Prognostic nomogram based on pre-treatment HALP score for patients with advanced non-small cell lung cancer.

BACKGROUND: To explore the correlation of pre-treatment Hemoglobin-Albumin-Lymphocyte-Platelet (HALP) score with the prognosis of patients with advanced Non-Small Cell Lung Cancer (NSCLC) undergoing first-line conventional platinum-based chemotherapy. METHODS: In this retrospective cohort study, 203 patients with advanced NSCLC were recruited from January 2017 to December 2021. The cut-off value for the HALP score was determined by Receiver Operating Characteristic (ROC) curve analysis. The baseline characteristics and blood parameters were recorded, and the Log-rank test and Kaplan-Meier curves were applied for the survival analysis. In the univariate and multivariate analyses, the Cox regression analysis was carried out. The predictive accuracy and discriminative ability of the nomogram were determined by the Concordance index (C-index) and calibration curve and compared with a single HALP score by ROC curve analysis. RESULTS: The optimal cut-off value for the HALP score was 28.02. The lower HALP score was closely associated with poorer Progression-Free Survival (PFS) and Overall Survival (OS). The male gender and other pathological types were associated with shorter OS. Disease progression and low HALP were correlated with shorter OS and PFS. In addition, nomograms were established based on HALP scores, gender, pathology type and efficacy rating, and used to predict OS. The C-index for OS prediction was 0.7036 (95% CI 0.643 to 0.7643), which was significantly higher than the C-index of HALP at 6-, 12-, and 24-months. CONCLUSION: The HALP score is associated with the prognosis of advanced NSCLC patients receiving conventional platinum-based chemotherapy, and the nomogram established based on the HALP score has a better predictive capability for OS.

Subject-Independent Emotion Recognition Based on EEG Frequency Band Features and Self-Adaptive Graph Construction.

Emotion is one of the most important higher cognitive functions of the human brain and plays an important role in transaction processing and decisions. In traditional emotion recognition studies, the frequency band features in EEG signals have been shown to have a high correlation with emotion production. However, traditional emotion recognition methods cannot satisfactorily solve the problem of individual differences in subjects and data heterogeneity in EEG, and subject-independent emotion recognition based on EEG signals has attracted extensive attention from researchers. In this paper, we propose a subject-independent emotion recognition model based on adaptive extraction of layer structure based on frequency bands (BFE-Net), which is adaptive in extracting EEG map features through the multi-graphic layer construction module to obtain a frequency band-based multi-graphic layer emotion representation. To evaluate the performance of the model in subject-independent emotion recognition studies, extensive experiments are conducted on two public datasets including SEED and SEED-IV. The experimental results show that in most experimental settings, our model has a more advanced performance than the existing studies of the same type. In addition, the visualization of brain connectivity patterns reveals that some of the findings are consistent with previous neuroscientific validations, further validating the model in subject-independent emotion recognition studies.

Effects of intracellular Ca2+ on developmental potential and ultrastructure of cryopreserved-warmed oocyte in mouse.

Maintaining appropriate intracellular calcium of oocytes is necessary to prevent ultrastructure and organelle damage caused by freezing and cryoprotectants. The present study aimed to investigate whether cryoprotectant-induced changes in the calcium concentrations of oocytes can be regulated to reduce damage to developmental potential and ultrastructure. A total of 33 mice and 1381 oocytes were used to explore the effects of intracellular calcium on the development and ultrastructures of oocytes subjected to 2-aminoethoxydiphenyl borate (2-APB) inhibition or thapsigargin (TG) stimulation. Results suggested that high levels intracellular calcium interfered with TG compromised oocyte survival (84.4 % vs. 93.4 %, p < 0.01) and blastocyst formation in fresh and cryopreservation oocytes (78.1 % vs. 86.4 %, and 60.5 % vs. 72.5 %, p < 0.05) compared with that of 2-APB pretreated oocytes in which Ca2+ was stabilized even though no differences in fertilization and cleavage was detected (p > 0.05). Examination by transmission electron microscopy indicated that the microvilli decreased and shortened, cortical granules considerably decreased in the cortex area, mitochondrial vesicles and vacuoles increased, and the proportion of vacuole mitochondria increased after oocytes were exposed to cryoprotectants. The cryopreservation-warming process deteriorated the negative effects on organelles of survival oocytes. By contrast, a low level of intracellular calcium mediated with 2-APB was supposed to contribute to the protection of organelles. These findings suggested oocyte injuries induced by cryoprotectants and low temperatures can be alleviated. More studies are necessary to confirm the relationship among Ca2+ concentration of the cytoplasm, ultrastructural injuries, and disrupted developmental potential in oocytes subjected to cryopreservation and warming.

