Methylisothiazolinone pollution inhibited root stem cells and regeneration through auxin transport modification in Arabidopsis thaliana.

Methylisothiazolinone (MIT) is a widely used preservative and biocide to prevent product degradation, yet its potential impact on plant growth remains poorly understood. In this study, we investigated MIT's toxic effects on Arabidopsis thaliana root growth. Exposure to MIT significantly inhibited Arabidopsis root growth, associated with reduced root meristem size and root meristem cell numbers. We explored the polar auxin transport pathway and stem cell regulation as key factors in root meristem function. Our findings demonstrated that MIT suppressed the expression of the auxin efflux carrier PIN1 and major root stem cell regulators (PLT1, PLT2, SHR, and SCR). Additionally, MIT hindered root regeneration by downregulating the quiescent center (QC) marker WOX5. Transcriptome analysis revealed MIT-induced alterations in gene expression related to oxidative stress, with physiological experiments confirming elevated reactive oxygen species (ROS) levels and increased cell death in root tips at concentrations exceeding 50 µM. In summary, this study provides critical insights into MIT's toxicity on plant root development and regeneration, primarily linked to modifications in polar auxin transport and downregulation of genes associated with root stem cell regulation.

Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway.

Introduction: Alcohol consumption alters the diversity and metabolic activities of gut microbiota, leading to intestinal barrier dysfunction and contributing to the development of alcoholic liver disease (ALD), which is the most prevalent cause of advanced liver diseases. In this study, we investigated the protective effects and action mechanism of an aqueous extraction of Pericarpium citri reticulatae and Amomi fructus (PFE) on alcoholic liver injury. Methods: C57BL/6 mice were used to establish the mouse model of alcoholic liver injury and orally administered 500 and 1,000 mg/kg/d of PFE for 2 weeks. Histopathology, immunohistochemistry, immunofluorescence, Western blotting, qRT-PCR, and 16S rDNA amplicon sequencing were used to analyze the mechanism of action of PFE in the treatment of alcohol-induced liver injury. Results: Treatment with PFE significantly improved alcohol-induced liver injury, as illustrated by the normalization of serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and cholesterol levels in ALD mice in a dose-dependent manner. Administration of PFE not only maintained the intestinal barrier integrity prominently by upregulating mucous production and tight junction protein expressions but also sensibly reversed the dysregulation of intestinal microecology in alcohol-treated mice. Furthermore, PFE treatment significantly reduced hepatic lipopolysaccharide (LPS) and attenuated oxidative stress as well as inflammation related to the TLR4/NF-κB signaling pathway. The PFE supplementation also significantly promoted the production of short-chain fatty acids (SCFAs) in the ALD mice. Conclusion: Administration of PFE effectively prevents alcohol-induced liver injury and may also regulate the LPS-involved gut-liver axis; this could provide valuable insights for the development of drugs to prevent and treat ALD.

SARS-CoV-2 pathogenesis in an angiotensin II-induced heart-on-a-chip disease model and extracellular vesicle screening.

Adverse cardiac outcomes in COVID-19 patients, particularly those with preexisting cardiac disease, motivate the development of human cell-based organ-on-a-chip models to recapitulate cardiac injury and dysfunction and for screening of cardioprotective therapeutics. Here, we developed a heart-on-a-chip model to study the pathogenesis of SARS-CoV-2 in healthy myocardium established from human induced pluripotent stem cell (iPSC)-derived cardiomyocytes and a cardiac dysfunction model, mimicking aspects of preexisting hypertensive disease induced by angiotensin II (Ang II). We recapitulated cytopathic features of SARS-CoV-2-induced cardiac damage, including progressively impaired contractile function and calcium handling, apoptosis, and sarcomere disarray. SARS-CoV-2 presence in Ang II-treated hearts-on-a-chip decreased contractile force with earlier onset of contractile dysfunction and profoundly enhanced inflammatory cytokines compared to SARS-CoV-2 alone. Toward the development of potential therapeutics, we evaluated the cardioprotective effects of extracellular vesicles (EVs) from human iPSC which alleviated the impairment of contractile force, decreased apoptosis, reduced the disruption of sarcomeric proteins, and enhanced beta-oxidation gene expression. Viral load was not affected by either Ang II or EV treatment. We identified MicroRNAs miR-20a-5p and miR-19a-3p as potential mediators of cardioprotective effects of these EVs.

