The impact of the doctor-nurse-patient workshop transitional care model on the post-operative quality of life of patients with laryngeal cancer.

OBJECTIVE: The aim of this study is to assess the efficacy of the doctor-nurse-patient workshop transitional care model on post-operative care for patients with laryngeal cancer and its influence on quality of life. METHODS: A total of 68 patients with laryngeal cancer who underwent surgical treatment at the hospital between 2021 and 2022 were included in the study. The patients were divided into two groups, a control group and a research group, each consisting of 34 patients, based on the chronological sequence of their surgeries. Patients in the control group received standard nursing care, while those in the research group received the doctor-nurse-patient workshop transitional care model in addition to standard nursing care. After 2 months of care, levels of albumin (ALB), total protein (TP), hemoglobin (Hb), and quality of life scores (measured using the Quality of Life Instrument for Head and Neck Cancer, QLICP-HN) were compared between the two groups. Additionally, the incidence of adverse events during the recovery period was assessed and compared between the two groups. RESULTS: Following 2 months of care, patients in the research group exhibited elevated ALB, TP, and Hb levels compared to those in the control group. Additionally, the average QLICP-HN scores were higher in the research group, while the incidence of adverse events was lower compared to the control group. CONCLUSION: Implementing the doctor-nurse-patient workshop transitional care model in home care for patients with laryngeal cancer can enhance their nutritional status post-surgery and improve their quality of life during home rehabilitation. This, in turn, leads to a reduction in the incidence of adverse events and complications during the recovery period.

Cancer-Associated-Fibroblast-Mediated Paracrine and Autocrine SDF-1/CXCR4 Signaling Promotes Stemness and Aggressiveness of Colorectal Cancers.

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide, and cancer-associated fibroblasts (CAFs) play a major role in the tumor microenvironment (TME), which facilitates the progression of CRC. It is critical to understand how CAFs promote the progression of CRC for the development of novel therapeutic approaches. The purpose of this study was to understand how CAF-derived stromal-derived factor-1 (SDF-1) and its interactions with the corresponding C-X-C motif chemokine receptor 4 (CXCR4) promote CRC progression. Our study focused on their roles in promoting tumor cell migration and invasion and their effects on the characteristics of cancer stem cells (CSCs), which ultimately impact patient outcomes. Here, using in vivo approaches and clinical histological samples, we analyzed the influence of secreted SDF-1 on CRC progression, especially in terms of tumor cell behavior and stemness. We demonstrated that CAF-secreted SDF-1 significantly enhanced CRC cell migration and invasion through paracrine signaling. In addition, the overexpression of SDF-1 in CRC cell lines HT29 and HCT-116 triggered these cells to generate autocrine SDF-1 signaling, which further enhanced their CSC characteristics, including those of migration, invasion, and spheroid formation. An immunohistochemical study showed a close relationship between SDF-1 and CXCR4 expression in CRC tissue, and this significantly affected patient outcomes. The administration of AMD3100, an inhibitor of CXCR4, reversed the entire phenomenon. Our results strongly suggest that targeting this signaling axis in CRC is a feasible approach to attenuating tumor progression, and it may, therefore, serve as an alternative treatment method to improve the prognosis of patients with CRC, especially those with advanced, recurrent, or metastatic CRC following standard therapy.

Correlation between inflammatory cytokines and the likelihood of developing multiple types of digestive system cancers: A Mendelian randomization study.

OBJECTIVE: Inflammatory cytokines have been linked to digestive system cancers, yet their exact causal connection remains uncertain. Consequently, we conducted a Mendelian randomization (MR) analysis to gauge how inflammatory cytokines are linked to the risk of five prevalent digestive system cancers (DSCs). METHODS: We collected genetic variation data for 41 inflammatory cytokines from genome-wide association studies (GWAS), and the results data for five common diseases from the Finnish database. Our primary analytical approach involved employing the inverse-variance weighted, residual sum (IVW) method, complemented by the MR-Egger method, the weighted median method, simple mode analysis, and weighted mode analysis as supplementary analytical techniques. Furthermore, we conducted multiple sensitivity analyses. RESULTS: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), macrophage colony-stimulating factor (M-CSF), and interleukin (IL)-18 showed a negative association with the risk of hepatocellular carcinoma. Conversely, TRAIL was inversely linked to the risk of gastric cancer, while IL-16 exhibited a positive correlation with gastric cancer risk. Stem cell factor (SCF) acted as a protective factor against pancreatic cancer. For colorectal cancer, IL-7, IL-9, IL-13, and vascular endothelial growth factor (VEGF) were identified as risk factors. Notably, our results did not indicate a significant correlation between inflammatory cytokines and the risk of esophageal cancer. CONCLUSION: Our research unveils potential connections between 41 inflammatory cytokines and the risk of five common DSCs through a MR analysis. These associations offer valuable insights that could aid in the development of diagnostic biomarkers and the identification of novel therapeutic targets for DSCs.