Vitiligo-like lesions induced by cyclin-dependent kinase 4/6 inhibitor Palbociclib: a case report and literature review.

Endocrine therapy has played an essential role in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. With the continuous development of endocrine targeting drugs, especially the emergence of selective cyclin-dependent kinase (CDK4/6) inhibitors, the overall survival time in patients with HR+HER2- advanced breast cancer has been greatly improved. Their adverse reactions also need more attention in response to the climbing number of CDK4/6 inhibitors. The common side effects of CDK4/6 inhibitors were hematological toxicity, diarrhea, and liver function damage. Skin toxicity related to CDK4/6 inhibitors was rare. We describe herein our preliminary observation of one HR+HER2- advanced metastatic breast cancer patient diagnosed with vitiligo-like lesions after 10 months of taking Palbociclib. Hoping to share our experience to increase the clinician awareness of this unusual adverse and contribute to the information in the literature.

First-in-human phase I/Ib study of QL1706 (PSB205), a bifunctional PD1/CTLA4 dual blocker, in patients with advanced solid tumors.

BACKGROUND: QL1706 (PSB205) is a single bifunctional MabPair (a novel technical platform) product consisting of two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1), with a shorter elimination half-life (t1/2) for CTLA-4. We report results from a phase I/Ib study of QL1706 in patients with advanced solid tumors who failed standard therapies. METHODS: In the phase I study, QL1706 was administered intravenously once every 3 weeks at one of five doses ranging from 0.3 to 10 mg/kg, and the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of QL1706 were investigated. In the phase Ib study, QL1706 was administered at the RP2D intravenously every 3 weeks, and the preliminary efficacies in non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma (NPC), cervical cancer (CC), and other solid tumors were evaluated. RESULTS: Between March 2020 and July 2021, 518 patients with advanced solid tumors were enrolled (phase I, n = 99; phase Ib, n = 419). For all patients, the three most common treatment-related adverse events (TRAEs) were rash (19.7%), hypothyroidism (13.5%), and pruritus (13.3%). The TRAEs and immune-related adverse events (irAEs) of grade ≥ 3 occurred in 16.0% and 8.1% of patients, respectively. In phase I, 2 of 6 patients in the 10mg/kg group experienced dose-limiting toxicities (DLTs) (grade 3 thrombocytopenia and grade 4 immune-mediated nephritis), so the maximum tolerated dose (MTD) was reached at 10 mg/kg. The RP2D was determined to be 5 mg/kg based on comprehensive analysis of tolerability, PK/PD, and efficacy. For all patients who received QL1706 at the RP2D, the objective response rate (ORR) and median duration of response were 16.9% (79/468) and 11.7 months (8.3-not reached [NR]), respectively; and the ORRs were 14.0% (17/121) in NSCLC, 24.5% (27/110) in NPC, 27.3% (15/55) in CC, 7.4% (2/27) in colorectal cancer, 23.1% (6/26) in small cell lung cancer. For immunotherapy-naive patients, QL1706 exhibited promising antitumor activities, especially in NSCLC, NPC, and CC, with ORRs of 24.2%, 38.7%, and 28.3%, respectively. CONCLUSIONS: QL1706 was well tolerated and demonstrated promising antitumor activity in solid tumors, especially in NSCLC, NPC, and CC patients. It is currently being evaluated in randomized phase II (NCT05576272, NCT05179317) and phase III (NCT05446883, NCT05487391) trials. Trial Registration ClinicalTrials.gov Identifier: NCT04296994 and NCT05171790.

Peripheral changes in T cells predict efficacy of anti-PD-1 immunotherapy in non-small cell lung cancer.

The application of programmed cell death protein 1 (PD-1) antibodies has brought great benefits to non-small cell lung cancer (NSCLC) patients. Nevertheless, not all patients respond to anti-PD-1 immunotherapy. This study aimed to find response markers to predict efficacy of anti-PD-1 immunotherapy in NSCLC patients. 80 patients with NSCLC who would accept anti-PD-1 immunotherapy were recruited, and peripheral blood was obtained before and after treatment. Flow cytometry was used to detect proportions of circulating cell subsets and expression of co-stimulatory molecules, co-inhibitory molecules and cytokines in T cells from pre- and post-treatment patients. Results showed that proportions of CD4+ and CD8+ T cells, NK, γδT and mucosal-associated invariant T (MAIT) cells were higher and regulatory T cells (Tregs) were lower in responders (n = 50) after treatment but no obvious difference was found in non-responders (n = 30). After treatment, responders showed an increase in the frequency of co-stimulatory and co-inhibitory molecules, as well as the production of cytokines in T cells. This study indicates that monitoring the alterations of immune markers in circulating cells from NSCLC patients may be helpful to discriminate responders and non-responders, which provides a potential novel way to assess efficacy of anti-PD-1 immunotherapy.