High-entropy selenides derived from Prussian blue analogues as electrode materials for sodium-ion batteries.

Transition metal selenides (TMS) have received much attention as anode materials for sodium-ion batteries (SIBs) because of their high theoretical capacity and excellent redox reversibility. However, their further development is constrained by the dissolution of transition metal ions and substantial volume changes experienced during cycling. Herein, the high-entropy Prussian blue analogues were selenized by the vapor infiltration method, resulting in the formation of a core-shell structured high-entropy selenides (HESe-6). The core-shell structure with voids and abundant selenium vacancies on the surface effectively mitigates bulk expansion and enhances electronic conductivity. Furthermore, the high-entropy property endows an ultra-stable crystal structure and inhibits the dissolution of metal ions. The ex-situ EIS and in-situ XRD results show that HESe-6 is able to be reversibly transformed into highly conductive ultrafine metal particles upon Na+ embedding, providing more Na+ reactive active sites. In addition, despite the incorporation of up to seven different elements, it exhibits minimal phase transitions during discharge/charge cycles, effectively mitigating stress accumulation. HESe-6 could retain an ultralong-term stability of 765.83 mAh g-1 after 1000 loops even at 1 A g-1. Furthermore, when coupled with the Na3V2(PO4)2O2F cathode, it maintains a satisfactory charge energy density of 303 Wh kg-1 after 300 cycles, which shows promising application prospect in the future.

New insights into membrane fouling in coagulation-ultrafiltration by cake characteristics analysis: A case study with PACl-Al13 and PACl.

Membrane fouling is a bottleneck issue that hindered the further application of ultrafiltration technology. To alleviate membrane fouling, coagulation-ultrafiltration (C-UF) process using polyaluminum chloride (PACl) and PACl-Al13 with high proportion of Al13O4(OH)247+ as coagulants, respectively, were investigated at various pH conditions. Results indicated that an increase in solution pH contributed to larger floc size and looser floc structure for both PACl and PACl-Al13. It was conducive to the formation of more porous cake, as evidenced by mean pore area and pore area distribution of cake, leading to lower reversible fouling. Furthermore, humic acid (HA) removal presented a trend of first increasing and then decreasing with the increase of pH. The optimal HA removal was achieved at pH 6 regardless of coagulant type, suggesting that the slightest irreversible fouling should be occurred at this point. Interestingly, the irreversible fouling with PACl coagulant achieved a minimum value at pH 9, while the minimal irreversible fouling with PACl-Al13 was observed at pH 6. We speculated that the cake formed by PACl could further intercept HA prior to UF process at alkaline pH. Furthermore, compared with PACl, PACl-Al13 had a stronger charge neutralization ability, thus contributing to more compact floc structure and higher HA removal at various pH conditions. By UF fractionation measurement, higher HA removal for PACl-Al13 was due to higher removal of HA with molecular weight less than 50 kDa.

Classification of brain tumor types through MRIs using parallel CNNs and firefly optimization.

Image segmentation is a critical and challenging endeavor in the field of medicine. A magnetic resonance imaging (MRI) scan is a helpful method for locating any abnormal brain tissue these days. It is a difficult undertaking for radiologists to diagnose and classify the tumor from several pictures. This work develops an intelligent method for accurately identifying brain tumors. This research investigates the identification of brain tumor types from MRI data using convolutional neural networks and optimization strategies. Two novel approaches are presented: the first is a novel segmentation technique based on firefly optimization (FFO) that assesses segmentation quality based on many parameters, and the other is a combination of two types of convolutional neural networks to categorize tumor traits and identify the kind of tumor. These upgrades are intended to raise the general efficacy of the MRI scan technique and increase identification accuracy. Using MRI scans from BBRATS2018, the testing is carried out, and the suggested approach has shown improved performance with an average accuracy of 98.6%.

