A nomogram and risk stratification system for predicting survival in T1-2N0-1 breast cancer patients with liver metastasis in females: a population-based study.

PURPOSE: Liver was one of the most common distant metastatic sites in breast cancer. Patients with distant metastasis were identified as American Joint Committee on Cancer (AJCC) stage IV indicating poor prognosis. However, few studies have predicted the survival in females with T1-2N0-1 breast cancer who developed liver metastasis. This study aimed to explore the clinical features of these patients and establish a nomogram to predict their overall survival. RESULTS: 1923 patients were randomly divided into training (n = 1154) and validation (n = 769) cohorts. Univariate and multivariate analysis showed that age, marital status, race, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), chemotherapy, surgery and bone metastasis, brain metastasis were considered the independent prognostic indicators. We developed a nomogram according to these ten parameters. The consistency index (c-index) was 0.72 (95% confidence interval CI 0.70-0.74) in the training cohort, 0.72 (95% CI 0.69-0.74) in the validation cohort. Calibration plots indicated that the nomogram-predicted survival was consistent with the recorded 1-, 3- and 5-year prognoses. Decision curve analysis curves in both the training and validation cohorts demonstrated that the nomogram showed better prediction than the AJCC TNM (8th) staging system. Kaplan Meier curve based on the risk stratification system showed that the low-risk group had a better prognosis than the high-risk group (P < 0.001). CONCLUSIONS: A predictive nomogram and risk stratification system were constructed to assess prognosis in T1-2N0-1 breast cancer patients with liver metastasis in females. The risk model established in this study had good predictive performance and could provide personalized clinical decision-making for future clinical work.

Single-cell analysis identified PDIA3 as regulator of malignant characteristics and macrophage function in human cancers.

Protein disulfide isomerase A3 (PDIA3) is an endoplasmic reticulum (ER) protein. It has different functions including glycoprotein folding in the ER. The unfavorable prognosis of cancer patients was related to the abnormal PDIA3 expression level. However, it is unclear how PDIA3 correlates with the malignant characteristics of different tumors and its impact on tumor immunity. Pan-cancer data were downloaded from several databases for large-scale bioinformatics analysis. The immunological functions of PDIA3 were systematically explored at the single-cell sequencing level, including cell communication, cell metabolism, cell evolution and epigenetic modification. We performed immunofluorescence staining to visualize PDIA3 expression and infiltration of macrophages in pan-cancer samples. Further, we performed a loss-of-function assay of PDIA3 in vitro. The CCK8 assay, clone formation assay, and transwell assay were performed. M2 macrophages were co-cultured with different cell lines before the transwell assay was performed. The immunofluorescence staining of pan-cancer samples presented a higher expression of PDIA3 than those of the paired normal tissues. According to single-cell sequencing analysis, expression of PDIA3 was closely associated with cell communication, cell metabolism, cell evolution and epigenetic modification. The knockdown of PDIA3 in tumor cells inhibited cell proliferation and invasion, and restrained cocultured M2 macrophage migration. Furthermore, PDIA3 displayed predictive value in immunotherapy response in human cancer cohorts, indicating a potential therapeutic target. Our study showed that PDIA3 was associated with tumor malignant characteristics and could mediate the migration of M2 macrophages in various tumor types. PDIA3 could be a promising target to achieve tumor control and improve the immune response on a pan-cancer scale.

Research progress on elemental mercury (Hg0) removal in flue gas using non-thermal plasma technology.