Silvaticusins A-D: ent-kaurane diterpenoids and a cyclobutane-containing ent-kaurane dimer from Isodon silvaticus.

Three new ent-kaurane diterpenoids, silvaticusins A-C (1-3), along with a new ent-kaurane dimer silvaticusin D (4) were isolated from the aerial parts of Isodon silvaticus. The structures of these new compounds were established mainly by comprehensive analysis of their NMR and MS data. The absolute configuration of compounds 1 and 4 were determined using a single-crystal X-ray diffraction and computational methods, respectively. Compounds 2 and 3 were found to exhibit remarkable cytotoxic effects against five human tumor cell lines (HL-60, A-549, SMMC-7721, MDA-MB-231, and SW-480), with IC50 values spanning from 1.27 ± 0.08 to 7.52 ± 0.33 µM.

Segmental mandibulectomy and microvascular reconstruction with fibula free flap: Comparison between intraoral and extraoral approaches.

BACKGROUND: Segmental mandibulectomy and reconstruction of resulting defect can be performed via intraoral approach (IOA) or extraoral approach (EOA). Both approaches have advantages, disadvantages, indications, and contraindications to consider during their selection. OBJECTIVE: To compare IOA vs EOA of segmental mandibulectomy and microvascular reconstruction with fibula free flap (FFF). METHODS: We conducted a retrospective cohort study in which 51 patients who underwent segmental mandibulectomy and microvascular reconstruction with FFF from 2020 to 2024 were included, especially 17 patients by IOA and 34 patients by EOA, representing both groups of this study. Clinical characteristics, surgery parameters, and patients' prognosis were evaluated. Patients' satisfaction and Derriford Appearance Scale (DAS59) were assessed during follow-up. RESULTS: Ameloblastoma was the most frequent diagnosis (52.9% managed by IOA vs 70.6% by EOA); FFF was frequently positioned as double barrel (94.1% managed by IOA vs 88.2% by EOA). Compared with EOA group, IOA group had less intraoperative blood loss (mean difference [MD] = -112.2, 95% confidence interval [CI]: -178.9 to -45.5, p = 0.001), higher satisfaction score (MD = 1.3, 95% CI: 0.9 to 1.7, p ˂ 0.001), and lower DAS59 score (MD = -0.5, 95% CI: -0.7 to -0.2, p ˂ 0.001). CONCLUSION: Both IOA and EOA were found safe and feasible, presenting similar perioperative features and postoperative outcomes. Patients managed with IOA were more satisfied with aesthetic outcomes than patients managed with EOA. In the absence of simultaneous immediate implant during mandibular FFF reconstruction, after stability of FFF on the defect site, patients should always be referred to an implantologist and/or prosthodontist for teeth restoration to improve functional and aesthetic outcomes.

Examining the emotional healing process through bibliotherapy in adolescents with cancer: A qualitative descriptive study.

PURPOSE: This study aimed to investigate how interactive bibliotherapy impacted the emotional healing process of adolescents with cancer, drawing upon the three-stage emotional healing process theory-identification, catharsis, and insight. METHOD: A qualitative descriptive study was conducted on data from 14 adolescents, aged 10-19 years, diagnosed with or relapsing from leukemia or osteosarcoma within the past two years. Participants received two interactive bibliotherapy sessions using The Rabbit Listened and You Are Special. Data were collected through semistructured interviews and content analyzed. RESULTS: Analysis identified six themes in The Rabbit Listened and eight in You Are Special. Adolescents primarily engaged in identification, empathizing with protagonists and recalling personal experiences. They underwent catharsis, releasing negative emotions and fostering positivity. Insights emerged on companionship, listening, and others' criticism. CONCLUSIONS: Our study validates the use of the three-stage emotional healing process in interdisciplinary bibliotherapy for understanding emotional changes in adolescents with cancer. It sheds light on their concerns and coping strategies. Healthcare practitioners can utilize interactive bibliotherapy based on this framework to initiate therapeutic communication with adolescent cancer patients and improve interventions and care.