Disproportionality Analysis of Nusinersen in the Food and Drug Administration Adverse Event Reporting System: A Real-World Postmarketing Pharmacovigilance Assessment.

BACKGROUND: Nusinersen is the first drug for precise targeted therapy of spinal muscular atrophy, a rare disease that occurs in one of 10,000 to 20,000 live births. Therefore, thorough and comprehensive reports on the safety of nusinersen in large, real-world populations are necessary. This study aimed to mine the adverse event (AE) signals related to nusinersen through the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: We extracted reports of AEs with nusinersen as the primary suspect from FAERS between December 2016 and March 2023. Reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) were used for AE signal detection. RESULTS: We extracted a total of 4807 suspected AE cases with nusinersen as the primary suspect from the FAERS database. Among them, 106 positive signals were obtained using the ROR and BCPNN. The highest frequency reported systemic organ class was general disorders and administration site conditions. Common clinical AEs of nusinersen were detected in the FAERS database, such as pneumonia, vomiting, back pain, headache, pyrexia, and post-lumbar puncture syndrome. In addition, we identified potential unexpected serious AEs through disproportionality analysis, including sepsis, seizure, epilepsy, brain injury, cardiorespiratory arrest, and cardiac arrest. CONCLUSIONS: Analyzing large amounts of real-world data from the FAERS database, we identified potential new AEs of nusinersen by disproportionate analysis. It is advantageous for health care professionals and pharmacists to concentrate on effectively managing high-risk AEs of nusinersen, improve medication levels in clinical settings, and uphold patient medication safety.

Huangqin Qingre Chubi Capsule inhibits rheumatoid arthritis by regulating intestinal flora and improving intestinal barrier.

Background: Changes in intestinal flora and intestinal barrier in patients with preclinical and diagnosed rheumatoid arthritis (RA) suggest that intestinal flora and intestinal barrier play an important role in the induction and persistence of RA. Huangqin Qingre Chubi Capsule (HQC) is a clinically effective herbal formula for the treatment of RA, but its therapeutic mechanism has not been fully clarified. Materials and methods: In this study, real-time qPCR (RT-qPCR), 16SrRNA sequencing, Western blot (WB), immunofluorescence and other methods were used to investigate whether HQC inhibited RA. Results: Based on research in collages-induced arthritis (CIA) model in mice, human colon cancer cell line (Caco-2), and fibroblast-like synoviocytes (FLS) from RA patients, we found that intestinal flora was disturbed in CIA model group, intestinal barrier was damaged, and lipolyaccharide (LPS) level was increased, and HQC could regulate intestinal flora and intestinal barrier and reduce LPS translocation into blood. Antibiotic depletion weakened the anti-RA effect of HQC, and HQC fecal microbiota transplantation alleviated RA pathology. In addition, LPS increased the expression of RA pathologic factors MMP3, Fibronectin and inflammatory factors IL-6, TNF-α, IL-1ß and IL-8, indicating that elevated peripheral blood level of LPS was related to RA pathology. Conclusion: The dysregulation of intestinal flora and the disruption of intestinal barrier are significant factors in the development of RA. HQC improves RA by regulating intestinal flora, intestinal barrier and inhibiting LPS translocation into blood. The study unveiles RA's new pathogenesis and laid a scientific groundwork for advancing HQC therapy for RA.

Revealing the dynamic whole transcriptome landscape of Clonorchis sinensis: Insights into the regulatory roles of noncoding RNAs and microtubule-related genes in development.

