Integrating network pharmacology and experimental models to investigate the efficacy and mechanism of Tiansha mixture on xerosis.

Epidermal Growth Factor Receptor Inhibitors (EGFRIs) is a common cancer therapy, but they occasionally cause severe side effects such as xerosis. Tiansha mixture (TM), a traditional Chinese medicines formulation, is develpoed to treat xerosis. This study aims to understand mechanisms of TM on xerosis. Bio-active compounds were selected from databases (TCMSP, TCM-ID, HERB, ETCM) and removed for poor oral bioavailability and low drug likeness. Then a network-based approach filtered out potential active compounds against xerosis. KEGG enrichment analysis identified PI3K/AKT and ERK/MAPK pathways, which were further verified by molecular docking. Afterwards, the effect of TM on activation of PI3K/AKT and ERK/MAPK pathways was validated in gefitinib-induced xerosis rats, where AKT-activator SC79 and MAPK-activator CrPic were also applied. Skin damage was assessed by dorsal score and HE and Tunel stainings. the levels of inflammation factors IL-6 and TNF-α in serum and skin tissue were measured by ELISA. Western blot was used to detect protein levels in the pathways. Network pharmacology identified 111 bio-active compounds from TM and 14 potential targets. Docking simulation showed apigenin, luteolin, and quercetin bio-active compounds in TM bound to IKBKG, INSR, and RAF-1 proteins. In xerosis model rats, TM mitigated xerosis damage, decreased inflammation factors, and phosphorylation of PI3K/AKT and ERK/MAPK proteins. SC79 or CrPic or their combination reversed TM's effect. The current study identified potential targets and PI3K/AKT and ERK/MAPK pathways involved in the effect of TM on xerosis, thus providing a foundation for TM clinical application.

Tea Polysaccharide Ameliorates High-Fat Diet-Induced Renal Tubular Ectopic Lipid Deposition via Regulating the Dynamic Balance of Lipogenesis and Lipolysis.

Renal tubular ectopic lipid deposition (ELD) plays a significant role in the development of chronic kidney disease, posing a great threat to human health. The present work aimed to explore the intervention effect and potential molecular mechanism of a purified tea polysaccharide (TPS3A) on renal tubular ELD. The results demonstrated that TPS3A effectively improved kidney function and slowed the progression of tubulointerstitial fibrosis in high-fat-diet (HFD)-exposed ApoE-/- mice. Additionally, TPS3A notably suppressed lipogenesis and enhanced lipolysis, as shown by the downregulation of lipogenesis markers (SREBP-1 and FAS) and the upregulation of lipolysis markers (HSL and ATGL), thereby reducing renal tubular ELD in HFD-fed ApoE-/- mice and palmitic-acid-stimulated HK-2 cells. The AMPK-SIRT1-FoxO1 axis is a core signal pathway in regulating lipid deposition. Consistently, TPS3A significantly increased the levels of phosphorylated-AMPK, SIRT1, and deacetylation of Ac-FoxO1. However, these effects of TPS3A on lipogenesis and lipolysis were abolished by AMPK siRNA, SIRT1 siRNA, and FoxO1 inhibitor, resulting in exacerbated lipid deposition. Taken together, TPS3A shows promise in ameliorating renal tubular ELD by inhibiting lipogenesis and promoting lipolysis through the AMPK-SIRT1-FoxO1 signaling pathway.

[The Effect of SIRT5 Deletion on Recovery of Hematopoietic Stem Cells after Injury in Mouse].

