A patient-based murine model recapitulates human STAT3 gain-of-function syndrome.

STAT3 gain-of-function (GOF) variants results in a heterogeneous clinical syndrome characterized by early onset immunodeficiency, multi-organ autoimmunity, and lymphoproliferation. While 191 documented cases with STAT3 GOF variants have been reported, the impact of individual variants on immune regulation and the broad clinical spectrum remains unclear. We developed a Stat3p.L387R mouse model, mirroring a variant identified in a family exhibiting common STAT3 GOF symptoms, and rare phenotypes including pulmonary hypertension and retinal vasculitis. In vitro experiments revealed increased STAT3 phosphorylation, nuclear migration, and DNA binding of the variant. Our Stat3p.L387R model displayed similar traits from previous Stat3GOF strains, such as splenomegaly and lymphadenopathy. Notably, Stat3p.L387R/+ mice exhibited heightened embryonic lethality compared to prior Stat3GOF/+ models and ocular abnormalities were observed. This research underscores the variant-specific pathology in Stat3p.L387R/+ mice, highlighting the ability to recapitulate human STAT3 GOF syndrome in patient-specific transgenic murine models. Additionally, such models could facilitate tailored treatment development.

Spiritual needs of women with breast cancer: A structural equation model.

PURPOSE: The purpose of this study was to develop a structural equation model (SEM) to explore the factors influencing the spiritual needs of breast cancer patients. METHODS: A cross-sectional study was conducted in the breast surgery department of a tertiary hospital in China from September 2020 to December 2020; convenience sampling and questionnaires were used to facilitate sampling and data collection. A total of 220 female breast cancer patients were included in the study. The data were analysed using multiple linear regression and structural equation modelling. RESULTS: Compared with patients with other diseases, patients with breast cancer have greater spiritual needs (76.16 ± 13.19). Multivariate analysis revealed that religious beliefs, education level, social support, and resilience are important factors affecting the mental health of women with cancer (p < 0.05). The structural equation model fit well (RMSEA = 0.056, χ2p = 0.002). Social support directly affected spiritual needs (ß = 0.607, p < 0.001) and indirectly affected spiritual needs through resilience (ß = 0.353, p < 0.001). Resilience directly affected spiritual needs (ß = 0.386, p < 0.05). Education level indirectly affected spiritual needs through social support (ß = 0.307, p < 0.001). CONCLUSION: This study provides a theoretical basis for intervention measures to improve the spiritual needs of female breast cancer patients. Paying more attention to social support and resilience may help solve the problem of meeting the high spiritual needs of breast cancer patients. Further research is needed to develop interventions.

Relationships Between Chemotherapy-Related Cognitive Impairment, Self-Care Ability, and Quality of Life in Breast Cancer Survivors: A Cross-Sectional Study.

OBJECTIVES: It is not clear how chemotherapy-related cognitive impairment and self-care ability affect the quality of life of women with breast cancer. The purpose of this study was to explore the relationships between chemotherapy-related cognitive impairment, self-care ability, and quality of life in breast cancer patients, and test whether self-care ability plays a mediating role in the association between cognitive impairment and quality of life. METHODS: This study was a cross-sectional study, conducted in China in 2022. Self-reported scales were used to assess cognitive function, self-care ability, and quality of life. Data were analyzed using descriptive statistics, spearman correlation analysis and hierarchical multiple regression analyses, the SPSS Process program was used to explore the mediating effect of self-care ability. RESULTS: A total of 218 participants were investigated, and approximately 79.3% of patients experienced mild chemotherapy-related cognitive impairment, the mean quality of life score was 59.96 ± 14.15, and the mean self-care ability score was 107.4 ± 24.09. Significant correlations among cognitive impairment, self-care ability, and quality of life were observed (P < .05). Additionally, self-care ability played a partial mediating role between cognitive impairment and quality of life (P < .05), accounting for 24.3% and 22.3%, respectively. CONCLUSIONS: Chemotherapy-related cognitive impairment and self-care ability are factors affecting the quality of life of breast cancer survivors. Self-care ability mediates the relationship between cognitive impairment and quality of life. Enhancing patients' self-care ability can improve the quality of life of patients with cognitive impairment. IMPLICATIONS FOR NURSING PRACTICE: In the future, oncology nurses should not only pay attention to the severity of cognitive impairment, but also assess the level of patients' self-care ability, provide relevant medical and healthcare guidance, train self-management behavior and strengthen self-care ability by integrating multidisciplinary forces to improve the quality of life of breast cancer patients effectively.

