Effect of Acoustic Environment in Wards on Postoperative Rehabilitation in Patients with Oral Cancer: A Retrospective Study.

OBJECTIVE: The increase in patient flow, replacement of medical equipment, and variations in surrounding environments induce increasingly serious acoustic environment problems in hospitals. This study aims to provide additional bases for the formulation of subsequent management plans in clinical practice by analyzing the influence of the acoustic environment in wards and the postoperative rehabilitation effect among patients with oral cancer. METHODS: The medical records of 210 patients with oral cancer undergoing surgical treatment in Jinan Stomatological Hospital from February 2020 to October 2022 were selected for retrospective analysis. Patients with the acoustic environment in wards >55 and ≤55 dB were classified as groups A and B, respectively, according to the acoustic environment in wards. The effects of the acoustic environment in wards on postoperative blood pressure, blood viscosity, and blood glucose fluctuation (BGF) were observed to further analyze their relationship. RESULTS: No significant difference was observed in indices such as preoperative systolic pressure (SP), diastolic pressure (DP), cardiac output (CO), postoperative CO, total cholesterol, and low- and high-density lipoproteins between the two groups (P > 0.05). The SP, DP, whole blood low-shear viscosity (WBLSV), whole blood middle-shear viscosity (WBMSV), whole blood high-shear viscosity (WBHSV), and BGF in group B were significantly lower than group A (P < 0.05). Correlation results showed that the total mean value of the acoustic environment in wards was positively correlated with SP, DP, WBLSV, WBMSV, WBHSV, and BGF (P < 0.05). CONCLUSION: The high acoustic environment in wards is significantly positively correlated with postoperative blood pressure, blood viscosity, and BGF in patients with oral cancer. The hospital should focus on and strengthen the management of the acoustic environment in wards, providing additional schemes to promote the postoperative recovery of patients with oral cancer.

Biosynthesis of Chryseno[2,1,c]oxepin-12-Carboxylic Acid from Glycyrrhizic Acid in Aspergillus terreus TMZ05-2, and Analysis of Its Anti-inflammatory Activity.

Glycyrrhizic acid, glycyrrhetinic acid, and their oxo, ester, lactone, and other derivatives, are known for their anti-inflammatory, anti-oxidant, and hypoglycemic pharmacological activities. In this study, chryseno[2,1-c]oxepin-12-carboxylic acid (MG) was first biosynthesized from glycyrrhizic acid through sequential hydrolysis, oxidation, and esterification using Aspergillus terreus TMZ05-2, providing a novel in vitro biosynthetic pathway for glycyrrhizic acid derivatives. Assessing the influence of fermentation conditions and variation of strains during culture under stress-induction strategies enhanced the final molar yield to 88.3% (5 g/L glycyrrhizic acid). CCK8 assays showed no cytotoxicity and good cell proliferation, and anti-inflammatory experiments demonstrated strong inhibition of NO release (36.3%, low-dose MG vs. model), transcriptional downregulation of classical effective cellular factors tumor necrosis factor-α (TNF-α; 72.2%, low-dose MG vs. model), interleukin-6 (IL-6; 58.3%, low-dose MG vs. model) and interleukin-1ß (IL-1ß; 76.4%, low-dose MG vs. model), and decreased abundance of P-IKK-α, P-IKB-α, and P-P65 proteins, thereby alleviating inflammatory responses through the NF-κB pathway in LPS-induced RAW264.7 cells. The findings provide a reference for the biosynthesis of lactone compounds from medicinal plants.

Safety and feasibility of anti-CD19 CAR T cells expressing inducible IL-7 and CCL19 in patients with relapsed or refractory large B-cell lymphoma.