Phase I study of A166, an antibody‒drug conjugate in advanced HER2-expressing solid tumours.

In this phase I study, the safety, pharmacokinetics, and antitumour activity of the HER2-targeted antibody-drug conjugate A166 were evaluated in patients with HER2-expressing advanced solid tumours. Patients with advanced solid tumours refractory to standard therapies received A166 at doses of 0.1, 0.3, 0.6, 1.2, 2.4, 3.6, 4.8 or 6.0 mg/kg Q3W in a standard "3 + 3" design. Dose cohorts were expanded at 4.8 and 6.0 mg/kg Q3W. Primary endpoints were assessment of the safety and tolerability of A166 and identification of the maximum tolerated dose or recommended phase II dose. In total, 81 patients were enroled and received A166 (n = 1 for 0.1 mg/kg; n = 3 for each of 0.3, 0.6, 1.2, 2.4 and 3.6 mg/kg doses; n = 27 for 4.8 mg/kg; n = 38 for 6.0 mg/kg). No dose-limiting toxicity or drug-related deaths occurred. The most common treatment-related adverse events at grade 3 or higher were corneal epitheliopathy (30.9%), blurred vision (18.5%), dry eyes (7.4%), and peripheral sensory neuropathy (6.2%). The Cmax and area under the curve of Duo-5, its free payload, were approximately 0.1% and 0.2% of those of the ADC, respectively. For all assessable HER2-positive breast cancer patients enroled in the 4.8 mg/kg and 6.0 mg/kg cohorts, the corresponding ORRs were 73.9% (17/23) and 68.6% (24/35), respectively, and the median PFS was 12.3 and 9.4 months, respectively. A166 has a recommended phase II dose of 4.8 mg/kg Q3W, manageable toxicity, good stability in the circulation and promising antitumour activities in HER2-positive breast cancer patients.

The relationship between metabolic dysfunction-associated fatty liver disease and the incidence rate of extrahepatic cancer.

Background: The associations between metabolic dysfunction-associated fatty liver disease (MAFLD) and cancer development, especially extrahepatic cancers, are unknown. The aims of the current study were to investigate the cancer incidence rates of MAFLD and analyze the associations between MAFLD and the development of cancers. Methods: This historical cohort study included participants who underwent ultrasonographic detection of hepatic steatosis at a tertiary hospital in China from January 2013 to October 2021. MAFLD was diagnosed in accordance with The International Expert Consensus Statement. Cox proportional hazards regression modeling was used to assess the associations between MAFLD and the development of cancers. Results: Of the 47,801 participants, 16,093 (33.7%) had MAFLD. During the total follow-up of 175,137 person-years (median 3.3 years), the cancer incidence rate in the MAFLD group was higher than that in the non-MAFLD group [473.5 vs. 255.1 per 100,000 person-years; incidence rate ratio 1.86; 95% confidence interval (CI) 1.57-2.19]. After adjustment for age, gender, smoking status, and alcohol status, MAFLD was moderately associated with cancers of the female reproductive system/organs (labium, uterus, cervix, and ovary) [hazard ratio (HR) 2.24; 95% CI 1.09-4.60], thyroid (HR 3.64; 95% CI 1.82-7.30), and bladder (HR 4.19; 95% CI 1.15-15.27) in the total study cohort. Conclusion: MAFLD was associated with the development of cancers of the female reproductive system/organs (labium, uterus, cervix, and ovary), thyroid, and bladder in the total study cohort.

A thresholding method based on society modularity and role division for functional connectivity analysis.

Objective. Inferring the optimized and sparse network structure from the fully connected matrix is a key step in functional connectivity (FC) analysis. However, it is still an urgent problem to be solved, how to exclude the weak and spurious connections contained in functional networks objectively. Most existing binarization methods assume that the network has some certain constraint structures, which lead to changes in the original topology of the network.Approach. To solve this problem, we develop a Trade-off Model between Cost and Topology under Role Division (MCT), which consists of three crucial strategies, including modularity detection, definition of node role, and E-cost optimization algorithm. This algorithm weighs the physical cost and adaptive value of the network while preserving the network structure. Reliability and validity of MCT were evaluated by comparing different binarization methods (efficiency cost optimization, cluster-span threshold, threshold method, and MCT) on synthetic and real data sets.Main results. Experiment results demonstrated that the recovery rate of MCT for networks under noise interference is superior to other methods. In addition, brain networks filtered with MCT had higher network efficiency and shorter characteristic path length, which is more in line with the small world characteristics. Finally, applying MCT to resting-state electroencephalography data from patients with major depression reveals abnormal topology of the patients' connectivity networks, manifested as lower clustering coefficient (CC) and higher global efficiency (GE).Significance. This study provides an objective method for complex network analysis, which may contribute to the future of FC research.