Berberine ameliorates chronic intermittent hypoxia-induced cardiac remodelling by preserving mitochondrial function, role of SIRT6 signalling.

Chronic intermittent hypoxia (CIH) is associated with an increased risk of cardiovascular diseases. Previously, we have shown that berberine (BBR) is a potential cardioprotective agent. However, its effect and mechanism on CIH-induced cardiomyopathy remain uncovered. This study was designed to determine the effects of BBR against CIH-induced cardiac damage and to explore the molecular mechanisms. Mice were exposed to 5 weeks of CIH with or without the treatment of BBR and adeno-associated virus 9 (AAV9) carrying SIRT6 or SIRT6-specific short hairpin RNA. The effect of BBR was evaluated by echocardiography, histological analysis and western blot analysis. CIH caused the inactivation of myocardial SIRT6 and AMPK-FOXO3a signalling. BBR dose-dependently ameliorated cardiac injury in CIH-induced mice, as evidenced by increased cardiac function and decreased fibrosis. Notably, SIRT6 overexpression mimicked these beneficial effects, whereas infection with recombinant AAV9 carrying SIRT6-specific short hairpin RNA abrogated them. Mechanistically, BBR reduced oxidative stress damage and preserved mitochondrial function via activating SIRT6-AMPK-FOXO3a signalling, enhancing mitochondrial biogenesis as well as PINK1-Parkin-mediated mitophagy. Taken together, these data demonstrate that SIRT6 activation protects against the pathogenesis of CIH-induced cardiac dysfunction. BBR attenuates CIH-induced myocardial injury by improving mitochondrial biogenesis and PINK1-Parkin-dependent mitophagy via the SIRT6-AMPK-FOXO3a signalling pathway.

Effectiveness of Virtual Reality-Based Interventions for Upper Limb Rehabilitation in Breast Cancer Patients: Systematic Review and Meta-Analysis.

Purpose: To investigate the effectiveness of virtual reality (VR)-based interventions for functional rehabilitation of the upper limb in breast cancer patients through a systematic review and meta-analysis. Methods: The PubMed, Cochrane, Web of Science, CINAHL, Scopus, CNKI, Wanfang, and VIP databases were systematically searched for relevant literature published from the establishment of the database to June 2023. Differences in the effectiveness of VR-based interventions and other intervention therapies were compared using random effects model meta-analysis and standard deviation (SMD). Results: Seven eligible articles were identified and included in the meta-analysis. The combined analysis found that VR-based interventions had a positive impact on patients' upper limb mobility in terms of flexion (SMD = 1.33, 95% confidence interval; CI [0.48-2.19], P = 0.002), abduction (SMD = 1.22, 95% CI [0.58-1.86], P = 0.0002), and external rotation (SMD = 0.94, 95% CI [0.48-1.40], P < 0.0001). In addition, VR-based interventions could significantly improve the postoperative pain of patients with breast cancer. However, in grip strength (SMD = 0.43, 95% CI [-3.05 to 3.92], P = 0.81), shoulder muscle strength in flexion strength (SMD = 0.05, 95% CI [-2.07 to 2.18], P = 0.96), abduction strength (SMD = -0.10, 95% CI [-1.32 to 1.12], P = 0.88), external rotation strength (SMD = 0.46, 95% CI [-1.96 to 2.88], P = 0.71), and lymphedema, VR was as effective as other intervention treatments. A subgroup analysis showed that patients younger than 55 years had more benefit with VR-based rehabilitation than with other interventions and showed improvements with the intervention within 2 weeks. The intervention effect of using auxiliary equipment such as robotic arms is better than VR exercise based solely on games. Conclusion: The results of meta-analysis show that the intervention measures based on VR have positive effects on the improvement of upper limb mobility and pain relief in breast cancer patients. However, considering the low quality of evidence and small sample size, more clinical studies should be conducted to improve the credibility of the results.