OBJECTIVE: To investigate the effect of deacylase Sirtuin 5 in the recovery of hematopoietic stem cells (HSCs) after treated by 5-FU in mouse. METHODS: Flow cytometry was used to analyze the effect of SIRT5 deletion on the proportion of hematopoietic stem/progenitor cells (HSPCs) in bone marrow (BM), the proportion of T cells, B cells and myeloid cells (TBM) in peripheral blood (PB) and spleen, and the development of T cells in thymus. Mouse were treated with 5-FU to study the effect of SIRT5 deletion on the cell cycle, apoptosis and the proportion of HSPCs in BM. The effect of SIRT5 deletion on the proliferation of HSCs was analyzed by flow sorting in vitro. RESULTS: SIRT5 deletion did not affect the development of T cells in thymus and the proportion of TBM cells in PB and spleen compared with wild type mice. SIRT5 deletion increased proportion of HSPCs in BM. After 5-FU treatment, the proportion of HSCs in SIRT5 deletion mice was significant decreased (P < 0.05), the HSPC in SIRT5 deletion mice was activated from G0 to G1 phase (P < 0.05), and the proportion of early apoptosis increased (P < 0.05). By monoclonal culture in vitro, the ability of HSCs to form clones in SIRT5 deletion mice was decreased significantly (P < 0.05). CONCLUSION: SIRT5 deletion lead to a decreased the ability of HSCs to clone in vitro. SIRT5 deletion is not conducive to the recovery of HSPCs injury in mice under hematopoietic stress.

ETV2 induces endothelial, but not hematopoietic, lineage specification in birds.

Cardiovascular system develops from the lateral plate mesoderm. Its three primary cell lineages (hematopoietic, endothelial, and muscular) are specified by the sequential actions of conserved transcriptional factors. ETV2, a master regulator of mammalian hemangioblast development, however, is absent in the chicken genome and acts downstream of NPAS4L in zebrafish. Here, we investigated the epistatic relationship between NPAS4L and ETV2 in avian hemangioblast development. We showed that ETV2 is deleted in all 363 avian genomes analyzed. Mouse ETV2 induced LMO2, but not NPAS4L or SCL, expression in chicken mesoderm. Squamate (lizards, geckos, and snakes) genomes contain both NPAS4L and ETV2 In Madagascar ground gecko, both genes were expressed in developing hemangioblasts. Gecko ETV2 induced only LMO2 in chicken mesoderm. We propose that both NPAS4L and ETV2 were present in ancestral amniote, with ETV2 acting downstream of NPAS4L in endothelial lineage specification. ETV2 may have acted as a pioneer factor by promoting chromatin accessibility of endothelial-specific genes and, in parallel with NPAS4L loss in ancestral mammals, has gained similar function in regulating blood-specific genes.

Tabersonine Induces the Apoptosis of Human Hepatocellular Carcinoma In vitro and In vivo.

BACKGROUND: Tabersonine, a natural indole alkaloid derived from Apocynaceae plants, exhibits antiinflammatory and acetylcholinesterase inhibitory activities, among other pharmacological effects. However, its anti-tumor properties and the underlying molecular mechanisms remain underexplored. OBJECTIVE: The present study aims to investigate the anti-tumor effects of tabersonine and its mechanisms in inducing apoptosis in hepatocellular carcinoma. METHODS: The inhibitory effects of tabersonine on the viability and proliferation of liver cancer cells were evaluated using MTT assay and colony formation assay. AO/EB, Hoechst, and Annexin V-FITC/ PI staining techniques were employed to observe cell damage and apoptosis. JC-1 staining was used to detect changes in mitochondrial membrane potential. Western blot analysis was conducted to study the anti-tumor mechanism of tabersonine on liver cancer cells. Additionally, a xenograft model using mice hepatoma HepG2 cells was established to assess the anti-tumor potency of tabersonine in vivo. RESULTS AND DISCUSSION: Our findings revealed that tabersonine significantly inhibited cell viability and proliferation, inducing apoptosis in liver cancer cells. Treatment with tabersonine inhibited Akt phosphorylation, reduced mitochondrial membrane potential, promoted cytochrome c release from mitochondria to the cytoplasm, and increased the ratio of Bax to Bcl-2. These findings suggested that tabersonine induces apoptosis in liver cancer cells through the mitochondrial pathway. Furthermore, tabersonine treatment activated the death receptor pathway of apoptosis. In vivo studies demonstrated that tabersonine significantly inhibited xenograft tumor growth. CONCLUSION: Our study is the first to demonstrate that tabersonine induces apoptosis in HepG2 cells through both mitochondrial and death receptor apoptotic pathways, suggesting its potential as a therapeutic agent candidate for hepatic cancer.