Central Nervous System Efficacy of Furmonertinib (AST2818) Versus Gefitinib as First-Line Treatment for EGFR-Mutated NSCLC: Results From the FURLONG Study.

INTRODUCTION: Furmonertinib (AST2818) is a pan-EGFR tyrosine kinase inhibitor with central nervous system (CNS) antitumor activity. We report the CNS efficacy of furmonertinib compared with gefitinib in untreated EGFR-sensitizing mutation-positive NSCLC from the FURLONG study. METHODS: FURLONG was a randomized, double-blind, phase 3 study conducted in 55 hospitals in the People's Republic of China. Patients 1:1 randomly received furmonertinib 80 mg once daily or gefitinib 250 mg once daily treatment. At screening, all the patients underwent brain imaging examination. Patients with asymptomatic steady CNS metastases at baseline constituted this preplanned CNS subgroup analysis. RESULTS: A total of 358 patients were enrolled in the FURLONG study. In the 133 (37%) patients who had measurable or nonmeasurable CNS lesions, CNS progression-free survival was 20.8 months (95% confidence interval [CI]: 15.2-25.3) in the furmonertinib group and 9.8 months (95% CI: 7.2-18.0) in the gefitinib group (hazard ratio = 0.40 [95% CI: 0.23-0.71], p = 0.0011). In the 60 patients (17%) who had measurable CNS lesions, CNS objective response rate was 91% (95% CI: 72-99) with furmonertinib and 65% (95% CI: 48-80) with gefitinib (OR = 6.82 [95% CI: 1.23-37.67], p = 0.0277). The least-square mean of CNS depth of response was 62% (95% CI: 51-72) in the furmonertinib group and 39% (95% CI: 30-47) in the gefitinib group, the mean difference was 23% (95% CI: 10-37, p = 0.0011). CONCLUSIONS: Furmonertinib first-line treatment was found to have superior efficacy in CNS progression-free survival, CNS objective response rate, and CNS depth of response compared with gefitinib in patients with EGFR-mutated NSCLC with CNS metastases.

Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study.

BACKGROUND: Furmonertinib (AST2818) is an irreversible, selective, third-generation EGFR tyrosine-kinase inhibitor. We aimed to investigate the efficacy and safety of furmonertinib versus the first-generation EGFR tyrosine-kinase inhibitor gefitinib as first-line treatment in patients with EGFR mutation-positive locally advanced or metastatic non-small-cell lung cancer (NSCLC). METHODS: The FURLONG study is a multicentre, double-blind, randomised, phase 3 study done in 55 hospitals across mainland China. We enrolled patients who were aged 18 years or older and had histologically confirmed, locally advanced or metastatic, stage IIIB, IIIC, or IV unresectable NSCLC with EGFR exon 19 deletions or exon 21 Leu858Arg mutation on tissue biopsy confirmed by a central laboratory. Eligible patients were stratified according to EGFR mutation (exon 19 deletions or exon 21 Leu858Arg) and CNS metastases (with or without) and randomly assigned (1:1) to receive either oral furmonertinib (80 mg/day) or oral gefitinib (250 mg/day) in 21-day cycles until disease progression, the occurrence of intolerable toxicities, withdrawal of consent, or other discontinuation reasons judged by the investigators. Investigators, clinicians, participants, independent review centre (IRC) members, the sponsor, and those analysing the data were all masked to treatment allocation. The primary endpoint was IRC-assessed progression-free survival and, along with safety, was analysed in the full analysis set, which comprised all randomly assigned patients who had received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03787992, and is ongoing for survival follow-up. FINDINGS: Between May 30, 2019, and Dec 5, 2019, 750 patients were screened, of whom 358 were randomly assigned to receive either furmonertinib and gefitinib-matching placebo (n=178) or gefitinib and furmonertinib-matching placebo (n=180). 178 patients randomly assigned to furmonertinib and 179 patients randomly assigned to gefitinib were treated and were included in the full analysis set. Median follow-up was 21·0 months (IQR 18·0-23·5) in the furmonertinib group and 21·0 months (18·0-23·5) in the gefitinib group. Median IRC-assessed progression-free survival was 20·8 months (95% CI 17·8-23·5) in the furmonertinib group and 11·1 months (9·7-12·5) in the gefitinib group (hazard ratio 0·44, 95% CI 0·34-0·58; p<0·0001). Treatment-related adverse events of a grade 3 or more occurred in 20 (11%) of 178 patients in the furmonertinib group and in 32 (18%) of 179 patients in the gefitinib group. Treatment-related serious adverse events were reported in ten (6%) patients in the furmonertinib group and in 11 (6%) patients in the gefitinib group. Ten (6%) patients in the furmonertinib group and three (2%) patients in the gefitinib group died due to adverse events, which were all judged to be possibly unrelated to study treatment by the investigators. INTERPRETATION: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in Chinese patients with EGFR mutation-positive NSCLC, along with an acceptable safety profile without new signals. Furmonertinib is a new potential treatment option for this population. FUNDING: Shanghai Allist Pharmaceuticals and the China National Major Project for New Drug Innovation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Depression, anxiety and post-traumatic growth among COVID-19 survivors six-month after discharge.