The regulatory effect of TiO2 nanotubes loaded with graphene oxide on macrophage polarization in an inflammatory environment.

BACKGROUND: Excessive inflammation is a major cause of implant failure. The surface morphology, hydrophilicity, and loading of biomaterials are major properties modulating anti-inflammatory macrophage activation. This paper investigates the regulatory effects of modifying the surface of Titanium dioxide nanotubes (TNTs) with graphene oxide (GO) on the polarization of mouse monocyte macrophages (RAW264.7). METHODS: TNT was produced by the anodic oxidation of titanium. GO was subsequently electrodeposited on the TNT to obtain a TNT-GO composite. The samples were characterised through scanning electron microscopy (SEM), Raman spectroscopy, and X-ray diffraction. RAW264.7 cells were separately seeded onto the surface of three groups of samples: pure Ti, TNT, and TNT-GO. Under the condition of lipopolysaccharide stimulation, the influence of the sample surfaces on the gene expression profiles was investigated through RNA sequence analysis. In addition, cell spreading was observed through SEM, cell adhesion and proliferation were analysed using the CCK8 assay, and the expression of inflammation-related factors was investigated by ELISA and cellular immunofluorescence staining. The production of reactive oxygen species (ROS) in the RAW264.7 cells on the surface of the three groups was detected via immunofluorescence staining. RESULTS: The CCK8 results indicated that the adhesion and proliferation of the RAW264.7 cells were reduced on the TNT and TNT-GO surfaces. ELISA results revealed significant differences in the pro-inflammatory factors tumour necrosis factor-α and interleukin-6 secretion among the three groups at 24 h (p < 0.05). The secretion of pro-inflammatory factors significantly reduced and the expression of anti-inflammatory factor IL-10 increased on the TNT and TNT-GO surfaces. The RNA sequencing, ELISA, and cell immunofluorescence staining test results suggested that the inflammatory response of M1 polarization was reduced and the M2 polarization of macrophages was induced on the TNT-GO surface, which may be attributed to the reduction in ROS production. CONCLUSIONS: Under lipopolysaccharide stimulation, the inflammatory response of the RAW264.7 cells was reduced and the M2 polarization of macrophages was promoted on the TNT-GO surface, which may be caused by the reduced ROS production. Consequently, the designed TNT-GO material is promising for implants owing to its excellent inflammation regulation ability.

Identification and transcriptome analysis of a photosynthesis deficient mutant of Populus davidiana Dode.

Photosynthesis is the main source of energy for plants to sustain growth and development. Abnormalities in photosynthesis may cause defects in plant development. The elaborate regulatory mechanism underlying photosynthesis remains unclear. In this study, we identified a natural mutant from the Greater Khingan Mountains and named it as "1-T". This mutant had variegated leaf with irregular distribution of yellow and green. Chlorophyll contents and photosynthetic capacity of 1-T were significantly reduced compared to other poplar genotypes. Furthermore, a transcriptome analysis revealed 3269 differentially expressed genes (DEGs) in 1-T. The products of the DEGs were enriched in photosystem I and photosystem II. Three motifs were significantly enriched in the promoters of these DEGs. Yeast one-hybrid, Electrophoretic mobility shift assays and tobacco transient transformation experiments indicated that PdGLKs may bind to the three motifs. Further analysis indicated that these photosystem related genes were also significantly down-regulated in PdGLK-RNAi poplars. Therefore, we preliminarily concluded that the down-regulation of PdGLKs in 1-T may affect the expression of photosystem-related genes, resulting in abnormal photosystem development and thus affecting the growth and development. Our results provide new insights into the molecular mechanism of photosynthesis regulating plant growth.

Interleukin-8/CXCR1 Signaling Contributes to the Progression of Pulmonary Adenocarcinoma Resulting in Malignant Pleural Effusion.