Photooxidation triggered ultralong afterglow in carbon nanodots.

It remains a challenge to obtain biocompatible afterglow materials with long emission wavelengths, durable lifetimes, and good water solubility. Herein we develop a photooxidation strategy to construct near-infrared afterglow carbon nanodots with an extra-long lifetime of up to 5.9 h, comparable to that of the well-known rare-earth or organic long-persistent luminescent materials. Intriguingly, size-dependent afterglow lifetime evolution from 3.4 to 5.9 h has been observed from the carbon nanodots systems in aqueous solution. With structural/ultrafast dynamics analysis and density functional theory simulations, we reveal that the persistent luminescence in carbon nanodots is activated by a photooxidation-induced dioxetane intermediate, which can slowly release and convert energy into luminous emission via the steric hindrance effect of nanoparticles. With the persistent near-infrared luminescence, tissue penetration depth of 20 mm can be achieved. Thanks to the high signal-to-background ratio, biological safety and cancer-specific targeting ability of carbon nanodots, ultralong-afterglow guided surgery has been successfully performed on mice model to remove tumor tissues accurately, demonstrating potential clinical applications. These results may facilitate the development of long-lasting luminescent materials for precision tumor resection.

Clinical outcomes, survival, and predictors in lower-risk myelodysplastic syndrome patients treated with cyclosporine A.

INTRODUCTION: Therapeutic options to improve myelodysplastic syndrome (MDS)-related cytopenias in patients with lower-risk MDS are limited, and cyclosporin A (CSA) is an available option. METHODS: We retrospectively analysed the clinical data of 153 consecutive patients with lower-risk MDS at our institution from July 1997 to October 2017. Propensity score matching method was used to balance the influence of confounding factors between patients with MDS treated with CSA and other conventional treatments (excluding CSA), and 50 pairs of cases were successfully identified for the final analysis. We assessed response rates, progression-free survival (PFS), overall survival (OS), and factors affecting response and survival. RESULTS: Haematological improvement (HI) was observed in 35 (70%) patients treated with CSA and in 25 (50%) patients treated with conventional therapies (P < 0.05), respectively. Treatment with CSA was a favourable prognostic factor for HI in lower-risk MDS patients of both cohorts in univariate analysis [odds ratio (OR) 2.333, P < 0.05], but not in multivariate analysis. In the multivariate analysis, hypocellular marrow was the only independent prognostic factor for HI in the CSA group (OR 6.259, P < 0.05), and in the overall cohort (OR 3.102, P < 0.05).CSA treatment did not improve PFS or OS (P > 0.05). CONCLUSION: CSA is a safe treatment and can significantly improve cytopenias in a substantial proportion of patients with MDS, especially in individuals with hypocellular bone marrow. However, CSA is not associated with PFS or OS.

IKZF4/NONO-RAB11FIP3 axis promotes immune evasion in gastric cancer via facilitating PD-L1 endosome recycling.