Although CD19-specific chimeric antigen receptor (CAR) T cells are curative for patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), disease relapse with tumor antigen-positive remains a challenge. Cytokine/chemokine-expressing CAR-T cells could overcome a suppressive milieu, but the clinical safety and efficacy of this CAR-T therapy remain unclear. Here we report the preclinical development of CD19-specific CAR-T cells capable of expressing interleukin (IL)-7 and chemokine (C-C motif) ligand (CCL)-19 upon CD19 engagement (referred to as 7 × 19 CAR-T cells) and results from a phase 1 and expansion phase trial of 7 × 19 CAR-T cell therapy in patients with R/R LBCL (NCT03258047). In dose-escalation phase, there were no dose-limiting toxicities observed. 39 patients with R/R LBCL received 7 × 19 CAR-T with doses ranged from 0.5 × 106-4.0 × 106 cells per kg body weight. Grade 3 cytokine release syndrome occurred in 5 (12.8%) patients and ≥ grade 3 neurotoxicity in 4 (10.3%) patients. The overall response rate at 3 months post-single infusion was 79.5% (complete remission, 56.4%; partial response, 23.1%). With a median follow-up of 32 months, the median progression-free survival was 13 months, and median overall survival was not reached, with an estimated rate of 53.8% (95% CI, 40.3% to 72.0%) at two years. Together, these long-term follow-up data from the multicenter clinical study suggest that 7 × 19 CAR-T cells can induce durable responses with a median overall survival of greater than 2 years, and have a manageable safety profile in patients with R/R LBCL.

An integrated analysis identifies six molecular subtypes of pancreatic ductal adenocarcinoma revealing cellular and molecular landscape.

Pancreatic ductal adenocarcinoma (PDA) has been found to have a high mortality rate. Despite continuous efforts, current histopathological classification is insufficient to guide individualized therapies of PDA. We first define the molecular subtypes of PDA (MSOP) based on a meta-cohort of 845 samples from 11 PDA datasets. We then performed functional analyses involving immunity, fibrosis and metabolism. We recognized six molecular subtypes with different survival statistics and molecular composition. The squamous basal-like (SBL) subtype had a poor prognosis and high infiltration of ENO1+ (Enolase 1)/ADM+ (Adrenomedullin) cancer-associated fibroblasts (CAFs). The immune mesenchymal-like (IML) subtype and the normal mesenchymal-like (NML) subtype were characterized by genes associated with extracellular matrix (ECM) activities and immune responses, having favorable prognoses. IML was featured by elevated exhausted immune signaling and inflammatory CAFs infiltration, whereas NML was featured with myofibroblastic CAFs infiltration. The exocrine-like (EL) subtype was high in exocrine signals, while the pure classical-like (PCL) subtype lacked immunocytes infiltration. The quiescent-like (QL) subtype had diminished metabolic signaling and high infiltration of NK cells. SBL, IML and NML were enriched in innate anti-PD-1 resistance signatures. In sum, this MSOP depicts a vivid cell-to-molecular atlas of the tumor microenvironment of PDA and might facilitate to design a precise combination of therapies that target immunity, metabolism and stroma.

Decrease of lncRNA MEG3 in Acute Myeloid Leukemia Affected the Expression of p53 and MDM2.

BACKGROUND: The aim was to determine the clinical role of long non coding maternally expressed gene 3 (lncRNA MEG3) in adult acute myeloid leukemia (AML). METHODS: The expression levels of lncRNA MEG3 in bone marrow of AML patients and healthy donors were determined by qPCR. The correlation between expression levels of lncRNA MEG3 and clinical features was also analyzed. MTT assay and flow-cytometric assay were employed to determine the role of lncRNA MEG3 on the cell viability and apoptosis of AML cell lines. Expression levels of caspase-9, Bcl-2, MDM2, and p53 in those cells were determined by western blot. RESULTS: The expression levels of lncRNA MEG3 was significantly down-regulated in AML patients. Expression levels of lncRNA MEG3 were positively correlated with overall survival of patients. Up-regulation of lncRNA MEG3 could not only inhibit the cell growth and promoted apoptosis, but also increased the expression of caspase-9 and p53 and decreased the expression of Bcl-2 and MDM2. CONCLUSIONS: These results suggest that down-regulation of lncRNA MEG3 in AML patients might promote tumor progression and affect the p53-MDM2 pathway.