Pulmonary adenocarcinoma (PADC) treatment limited efficacy in preventing tumor progression, often resulting in malignant pleural effusion (MPE). MPE is filled with various mediators, especially interleukin-8 (IL-8). However, the role of IL-8 and its signaling mechanism within the fluid microenvironment (FME) implicated in tumor progression warrants further investigation. Primary cultured cells from samples of patients with MPE from PADC, along with a commonly utilized lung cancer cell line, were employed to examine the role of IL-8 and its receptor, CXCR1, through comparative analysis. Our study primarily assessed migration and invasion capabilities, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) properties. Additionally, IL-8 levels in MPE fluid versus serum, along with immunohistochemical expression of IL-8/CXCR1 signaling in tumor tissue and cell blocks were analyzed. IL-8/CXCR1 overexpression enhanced EMT and CSC properties. Furthermore, the immunocytochemical examination of 17 cell blocks from patients with PADC and MPE corroborated the significant correlation between upregulated IL-8 and CXCR1 expression and the co-expression of IL-8 and CXCR1 in MPE with distant metastasis. In summary, the IL-8/ CXCR1 axis in FME is pivotal to tumor promotion via paracrine and autocrine signaling. Our study provides a therapeutic avenue for improving the prognosis of PADC patients with MPE.

[Effect of TP53 Allelic State on Clinical Performance and Prognosis of Patients with Myelodysplastic Syndrome].

OBJECTIVE: To investigate the clinical significance of TP53 allelic state in patients with myelodysplastic syndromes (MDS). METHODS: The clinical data of 858 MDS patients who underwent second-generation sequencing (NGS) testing in the First Affiliated Hospital of Soochow University from January 2019 to December 2021 were retrospectively analyzed. RESULTS: The median age of the patients was 52 years old, and median follow-up time was 23.8 (0.4-109.6) months. Four hundred and one patients (46.7%) had at least one chromosomal abnormality, including 106 complex karyotypes and 78 monosomal karyotypes. A total of 103 cases of TP53 mutations were identified, with a mutation rate of 12%. Compared with TP53 wild-type, various types of chromosomal abnormalities were significantly more common in patients with TP53 mutations (all P < 0.001). Patients with TP53 mutations had lower hemoglobin levels, lower platelet counts and higher percentage of bone marrow primitive cell compared with TP53 wild type (all P < 0.05), and significantly shorter overall survival (OS). Among 97 evaluable patients, 33 cases (34%) were mono-allelic TP53 mutation, while 64 cases were bi-allelic TP53 mutation. Patients in bi-allelic TP53 mutation subgroup had a higher proportion of chromosomal abnormalities and a lower number of co-mutations compared with mono-allelic TP53 mutation. The median OS was 33.6 months in patients with mono-allelic state and only 11.4 months in patients with bi-allelic state (HR=2.138, 95%CI : 1.053-4.343, P >0.05). Median OS was not reached in TP53 wild-type patients, and there was a significant difference in OS among TP53 wild-type, mono-allelic and bi-allelic TP53 mutation patients (P < 0.001). Multivariable Cox regression analysis showed that bi-allelic TP53 was an independent predictor of poor outcomes (HR=2.808, 95%CI : 1.487-5.003, P =0.001), while mono-allelic TP53 mutation and wild-type TP53 were not. CONCLUSION: Patients with TP53 mutations have a poor prognosis, and bi-allelic TP53 mutations have a worse prognosis compared with mono-allelic TP53 mutations and independently affect the prognosis of MDS patients.

Discovery and validation of combined biomarkers for the diagnosis of esophageal intraepithelial neoplasia and esophageal squamous cell carcinoma.

Early diagnosis and intervention of esophageal squamous cell carcinoma (ESCC) can improve the prognosis. The purpose of this study was to identify biomarkers for ESCC and esophageal precancerous lesions (intraepithelial neoplasia, IEN). Based on the proteomic and genomic data of esophageal tissue including previously reported data, up-regulated proteins with copy number amplification in esophageal cancer were screened as candidate biomarkers. Five proteins, including KDM2A, RAD9A, ECT2, CYHR1 and TONSL, were confirmed by immunohistochemistry on ESCC and normal esophagus (NE). Then, we investigated the expression of 5 proteins in 236 participants (60 NEs, 93 IENs and 83 ESCCs) which were randomly divided into training set and test set. When distinguishing ESCC from NE, the area under curve (AUC) of the multiprotein model was 0.940 in the training set, while the lowest AUC of a protein was 0.735. In the test set, the results were similar. When distinguishing ESCC from IEN or distinguishing IEN from NE, the diagnostic efficiency of the multi-protein models were also improved compared with that of single protein. Our findings suggest that combined detection of KDM2A, RAD9A, ECT2, CYHR1 and TONSL can be used as potential biomarkers for the early diagnosis of ESCC and precancerous lesion development prediction. SIGNIFICANCE: Candidate biomarkers including KDM2A, RAD9A, ECT2, CYHR1 and TONSL screened by integrating genomic and proteomic data from the esophagus can be used as potential biomarkers for the early diagnosis of esophageal squamous cell carcinoma and precancerous lesion development prediction.