Clonorchis sinensis is a significant zoonotic food-borne parasite that causes a range of hepatobiliary diseases, which in severe cases can even lead to cholangiocarcinoma. To explore new diagnostic and treatment strategies, the dynamic RNA regulatory processes across different developmental stages of C. sinensis were analyzed by using whole-transcriptome sequencing. The chromosomal-level genome of C. sinensis was used for sequence alignment and annotation. In this study, we identified a total of 59,103 RNAs in the whole genome, including 2,384 miRNAs, 25,459 mRNAs, 27,564 lncRNAs and 3,696 circRNAs. Differential expression analysis identified 6,556 differentially expressed mRNAs, 2,231 lncRNAs, 877 miRNAs and 20 circRNAs at different developmental stages. Functional enrichment analysis highlighted the critical role of microtubule-related biological processes in the growth and development of C. sinensis. And coexpression analysis revealed 97 lncRNAs and 85 circRNAs that were coexpressed with 42 differentially expressed mRNAs that associated with microtubules at different developmental stages of C. sinensis. The expression of the microtubule-related genes dynein light chain 2 (DLC2) and dynein light chain 4 (DLC4) increased with C. sinensis development, and DLC2/4 could be inhibited by albendazole. Finally, by constructing competing endogenous RNA (ceRNA) networks, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA regulatory relationships were constructed, and the ceRNA networks of MSTRG.14258.5-novel_miR_2287-newGene_28215 and MSTRG.14258.5-novel_miR_2216-CSKR_109340 were verified. This study suggests, through whole transcriptome sequencing, that the context of microtubule regulation may play an essential role in the development and growth of C. sinensis.

The Utility of a Novel Neuropsychological Measurement to Analyze Event-Related Attentional Behaviors among Young Children with Attention Deficit Hyperactivity Disorder-a Pilot Study.

OBJECTIVE: The identification and diagnosis of children with attention deficit hyperactivity disorder (ADHD) traits is challenging during the preschool stage. Neuropsychological measures may be useful in early assessments. Furthermore, analysis of event-related behavior appears to be an unmet need for clinical treatment planning. Conners' Kiddie Continuous Performance Test (K-CPT) is the most popular well-established neuropsychological measurement but lacks event markers to clarify the heterogeneous behaviors among children. This study utilized a novel commercially available neuropsychological measure, the ΣCOG, which was more game-like and provided definite event markers of individual trial in the test. METHODS: Thirty-three older preschool children (14 were diagnosed with ADHD, mean age: 66.21 ± 5.48 months; 19 demonstrated typical development, mean age: 61.16 ± 8.11 months) were enrolled and underwent comprehensive medical and developmental evaluations. All participants underwent 2 versions of neuropsychological measures, including the K-CPT, Second Edition (K-CPT 2) and the ΣCOG, within a short interval. RESULTS: The study indicated the omissions and response time scores measured in this novel system correlated with clinical measurement of the behavioral scales in all participants and in the group with ADHD; additionally, associations with the traditional K-CPT 2 were observed in commissions and response time scores. Furthermore, this system provided a within-task behavioral analysis that identified the group differences in the specific trial regarding omission and commission errors. CONCLUSIONS: This innovative system is clinically feasible and can be further used as an alternative to the K-CPT 2 especially in research by revealing within-task event-related information analysis.

Varied immune responses of HBV-specific B cells in patients undergoing pegylated interferon-alpha treatment for chronic hepatitis B.