As an immune checkpoint protein expressed by diverse cancer cells, programmed death ligand 1 (PD-L1) facilitates immune evasion by interacting with programmed cell death-1 (PD-1) on T cells. Despite the clinical benefits observed in various cancer types, strategies targeting PD-1/PD-L1 have demonstrated limited efficacy in gastric cancer (GC). Furthermore, the regulation of PD-L1, especially at post-translational modification levels, remains largely unknown. Therefore, it is crucial to elucidate the mechanisms governing PD-L1 expression to enhance anti-tumor immunity. In this study, we have identified that IKAROS family zinc finger 4 (IKZF4) and Non-POU domain-containing octamer-binding (NONO) synergistically regulate and enhance the expression of RAB11 family-interacting protein 3 (RAB11FIP3) in GC. The IKZF4/NONO-RAB11FIP3 axis facilitates the endosomal recycling of PD-L1, particularly on the cell membrane of GC cells. Moreover, overexpression of RAB11FIP3 mitigates the hypo-expression of PD-L1 protein resulting from IKZF4 or NONO deletion. Functionally, the silencing of RAB11FIP3 or IKZF4 promotes T cell proliferation, and enhances T-cell cytotoxicity towards GC cells in vitro, which further inhibits tumor immune evasion in mice via increasing the infiltration of CD8+ T cells into the tumor microenvironment (TME) to suppress GC progression. Our study suggests that the IKZF4/NONO-RAB11FIP3 axis promotes immune evasion by facilitating PD-L1 endosome recycling, thus presenting a potential therapeutic target for GC treatment.

Galectin-7 Induction by EHMT2 Inhibition Enhances Immunity in Microsatellite Stability Colorectal Cancer.

BACKGROUND & AIMS: Although immunotherapy shows substantial advancement in colorectal cancer (CRC) with microsatellite instability high, it has limited efficacy for CRC with microsatellite stability (MSS). Identifying combinations that reverse immune suppression and prime MSS tumors for current immunotherapy approaches remains an urgent need. METHODS: An in vitro CRISPR screen was performed using coculture models of primary tumor cells and autologous immune cells from MSS CRC patients to identify epigenetic targets that could enhance immunotherapy efficacy in MSS tumors. RESULTS: We revealed EHMT2, a histone methyltransferase, as a potential target for MSS CRC. EHMT2 inhibition transformed the immunosuppressive microenvironment of MSS tumors into an immunomodulatory one by altering cytokine expression, leading to T-cell-mediated cytotoxicity activation and improved responsiveness to anti-PD1 treatment. We observed galectin-7 up-regulation upon EHMT2 inhibition, which converted a "cold" MSS tumor environment into a T-cell-inflamed one. Mechanistically, CHD4 repressed galectin-7 expression by recruiting EHMT2 to form a cotranscriptional silencing complex. Galectin-7 administration enhanced anti-PD1 efficacy in MSS CRC, serving as a potent adjunct cytokine therapy. CONCLUSIONS: Our findings suggest that targeting the EHMT2/galectin-7 axis could provide a novel combination strategy for immunotherapy in MSS CRC.

Metabolic flux and catabolic kinetics of prebiotic-like dietary polyphenol phlorizin in association with gut microbiota in vitro.

As ubiquitous components among fruits, polyphenols, including flavonoids and phenolic acids, are somewhat embarrassed on their health benefits but low bioavailability, triggering a hotspot on their interaction with microbiota. Due to its structural characteristics similar to flavonoids and phenolic acids, dihydrochalcone phlorizin (PHZ) was selected as a reference, to illustrate its step-by-step metabolic fate associated with microbiota. The results confirmed that the metabolic flux of PHZ starts with its conversion to phloretin (PHT), sequentially followed by the formation of 3-(4-hydroxyphenyl) propionic acid (PHA), and 4-hydroxyphenylacetic acid (4-HPAA). Catabolic characteristics was comparatively elucidated by introducing apparent and potential kinetics. Besides, coupling catabolic processes with microbial changes suggested several potential bacteria involving in PHZ metabolism, as well as those regulated by PHZ and its metabolites. In particular, seven strains from Lactobacillus were selectively isolated and confirmed to be essential for deglycosylation of PHZ, implying a potential synergistic effect between PHZ and Lactobacillus.

A preoperative nomogram predicting risk of lymph node metastasis for early-stage cervical cancer.