Risk factors for methotrexate resistance in low-risk gestational trophoblastic neoplasia patients (FIGO score 0-4).

The challenge of methotrexate (MTX) resistance among low-risk gestational trophoblastic neoplasia (GTN) patients has always been prominent. Despite the International Federation of Gynaecology and Obstetrics (FIGO) score of 0-4 patients comprising the majority of low-risk GTN patients, a comprehensive exploration of the prevalence and risk factors associated with MTX resistance has been limited. Therefore, we aimed to identify associated risk factors in GTN patients with a FIGO score of 0-4. Between January 2005 and December 2020, 310 low-risk GTN patients received primary MTX chemotherapy in two hospitals, with 265 having a FIGO score of 0-4. In the FIGO 0-4 subgroup, 94 (35.5%) were resistant to MTX chemotherapy, and 34 (12.8%) needed multi-agent chemotherapy. Clinicopathologic diagnosis of postmolar choriocarcinoma (OR = 17.18, 95% CI: 4.64-63.70, P < 0.001) and higher pretreatment human chorionic gonadotropin concentration on a logarithmic scale (log-hCG concentration) (OR = 18.11, 95% CI: 3.72-88.15, P < 0.001) were identified as independent risk factors associated with MTX resistance according to multivariable logistic regression. The decision tree model and regression model were developed to predict the risk of MTX resistance in GTN patients with a FIGO score of 0-4. Evaluation of model discrimination, calibration and net benefit revealed the superiority of the decision tree model, which comprised clinicopathologic diagnosis and pretreatment hCG concentration. The patients in the high- and medium-risk groups of the decision tree model had a higher probability of MTX resistance. This study represents the investigation into MTX resistance in GTN patients with a FIGO score of 0-4 and disclosed a remission rate of approximately 65% with MTX chemotherapy. Higher pretreatment hCG concentration and clinicopathologic diagnosis of postmolar choriocarcinoma were independent risk factors associated with resistance to MTX chemotherapy. The decision tree model demonstrated enhanced predictive capabilities regarding the risk of MTX resistance and can serve as a valuable tool to guide the clinical treatment decisions for GTN patients with a FIGO score of 0-4.

Dexrazoxane inhibits the growth of esophageal squamous cell carcinoma by attenuating SDCBP/MDA-9/syntenin-mediated EGFR-PI3K-Akt pathway activation.

Syndecan-binding protein (SDCBP) was reported to stimulate the advancement of esophageal squamous cell carcinoma (ESCC) and could potentially be a target for ESCC treatment. There is a growing corpus of research on the anti-tumor effects of iron chelators; however, very few studies have addressed the involvement of dexrazoxane in cancer. In this study, structure-based virtual screening was employed to select drugs targeting SDCBP from the Food and Drug Administration (FDA)-approved drug databases. The sepharose 4B beads pull-down assay revealed that dexrazoxane targeted SDCBP by interacting with its PDZ1 domain. Additionally, dexrazoxane inhibited ESCC cell proliferation and anchorage-independent colony formation via SDCBP. ESCC cell apoptosis and G2 phase arrest were induced as measured by the flow cytometry assay. Subsequent research revealed that dexrazoxane attenuated the binding ability between SDCBP and EGFR in an immunoprecipitation assay. Furthermore, dexrazoxane impaired EGFR membrane localization and inactivated the EGFR/PI3K/Akt pathway. In vivo, xenograft mouse experiments indicated that dexrazoxane suppressed ESCC tumor growth. These data indicate that dexrazoxane might be established as a potential anti-cancer agent in ESCC by targeting SDCBP.

Risk assessment of antimony-arsenic contaminated soil remediated using zero-valent iron at different pH values combined with freeze-thaw cycles.