Protocol to test for the formation of ternary protein complexes in vivo or in vitro using a two-step immunoprecipitation approach.

Co-immunoprecipitation (coIP) is an experimental technique to study protein-protein interactions (PPIs). However, single-step coIP can only be used to identify the interaction between two proteins and does not solve the interaction testing of ternary complexes. Here, we present a protocol to test for the formation of ternary protein complexes in vivo or in vitro using a two-step coIP approach. We describe steps for cell culture and transfection, elution of target proteins, and two-step coIP including western blot analyses. For complete details on the use and execution of this protocol, please refer to Li et al.1.

Dose-response study of propofol combined with two different doses of esketamine for laryngeal mask airway insertion in women undergoing hysteroscopy.

Objective: To prospectively determine the median effective dose (ED50) of propofol for inhibiting a response to laryngeal mask airway (LMA) insertion when combined with different doses of esketamine in female patients. Methods: A total of 58 female patients (aged 20-60 years, ASAⅠ-Ⅱ) scheduled for elective hysteroscopy were enrolled and randomly divided into 2 groups, one of which was administered 0.2 mg/kg of esketamine (K1 group, n = 28) and the other 0.3 mg/kg of esketamine (K2 group, n = 30). The 2 groups received the corresponding doses of esketamine intravenously, followed by an intravenous injection of propofol (injection time was 30 s). The initial dose of propofol was 2 mg/kg, and the dose ratio of propofol in the adjacent patients was 0.9. If a positive reaction occurred due to LMA insertion, the dose ratio in the next patient was increased by 1 gradient; if not, the dose ratio was decreased by 1 gradient. The ED50, 95 % effective dose (ED95) and 95 % confidence interval (CI) of propofol for inhibiting a response to LMA insertion in the 2 esketamine groups were calculated using probit analysis. Results: The ED50 of propofol for inhibiting a response to LMA insertion in female patients was 1.95 mg/kg (95 % CI, 1.82-2.08 mg/kg) in the K1 group and 1.60 mg/kg (95 % CI, 1.18-1.83 mg/kg) in the K2 group. The ED95 of propofol for inhibiting a response to LMA insertion in female patients was 2.22 mg/kg (95 % CI, 2.09-2.86 mg/kg) in the K1 group and 2.15 mg/kg (95 % CI, 1.88-3.09 mg/kg) in the K2 group. Conclusion: Propofol combined with 0.3 mg/kg of esketamine has low ED50 and ED95 effective doses for inhibiting an LMA insertion response in female patients undergoing hysteroscopy and surgery. There were no significant adverse effects, but the additional dose of propofol and airway pressure were significantly higher than those in the group administered 0.2 mg/kg of esketamine. Based on the results, we recommend the combination of propofol with 0.2 mg/kg esketamine for optimal conditions during LMA insertion in women undergoing hysteroscopy.

Exploring the efficacy and mechanism of Bailing capsule to improve polycystic ovary syndrome in mice based on intestinal-derived LPS-TLR4 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. AIM OF THE STUDY: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. METHODS: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. RESULTS: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. CONCLUSION: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.

Effects of Total Intravenous Anesthesia on Circadian Rhythms in Patients Undergoing Cardiac Transcatheter Closure.