Background: Pre-hospitalisation, hospitalisation and post-hospitalisation factors may significantly affect depression, anxiety and post-traumatic growth (PTG) among COVID-19 survivors. Objective: Our study investigated depression, anxiety and PTG and their correlates among COVID-19 survivors. Method: A cross-sectional telephone survey recruited 199 COVID-19 patients (Mean age = 42.7; 53.3% females) at six-month follow-up after hospital discharge in five Chinese cities (i.e. Wuhan, Shenzhen, Zhuhai, Dongguan and Nanning). Their demographic information, clinical records and experiences during (e.g. severity of covid-19 symptoms, treatment and exposure to other patients' suffering) and after hospitalisation (e.g. perceived impact of covid-19, somatic symptoms after hospitalisation), and psychosocial factors (e.g. perceived discrimination, self-stigma, affiliate stigma, resilience and social support) were investigated. Depressive and anxiety symptoms were measured by the Patient Health Questionnaire (PHQ-9) and the Generalised anxiety disorder (GAD-7) scale, respectively. PTG was examined by the Post-traumatic Growth Inventory (PTGI) instrument. Results: The proportion of depressive symptoms <5, ≥5 and <10, ≥10 were 76.9%, 12.0% and 11.1%, respectively. The proportion of anxiety symptoms <5, ≥5 and <10, ≥10 were 77.4%, 15.1% and 7.5%, respectively. Multivariate logistic regression showed that receiving mental health care services during hospitalisation, somatic symptoms after discharge, perceived affiliate stigma and perceived impact of being infected with COVID-19 were significantly and positively associated with probable depression. Significant correlates of probable anxiety also included permanent residents of the city, somatic symptoms after discharge, perceived impact of being infected with COVID-19 and self-stigma. Social support, self-stigma and receiving mental health care services during hospitalisation were positively associated with PTG.Conclusions: The results suggest that post-hospitalisation and psychosocial factors had relatively stronger associations with depression, anxiety and PTG than pre-hospitalisation and hospitalisation factors. Promoting social support and social inclusion may be useful strategies to improve the mental health of COVID-19 survivors. HIGHLIGHTS: • Post-hospitalisation and psychosocial factors had relatively stronger associations with depression, anxiety and PTG than pre-hospitalisation and hospitalisation factors, promoting social support and social inclusion may be useful strategies to improve mental health of COVID-19 survivors.

Antecedentes: Los factores pre-hospitalización, durante la hospitalización y post-hospitalización pueden afectar significativamente la depresión, la ansiedad y el crecimiento postraumático (CPT) en los sobrevivientes de COVID-19.Objetivo: Nuestro estudio investigó la depresión, la ansiedad y el CPT y sus correlatos en sobrevivientes de COVID-19.Método: Una encuesta telefónica transversal reclutó a 199 pacientes con COVID-19 (edad promedio = 42,7; 53,3% mujeres) a los seis meses de seguimiento después del alta hospitalaria en cinco ciudades chinas (Wuhan, Shenzhen, Zhuhai, Dongguan y Nanning). Su información demográfica, registros clínicos y experiencias durante la hospitalización (e.g. gravedad de los síntomas de COVID-19, tratamiento, exposición al sufrimiento de otros pacientes) y después de la hospitalización (e.g. impacto percibido de COVID-19, síntomas somáticos después de la hospitalización) y factores psicosociales (e.g. discriminación percibida, autoestigma, estigma de afiliación, resiliencia, apoyo social) fueron investigados. Los síntomas depresivos y de ansiedad se midieron mediante el Cuestionario de Salud del Paciente (PHQ-9 en su sigla en inglés) y la escala de trastorno de ansiedad generalizada (GAD-7 en su sigla en inglés) respectivamente, el CPT se examinó mediante el instrumento Inventario de Crecimiento Postraumático (PTGI en su sigla en inglés).Resultados: La proporción de síntomas depresivos <5, ≥5 y <10, y ≥10 fue 76,9%, 12,0% y 11,1% respectivamente. La proporción de síntomas de ansiedad <5, ≥5 y <10, y ≥10 fue del 77,4%, 15,1% y 7,5% respectivamente. La regresión logística multivariante mostró que recibir servicios de atención de salud mental durante la hospitalización, los síntomas somáticos después del alta, el estigma de afiliación percibido y el impacto percibido de estar infectado con COVID-19 se asociaron significativa y positivamente con una probable depresión. Los correlatos significativos de ansiedad probable también incluyeron ser residente permanente de la ciudad, síntomas somáticos después del alta, impacto percibido de estar infectado con COVID-19 y autoestigma. El apoyo social, el autoestigma y recibir servicios de salud mental durante la hospitalización se asociaron positivamente con el CPT.Conclusiones: Los resultados sugieren que los factores psicosociales y posteriores a la hospitalización tuvieron asociaciones relativamente más fuertes con la depresión, la ansiedad y el CPT que los factores previos a la hospitalización y hospitalización. Promover el apoyo social y la inclusión social pueden ser estrategias útiles para mejorar la salud mental de los sobrevivientes de COVID-19.