Soil in mining wastelands is seriously polluted with heavy metals. Zero-valent iron (ZVI) is widely used for remediation of heavy metal-polluted soil because of its excellent adsorption properties; however, the remediation process is affected by complex environmental conditions, such as acid rain and freeze-thaw cycles. In this study, the effects of different pH values and freeze-thaw cycles on remediation of antimony (Sb)- and arsenic (As)-contaminated soil by ZVI were investigated in laboratory simulation experiments. The stability and potential human health risks associated with the remediated soil were evaluated. The results showed that ZVI has a significant stabilizing effect on Sb and As in both acidic and alkaline soils contaminated with dual levels of Sb and As, and the freeze-thaw process in different pH value solution systems further enhances the ability of ZVI to stabilize Sb and As, especially in acidic soils. However, it should be noted that apart from the pH=1.0 solution environment, ZVI's ability to stabilize As is attenuated under other circumstances, potentially leading to leaching of its unstable form and thereby increasing contamination risks. This indicates that the F1 (2% ZVI+pH=1 solution+freeze-thaw cycle) processing exhibits superior effectiveness. After F1 treatment, the bioavailability of Sb and As in both soils also significantly decreased during the gastric and intestinal stages (about 60.00%), the non-carcinogenic and carcinogenic risks of Sb and As in alkaline soils are eliminated for children and adults, with a decrease ranging from 60.00% to 70.00%, while in acidic soil, the non-carcinogenic and carcinogenic risks of As to adults and children is acceptable, but Sb still poses non-carcinogenic risks to children, despite reductions of about 65.00%. These findings demonstrate that soil pH is a crucial factor influencing the efficacy of ZVI in stabilizing Sb and As contaminants during freeze-thaw cycles. This provides a solid theoretical foundation for utilizing ZVI in the remediation of Sb- and As-contaminated soils, emphasizing the significance of considering both pH levels and freeze-thaw conditions to ensure effective and safe treatment.

Mechanistic complement of autosomal dominant polycystic kidney disease: the role of aquaporins.

Autosomal dominant polycystic kidney disease is a genetic kidney disease caused by mutations in the genes PKD1 or PKD2. Its course is characterized by the formation of progressively enlarged cysts in the renal tubules bilaterally. The basic genetic explanation for autosomal dominant polycystic kidney disease is the double-hit theory, and many of its mechanistic issues can be explained by the cilia doctrine. However, the precise molecular mechanisms underpinning this condition's occurrence are still not completely understood. Experimental evidence suggests that aquaporins, a class of transmembrane channel proteins, including aquaporin-1, aquaporin-2, aquaporin-3, and aquaporin-11, are involved in the mechanism of autosomal dominant polycystic kidney disease. Aquaporins are either a potential new target for the treatment of autosomal dominant polycystic kidney disease, and further study into the physiopathological role of aquaporins in autosomal dominant polycystic kidney disease will assist to clarify the disease's pathophysiology and increase the pool of potential treatment options. We primarily cover pertinent findings on aquaporins in autosomal dominant polycystic kidney disease in this review.

Effect of superior laryngeal nerve block in alleviating sore throat after application of i-gel supraglottic airway: a randomized controlled trial.

BACKGROUND: Postoperative sore throat (POST) is a common complaint after supraglottic airway device (SAD) application. Internal branch of the superior laryngeal nerve (iSLN) block has the potential to alleviate POST. The aim of this trial was to explore the effect of iSLN block in alleviating sore throat, as well as to identify the potential risk factors for POST after SAD insertion. METHODS: One hundred thirty-four patients scheduled for elective gynecological surgery were randomized to either group T: tetracaine syrup (1%) for local lubrication on i-gel supraglottic device (n = 67) or group B: i-gel insertion with water based lubricant on it and followed by bilateral iSLN block (ropivacaine, 0.375%, 2 ml for each side) (n = 67). Under ultrasound guidance, iSLN was exposed below thyrohyoid membrane. The primary outcome was the intensity of sore throat at 6 h after surgery. In addition, POST score at 0.5 h and 24 h, the severity of postoperative swallowing discomfort, acoustic analysis and complications were measured. RESULTS: Compared with tetracaine syrup for local lubrication, iSLN block resulted in a reduced intensity of POST at 0.5 h (P = 0.044, OR = 1.99, 95%CI 1.02 to 3.88) and 6 h (P < 0.001, OR = 5.07, 95%CI 2.53 to 10.14) after surgery, as well as less severity of swallowing discomfort (P < 0.001, OR = 2.21, 95%CI 1.63 to 2.99) and cough (P = 0.039, OR = 1.97, 95%CI 1.04 to 3.73). The patients after iSLN block presented lower jitter and shimmer value in acoustic analysis at 6 h after surgery (P < 0.001). CONCLUSIONS: iSLN block was effective in alleviating POST, improving voice function, as well as reducing postoperative swallowing discomfort and coughing. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2000037974) on 8th Sept 2020.