Objective To evaluate the effects of total intravenous anesthesia on the circadian rhythms in the patients undergoing cardiac transcatheter closure. Methods Thirty patients undergoing cardiac transcatheter closure under elective intravenous anesthesia were included in this study.Paired t-tests were performed to compare the mRNA levels of the genes encoding circadian locomotor output cycles kaput(CLOCK),brain and muscle ARNT-1 like protein-1(BMAL1),cryptochrome 1(CRY1),and period circadian clock 2(PER2),the Munich Chronotype Questionnaire(MCTQ)score,and the Pittsburgh Sleep Quality Index(PSQI)score before and after anesthesia.Multiple stepwise regression analysis was performed to screen the factors influencing sleep chronotype and PSQI total score one week after surgery. Results The postoperative mRNA level of CLOCK was higher [1.38±1.23 vs.1.90±1.47;MD(95%CI):0.52(0.20-0.84),t=3.327,P=0.002] and the postoperative mRNA levels of CRY1 [1.56±1.50 vs.1.13±0.98;MD(95%CI):-0.43(-0.81--0.05),t=-2.319,P=0.028] and PER2 [0.82±0.63 vs.0.50±0.31;MD(95%CI):-0.33(-0.53--0.12),t=-3.202,P=0.003] were lower than the preoperative levels.One week after surgery,the patients presented advanced sleep chronotype [3∶03±0∶59 vs.2∶42±0∶37;MD(95%CI):-21(-40--1),t=-2.172,P=0.038],shortened sleep latency [(67±64)min vs.(37±21)min;MD(95%CI):-30.33(-55.28--5.39),t=-2.487,P=0.019],lengthened sleep duration [(436±83)min vs.(499±83)min;MD(95%CI):62.80(26.93-98.67),t=3.581,P=0.001],increased sleep efficiency [(87.59±10.35)% vs.(92.98±4.27)%;MD(95%CI):5.39(1.21-9.58),t=2.636,P=0.013],decreased sleep quality score [1.13±0.78 vs.0.80±0.71;MD(95%CI):-0.33(-0.62--0.05),t=-2.408,P=0.023],and declined PSQI total score [6.60±3.17 vs.4.03±2.58;MD(95%CI):-2.57(-3.87--1.27),t=-4.039,P<0.001].Body mass index(BMI)(B=-227.460,SE=95.475,t=-2.382,P=0.025),anesthesia duration(B=-47.079,SE=18.506,t=-2.544,P=0.017),and mRNA level of PER2(B=2815.804,SE=1080.183,t=2.607,P=0.015)collectively influenced the sleep chronotype,and the amount of anesthesia medicine(B=0.067,SE=0.028,t=2.385,P=0.024)independently influenced the PSQI one week after surgery. Conclusions Total intravenous anesthesia can improve sleep habits by advancing sleep chronotype.BMI,anesthesia duration,and mRNA level of PER2 collectively influence sleep chronotype one week after surgery.The amount of anesthesia medicine independently influences the PSQI total score one week after surgery.

Effective Management of Polycythemia Vera With Ropeginterferon Alfa-2b Treatment.

Background: Polycythemia vera (PV) is a myeloproliferative neoplasm. Ropeginterferon alfa-2b is a new-generation polyethylene glycol-conjugated proline-interferon. It is approved for the treatment of PV at a starting dose of 100 µg (50 µg for patients receiving hydroxyurea (HU)) and dose titrations up to 500 µg by 50 µg increments. The study was aimed at assessing its efficacy and safety at a higher starting dose and simpler intra-patient dose escalation. Methods: Forty-nine patients with PV having HU intolerance from major hospitals in China were treated biweekly with an initial dose of 250 µg, followed by 350 µg and 500 µg thereafter if tolerated. Complete hematological response (CHR) was assessed every 12 weeks based on the European LeukemiaNet criteria. The primary endpoint was the CHR rate at week 24. The secondary endpoints included CHR rates at weeks 12, 36 and 52, changes of JAK2V617F allelic burden, time to first CHR, and safety assessments. Results: The CHR rates were 61.2%, 69.4% and 71.4% at weeks 24, 36, and 52, respectively. Mean allele burden of the driver mutation JAK2V617F declined from 58.5% at baseline to 30.1% at 52 weeks. Both CHR and JAK2V617F allele burden reduction showed consistent increases over the 52 weeks of the treatment. Twenty-nine patients (63.0%) achieved partial molecular response (PMR) and two achieved complete molecular response (CMR). The time to CHR was rapid and median time was 5.6 months according to central lab results. The CHRs were durable and median CHR duration time was not reached at week 52. Mean spleen index reduced from 55.6 cm2 at baseline to 50.2 cm2 at week 52. Adverse events (AEs) were mostly mild or moderate. Most common AEs were reversible alanine aminotransferase and aspartate aminotransferase increases, which were not associated with significant elevations in bilirubin levels or jaundice. There were no grade 4 or 5 AEs. Grade 3 AEs were reversible and manageable. Only one AE led to discontinuation. No incidence of thromboembolic events was observed. Conclusion: The 250-350-500 µg dosing regimen was well tolerated and effectively induced CHR and MR and managed spleen size increase. Our findings demonstrate that ropeginterferon alfa-2b at this dosing regimen can provide an effective management of PV and support using this dosing regimen as a treatment option.