The roles and potential mechanisms of HCST in the prognosis and immunity of KIRC via comprehensive analysis.

OBJECTIVES: Hematopoietic cell signal transducer (HCST) participates in the activation of phosphatidylinositol 3 kinase-dependent signaling pathway and in the natural killer (NK) and T cell responses, which affect cell survival and proliferation. Here, the values of HCST in kidney renal clear cell carcinoma (KIRC) are analyzed. METHODS: We used GEO, TCGA, GEPIA, UALCAN and TIMER databases to profile the expression of HCST in KIRC tissues, and define its clinical roles. The biological functions and signaling mechanisms modulated by HCST and its co-expressed genes were identified and analyzed via the GO and KEGG databases. On the other hand, the potential value of HCST expression in KIRC immunity was explored using the TIMER and GEPIA databases. RESULTS: Our analysis demonstrated that HCST is significantly overexpressed in KIRC tissues. The upregulation of HCST is associated with clinical stage, tumor grade, tissue subtype and poor prognosis of KIRC patients. Increased HCST expression might be involved in signaling pathways such as antigen processing and presentation, cell adhesion molecules, cytokine-cytokine receptor, chemokine signaling pathway, T cell receptor signaling pathway, FC gammar mediated phagocytosis and B cell receptor signaling pathway. In addition, the expression of HCST was significantly correlated with the levels of KIRC purity, B cells, CD8+ T Cell, CD4+ T cells, macrophages, neutrophils and dendritic cells (DC). Furthermore, the HCST expression is associated with levels of immune infiltration B cells, CD8+ T Cell, CD4+ T cells, macrophages, neutrophils and DC. CONCLUSIONS: Our data demonstrated that HCST could be a potential prognostic biomarker, and is related to the immune infiltration in KIRC.

Hospitalization, interpersonal and personal factors of social anxiety among COVID-19 survivors at the six-month follow-up after hospital treatment: the minority stress model.

Background: As a highly infectious disease with human-to-human transmission characteristics, COVID-19 has caused panic in the general public. Those who have recovered from COVID-19 may experience discrimination and internalized stigma. They may be more likely to worry about social interaction and develop social anxiety. Objectives: This study investigated the associations among hospitalization factors, social/interpersonal factors, personal factors, and social anxiety to reveal the mechanism of social anxiety in COVID-19 survivors. Methods: A cross-sectional, multicenter telephone survey was conducted from July to September 2020 in five Chinese cities (i.e. Wuhan, Nanning, Shenzhen, Zhuhai, and Dongguan); adult COVID-19 survivors were recruited 6 months after they were discharged from the hospital. Linear regressions and path analysis based on the minority stress model were conducted to test the relationships among hospitalization, social/interpersonal factors, personal factors, and social anxiety. Results: The response rate was 74.5% (N = 199, 55.3% females). Linear regression analyses showed that various hospitalization, social/interpersonal, and personal factors were statistically significantly associated with social anxiety. Path analysis showed that the proposed model fit the data well (χ2(df) = 3.196(3), p = .362, CFI = .999, NNFI = .996, RMSEA = .018). Internalized stigma fully mediated the association between perceived discrimination/social support and social anxiety, while it partially mediated the association between perceived affiliate stigma and social anxiety. Conclusions: The results suggest that social/interpersonal and personal factors have a stronger association with social anxiety than hospitalization factors and highlight the importance of internalized stigma in understanding the mechanisms of these relationships. Clinical psychologists can refer to these modifiable psychosocial factors to develop efficient interventions for mental health promotion.