Transversus abdominis plane block versus local anesthetic infiltration for anesthetic effect in peritoneal dialysis catheter insertion: A systematic review and meta-analysis.

BACKGROUND: The transversus abdominis plane (TAP) block is commonly used in surgical practice for postoperative analgesia in abdominal surgery. However, numerous studies have demonstrated that TAP block is also suitable for intraoperative anesthesia of peritoneal dialysis catheter (PDC) insertion, although its efficacy and safety are still controversial. Local anesthetic infiltration (LAI) is currently the most general anesthesia strategy for PDC insertion. Consequently, we conducted this systematic review and meta-analysis to identify which anesthesia strategy is better between TAP block and LAI. METHODS: A systematic and comprehensive search was conducted on 5 databases, retrieving published and registered randomized controlled trials as of March 10, 2022, comparing the anesthesia effects of TAP block and LAI. The primary outcomes are the visual analogue scale (VAS) pain score of patients at various time points in the surgery. The secondary outcomes are the VAS pain score at rest at 2 and 24 hours postoperatively, intraoperative rescue anesthesia, general anesthesia switching rate, and PD-related complications. RESULTS: There were 9 trials with 432 patients identified. TAP block was more effective than LAI at reducing intraoperative and postoperative VAS pain scores in patients. Compared to LAI, TAP block significantly reduces the dosage of anesthetics used to rescue anesthesia during surgery, the general anesthesia switching rate, and the incidence of postoperative PD-related complications in patients. CONCLUSIONS: Our systematic review and meta-analysis proved that TAP block could be used as the primary anesthetic technique for PDC insertion, with superior anesthetic effects to LAI.

Integrated Cascade Nanozymes with Antisenescence Activities for Atherosclerosis Therapy.

Senescent cells are the critical drivers of atherosclerosis formation and maturation. Mitigating senescent cells holds promise for the treatment of atherosclerosis. In an atherosclerotic plaque microenvironment, senescent cells interact with reactive oxygen species (ROS), promoting the disease development. Here, we hypothesize that a cascade nanozyme with antisenescence and antioxidant activities can serve as an effective therapeutic for atherosclerosis. An integrated cascade nanozyme with superoxide dismutase- and glutathione peroxidase-like activities, named MSe1 , is developed in this work. The obtained cascade nanozyme can attenuate human umbilical vein endothelial cell (HUVEC) senescence by protecting DNA from damage. It significantly weakens inflammation in macrophages and HUVECs by eliminating overproduced intracellular ROS. Additionally, the MSe1 nanozyme effectively inhibits foam cell formation in macrophages and HUVECs by decreasing the internalization of oxidized low-density lipoprotein. After intravenous administration, the MSe1 nanozyme significantly inhibits the formation of atherosclerosis in apolipoprotein E-deficient (ApoE-/- ) mice by reducing oxidative stress and inflammation and then decreases the infiltration of inflammatory cells and senescent cells in atherosclerotic plaques. This study not only provides a cascade nanozyme but also suggests that the combination of antisenescence and antioxidative stress holds considerable promise for treating atherosclerosis.