OBJECTIVE: This study aimed to develop a preoperative nomogram based on clinical and pathological characteristics to provide a more individualized and accurate estimation of lymph node metastasis (LNM) in patients with early-stage cervical cancer. METHODS: A total of 7,349 early-stage cervical cancer patients with pathologically confirmed between 1988 and 2015 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. All the patients were divided into training (n = 5,500) and validation (n = 1,849) cohorts randomly. A cohort of 455 patients from multicenter was used for the external validation. We established a multivariate logistic regression model based on preoperative clinicopathological data, from which a nomogram was developed and validated. A predicted probability of LNM < 5% was defined as low risk. RESULTS: From multivariate logistic regression analysis, age at diagnosis, histologic subtype, tumor grade, tumor size and FIGO stage were identified as preoperative independent risk factors of LNM. The nomogram incorporating these factors demonstrated good discrimination and calibration (concordance index = 0.723; 95% confidence interval (CI), 0.707-0.738). In the validation cohort, the discrimination accuracy was 0.745 (95% CI, 0.720-0.770) and 0.747 (95% CI, 0.690-0.804), respectively. The nomogram was well calibrated with a high concordance probability. We also established an R-enabled Internet browser for LNM risk assessment, which tool may be convenient for physicians. CONCLUSIONS: We developed an effective preoperative nomogram based on clinical and pathological characteristics to predict LNM for early-stage cervical cancer. This model could improve clinical trial design and help physicians to decide whether to perform lymphadenectomy or not.

Tertiary lymphoid structures in gynecological cancers: prognostic role, methods for evaluating, antitumor immunity, and induction for therapy.

Tertiary lymphoid structures (TLSs), referred to as tertiary lymphoid organs and lymphoid tissue neogenesis, are aggregates of immune cells that occur in nonlymphoid tissues. In recent years, it has been found that TLSs within the tumor microenvironment have been associated with local adaptive immune immunity against cancer and favorable prognosis in several human solid tumors, including gynecological cancers. The issue of the prognosis of gynecological cancers, including endometrial, cervical, and ovarian cancer, is an enormous challenge that many clinical doctors and researchers are now facing. Concerning the predictive prognostic role of TLSs, effective evaluation, and quantification of TLSs in human tissues may be used to assist gynecologists in assessing the clinical outcome of gynecological cancer patients. This review summarizes the current knowledge of TLSs in gynecological cancers, mainly focusing on the potential mechanism of TLS neogenesis, methods for evaluating TLSs, their prognostic value, and their role in antitumor immune immunity. This review also discusses the new therapeutic methods currently being explored in gynecological cancers to induce the formation of TLSs.

Loss of chromosome 9p21 is associated with a poor prognosis in adenosquamous carcinoma of the pancreas.

Adenosquamous carcinoma of the pancreas (ASCP) is a rare histological subtype of pancreatic cancer with a poor prognosis and a high metastasis rate. However, little is known about its genomic landscape and prognostic biomarkers. A total of 48 ASCP specimens and 98 pancreatic ductal adenocarcinoma (PDAC) tumour specimens were sequenced to explore the genomic landscape and prognostic biomarkers. The homozygous deletion of the 9p21.3 region (including CDKN2A, CDKN2B, and MTAP) (9p21 loss) occurred in both ASCP and PDAC, and a higher frequency of 9p21 loss was observed in ASCP (12.5% vs 2.0%, P = 0.022). Notably, 9p21 loss was significantly associated with poor disease-free survival (DFS) in ASCP patients (mDFS (Median DFS) = 4.17 vs 7.33 months, HR (Hazard Ratio) = 3.70, P = 0.009). The most common gene alterations in patients with ASCP were KRAS (96%), TP53 (81%), CDKN2A (42%), SMAD4 (21%), CDKN2B (13%), and FAT3 (13%). The mutation rates of ACVR2A (6.25% vs 0%), FANCA (6.25% vs 0%), RBM10 (6.25% vs 0%), and SPTA1 (8.33% vs 1.02%) were significantly higher in ASCP than in PDAC. In conclusion, we have comprehensively described the genomic landscape of the largest cohort of ASCP patients to date and highlight that 9p21 loss may be a promising prognostic biomarker for ASCP, which provides a molecular basis for prognosis prediction and new therapeutic strategies for ASCP.