Elemental mercury (Hg0) removal is a crucial target for mercury pollution control in flue gas. This article focuses on Hg0 removal in flue gas using corona discharge (CD) and dielectric barrier discharge (DBD) technologies, and provides a mechanistic perspective on the development and influencing factors of non-thermal plasma (NTP) technology for Hg0 removal. The influence factors include reactor configurations, power supplies, energy density, residence time, oxidation methods, gas composition, and the synergy between NTP and catalysis/adsorption, etc. This study reveals that the use of a pulsating electrical power supply significantly increases electron densities in both CD and DBD systems, thereby ensuring high energy efficiency and economic viability. Cl2 proves to be more effective than HCl as a chlorine source for Hg0 removal. NO significantly reduces Hg0 oxidation efficiency, while the effects of SO2 and H2O remain unclear. Energy density distribution is closely related to plasma devices, power supplies, and overall reactor configurations. Direct oxidation proves to be more effective than indirect oxidation for Hg0 removal. The combination of NTP with adsorption/catalysis technologies shows significantly better Hg0 removal efficiency compared to using NTP alone. This study can provide theoretical support for enhancing Hg0 removal mechanisms and optimizing process control parameters in industrial applications of NTP technology.

Targeting histone methylation and demethylation for non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease worldwide, facing increasing challenges in terms of prevention and treatment. The methylation of lysine and arginine residues on histone proteins is dynamically controlled by histone methyltransferases (HMTs) and histone demethylases (HDMs), regulating chromatin structure and gene transcription. Mutations, genetic translocations, and altered gene expression involving HMTs and HDMs are frequently observed in NAFLD. HMTs and HDMs are receiving increasing attention in regulating NALFD. Targeting specific HMTs and HDMs for drug development is becoming a new strategy for treating NAFLD. This review provides a comprehensive summary of the regulatory mechanism of histone methylation/demethylation in NAFLD. Additionally, we discuss the potential applications of HMTs and HDMs inhibitors in preventing NAFLD, which may provide a scientific basis for the treatment of NAFLD.

Efficacy and safety of 3-dimensional printing noncoplanar template (3D-PNCT)-assisted high-dose-rate interstitial brachytherapy (HDR-ISBT) for reirradiation of recurrent cervical cancer: a prospective cohort.

OBJECTIVE: This study aimed to investigate the efficacy and safety of 3-dimensional printing noncoplanar template (3D-PNCT)-assisted computed tomography (CT)-guided high-dose-rate interstitial brachytherapy (HDR-ISBT) for reirradiation of pelvic recurrent cervical carcinoma after external beam radiotherapy. METHODS: From January 2019 to August 2023, 45 eligible patients were enrolled in this prospective cohort. All patients underwent 3D-PNCT-assisted CT-guided HDR-ISBT with a prescribed dose of 4-7 Gy/fraction to the high-risk clinical target volume (HR-CTV) over 3-8 fractions, either for curative or palliative purposes. The primary endpoints were local progression-free survival (LPFS) and tumor response rate (TRR). The secondary outcome measures included overall survival (OS), toxicities, and symptom resolution. RESULTS: Forty-five patients received 261 fractions of 3D-PNCT-assisted HDR-ISBT. Twenty-nine patients had isolated pelvic recurrence, and 16 patients had simultaneous extra-pelvic or distant recurrences. The TRR was 66.7%. The 2- and 5-year LPFS rates were 30.0% and 25.7%, respectively. The median OS was 23.2 months, and 2- and 5-year OS rates were 49.5% and 34.0%, respectively. The multivariate analysis indicated that squamous cell carcinoma, radical surgery, recurrence-free interval≥12 months, tumor diameter, pelvic recurrence type, and HR-CTV D90≥45 Gy were independent factors influencing LPFS (all p<0.05). D100≥21 Gy, V100≥83%, and V150≥45% were associated with better LPFS (all p<0.05). Tumor diameter and metastasis were independent predictive factors for OS (all p<0.05). The pain relief rate was 66.7% (10/15). Grade 3-4 toxicities occurred in 20.0% of patients. CONCLUSION: 3D-PNCT-assisted HDR-ISBT for reirradiation of recurrent cervical cancer proved to be an effective and safe alternative to radical surgery.

Hexa-atom Pt Catalyst Fabricated by a Ligand Engineering Strategy for Efficient Hydrogen Oxidation Reaction.