Paeonia lactiflora Pall. Polysaccharide alleviates depression in CUMS mice by inhibiting the NLRP3/ASC/Caspase-1 signaling pathway and affecting the composition of their intestinal flora.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia lactiflora Pall. (PL) has been commonly used to de-stressing the liver and relieve depression in traditional Chinese medicine for over a thousand years. Recently, it has been widely used in studies on anti-depressant, anti-inflammatory and regulation of intestinal flora. However, the polysaccharide component has received less attention than the saponin component of PL. AIM OF THE STUDY: This study aimed to elucidate the effects of Paeonia lactiflora polysaccharide (PLP) on depressive behavior in mice in a chronic unpredictable mild stress (CUMS) model and its possible action mechanisms. MATERIALS AND METHODS: A model of chronic depression induced by the CUMS approach. Behavioral experiments were used to assess the success of the CUMS model and the therapeutic impact of PLP. Then the extent of damage to the colonic mucosa was assessed by H&E staining; the extent of neuronal damage was assessed by Nissler staining. Inflammatory factor expression was assessed at different sites in the mouse by enzyme-linked immunoassay (Elisa). The alterations of faecal microflora were detected by 16S rRNA gene sequencing. In the colonic tissues, NLRP3, ASC and Caspase-1 mRNA and protein levels detected by quantitative real-time PCR (qRT-PCR) and Western blot(WB). RUSULTS: PLP can improve depressive behavior in CUMS mice, and colonic mucosal and neuronal damage. Elisa assay showed that PLP could reduce interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) levels, and increase 5-Hydroxytryptamine(5-HT) levels in CUMS mice. 16S sequencing analysis showed that PLP could regulate the intestinal flora of CUMS mice and increase their species richness. In addition, PLP significantly inhibited NLRP3/ASC/Caspase-1 signalling pathways activation in the colonic tissues of CUMS mice. CONCLUSIONS: PLP modulates depression-related intestinal ecological dysregulation, increases species richness, and inhibits inflammatory factors levels and NLRP3 inflammasome activation to reduce colonic mucosal and neurons damage, thereby improving depression-like behavior and neurotransmitter release in CUMS mice.

Bioinformatics and experimental validation of an AURKA/TPX2 axis as a potential target in esophageal squamous cell carcinoma.

Aurora kinase A (AURKA), a serine/threonine kinase that regulates mitotic processes, has garnered significant interest given its association with the development of several types of cancer. In the present study, it was shown that AURKA expression was significantly upregulated in esophageal squamous cell carcinoma (ESCC) and could serve as a diagnostic and prognostic indicator based on data obtained from The Cancer Genome Atlas (TCGA) and immunohistochemical analysis. In addition, AURKA was functionally associated with ESCC cell proliferation and colony formation in vitro and knockdown of AURKA inhibited ESCC tumor growth in vivo. Both bioinformatics analysis and pull­down assays demonstrated that TPX2 interacted with AURKA, and their expression was correlated. AURKA cooperated with TPX2 to regulate ESCC progression via the PI3K/Akt pathway. Furthermore, AURKA or TPX2 expression levels were negatively associated with the infiltration of cytotoxic cells, CD8+ T cells and mast cells, but positively associated with Th2 cells. The present study provided a relatively comprehensive understanding of the oncogenic roles of AURKA in ESCC based on data obtained from TCGA combined with experimental analysis.

Experience of using a virtual reality rehabilitation management platform for breast cancer patients: a qualitative study.

PURPOSES: Postoperative rehabilitation of upper limb function is crucial for breast cancer. Therefore, we developed a rehabilitation management platform using virtual reality to improve rehabilitation compliance and effect. The purpose of this research was to understand the user usability experience of breast cancer patients about the postoperative rehabilitation management of upper limb function using virtual reality. METHODS: A qualitative descriptive research was designed. We used a maximum difference purpose sampling method. According to the inclusion and exclusion criteria, a 3-armor hospital in Changchun was selected for the recruitment. A one-on-one semi-structured interviews were conducted with patients after breast cancer operation. The Colaizzi seven-step analysis method was used to classify data under summarized themes. RESULTS: Twenty patients participated in this semi-structured interview. User experience could be summarized into four themes as follows: 1) experience and feeling after using the virtual reality rehabilitation management platform; 2) factors influencing the use of the virtual reality rehabilitation management platform; 3) willingness to recommend the virtual reality rehabilitation management platform to peers; and 4) suggestions to improve the virtual reality rehabilitation management platform. CONCLUSIONS: Breast cancer patients who used the rehabilitation management platform had a good experience, and their recognition and satisfaction were high. The use of the platform is influenced by many factors, and most patients are willing to recommend this platform to their peers. Future studies should be conducted according to patients' feedback and suggestions on how to further optimize and improve the platform.

Pharmacodynamic structure of deer antler base protein and its mammary gland hyperplasia inhibition mechanism by mediating Raf-1/MEK/ERK signaling pathway activation.