Antecedentes: Como una enfermedad altamente infecciosa con características de transmisión de persona a persona, el COVID-19 ha causado pánico en el público en general. Aquellos que se han recuperado del COVID-19 pueden experimentar discriminación y estigma internalizado. Es más probable que se preocupen por la interacción social y desarrollen ansiedad social.Objetivos: Este estudio investigó las asociaciones entre factores de hospitalización, factores sociales /interpersonales, factores personales y ansiedad social para revelar el mecanismo de ansiedad social en sobrevivientes de COVID-19.Métodos: Se realizó una encuesta telefónica transversal multicentro de julio a septiembre de 2020 en cinco ciudades chinas (es decir, Wuhan, Nanning, Shenzhen, Zhuhai y Dongguan). Se reclutaron sobrevivientes adultos de COVID-19 seis meses después de ser dados de alta del hospital. Se realizaron regresiones lineales y análisis de ruta basados en el modelo de estrés de minoría para probar las relaciones entre la hospitalización, los factores sociales/interpersonales, los factores personales y la ansiedad social.Resultados: La tasa de respuesta fue del 74,5% (N = 199, 55,3% mujeres). Los análisis de regresión lineal mostraron que varios factores de hospitalización, sociales/interpersonales y personales se asociaron de manera estadísticamente significativa con la ansiedad social. El análisis de ruta mostró que el modelo propuesto se ajustaba bien a los datos (χ2 (df) = 3.196 (3), p = .362, CFI = .999, NNFI = .996, RMSEA = .018). El estigma internalizado medió completamente la asociación entre discriminación/apoyo social percibido y ansiedad social, mientras que medió parcialmente la asociación entre el estigma percibido de afiliados y ansiedad social.Conclusiones: Los resultados sugieren que los factores sociales/interpersonales y personales tienen una asociación más fuerte con la ansiedad social que los factores de hospitalización y resaltan la importancia del estigma internalizado en la comprensión de los mecanismos de estas relaciones. Los psicólogos clínicos pueden referirse a estos factores psicosociales modificables para desarrollar intervenciones eficientes para la promoción de la salud mental.

Associations between COVID-19 related stigma and sleep quality among COVID-19 survivors six months after hospital discharge.

BACKGROUND: Many COVID-19 survivors reported stigmatization after recovery. This study investigated the association between stigma (discrimination experiences, self-stigma and perceived affiliate stigma) and sleep quality among COVID-19 survivors six months after hospital discharge. METHODS: Participants were recovered adult COVID-19 survivors discharged between February 1 and April 30, 2020. Medical staff of five participating hospitals approached all discharged COVID-19 period during this period. A total of 199 participants completed the telephone interview during July to September, 2020. Structural equation modeling was performed to test the hypothesize that resilience and social support would mediate the associations between stigma and sleep quality. RESULTS: The results showed that 10.1% of the participants reported terrible/poor sleep quality, 26.1% reported worse sleep quality in the past week when comparing their current status versus the time before COVID-19. After adjusting for significant background characteristics, participants who had higher number of discrimination experience, perceived stronger self-stigma and stronger perceived affiliate stigma reported poorer sleep quality. Resilience and social support were positively and significantly associated with sleep quality. The indirect effect of self-stigma on sleep quality through social support and resilience was significant and negative. Perceived affiliate stigma also had a significant and negative indirect effect on sleep quality through social support and resilience. CONCLUSIONS: Various types of stigma after recovery were associated with poor sleep quality among COVID-19 survivors, while social support and resilience were protective factors. Resilience and social support mediated the associations between self-stigma/perceived affiliate stigma and sleep quality.

CircMAN1A2 promotes vasculogenic mimicry of nasopharyngeal carcinoma cells through upregulating ERBB2 via sponging miR-940.

Nasopharyngeal carcinoma (NPC) is the most prevalent human primary malignancy of the head and neck, and the presence of vasculogenic mimicry (VM) renders anti-angiogenic therapy ineffective and poorly prognostic. However, the underlying mechanisms are unclear. In the present study, we used miR-940 silencing and overexpression for in vitro NPC cell EdU staining, wound healing assay and 3D cell culture assay, and in vivo xenograft mouse model and VM formation to assess miR-940 function. We found that ectopic miR-940 expression reduced NPC cell proliferation, migration and VM, as well as tumorigenesis in vivo. By bioinformatic analysis, circMAN1A2 was identified as a circRNA that binds to miR-940. Mechanistically, we confirmed that circMAN1A2 acts as a sponge for miR-940, impairs the inhibitory effect of miR-940 on target ERBB2, and then activates the PI3K/AKT/mTOR signaling pathway using RNA-FISH, dual luciferase reporter gene and rescue analysis assays. In addition, upregulation of ERBB2 expression is associated with clinical staging and poor prognosis of NPC. Taken together, the present findings suggest that circMAN1A2 promotes VM formation and progression of NPC through miR-940/ERBB2 axis and further activates the PI3K/AKT/mTOR pathway. Therefore, circMAN1A2 may become a biomarker and therapeutic target for anti-angiogenic therapy in patients with nasopharyngeal carcinoma.