Atomically precise supported nanocluster catalysts (APSNCs), which feature exact atomic composition, well-defined structures, and unique catalytic properties, offer an exceptional platform for understanding the structure-performance relationship at the atomic level. However, fabricating APSNCs with precisely controlled and uniform metal atom numbers, as well as maintaining a stable structure, remains a significant challenge due to uncontrollable dispersion and easy aggregation during synthetic and catalytic processes. Herein, we developed an effective ligand engineering strategy to construct a Pt6 nanocluster catalyst stabilized on oxidized carbon nanotubes (Pt6/OCNT). The structural analysis revealed that Pt6 nanoclusters in Pt6/OCNT were fully exposed and exhibited a planar structure. Furthermore, the obtained Pt6/OCNT exhibited outstanding acidic HOR performances with a high mass activity of 18.37 A ⋅ mgpt -1 along with excellent stability during a 24 h constant operation and good CO tolerance, surpassing those of the commercial Pt/C. Density functional theory (DFT) calculations demonstrated that the unique geometric and electronic structures of Pt6 nanoclusters on OCNT altered the hydrogen adsorption energies on catalytic sites and thus lowered the HOR theoretical overpotential. This work presents a new prospect for designing and synthesizing advanced APSNCs for efficient energy electrocatalysis.

Targeting DNA methyltransferases for cancer therapy.

DNA methyltransferases (DNMTs) play a crucial role in genomic DNA methylation. In mammals, DNMTs regulate the dynamic patterns of DNA methylation in embryonic and adult cells. Abnormal functions of DNMTs are often indicative of cancers, including overall hypomethylation and partial hypermethylation of tumor suppressor genes (TSG), which accelerate the malignancy of tumors, worsen the condition of patients, and significantly exacerbate the difficulty of cancer treatment. Currently, nucleoside DNMT inhibitors such as Azacytidine and Decitabine have been approved by the FDA and EMA for the treatment of acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), and myelodysplastic syndrome (MDS). Therefore, targeting DNMTs is a very promising anti-tumor strategy. This review mainly summarizes the therapeutic effects of DNMT inhibitors on cancers. It aims to provide more possibilities for the treatment of cancers by discovering more DNMT inhibitors with high activity, high selectivity, and good drug-like properties in the future.

Efficacy and safety of Shenmai injection for acute ischemic stroke: a systematic review and meta-analysis.

Background: Ischemic stroke is a serious and sudden cerebrovascular condition that significantly affects individual's health and imposes a substantial economic burden on medical management. Despite its widespread use in China, there is still a lack of reliable evidence regarding the efficacy of Shenmai injection (SMI) in acute ischemic stroke (AIS). We aimed to comprehensively assess the effectiveness and safety of SMI in treating AIS through a systematic review and meta-analysis. Methods: Randomized controlled studies (RCTs) investigating the efficacy of SMI in treating AIS were searched for in eight databases from the inception of each database till January 2024. We utilized the ROB 2.0 to assess the risk of bias. A meta-analysis was conducted using Review Manager 5.4, while sensitivity analyses and publication bias assessments were conducted using Stata 16.1. Results: A total of 17 studies involving 1,603 AIS patients were included in our meta-analysis. Our results showed that SMI plus conventional treatments (CTs) was more effective than CTs alone in improving the total effective rate (RR 1.22, 95% CI: 1.14 to 1.30, p < 0.00001), the Barthel index (BI) (MD 12.18, 95% CI: 10.30 to 14.06, p < 0.00001), and reducing the National Institute of Health Stroke Scale Score (NIHSS) score (MD -3.05, 95% CI: 3.85 to -2.24, p < 0.00001) and Modified Rankin Scale (mRS) (MD -0.68, 95% CI: 0.86 to-0.49, p < 0.00001). In addition, SMI combination therapy was better than CTs alone in decreasing the levels of IL-6, IL-18, and hs-CRP. SMI therapy also enhanced the cerebral hemorheology of patients by reducing levels of fibrinogen and plasma viscosity. However, there was no significant difference in the incidence of adverse events, including elevated transaminase, rash, nausea, bleeding, urticaria, headache, vomiting, chest tightness, and facial flushes. Moreover, no serious adverse effects or life-threatening events were reported. Conclusion: Our study shows that combining SMI with CTs effectively enhances the neurological function of patients with acute cerebral infarction. However, our findings should be interpreted considering the significant heterogeneity and suboptimal quality of the analyzed trials. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024504675, Identifier PROSPERO, CRD42024504675.