Analysis of sports behavior and the current situation of young students under the background of covid-19 / Análise do comportamento esportivo e da situação atual dos jovens estudantes sob o contexto da covid-19 / Análisis del comportamiento deportivo y de la situación actual de los jóvenes estudiantes en el contexto del covid-19

ABSTRACT Introduction With the repeated covid-19 epidemic, people have gradually realized the importance of physical exercise, so the sports enthusiasm of young students has also been improved to a certain extent. Objective Analyze the sports behavior and status in adolescent students under the background of covid-19. Methods A questionnaire survey was used in this paper. The questionnaire design is carried out from three aspects: current exercise status, changes of physical exercise, and sports behavior motivation of young students. Results Students and parents prefer exercises at home or in the open space of a relatively safe and single community, choosing non-contact sports that can be completed by a single person or are far away from each other. Improvement in both frequency and duration of exercise was observed in the young students, and most had a gain in psychological quality. Conclusion Physical education teachers must fully match the actual situation of the epidemic's current development by choosing effective teaching methods to promote the continuous development of young students' physical quality. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução Com a repetida epidemia da covid-19, as pessoas foram gradualmente percebendo a importância do exercício físico e um crescimento no engajamento esportivo entre os jovens estudantes foi observado. Objetivo Analisar o comportamento e o status esportivo dos estudantes adolescentes sob o contexto da covid-19. Métodos Este trabalho utilizou uma pesquisa por questionário com desenho realizado a partir de três aspectos: estado atual do exercício físico, alterações do exercício físico, e motivação do comportamento esportivo nos jovens estudantes. Resultados Os estudantes e seus pais preferem exercícios em casa ou em espaço aberto relativamente seguro e isolado, escolhendo esportes sem contato que podem ser realizados por uma única pessoa ou em que estejam longe um do outro. Observou-se uma melhora tanto na frequência quanto na duração dos exercícios físicos dos jovens estudantes e a maioria teve um ganho na qualidade psicológica. Conclusão Os professores de educação física devem combinar plenamente a situação real do atual desenvolvimento da epidemia escolhendo métodos de ensino eficazes que promovam o desenvolvimento contínuo da qualidade física dos jovens estudantes. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción Con la repetida epidemia del covid-19, la gente se fue dando cuenta de la importancia del ejercicio físico y se observó un aumento del interés por el deporte entre los jóvenes estudiantes. Objetivo Analizar el comportamiento y la situación deportiva de los estudiantes adolescentes en el contexto del covid-19. Métodos Este trabajo utilizó una encuesta con diseño de cuestionario realizada desde tres aspectos: estado actual del ejercicio, cambios de ejercicio y motivación del comportamiento deportivo en jóvenes estudiantes. Resultados Los estudiantes y sus padres prefieren hacer ejercicio en casa o en un espacio abierto relativamente seguro y aislado, eligiendo deportes sin contacto que puedan ser realizados por una sola persona o donde estén alejados unos de otros. Se observó una mejora tanto en la frecuencia como en la duración del ejercicio en los jóvenes estudiantes y la mayoría tuvo una ganancia en la calidad psicológica. Conclusión Los profesores de educación física deben ajustarse plenamente a la situación real del desarrollo actual de la epidemia eligiendo métodos de enseñanza eficaces que promuevan el desarrollo continuo de la calidad física de los jóvenes estudiantes. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Secondary myeloid neoplasms after CD19 CAR T therapy in patients with refractory/relapsed B-cell lymphoma: Case series and review of literature.