An Association between Decreased Small Intestinal RNA Modification and Disturbed Glucagon-like Peptide-1 Secretion under High-Fat Diet Stress.

Unhealthy diets rich in fats and/or sugar are considered as the major external cause of the obesity epidemic, which is often accompanied by a significant decrease in gut hormone glucagon-like peptide-1 (GLP1) levels. Numerous studies have demonstrated notable contributions of the gut microbiota in this process. Nevertheless, the underlying mechanism still needs further investigation. The role of epigenetic modifications in gene expression and metabolism has been well demonstrated, with m6A methylation on RNAs being the most prevalent modification throughout their metabolism. In the present study, we found that the expressions of small intestinal Gcg and Pc3, two key genes regulating GLP1 expression, were significantly downregulated in obese mice, associated with reduced GLP1 level. Immunohistochemistry analysis indicated that a high-fat diet slightly increased the density of enteroendocrine L cells in the small intestine, implying that decreased GLP1 levels were not caused by the changes in L cell intensity. Instead, the small intestinal m6A level as well as the expression of known "writers", mettl3/14 and wtap, were found to be positively correlated with the expression of Gcg and Pc3. Fecal microbiota transplantation with feces from normal and obese mice daily to antibiotic-treated mice revealed that dysbiosis in diet-induced obesity was sufficient to reduce serum GLP1, small intestinal m6A level, and intestinal expressions of Gcg, Pc3, and writer genes (mettl3/14, wtap). However, as the most direct and universal methyl donor, the production of fecal S-adenosylmethionine was neither affected by the different dietary patterns nor their shaped microbiota. These results suggested that microbial modulation of the epitranscriptome may be involved in regulating GLP1 expression, and highlighted epitranscriptomic modifications as an additional level of interaction between diet and individual health.

Discovery of CTSK+ Periosteal Stem Cells Mediating Bone Repair in Orbital Reconstruction.

Purpose: The purpose of this study was to explore the role of cathepsin K positive (CTSK+) periosteal stem cells (PSCs) in orbital bone repair and to clarify the source of endogenous stem cells for orbital bone self-repair. Methods: Periosteum samples obtained by clinical orbital bone repair surgery were analyzed, after which immunofluorescence and immunohistochemical staining were used to detect the content of bone marrow-derived cells and CTSK+ PSCs in periosteum as well as the mobilization of PSCs. CTSK+ PSCs were characterized by flow cytometry. Transcriptome sequencing was used to compare the transcriptomic characteristics of CTSK+ PSCs and bone marrow mesenchymal stem cells (BMSCs). Results: The orbital periosteum contained CTSK+CD200+ cell lineage, including CD200+CD105- PSCs and CD200+CD105+ progenitor cells. CTSK and osteocalcin (OCN) colocalized in the inner layer of the orbital periosteum, suggesting the osteogenic differentiation potential of CTSK+ PSCs. CTSK expression was much higher in periosteum after mobilization. Immunofluorescence showed low amounts of scattered CD31+ and CD45+ cells in the orbital periosteum. The stem cell characteristics of CTSK+ PSCs were verified by multidirectional differentiation. Flow cytometry found CD200+CD105- CTSK+ PSCs and CD200variantCD105+ progenitor cells. Transcriptome sequencing of CTSK+ PSCs and BMSCs found 3613 differential genes with significant differences. Gene Ontology (GO) analysis showed the differences between the two types of stem cells, revealing that PSCs were more suitable for intramembranous osteogenesis. Conclusions: CTSK+ PSCs may be endogenous stem cells for orbital bone repair. They are mobilized after orbital fracture and have unique features suitable for intramembranous osteogenesis, completely different from BMSCs.