Comprehensive analysis of cuproptosis-related genes involved in immune infiltration and their use in the diagnosis of hepatic ischemia‒reperfusion injury: an experimental Study.

BACKGROUND: Hepatic ischemia reperfusion injury (HIRI) is a common injury not only during liver transplantation but also during major hepatic surgery. HIRI causes severe complications and affects the prognosis and survival of patients. Cuproptosis, a newly identified form of cell death, plays an important role in a variety of illnesses. However, its role in HIRI remains unknown. MATERIALS AND METHODS: The GSE151648 dataset was mined from the Gene Expression Omnibus (GEO) database, and differences were analyzed for intersections. Based on the differentially expressed genes (DEGs), functional annotation, differentially expressed cuproptosis-related genes (DE-CRGs) identification and lasso logistic regression were conducted. Correlation analysis of DE-CRGs and immune infiltration was further conducted, and DE-CRGs were applied to construct an HIRI diagnostic model. The hierarchical clustering method was used to classify the specimens of HIRI, and functional annotation was conducted to verify the accuracy of these DE-CRGs in predicting HIRI progression. The GSE14951 microarray dataset and GSE171539 single-cell sequencing dataset were chosen as validation datasets. At the same time, the significance of DE-CRGs was verified using a mouse model of HIRI with cuproptosis inhibitors and inducers. Finally, a network of transcription-factor-DE-CRGs and miRNA-DE-CRGs was constructed to reveal the regulation mechanisms. And potential drugs for DE-CRGs were predicted using Drug Gene Interaction Database (DGIdb). RESULTS: Overall, 2390 DEGs and 19 DE-CRGs were identified. Through machine learning algorithms, 8 featured DE-CRGs (GNL3, ALAS1, TSC22D2, KLF5, GTF2B, DNTTIP2, SLFN11 and HNRNPU) were screened, and 2 cuproptosis-related subclusters were defined. Based on the 8 DE-CRGs obtained from the HIRI model (AUC=0.97), the nomogram model demonstrated accuracy in predicting HIRI. Eight DE-CRGs were highly expressed in HIRI samples and were negatively related to immune cell infiltration. A higher level of immune infiltration and expression of CRG group B was found in the HIRI population. Differences in cell death and immune regulation were found between the 2 groups. The diagnostic value of the 8 DE-CRGs was confirmed in the validation of two datasets. The identification of 7 DE-CRGs (SLFN11 excluded) by HIRI animal model experiments was also confirmed. Using hTFtarget, miRWalk and DGIDB database, we predicted that 17 transcription factors, 192 miRNAs and 10 drugs might interact with the DE-CRGs. CONCLUSION: This study shows that cuproptosis may occur in HIRI and is correlated with immune infiltration. Additionally, a cuproptosis-related predictive model was constructed for studying the causes of HIRI and developing targeted treatment options for HIRI.

An overview of cyclopropenone derivatives as promising bioactive molecules.

Cyclopropenone is a valuable electrophilic reagent that can react with electrophilic reagents, nucleophilic reagents, free radicals, organic metals, etc. Furthermore, cyclopropenone derivatives have shown significant biological activity in various diseases, such as triple-negative breast cancer (TNBC), melanoma, and alopecia areata (AA). The cyclopropenone analogue diphenylcyclopropenone (DPCP) has been approved for the treatment of AA. Given the potential therapeutic benefits of cyclopropenone derivatives, this review aims to systematically summarize the structures, synthesis routes, and potential pharmacological functions of cyclopropenone analogues in the hope of offering novel insights for further rational design of more drugs based on the cyclopropenone skeleton for the treatment of human diseases.

The Basic Units of Working Memory Manipulation Are Boolean Maps, Not Objects.