Background: Several chimeric antigen receptor T cells (CAR T) targeting CD19 have induced profound and prolonged remission for refractory/relapsed (R/R) B-cell lymphoma. The risk of secondary malignancies, especially myeloid neoplasms, is of particular concern in the CAR T community, which still remains unclear. Methods: Four patients with R/R B-cell lymphoma after CD19 CAR T therapy diagnosed with secondary myeloid neoplasms (SMN) from 2 hospitals in eastern China were presented, including 3 with myelodysplastic syndrome (MDS) and 1 with acute myeloid leukemia (AML). Using single-cell RNA sequencing (scRNA-seq), we compared the cellular components of bone marrow (BM) samples obtained from one of these MDS patients and a health donor. We also provided a review of recently published literature concerning SMN risk of CAR T therapy. Results: Relevant demographic, clinical, laboratory, therapeutic and outcome data were collected and presented by chart review. In our case series, the male-female ratio was 3.0 and the median age at MDS onset was 61.25 years old (range, 50-78). Median number of previous systemic therapies was 4.5 (range, 4-5), including autologous hematopoietic stem cell transplantation (auto-HSCT) in one patient. BM assessments prior to CAR T therapy confirmed normal hematopoiesis without myeloid neoplasms. Moreover, for 3 patients with SMN in our series, cytogenetic analysis predicted a relatively adverse outcome. In our experience and in the literature, treatment choices for the patients with SMN included allogeneic hematopoietic stem cell transplantation (allo-HSCT), hypomethylating agent (HMA), period filgrastim, transfusions and other supportive care. Finally, treatment responses of lymphoma, together with SMN, directly correlated with the overall survival of this community. Of note, it appeared that pathogenesis of MDS wasn't associated with the CAR T toxicities, since all 4 patients experienced a pretty mild CRS of grade 1-2. Additionally, scRNA-seq analysis described the transcriptional alteration of CD34+ cells, identified 13 T/NK clusters, and also indicated increased cytotoxic T cells in MDS BM. Conclusion: Our study illustrated the onset and progression of SMN after CD19 CAR T therapy in patients with R/R B-cell lymphoma, which provides useful information of this uncommon later event.

Activation-induced cytidine deaminase overexpression in double-hit lymphoma: potential target for novel anticancer therapy.

Activation-induced cytidine deaminase (AID) is one kind of the mutant enzymes, which target regulating the immunoglobulin (Ig) gene in Burkitt's lymphoma to initiate class switch recombination (CSR), resulting in c-Myc chromosomal translocation. However, it is not clear that whether AID induces c-Myc/IgH translocation in double-hit lymphoma (DHL) with c-Myc gene translocation. In this study, the AID in DHL tissues and classical diffuse large b-cell lymphoma (DLBCL) tissues were compared. The results suggested that AID is of important value in predicting DHL, stronger CSR of AID was observed in DHL patients, which exhibited AID overexpression and c-Myc gene translocation of DHL after CSR induction. It is concluded that AID directly induces CSR in DHL and may result in c-Myc gene translocation. Targeting AID may be a good treatment regimen for DHL.

Interaction of estrogen receptor ß and negative life events in susceptibility to major depressive disorder in a Chinese Han female population.

BACKGROUND: Both genetic and environmental factors as well as their interaction contribute to the etiology of major depressive disorder (MDD). Estrogen receptor ß (ESR2) may play a vital role in the development of MDD in females. The aim of this study is to analyze ESR2 gene polymorphisms and the interaction of ESR2 gene variation and negative life events concerning the risk of developing MDD in females, especially during menopausal stage. METHODS: Genotyping was performed by Taqman allelic discrimination assay among 191 female MDD patients and 200 healthy females. Life Events Scale and the generalized multifactor dimensionality reduction method were employed to assess the frequency and severity of negative life events and gene-environment interaction (G×E), respectively. All subjects were regrouped into reproductive and menopausal group based on age. Logistic regression was used to evaluate the set of risk factors. RESULTS: No association of ESR2 G×E interaction with MDD was found in the reproductive group. However, in menopausal females, significant G×E interactions between negative life events and allelic variation of rs1256049 and rs4986938 were observed. Individuals with the A+ allele of rs1256049 and rs4986938 were susceptible to MDD when exposed to low negative life events. LIMITATION: Assessment of negative life events was influenced by subjective interpretation. CONCLUSIONS: ESR2 may modify the interaction between negative life events and MDD in the Chinese Han menopausal females. To our knowledge, this study is the first to report an effect modification between negative life events and ESR2 variations in female MDD patients.

MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance.