BACKGROUND & AIMS: The changes of HBV-specific B-cells in chronic hepatitis B (CHB) patients underwent pegylated interferon-alfa (PEG-IFNα) treatment and achieved functional cure remain unclear. We aimed to evaluate the alterations in HBV-specific B-cells during treatment and therefore explored the mechanism of functional recovery of HBsAg-specific B-cells. METHODS: We included 39 nucleos(t)ide analogues-treated CHB patients who received sequential combination therapy with PEG-IFNα and 8 treatment-naive CHB patients. HBV-specific B-cells were characterized ex vivo using fluorescent labeled HBsAg and HBcAg. The frequency, phenotype, and subsets of HBV-specific B-cells and follicular helper T cells (Tfh-cells) were detected using flow cytometry. The functionality of HBV-specific B-cells was quantified through ELISpot assays. RESULTS: During treatment, the fraction of activated memory B-cells (MBCs) among HBsAg-specific B-cells and the expression of IgG, CXCR3, and CD38 increased. Antibody-secretion capacity of HBsAg-specific B-cell was restored after treatment only in patients with a functional cure and it showed a positive correlation with serum hepatitis B surface antibody levels. The phenotype and function of HBsAg-specific B-cells differed between patients with and without functional cure. Patients with functional cure exhibited IgG+ classical MBCs and plasmablasts in HBsAg-specific B-cells. HBcAg-specific B-cells displayed both attenuated antibody secretion with reduced IgG expression and an IgM+ atypical type of MBCs after treatment, irrespective of with and without functional cure. The number of CD40L+ Tfh-cells increased after PEG-IFNα treatment and positively correlated with HBsAg-specific B-cell activation. CONCLUSIONS: After PEG-IFNα treatment, HBsAg- and HBcAg-specific B-cells exhibit various changes in antibody secretion. Their functional differences are reflected in the alterations in phenotypes and subtypes. The presence of CD40L+ Tfh-cells is associated with the active recovery of HBsAg-specific B-cells. IMPACT AND IMPLICATIONS: HBV-related complications and hepatocellular carcinoma remain the leading causes of mortality from chronic liver disease worldwide, and a cure is rarely achieved with antiviral therapies. Elucidating the immunological mechanisms underlying the functional cure of CHB patients offers a promising therapeutic strategy for viral clearance, such as therapeutic vaccine. We analyzed the alterations in HBV-specific B-cells in patients treated with PEG-IFNα and identified novel pathways for immunotherapeutic boosting of B cell immunity.

Memory inflation: Beyond the acute phase of viral infection.

Memory inflation is confirmed as the most commonly dysregulation of host immunity with antigen-independent manner in mammals after viral infection. By generating large numbers of effector/memory and terminal differentiated effector memory CD8+ T cells with diminished naïve subsets, memory inflation is believed to play critical roles in connecting the viral infection and the onset of multiple diseases. Here, we reviewed the current understanding of memory inflated CD8+ T cells in their distinct phenotypic features that different from exhausted subsets; the intrinsic and extrinsic roles in regulating the formation of memory inflation; and the key proteins in maintaining the expansion and proliferation of inflationary populations. More importantly, based on the evidences from both clinic and animal models, we summarized the potential mechanisms of memory inflation to trigger autoimmune neuropathies, such as Guillain-Barré syndrome and multiple sclerosis; the correlations of memory inflation between tumorigenesis and resistance of tumour immunotherapies; as well as the effects of memory inflation to facilitate vascular disease progression. To sum up, better understanding of memory inflation could provide us an opportunity to beyond the acute phase of viral infection, and shed a light on the long-term influences of CD8+ T cell heterogeneity in dampen host immune homeostasis.

A hypoxia-derived gene signature to suggest cisplatin-based therapeutic responses in patients with cervical cancer.

Cervical cancer remains a significant global public health concern, often exhibits cisplatin resistance in clinical settings. Hypoxia, a characteristic of cervical cancer, substantially contributes to cisplatin resistance. To evaluate the therapeutic efficacy of cisplatin in patients with cervical cancer and to identify potential effective drugs against cisplatin resistance, we established a hypoxia-inducible factor-1 (HIF-1)-related risk score (HRRS) model using clinical data from patients treated with cisplatin. Cox and LASSO regression analyses were used to stratify patient risks and prognosis. Through qRT-PCR, we validated nine potential prognostic HIF-1 genes that successfully predict cisplatin responsiveness in patients and cell lines. Subsequently, we identified fostamatinib, an FDA-approved spleen tyrosine kinase inhibitor, as a promising drug for targeting the HRRS-high group. We observed a positive correlation between the IC50 values of fostamatinib and HRRS in cervical cancer cell lines. Moreover, fostamatinib exhibited potent anticancer effects on high HRRS groups in vitro and in vivo. In summary, we developed a hypoxia-related gene signature that suggests cisplatin response prediction in cervical cancer and identified fostamatinib as a potential novel treatment approach for resistant cases.