Mammary gland hyperplasia (MGH) is a common mammary disease whose main pathogenesis is the disruption of estradiol (E2) and progesterone (P) secretion, thereby causing overproliferation of mammary epithelial cells and mammary gland tissue hyperplasia. Deer antler base is a traditional Chinese medicine that has been used for many years to treat MGH. However, its pharmacological mechanism and pharmacodynamic material basis are unclear. In this study, we for the first time used the graded salting method to classify deer antler base protein (CNCP) as CNCP-A, CNCP-B, and CNCP-C and explored the pharmacological mechanism of the anti-MGH properties of CNCP. We found that CNCP could regulate the hormonal levels of E2, P, and follicle stimulating hormone (FSH) and improve the histopathological condition. The potential mechanism might be related to the recombinant C-Raf proto oncogene serine/threonine protein kinase/mitogen-activated protein/extracellular regulated protein kinase (Raf-1/MEK/ERK) signaling pathway. By upregulating the protein expression of the follicle stimulating hormone receptor (FSHR), cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) inhibited the activation of the downstream Raf-1/MEK/ERK signaling pathway, which in turn inhibited the proliferation of mammary epithelial cells. We analyzed the physicochemical properties of CNCP-A, CNCP-B, and CNCP-C and obtained CNCP-C-I by column chromatographic purification of the best pharmacophore protein CNCP. Using high-performance liquid gel filtration chromatography (HPGFC), we determined the molecular weight of CNCP-C-I and identified it by high-performance liquid tandem mass spectrometry (LC-MS/MS) to obtain the first match for a high confidence protein KRT1. This study provides a theoretical basis for the development of effective traditional Chinese medicines with low toxicity levels for the prevention and treatment of mammary gland diseases.

Cadmium-resistant phosphate-solubilizing bacteria immobilized on phosphoric acid-ball milling modified biochar enhances soil cadmium passivation and phosphorus bioavailability.

Cadmium (Cd) can accumulate in agriculture soil from the regular application of phosphorus (P) fertilizer. Microbiological method is considered as a potentially effective strategy that can not only remediate the Cd-contaminated soil but also provide the phosphorus needed for crop growth. However, the toxicity of Cd may affect the activity of microorganisms. To solve this problem, Klebsiella variicola with excellent phosphate solubilization ability (155.30 mg L-1 at 48 h) and Cd adsorption rate (90.84 % with 10 mg L-1 Cd initial concentration) was firstly isolated and identified in this study. Then, a phosphoric acid and ball milling co-modified biochar (PBC) was selected as the carrier to promote the activities of K. variicola under Cd pollution. Surface characterization revealed that the promotion of K. variicola by PBC was mainly attributed to the large specific surface area and diverse functional groups. Compared to contaminated soil, microbial PBC (MPBC) significantly increased the pakchoi biomass and phosphorus (P) content, while the Cd content in leave and root of pakchoi (Brassica chinensis L.) decreased by 25.90-43.46 % (P < 0.05). The combined application also favored the transformation of the resistant P fractions to bioavailable P, and facilitated the immobilization of 20.12 % exchangeable Cd to reducible, oxidizable, and residual Cd in the treated soil. High-throughput sequencing revealed that the response of the soil microbial community to the MPBC was more beneficial than K. variicola or PBC alone. Therefore, the application of MPBC has the potential to act as an efficient, stable, and environmentally friendly sustainable product for Cd remediation and enhanced P bioavailability in agricultural production.

Predictors of Postoperative Nausea and Vomiting After Same-day Surgery: A Retrospective Study.