MicroRNAs (miRs) play an important role in tumorogenesis and chemoresistance in lymphoid malignancies. Comparing with reactive hyperplasia, miR181a was overexpressed in 130 patients with T-cell leukemia/lymphoma, including acute T-cell lymphoblastic leukemia (n = 32), T-cell lymphoblastic lymphoma (n = 16), peripheral T-cell lymphoma, not otherwise specified (n = 45), anaplastic large cell lymphoma (n = 15), and angioimmunoblastic T-cell lymphoma (n = 22). Irrespective to histological subtypes, miR181a overexpression was associated with increased AKT phosphorylation. In vitro, ectopic expression of miR181a in HEK-293T cells significantly enhanced cell proliferation, activated AKT, and conferred cell resistance to doxorubicin. Meanwhile, miR181a expression was upregulated in Jurkat cells, along with AKT activation, during exposure to chemotherapeutic agents regularly applied to T-cell leukemia/lymphoma treatment, such as doxorubicin, cyclophosphamide, cytarabine, and cisplatin. Isogenic doxorubicin-resistant Jurkat and H9 cells were subsequently developed, which also presented with miR181a overexpression and cross-resistance to cyclophosphamide and cisplatin. Meanwhile, specific inhibition of miR181a enhanced Jurkat and H9 cell sensitivity to chemotherapeutic agents, further indicating that miR181a was involved in acquired chemoresistance. Collectively, miR181a functioned as a biomarker of T-cell leukemia/lymphoma through modulation of AKT pathway. Related to tumor cell chemoresistance, miR181a could be a potential therapeutic target in treating T-cell malignancies.

Comparison of Soybean Transformation Efficiency and Plant Factors Affecting Transformation during the Agrobacterium Infection Process.

The susceptibility of soybean genotype to Agrobacterium infection is a key factor for the high level of genetic transformation efficiency. The objective of this study is to evaluate the plant factors related to transformation in cotyledonary nodes during the Agrobacterium infection process. This study selected three genotypes (Williams 82, Shennong 9 and Bert) with high transformation efficiency, which presented better susceptibility to Agrobacterium infection, and three low transformation efficiency genotypes (General, Liaodou 16 and Kottman), which showed a relatively weak susceptibility. Gibberellin (GA) levels and soybean GA20ox2 and CYP707A2 transcripts of high-efficiency genotypes increased and were higher than those of low-efficiency genotypes; however, the opposite performance was shown in abscisic acid (ABA). Higher zeatin riboside (ZR) content and DNA quantity, and relatively higher expression of soybean IPT5, CYCD3 and CYCA3 were obtained in high-efficiency genotypes. High-efficiency genotypes had low methyl jasmonate (MeJA) content, polyphenol oxidase (PPO) and peroxidase (POD) activity, and relatively lower expression of soybean OPR3, PPO1 and PRX71. GA and ZR were positive plant factors for Agrobacterium-mediated soybean transformation by facilitating germination and growth, and increasing the number of cells in DNA synthesis cycle, respectively; MeJA, PPO, POD and ABA were negative plant factors by inducing defence reactions and repressing germination and growth, respectively.

Serum peptidome profiling for identifying pathological patterns in patients with primary nephrotic syndrome.

BACKGROUND: Renal biopsy is necessary for diagnosing the pathological changes of primary nephrotic syndrome (NS). However, it is invasive, time-consuming and can not be performed frequent on the same patient. Thus, development of a non-invasive and rapid diagnostic method may improve clinical patient management. METHODS: Proteomic tool magnetic bead-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MB-based MALDI TOF MS) was applied to serum to determine peptidome patterns that are characteristic of different pathological changes. RESULTS: Serum specimen from 114 patients with NS (62 were minimal change disease (MCD), 30 were membranous nephropathy (MN), and 22 were focal segmental glomerulosclerosis (FSGS)) and 60 normal individuals were analyzed using MB-based MALDI TOF MS. The peptidome pattern was generated by genetic algorithms using a training set of 31 MCD, 15 MN, 11 FSGS and 30 normal individuals and was validated by an independent testing set of the remaining samples. The serum peptidome pattern, based on a panel of 14 peaks, accurately recognized samples from MCD, MN, FSGS and healthy control with sensitivities of 93.5%, 86.7%, 63.6% and 90.0%, and specificities of 98.2%, 94.4%, 100% and 89.5%, respectively. Moreover, one peptide from peptidome pattern was identified by liquid chromatography tandem mass spectrometry (LC MS/MS) as fibrinogen A. CONCLUSION: Detection of the serum peptidome pattern is a rapid, non-invasive, high-throughout, and reproducible method for identifying the pathological patterns of patients with nephrotic syndrome.