The novel TERF2::PDGFRB fusion gene enhances tumorigenesis via PDGFRB/STAT5 signalling pathways and sensitivity to TKI in ph-like ALL.

Patients with Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like ALL) often face a grim prognosis, with PDGFRB gene fusions being commonly detected in this subgroup. Our study has unveiled a newfound fusion gene, TERF2::PDGFRB, and we have found that patients carrying this fusion gene exhibit sensitivity to dasatinib. Ba/F3 cells harbouring the TERF2::PDGFRB fusion display IL-3-independent cell proliferation through activation of the p-PDGFRB and p-STAT5 signalling pathways. These cells exhibit reduced apoptosis and demonstrate sensitivity to imatinib in vitro. When transfused into mice, Ba/F3 cells with the TERF2::PDGFRB fusion gene induce tumorigenesis and a shortened lifespan in cell-derived graft models, but this outcome can be improved with imatinib treatment. In summary, we have identified the novel TERF2::PDGFRB fusion gene, which exhibits oncogenic potential both in vitro and in vivo, making it a potential therapeutic target for tyrosine kinase inhibitors (TKIs).

Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

Effects of different aging methods on the ability of biochar to adsorb heavy metal cadmium and its physical and chemical properties.

The aging process can affect the physical and chemical properties as well as adsorption capacity of biochar. This study focuses on the heavy metal cadmium (Cd) as the research object, and artificially ages biochar prepared from rice straw and corn straw through accelerated freeze-thaw cycles, alternating dry wet cycles, and ultraviolet light treatment, in order to evaluate the effects of different aging conditions on the physical and chemical properties of the two different types of biochar and on their adsorption capacities for Cd. After aging, the pH of rice and corn biochar decreased to varying degrees, respectively. The surface structure was ruptured, the average pore diameter was decreased, and the specific surface area was increased by 27.3%, 21.9%, and 9.8% (rice) and 95.4%, 27.7%, and 13.4% (corn). Ultraviolet light aging has the most significant impact on the elemental content of biochar, and the C content was decreased by 12.4% (rice) and 9.3% (corn). The O content was increased by 11.2% (rice) and 44.1% (corn), and the numbers of O/C, H/C, (O + N)/C, and oxygen-containing functional groups were increased. These results demonstrate that the aging process reduces the degree of aromatization of biochar, while enhancing its polarity and Cd adsorption capacity. Rice straw biochar (RSB) has a greater ability to adsorb Cd than corn straw biochar (CSB). In addition, ultraviolet light aging is particularly effective in increasing heavy metal adsorption.

A retrospective study on the mechanism underlying quick transfer from response to resistance in a repeated recurrent chordoma patient with molecular alterations treated with Palbociclib.

PURPOSE: There is no approved targeted therapy for chordoma at present. Although several preclinical studies have implied the potential applicability of CDK4/6 inhibitor for this rare tumor, no clinical evidence has been documented so far. The purpose of this study was to elucidate the therapeutic efficacy of CDK4/6 inhibitor for chordoma. METHODS: The next generation sequencing (as for whole-exome sequencing, WES assay) and immunohistochemical (IHC) staining of the chordoma tissue from a patient with an advanced lesion were performed before treatment. Then, the patient was treated with Palbociclib for 4 months until progression occurred in the 5th month. Surgical resection was implemented and the tumor tissue was obtained postoperatively for assessment of molecular alterations. RESULTS: Molecular features of the tumor before medical treatment suggested applicability of CDK4/6 inhibitor and the patient showed partial response (PR) according to Choi Criteria after 4 months treating with Palbociclib until progression occurred. Then, a drastic molecular alteration of the tumor as represented by emergence of dramatic E2F amplification, which is known to induce CDK4/6 independent cell-cycle entry and progression after treatment, was detected. The findings in this patient demonstrated tumor evolution under drug pressure. CONCLUSION: The findings of the present study suggest the feasibility of Palbociclib for the clinical treatment of chordoma, and imply the necessity of combination therapies rather single drug administration due to the quick resistance of the tumor to Palbociclib treatment.