Determining the manipulation unit of working memory is one of the fundamental questions in understanding how working memory functions. The prevalent object-based theory in cognitive research predicts that memory manipulation is performed on the level of objects. Here we show instead that the basic units of working memory manipulation are Boolean maps, a data structure describing what can be perceived in an instant. We developed four new manipulation tasks (with data from 80 adults) and showed that manipulation times only increased when the number of Boolean maps manipulated increased. Increasing the number of orientations manipulated did not induce longer manipulation times, consistent with a key prediction of the Boolean map theory. Our results show that Boolean maps are the manipulation unit of working memory.

Healthy Lifestyle and the Likelihood of Becoming a Centenarian.

Importance: Previous studies have reported that lifestyle factors were associated with life expectancy and/or mortality, but most of them studied the middle-aged or older age groups (aged ≥60 years), and few focused on people aged 80 years or older. Objectives: To examine healthy lifestyle and the likelihood of becoming centenarians among people aged 80 years or older in China. Design, Settings, and Participants: Using data from the Chinese Longitudinal Healthy Longevity Survey, a nationally representative and one of the largest prospective cohorts targeting people aged 80 years or older established in 1998, a community-based, prospective nested case-control study was performed. Data were analyzed from December 1, 2022, to April 15, 2024. Exposures: A healthy lifestyle score for 100 (HLS-100, ranging from 0 to 6), including smoking, exercise, and dietary diversity, was constructed, with higher scores indicating potentially better health outcomes. Main Outcomes and Measures: The primary outcome was survivorship to becoming a centenarian by 2018 (the end of follow-up). Information on sociodemographic characteristics, lifestyle factors, and other covariates was collected. Results: The sample comprised 5222 individuals (61.7% women, mean [SD] age, 94.3 [3.3] years), including 1454 identified centenarians and 3768 controls (died before becoming centenarians) matched by age, sex, and year of entry. During a median follow-up of 5 (IQR, 3-7) years, 373 of 1486 individuals among the lowest HLS-100 (0-2) group and 276 of 851 individuals among the highest HLS-100 (5-6) group became centenarians. The adjusted odds ratio (AOR) comparing the highest vs the lowest HLS-100 groups was 1.61 (95% CI, 1.32-1.96; P < .001 for trend). An association was noted when we further treated centenarians with relatively healthy status as the outcome, as evaluated by self-reported chronic conditions, physical and cognitive function, and mental wellness (AOR, 1.54; 95% CI, 1.05-2.26). Similar results were observed in other sensitivity analyses. Conclusions and Relevance: In this case-control study of Chinese older adults, adhering to a healthy lifestyle appears to be important even at late ages, suggesting that constructing strategic plans to improve lifestyle behaviors among all older adults may play a key role in promoting healthy aging and longevity.

Gardening and subjective cognitive decline: a cross-sectional study and mediation analyses of 136,748 adults aged 45+ years.

BACKGROUND: Given the benefits of gardening for physical and psychological health, we explored whether gardening was associated with lower risks of subjective cognitive decline (SCD), a precursor of dementia, and SCD-related functional limitations. METHODS: Included in this cross-sectional study were 136,748 participants aged 45 + years old from the Behavioral Risk Factor Surveillance System 2019 survey, who were then categorized into three groups according to self-reported exercise status: non-exercisers, gardeners, and other exercisers. SCD was assessed via a questionnaire, and SCD-related functional limitations were referred to as having difficulties in engaging in household or social activities due to SCD. The odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the associations of gardening with SCD and SCD-related functional limitations, adjusted for age, sex, socioeconomic status, lifestyle factors, and health status. Mediation analyses were conducted to examine whether the observed association between gardening and SCD was mediated by energy expenditure (MET-hours/week), depression status, and consumption of fruits and vegetables. RESULTS: Overall, 11.1% and 5.4% of participants self-reported experiencing SCD and SCD-related functional limitations, respectively. The adjusted OR for gardeners vs. non-exercisers, was 0.72 (95% CI 0.62-0.83) for SCD and 0.57 (95% CI 0.44-0.73) for SCD-related functional limitations. The observed association between gardening and SCD was explained by higher energy expenditure (39.0%), lower likelihood of having depression (21.5%), and higher consumption of fruits and vegetables (3.4%) (P<0.05 for all). Similar patterns were observed for SCD-related functional limitations. CONCLUSION: In this nationally representative sample, gardening was associated with better cognitive status, which may be mainly attributed to better depression status and energy expenditure.