Inverse design of mid-infrared diamond waveguide beam splitter.

Diamond is a supreme material for mid-infrared (MIR) integrated photonics as it has a transparency window up to 20 µm that covers the entire fingerprint region. However, its relatively low refractive index poses a challenge in designing an MIR diamond functional device with both small footprint and high transmission efficiency. Here we propose and demonstrate the inverse design of an MIR diamond waveguide beam splitter operating at the wavelength of 15 µm with a small footprint of ∼15 µm × âˆ¼15 µm and a total transmission efficiency above 95%. Our work paves a new avenue for the design of compact and high-efficiency MIR diamond photonic devices.

The role of Phafin proteins in cell signaling pathways and diseases.

Membrane-associated proteins are important membrane readers that mediate and facilitate the signaling and trafficking pathways in eukaryotic membrane-bound compartments. The protein members in the Phafin family are membrane readers containing two phosphoinositide recognition domains: the Pleckstrin Homology domain and the FYVE (Fab1, YOTB, Vac1, and early endosome antigen 1) domain. Phafin proteins, categorized into two subfamilies, Phafin1 and Phafin2, associate with cellular membranes through interactions involving membrane-embedded phosphoinositides and phosphoinositide-binding domains. These membrane-associated Phafin proteins play pivotal roles by recruiting binding partners and forming complexes, which contribute significantly to apoptotic, autophagic, and macropinocytotic pathways. Elevated expression levels of Phafin1 and Phafin2 are observed in various cancers. A recent study highlights a significant increase in Phafin1 protein levels in the lungs of idiopathic pulmonary fibrosis patients compared to normal subjects, suggesting a crucial role for Phafin1 in the pathogenesis of pulmonary fibrosis. Additionally, phosphatidylinositol-3-phosphate-binding 2 (Pib2), a close relative of the Phafin1 protein, functions as an amino acid sensor activating the TOCR1 pathway in yeasts. This review focuses on delineating the involvement of Phafin proteins in cellular signaling and their implications in diseases and briefly discusses the latest research findings concerning Pib2.

Genetics of causal relationships between circulating inflammatory proteins and postherpetic neuralgia: a bidirectional Mendelian randomization study.

Objective: According to data from several observational studies, there is a strong association between circulating inflammatory cytokines and postherpetic neuralgia (PHN), but it is not clear whether this association is causal or confounding; therefore, the main aim of the present study was to analyze whether circulating inflammatory proteins have a bidirectional relationship with PHN at the genetic inheritance level using a Mendelian randomization (MR) study. Methods: The Genome-Wide Association Study (GWAS) database was used for our analysis. We gathered data on inflammation-related genetic variation from three GWASs of human cytokines. These proteins included 91 circulating inflammatory proteins, tumor necrosis factor-alpha (TNF-α), macrophage inflammatory protein 1b (MIP-1b), and CXC chemokine 13 (CXCL13). The PHN dataset was obtained from the FinnGen biobank analysis round 5, and consisted of 1,413 cases and 275,212 controls. We conducted a two-sample bidirectional MR study using the TwoSampleMR and MRPRESSO R packages (version R.4.3.1). Our main analytical method was inverse variance weighting (IVW), and we performed sensitivity analyses to assess heterogeneity and pleiotropy, as well as the potential influence of individual SNPs, to validate our findings. Results: According to our forward analysis, five circulating inflammatory proteins were causally associated with the development of PHN: interleukin (IL)-18 was positively associated with PHN, and IL-13, fibroblast growth factor 19 (FGF-19), MIP-1b, and stem cell growth factor (SCF) showed reverse causality with PHN. Conversely, we found that PHN was closely associated with 12 inflammatory cytokines, but no significant correlation was found among the other inflammatory factors. Among them, only IL-18 had a bidirectional causal relationship with PHN. Conclusion: Our research advances the current understanding of the role of certain inflammatory biomarker pathways in the development of PHN. Additional verification is required to evaluate the viability of these proteins as targeted inflammatory factors for PHN-based treatments.