Human Papillomavirus and Retinoblastoma: Evidence From a Systematic Review and Meta-analysis of Cross-Sectional Studies.

Objectives: To study the prevalence and the association of HPV infection in retinoblastoma and to determine the most common genotype presented in RB. Methods: Following the PRIMSA guideline, 14 studies reporting HPV infection in RB acquired from six databases were included. Results: The prevalence of HPV from 941 RB samples was 15.6% [95% confidence interval (CI): 7.3-30]. Mexico followed by India and Brazil had the highest HPV prevalence in RB samples, 61.7% (95% CI: 17-93), 22.5% (95% CI: 9-47), and 12.1% (95% CI: 2-52), in order. HPV 16 was the most common genotype presented in RB samples 23% (95% CI: 9-47), followed by HPV 18 10% (95% CI: 3-30) and the combined HPV 16-18 6% (95% CI: 0-50). We did not find a significant association between HPV and RB [odds ratio (OR): 12.2; 95% CI: 0.65-232; p = 0.09]. However, after removing the largest-weighted study, a significant association between HPV and RB was observed (OR: 45.9; 95% CI; 8.6-245; p < 0.001). Conclusion: HPV prevalence in RB samples was 15% and HPV 16 was the most presented genotype in RB samples. There may be an association between HPV and RB that is needed to be confirmed by high quality future studies. Preventive and treatment measures against HPV infection are essential for the prevention of any possible consequences, in particular, RB.

HLA-mismatched micro-transplantation as post-remission treatment compared to autologous hematopoietic stem cell transplantation or consolidation with single agent cytarabine for favorable-or intermediate-risk acute myeloid leukemia.

OBJECTIVES: Optimal post-remission treatment for individual favorable and intermediate risk acute myeloid leukemia (AML) patients has not yet been established. Human leukocyte antigen (HLA)-mismatched stem cell microtransplantation (MST), may improve outcomes and avoid graft-versus-host disease in patients with first complete remission of AML. METHODS: We retrospectively analyzed the efficacy, safety, and survival of 63 patients with favorable- or intermediate-risk AML who received MST, autologous stem cell transplantation (ASCT), or cytarabine single agent (CSA) as post-remission treatment from January 2014 to August 2021. RESULTS: The neutrophil recovery time was shorter in the MST group than in the CSA group. The 2-year cumulative incidences of relapse in the MST, ASCT, and CSA groups were 27.27%, 29.41%, and 41.67%, respectively. During follow-up, 21 patients (33.30%) died of relapse, including six (9.52%), five (7.94%), and 10 (15.84%) in the MST, ASCT, and CSA groups, respectively. The estimated 2-year overall survival (OS) and relapse-free survival (RFS) were 62.20% vs. 50.00% (P = 0.101) and 57.10% vs. 50.00% (P = 0.136), in the >60 years MST and CSA groups (P = 0.101). The estimated 2-year OS was 100%, 66.20%, and 69.10% in the MST, ASCT, and CSA groups (MST vs CSA, P = 0.044), meanwhile, the estimated 2-year RFS was 100%, 65.40%, and 59.80% in patients ≤60 years. CONCLUSION: MST, ASCT, and CSA are acceptable post-remission treatments for patients with favorable- and intermediate-risk AML and may not only improve the prognosis of the elderly but also prolong the OS and RFS of favorable- or intermediate-risk patients ≤60 years.

Characterization of the fragmented mitochondrial genome of domestic pig louse Haematopinus suis (Insecta: Haematopinidae) from China.