Paracoccus benzoatiresistens sp. nov., a benzoate resistance and selenite reduction bacterium isolated from wetland.

A Gram-stain-negative, aerobic, non-motile, catalase- and oxidase-positive, pale orange, rod-shaped strain EF6T, was isolated from a natural wetland reserve in Hebei province, China. The strain grew at 25-37 °C (optimum, 30 °C), pH 5-9 (optimum, pH 7), and in the presence of 1.0-4.0% (w/v) NaCl (optimum, 2%). A phylogenetic analysis based on 16S rRNA gene sequence revealed that strain EF6T belongs to the genus Paracoccus, and the closest members were Paracoccus shandongensis wg2T with 98.1% similarity, Paracoccus fontiphilus MVW-1 T (97.9%), Paracoccus everestensis S8-55 T (97.7%), Paracoccus subflavus GY0581T (97.6%), Paracoccus sediminis CMB17T (97.3%), Paracoccus caeni MJ17T (97.0%), and Paracoccus angustae E6T (97.0%). The genome size of strain EF6T was 4.88 Mb, and the DNA G + C content was 65.3%. The digital DNA-DNA hybridization, average nucleotide identity, and average amino acid identity values between strain EF6T and the reference strains were all below the threshold limit for species delineation (< 32.8%, < 88.0%, and < 86.7%, respectively). The major fatty acids (≥ 5.0%) were summed feature 8 (86.3%, C18:1 ω6c and/or C18:1 ω7c) and C18:1 (5.0%) and the only isoprenoid quinone was Q-10. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, two unidentified glycolipids, five unidentified phospholipids, and an unidentified aminolipid. Strain EF6T displays notable resistance to benzoate and selenite, with higher tolerance levels (25 g/L for benzoate and 150 mM for selenite) compared to the closely related species. Genomic analysis identified six benzoate resistance genes (acdA, pcaF, fadA, pcaC, purB, and catA) and twenty selenite resistance and reduction-related genes (iscR, ssuB, ssuD, selA, selD and so on). Additionally, EF6T possesses unique genes (catA, ssuB, and ssuC) absent in the closely related species for benzoate and selenite resistance. Its robust resistance to benzoate and selenite, coupled with its genomic makeup, make EF6T a promising candidate for the remediation of both organic and inorganic pollutants. It is worth noting that the specific resistance phenotypes described above were not reported in other novel species in Paracoccus. Based on the results of biochemical, physiological, phylogenetic, and chemotaxonomic analyses, combined with comparisons of the 16S rRNA gene sequence and the whole genome sequence, strain EF6T is considered to represent a novel species of the genus Paracoccus within the family Rhodobacteraceae, for which the name Paracoccus benzoatiresistens sp. nov. is proposed. The type strain is EF6T (= GDMCC 1.3400 T = JCM 35642 T = MCCC 1K08702T).

A deep learning-based 3D Prompt-nnUnet model for automatic segmentation in brachytherapy of postoperative endometrial carcinoma.