Pre-hospital, in-hospital and post-hospital factors associated with sleep quality among COVID-19 survivors 6 months after hospital discharge: cross-sectional survey in five cities in China.

Background: Understanding factors associated with post-discharge sleep quality among COVID-19 survivors is important for intervention development. Aims: This study investigated sleep quality and its correlates among COVID-19 patients 6 months after their most recent hospital discharge. Method: Healthcare providers at hospitals located in five different Chinese cities contacted adult COVID-19 patients discharged between 1 February and 30 March 2020. A total of 199 eligible patients provided verbal informed consent and completed the interview. Using score on the single-item Sleep Quality Scale as the dependent variable, multiple linear regression models were fitted. Results: Among all participants, 10.1% reported terrible or poor sleep quality, and 26.6% reported fair sleep quality, 26.1% reported worse sleep quality when comparing their current status with the time before COVID-19, and 33.7% were bothered by a sleeping disorder in the past 2 weeks. After adjusting for significant background characteristics, factors associated with sleep quality included witnessing the suffering (adjusted B = -1.15, 95% CI = -1.70, -0.33) or death (adjusted B = -1.55, 95% CI = -2.62, -0.49) of other COVID-19 patients during hospital stay, depressive symptoms (adjusted B = -0.26, 95% CI = -0.31, -0.20), anxiety symptoms (adjusted B = -0.25, 95% CI = -0.33, -0.17), post-traumatic stress disorders (adjusted B = -0.16, 95% CI = -0.22, -0.10) and social support (adjusted B = 0.07, 95% CI = 0.04, 0.10). Conclusions: COVID-19 survivors reported poor sleep quality. Interventions and support services to improve sleep quality should be provided to COVID-19 survivors during their hospital stay and after hospital discharge.

Long intergenic non-protein coding RNA 02570 promotes nasopharyngeal carcinoma progression by adsorbing microRNA miR-4649-3p thereby upregulating both sterol regulatory element binding protein 1, and fatty acid synthase.

Our previous studies have elucidated a possible connection between long intergenic non-protein coding RNA 2570 (LINC02570) and nasopharyngeal carcinoma (NPC). However, the precise mechanism by which LINC02570 promotes NPC remains unknown. We used quantitative polymerase chain reaction (qPCR) to detect LINC02570 expression in nasopharyngeal cell lines, NPC tissues, and chronic rhinitis tissues. Subcellular LINC02570 localization was confirmed by fluorescence in situ hybridization (FISH). The effects of LINC02570 stable knockdown and overexpression on viabillity, proliferation, migration, and invasion were analyzed using 3-(4,5-Dimethyl-2-Thiazolyl)-2,5-Diphenyl-2-H-Tetrazolium bromide (MTT), a colorimetric focus-formation assay, a wound healing assay, and transwell assays. RNA crosstalk analysis in silico predicted microRNA-4649-3p (miR-4649-3p) binding to LINC02570 or sterol regulatory element binding transcription factor 1 (SREBF1). A dual luciferase reporter assay was used to confirm potential interactions. Sterol regulatory element binding protein 1 (SREBP1) and fatty acid synthase (FASN) expression were detected by western blotting. The results suggest that LINC02570 is upregulated in late clinical stage NPC patients, and promotes NPC progression by adsorbing miR-4649-3p to up-regulate SREBP1 and FASN. This study elucidates a potential chemotherapeutic target involved in lipid metabolism in NPC.

Elucidation of the Regulatory Network of Flavonoid Biosynthesis by Profiling the Metabolome and Transcriptome in Tartary Buckwheat.

The characteristics of flavonoid metabolism in different Tartary buckwheat (TB) tissues and the related gene regulation network are still unclear at present. One hundred forty-seven flavonoids were identified from six TB tissues using the ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. The roadmap of the rutin synthesis pathway was revealed. Through transcriptomic analysis it was revealed that the differentially expressed genes (DEGs) are mainly enriched in the "Phenylpropanoid biosynthesis" pathway. Fifty-two DEGs involved in the "flavonol synthesis" pathway were identified. The weighted gene correlation network analysis revealed four co-expression network modules correlated with six flavonol metabolites. Eventually, 74 genes revealed from MEblue and MElightsteelblue modules were potentially related to flavonol synthesis. Of them, 7 MYB transcript factors had been verified to regulate flavonoid synthesis. Furthermore, overexpressed FtMYB31 enhanced the rutin content in vivo. The present findings provide a dynamic flavonoid metabolism profile and co-expression network related to rutin synthesis and are thus valuable in understanding the molecular mechanisms of rutin synthesis in TB.