Dimethylamine Copper(I) Halide Single Crystals: Structure, Physical Properties, and Scintillation Performance.

Hybrid copper(I) halides have garnered a significant amount of attention as potential substitutes in luminescence and scintillation applications. Herein, we report the discovery and crystal growth of new zero-dimensional compounds, (C2H8N)3Cu2I5 and (C2H8N)4Cu2Br6. The bromide and iodide have a triclinic structure with space group P1̅ and an orthorhombic structure with space group Pnma, respectively. (C2H8N)3Cu2I5 exhibits cyan emission peaking at 504 nm with a photoluminescence quantum yield (PLQY) of 34.79%, while (C2H8N)4Cu2Br6 shows yellowish-green emission peaking at 537 nm with a PLQY of 38.45%. The temperature-dependent photoluminescence data of both compounds were fitted to theoretical models, revealing that nonradiative intermediate states significantly affect thermal quenching and antiquenching. Electron-phonon interactions, the origin of emission line width broadening and peak shifting, were also investigated via fittings. The scintillation properties of (C2H8N)3Cu2I5 were evaluated, and an X-ray imaging device was successfully fabricated using (C2H8N)3Cu2I5. This work demonstrates the potentiality of copper halides in lighting and X-ray imaging applications.

Clinicopathological characteristics and prognosis of uterine sarcoma: a 10-year retrospective single-center study in China.

BACKGROUND: Uterine sarcoma is a rare and heterogeneous gynecological malignancy characterized by aggressive progression and poor prognosis. The current study aimed to investigate the relationship between clinicopathological characteristics and the prognosis of uterine sarcoma in Chinese patients. METHODS: In this single-center retrospective study, we reviewed the medical records of 75 patients with histologically verified uterine sarcoma treated at the First Affiliated Hospital of Xi'an Jiaotong University between 2011 and 2020. Information on clinical characteristics, treatments, pathology and survival was collected. Progression-free survival (PFS) and overall survival (OS) were visualized in Kaplan-Meier curves. Prognostic factors were identified using the log-rank test for univariate analysis and Cox-proportional hazards regression models for multivariate analysis. RESULTS: The histopathological types included 36 endometrial stromal sarcomas (ESS,48%), 33 leiomyosarcomas (LMS,44%) and 6 adenosarcomas (8%). The mean age at diagnosis was 50.2 ± 10.7 years. Stage I and low-grade accounted for the majority. There were 26 recurrences and 25 deaths at the last follow-up. The mean PFS and OS were 89.41 (95% CI: 76.07-102.75) and 94.03 (95% CI: 81.67-106.38) months, respectively. Univariate analysis showed that > 50 years, post-menopause, advanced stage, ≥ 1/2 myometrial invasion, lymphovascular space invasion and high grade were associated with shorter survival (P < 0.05). Color Doppler flow imaging positive signals were associated with shorter PFS in the LMS group (P = 0.046). The ESS group had longer PFS than that of the LMS group (99.56 vs. 76.05 months, P = 0.043). The multivariate analysis showed that post-menopause and advanced stage were independent risk factors of both PFS and OS in the total cohort and LMS group. In the ESS group, diagnosis age > 50 years and high-grade were independent risk factors of PFS, while high-grade and lymphovascular space invasion were independent risk factors of OS. CONCLUSION: In Chinese patients with uterine sarcoma, post-menopause and advanced stage were associated with a significantly poorer prognosis. The prognosis of ESS was better than that of LMS. Color Doppler flow imaging positive signals of the tumor helped to identify LMS, which needs to be further tested in a larger sample in the future.