PURPOSE: To create and evaluate a three-dimensional (3D) Prompt-nnUnet module that utilizes the prompts-based model combined with 3D nnUnet for producing the rapid and consistent autosegmentation of high-risk clinical target volume (HR CTV) and organ at risk (OAR) in high-dose-rate brachytherapy (HDR BT) for patients with postoperative endometrial carcinoma (EC). METHODS AND MATERIALS: On two experimental batches, a total of 321 computed tomography (CT) scans were obtained for HR CTV segmentation from 321 patients with EC, and 125 CT scans for OARs segmentation from 125 patients. The numbers of training/validation/test were 257/32/32 and 87/13/25 for HR CTV and OARs respectively. A novel comparison of the deep learning neural network 3D Prompt-nnUnet and 3D nnUnet was applied for HR CTV and OARs segmentation. Three-fold cross validation and several quantitative metrics were employed, including Dice similarity coefficient (DSC), Hausdorff distance (HD), 95th percentile of Hausdorff distance (HD95%), and intersection over union (IoU). RESULTS: The Prompt-nnUnet included two forms of parameters Predict-Prompt (PP) and Label-Prompt (LP), with the LP performing most similarly to the experienced radiation oncologist and outperforming the less experienced ones. During the testing phase, the mean DSC values for the LP were 0.96 ± 0.02, 0.91 ± 0.02, and 0.83 ± 0.07 for HR CTV, rectum and urethra, respectively. The mean HD values (mm) were 2.73 ± 0.95, 8.18 ± 4.84, and 2.11 ± 0.50, respectively. The mean HD95% values (mm) were 1.66 ± 1.11, 3.07 ± 0.94, and 1.35 ± 0.55, respectively. The mean IoUs were 0.92 ± 0.04, 0.84 ± 0.03, and 0.71 ± 0.09, respectively. A delineation time < 2.35 s per structure in the new model was observed, which was available to save clinician time. CONCLUSION: The Prompt-nnUnet architecture, particularly the LP, was highly consistent with ground truth (GT) in HR CTV or OAR autosegmentation, reducing interobserver variability and shortening treatment time.

[The Efficacy and Safety of Venetoclax Combined with Azacitidine in the Treatment of Adult Patients with Acute Myeloid Leukemia Who Are Unfit for Intensive Chemotherapy].

OBJECTIVE: To observe the clinical efficacy and safety of venetoclax (VEN) combined with azacitidine (AZA) in the treatment of adult acute myeloid leukemia (AML) patients who are unfit for intensive chemotherapy. METHODS: The clinical data of 21 adult patients with unfit AML who were treated with VEN combined with AZA in the Second Hospital of Shanxi Medical University from January 2021 to May 2022 were collected, and the efficacy and safety were analyzed retrospectively. RESULTS: After one course of treatment with VEN and AZA, 16 out of 21 unfit AML patients reached complete remission (CR)/CR with incomplete hematologic recovery (CRi), 2 patients reached partial remission (PR), the overall response rate (ORR) was 85.7%. Among the 16 patients with CR/CRi, 13 achieved minimal residual disease (MRD) negativity. Among the 11 patients with adverse prognosis, 8 achieved CR/CRi. By the deadline of follow-up, the median overall suivival (OS) of the entire cohort was not reached, with 1-year OS rate of 61.7%. The main adverse events of VEN combined with AZA were myelosuppression, gastrointestinal reactions and infections. There were 13 cases of leukopenia, 7 cases of neutropenia, 7 cases of anemia, 4 cases of thrombocytopenia, and these hematologic adverse events were all grade 3-4. There were 11 cases with gastrointestinal reactions and 7 cases with infections. The above adverse events were controllable and tolerable. No tumor lysis syndrome or infection related death occurred. CONCLUSION: VEN combined with AZA can quickly achieve deep remission in adult patients with unfit AML, and it shows a good safety profile.

Retinal structure and vessel density changes in cerebral small vessel disease.

Background: Cerebral small vessel disease (CSVD) attaches people's attention in recent years. In this study, we aim to explore retinal structure and vessel density changes in CSVD patients. Methods: We collected information on retinal metrics assessed by optical coherence tomography (OCT) and OCT angiography and CSVD characters. Logistic and liner regression was used to analyze the relationship between retinal metrics and CSVD. Results: Vessel density of superficial retinal capillary plexus (SRCP), foveal density- 300 length (FD-300), radial peripapillary capillary (RPC) and thickness of retina were significantly lower in CSVD patients, the difference only existed in the thickness of retina after adjusted relevant risk factors (OR (95% CI): 0.954 (0.912, 0.997), p = 0.037). SRCP vessel density showed a significant downward trend with the increase of CSVD scores (ß: -0.087, 95%CI: -0.166, -0.008, p = 0.031). SRCP and FD-300 were significantly lower in patients with lacunar infarctions and white matter hypertensions separately [OR (95% CI): 0.857 (0.736, 0.998), p = 0.047 and OR (95% CI): 0.636 (0.434, 0.932), p = 0.020, separately]. Conclusion: SRCP, FD-300 and thickness of retina were associated with the occurrence and severity of total CSVD scores and its different radiological manifestations. Exploring CSVD by observing alterations in retinal metrics has become an optional research direction in future.

