional processing was more dependent on the environmental cues derived from gestures, which helps to clarify the reasons for biases in the interpretation of emotional information in people with HSA.

Immunotherapy combined with chemotherapy improved clinical outcomes over bevacizumab combined with chemotherapy as first-line therapy in adenocarcinoma patients.

PURPOSE: No definite conclusion has yet to be reached for the first-line treatment combined with chemotherapy for advanced adenocarcinoma NSCLC patients with negative driver genes. This study sought to compare the clinical outcomes of Beva+ChT and IO+ChT as first-line treatment for this population and investigated whether the statuses of BM, PD-L1 expression, and KRAS and TP53 mutations could influence the results. PATIENTS AND METHODS: The clinical data of patients with adenocarcinoma NSCLC who received first-line therapy were retrospectively collected and the patients were assigned to the IO+ChT and Beva+ChT groups. The disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated between the two groups. The survival effects of BM, PD-L1 expression, and KRAS and TP53 mutations were also evaluated. RESULTS: From April 2018 to October 2020, a total of 105 patients with first-line therapy were included in our analysis; 54 (51.4%) patients were included in the IO+ChT group and 51 (48.6%) patients were included in the Beva+ChT group. The results showed that OS (NR vs. 18.3 m, p = 0.011) and PFS (14.9 m vs. 6.3 m, p < 0.001) were superior in patients in the IO+ChT group than in patients in the Beva+ChT group. Further analysis revealed that the OS (median OS: NR vs. 14.7 months, p = 0.039) and PFS (median PFS: 18.5 vs. 5.5 months, p < 0.001) advantages of the IO+ChT group were also seen in the PD-L1 > 1% subgroup but were not seen in the PD-L1 < 1%, BM or KRAS mutation subgroups. CONCLUSIONS: ICIs combined with ChT improved clinical outcomes over Beva combined with ChT as first-line therapy for adenocarcinoma patients without driver gene alterations, especially in patients with PD-L1 ≥ 1%.

Interlukin-4 weakens resistance to stress injury and megakaryocytic differentiation of hematopoietic stem cells by inhibiting Psmd13 expression.

Thrombocytopenia is a major and fatal complication in patients with acute myeloid leukemia (AML), which results from disrupted megakaryopoiesis by leukemic niche and blasts. Our previous research revealed that elevated interleukin-4 (IL-4) in AML bone marrow had adverse impact on multiple stages throughout megakaryopoiesis including hematopoietic stem cells (HSCs), but the specific mechanism remains unknown. In the present study, we performed single-cell transcriptome analysis and discovered activated oxidative stress pathway and apoptosis pathway in IL-4Rαhigh versus IL-4Rαlow HSCs. IL-4 stimulation in vitro led to apoptosis of HSCs and down-regulation of megakaryocyte-associated transcription factors. Functional assays displayed higher susceptibility of IL-4Rαhigh HSCs to tunicamycin and irradiation-induced apoptosis, demonstrating their vulnerability to endoplasmic reticulum (ER) stress injury. To clarify the downstream signaling of IL-4, we analyzed the transcriptomes of HSCs from AML bone marrow and found a remarkable down-regulation of the proteasome component Psmd13, whose expression was required for megakaryocytic-erythroid development but could be inhibited by IL-4 in vitro. We knocked down Psmd13 by shRNA in HSCs, and found their repopulating capacity and megakaryocytic differentiation were severely compromised, with increased apoptosis in vivo. In summary, our study uncovered a previous unrecognized regulatory role of IL-4-Psmd13 signaling in anti-stress and megakaryocytic differentiation capability of HSCs.