PURPOSE: Postoperative nausea and vomiting (PONV) are main issues after same-day surgery. This study aimed to retrospectively evaluate the electronic medical records of patients who underwent same-day operations under general anesthesia to identify the potential risk factors for PONV. METHODS: Records of 7759 adult patients who received general anesthesia with remifentanil were reviewed. The patients were assessed for the incidence and severity of PONV. Multiple logistic regression was used to identify risk factors for PONV. A nomogram was established to predict PONV after same-day operations. FINDINGS: Of 7759 patients, 2317 (29.9%) experienced PONV. In multiple logistic regression analysis, female sex, nonsmoker status, history of motion sickness or nausea, high body mass index (BMI), long surgical duration, laparoscopic procedure, and preoperative analgesic intake within 30 days were independent risk factors for PONV. No correlation was found between the severity of PONV and remifentanil exposure (odds ratio = 1.018; 95% CI, 0.861-1.204; P = 0.834) or remifentanil dose (odds ratio = 1.294; 95% CI, 0.760-2.205; P = 0.343). For the nomogram, which involved sex, laparoscopic procedure, BMI, history of nausea or motion sickness, and analgesic intake within 30 days, the receiver operating characteristic analysis revealed that the AUC values in the training and validation cohorts were 0.81 and 0.83, respectively. IMPLICATIONS: Predictors for PONV in same-day surgery include female sex, nonsmoker, history of motion sickness or nausea, high BMI, surgical duration >1 hour, laparoscopic procedure, and preoperative analgesic intake within 30 days. A new predictive model is feasible for predicting the incidence of PONV based on the preoperative and intraoperative predictors.

Inhibition of ferroptosis by icariin treatment attenuates excessive ethanol consumption-induced atrial remodeling and susceptibility to atrial fibrillation, role of SIRT1.

Ferroptosis contributes to the pathogenesis of atrial fibrillation (AF), although the mechanisms are still largely uncovered. The current study was designed to explore the pharmacological effects of icariin against ethanol-induced atrial remodeling, if any, and the mechanisms involved with a focus on SIRT1 signaling. Excessive ethanol-treated animals were administered with Ferrostatin-1, Erastin or icariin to evaluate the potential effects of icariin or ferroptosis. Then, the underling mechanisms was further explored in the in vitro experiments using HL-1 atrial myocytes. Excessive ethanol administration caused significant atrial damage as evidenced by increased susceptibility to AF, altered atrial conduction pattern, atrial enlargement, and enhanced fibrotic markers. These detrimental effects were reversed by Ferrostatin-1 or icariin treatment, while Erastin co-administration markedly abolished the beneficial actions conferred by icariin. Mechanistically, ethanol-treated atria exhibited markedly up-regulated pro-ferroptotic protein (PTGS2, ACSL4, P53) and suppressed anti-ferroptotic molecules (GPX4, FTH1). Icariin treatment inhibited ethanol-induced atrial ferroptosis by reducing atrial mitochondrial damage, ROS accumulation and iron overload. Interestingly, the in vivo and in vitro data showed that icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to AF. Icariin protects against atrial damage by inhibiting ferroptosis via SIRT1 signaling. Its role as a prophylactic/therapeutic drug deserves further clinical study.

Soil potentially toxic element pollution at different urbanization intensities: Quantitative source apportionment and source-oriented health risk assessment.

Potentially toxic element (PTE) pollution of urban soils has become the focus of social concern, but the differences of the sources, pollution levels and source-oriented human health risks (HHR) of PTE in urban soils among different urban intensity areas is rarely known. This study explored a comprehensive scheme that combined positive matrix factorization model and source-oriented assessment to quantitatively assess the priority pollution sources and HHR in urban soils from areas with different urbanization intensities. All the average values for PTE concentrations, except for Cr, were higher than their corresponding background values. The contributions made by the four sources (atmospheric deposition, agricultural activities, traffic activities, and natural sources) were relatively similar (22.29-29.89%) in the low urbanization intensity (LUI) area, whereas traffic activities and atmospheric deposition made the greatest contributions in the medium urbanization intensity (MUI) (29.12%) and the high urbanization intensity (HUI) (38.97%) areas, respectively. The geo-accumulation index results revealed that Cd was the most polluting element and the HUI area had the highest pollution levels. The content-oriented assessment of HHR demonstrated that the non-carcinogenic risks were acceptable, but the carcinogenic risks were unacceptable. According to the source-oriented HHR assessment, among the anthropogenic activities, atmospheric deposition contributed the most to carcinogenic risk of children in all areas, and atmospheric deposition, traffic activities and agricultural activities contributed the most to the carcinogenic risk of adults in HUI, MUI and LUI, respectively. This suggest that control measures need to be tailored to the appropriate urbanization intensity to effectively curb PTE pollution caused by anthropogenic activities.