[Nutrients and Ecological Stoichiometry Characteristics of Typical Wetland Soils in the Lower Yellow River].

Carbon, nitrogen, phosphorus, and potassium in the soil are the necessary nutrient elements for plant growth, and their contents and ecological stoichiometry can reflect the status of soil quality and nutrient limitation. The Huayuankou Yellow River Floating Bridge Wetland in the lower Yellow River was selected as the research object. The methods of ANOVA, redundancy analysis, and linear regression fitting were used to study the contents of organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), total potassium (TK), alkaline nitrogen (AN), available phosphorus (AP), available potassium (AK), and their ecological stoichiometric ratios as well as the limiting elements of soil nutrients, and the key physicochemical properties that affect soil nutrients and their ecological stoichiometry in the wetland were revealed. The results showed that the mean values of ω(SOC), ω(TN), ω(TP), ω(TK), ω(AN), ω(AP), and ω(AK) in wetland soil were 5.46 g·kg-1, 0.60 g·kg-1, 0.28 g·kg-1, 17.06 g·kg-1, 13.75 mg·kg-1, 6.54 mg·kg-1, and 158.56 mg·kg-1, respectively, which showed an increasing trend from the river bank to the shoaly land and were generally higher at the high vegetation coverage areas than at the low vegetation coverage areas. There were significant correlations among SOC, TN, TP, and TK. Soil C/P, C/K, N/P, and N/K showed a consistent trend with soil nutrients, whereas C/N showed the opposite. The coefficients of variation of SOC, TN, AN, N/P, and N/K in the soil exceeded 50.00%, with significant spatial differences. The average value of C/N in wetland soil was 11.882, which was close to the average level of soils in China, whereas the average values of C/P and N/P were 49.119 and 4.516, respectively, both of which were lower than the average level of soils in China, and the N/P of soil was far less than 14, which indicated that N was limited in the soil. The proportion of clay and electrical conductivity combined to explain 61.4% and 43.9% of the variation in the soil nutrients and their ecological stoichiometry, respectively, which were the dominant soil physicochemical properties affecting the soil nutrients and their ecological stoichiometry of Huayuankou Yellow River Floating Bridge Wetland. The research results are helpful to improve our knowledge of nutrients and their influencing factors in the wetland soil of the lower Yellow River and provide an important scientific basis for the ecological restoration and management of the wetland in the lower Yellow River.

Processable Pickering emulsion for composite cryogel with cellulose nanofibrils and nanochitin.

Cryogels that are constructed with cellulose nanofibrils (CNF) are important as green materials for a wide range of applications. However, their utilization is limited by inherent hydrophilicity and insufficient mechanical properties. Herein, a processable CNF/nanochitin (NCh)-stabilized Pickering emulsion that contains polylactide (PLA) in the oil phase is developed to directly produce ternary composite cryogels via freeze-drying. The complexation of CNF with NCh promotes CNF adsorption at the surface of PLA droplets, resulting in formation of uniform Pickering PLA droplets. The CNF/NCh complex-stabilized PLA droplets are easy to be translated to the internal structure of the cryogels, exhibiting lightweight nature and possessing highly porous structure. The interconnected network and lamellar structure formed by the CNF/NCh complexes, associating with inclusion of PLA particles, improve the cryogel structure integrity upon post-processing and endow hydrophilic cryogel with water resistance. This study offers a straightforward and eco-friendly Pickering emulsion template on fabrication of the CNF-based composite cryogel with controllable microstructure and mechanical performance, broadening construction of nanocellulose-based composites.