The domestic pig louse Haematopinus suis (Linnaeus, 1758) (Phthiraptera: Anoplura) is a common ectoparasite of domestic pigs, which can act as a vector of various infectious disease agents. Despite its significance, the molecular genetics, biology and systematics of H. suis from China have not been studied in detail. In the present study, the entire mitochondrial (mt) genome of H. suis isolate from China was sequenced and compared with that of H. suis isolate from Australia. We identified 37 mt genes located on nine circular mt minichromosomes, 2.9 kb-4.2 kb in size, each containing 2-8 genes and one large non-coding region (NCR) (1,957 bp-2,226 bp). The number of minichromosomes, gene content, and gene order in H. suis isolates from China and Australia are identical. Total sequence identity across coding regions was 96.3% between H. suis isolates from China and Australia. For the 13 protein-coding genes, sequence differences ranged from 2.8%-6.5% consistent nucleotides with amino acids. Our result is H. suis isolates from China and Australia being the same H. suis species. The present study determined the entire mt genome of H. suis from China, providing additional genetic markers for studying the molecular genetics, biology and systematics of domestic pig louse.

Nuclear transport maintenance of USP22-AR by Importin-7 promotes breast cancer progression.

The translocation of biological macromolecules between cytoplasm and nucleus is of great significance to maintain various life processes in both normal and cancer cells. Disturbance of transport function likely leads to an unbalanced state between tumor suppressors and tumor-promoting factors. In this study, based on the unbiased analysis of protein expression differences with a mass spectrometer between human breast malignant tumors and benign hyperplastic tissues, we identified that Importin-7, a nuclear transport factor, is highly expressed in breast cancer (BC) and predicts poor outcomes. Further studies showed that Importin-7 promotes cell cycle progression and proliferation. Mechanistically, through co-immunoprecipitation, immunofluorescence, and nuclear-cytoplasmic protein separation experiments, we discovered that AR and USP22 can bind to Importin-7 as cargoes to promote BC progression. In addition, this study provides a rationale for a therapeutic strategy to restream the malignant progression of AR-positive BC by inhibiting the high expression state of Importin-7. Moreover, the knockdown of Importin-7 increased the responsiveness of BC cells to the AR signaling inhibitor, enzalutamide, suggesting that targeting Importin-7 may be a potential therapeutic strategy.

Efficacy of vaginal natural orifice transluminal endoscopic sentinel lymph node biopsy for endometrial cancer: a prospective multicenter cohort study.

INTRODUCTION: Natural orifice transluminal endoscopic surgery (NOTES) is performed increasingly often despite the lack of high-quality evidence confirming its safety, especially for malignant diseases. The aim of this prospective study is to verify that vaginal NOTES (vNOTES) can be performed safely and effectively in early endometrial cancer staging surgery. MATERIALS AND METHODS: This prospective study was conducted in two tertiary hospitals in southern China from January 2021 to May 2022. A total of 120 patients with stage I endometrial cancer were included. vNOTES or multiport laparoscopic staging surgery was selected according to each patient's wishes. The primary outcome was the sentinel lymph node detection rate, analyzed by a noninferiority test. The secondary outcomes were perioperative outcomes. RESULTS: Among the 120 patients enrolled, 57 underwent vNOTES, and 63 underwent multiport laparoscopy. The patient-specific detection rates of sentinel lymph nodes were 94.73 and 96.82% in the vNOTES and laparoscopy groups, respectively. Additionally, the bilateral detection rates were 82.46 and 84.13%, and the side-specific detection rates were 88.60 and 90.48% in these two groups, respectively. All three detection rates in the vNOTES group were noninferior to those of laparoscopy group at a noninferiority cutoff of -15%. The median operation times of the vNOTES and laparoscopy groups were 132.35 and 138.73 min ( P =0.362), and the median estimated blood loss were 75 and 50 ml ( P =0.096), respectively. No intraoperative complications occurred in either group. The pain scores on the Numerical Rating Scale at both 12 h and 24 h after operation were significantly lower in the vNOTES group ( P <0.001) and the median postoperative hospital stay was significantly shorter in the vNOTES group ( P =0.001). CONCLUSION: This study illustrates the potential applicability of vNOTES in gynecological malignancy surgery by demonstrating its safety and effectiveness in endometrial cancer staging. However, its long-term survival outcomes require further exploration.