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To overcome the problem of Cr2O3 and Al2O3 inclusions in CuCr50 alloy prepared by aluminothermic reduction method, in this paper, a novel methodology for strengthening metal-slag separation through in situ slagging is proposed. CuCr50 alloys were prepared by metallothermic reduction using Al and Al-Mg as reducing agents, and the physical properties of the slag, such as viscosity, density, and surface tension, were adjusted by controlling the proportion of CaO in the slagging agent in the raw material to achieve good separation of the slag-metal. The results show that with the ratio of CaO increased, CaO and MgO were coupled to make slag, which combined with Cr2O3 and Al2O3 to form CaCr2O4, MgCr2O4, and CaAl4O7 in the slag, thus reducing the content of impurities in the alloy. When RCaO/(CaO + Al2O3 + MgO) = 20%, the Cr content ranged from 46.61% to 47.09%, the inclusions accounted for 1.60%, the Cr particle size was refined to 20 µm, the number of Cr spherical crystals accounted for 9.88%, the conductivity reached 14.96 MS/m, and the hardness reached 100.23 HB. After heat treatment, the Cr phase was refined in the alloy, the conductivity increased from 14.96 MS/m to 18.27 MS/m, and the hardness increased from 100.23 HB to 103.1 HB. This method is expected to provide an effective method for the preparation of CuCr50 contact materials.
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Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , HMGA1a Protein , MTOR Inhibitors , Proto-Oncogene Protein c-ets-1 , Tacrolimus Binding Protein 1A , Animals , Humans , Mice , Cell Line, Tumor , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/genetics , Esophageal Squamous Cell Carcinoma/metabolism , Esophageal Squamous Cell Carcinoma/drug therapy , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/pathology , HMGA1a Protein/metabolism , HMGA1a Protein/genetics , Mice, Nude , MTOR Inhibitors/pharmacology , MTOR Inhibitors/therapeutic use , Proto-Oncogene Protein c-ets-1/metabolism , Proto-Oncogene Protein c-ets-1/genetics , Signal Transduction/drug effects , Sirolimus/pharmacology , Sirolimus/therapeutic use , Tacrolimus Binding Protein 1A/metabolism , Tacrolimus Binding Protein 1A/genetics , TOR Serine-Threonine Kinases/metabolismABSTRACT
BACKGROUND: O-GlcNAcylation modification affects multiple physiological and pathophysiolocal functions of cells. Altered O-GlcNAcylation was reported to participate in antivirus response. Stimulator of interferon genes (STING) is an adaptor mediating DNA virus-induced innate immune response. Whether STING is able to be modified by O-GlcNAcylation and how O-GlcNAcylation affects STING-mediated anti-DNA virus response remain unknown. METHODS: Metabolomics analysis was used for detecting metabolic alterations in HSV-1 infection cells. Succinylated wheat germ agglutinin (sWGA), co-immunoprecipitation, and pull-down assay were employed for determining O-GlcNAcylation. Mutagenesis PCR was applied for the generation of STING mutants. WT and Sting1-/- C57BL/6 mice (KOCMP-72512-Sting1-B6NVA) were infected with HSV-1 and treated with O-GlcNAcylation inhibitor for validating the role of STING O-GlcNAcylation in antiviral response. RESULTS: STING was functionally activated by O-GlcNAcylation in host cells challenged with HSV-1. We demonstrated that this signaling event was initiated by virus infection-enhanced hexosamine biosynthesis pathway (HBP). HSV-1 (or viral DNA mimics) promotes glucose metabolism of host cells with a marked increase in HBP, which provides donor glucosamine for O-GlcNAcylation. STING was O-GlcNAcylated on threonine 229, which led to lysine 63-linked ubiquitination of STING and activation of antiviral immune responses. Mutation of STING T229 to alanine abrogated STING activation and reduced HSV-1 stimulated production of interferon (IFN). Application of 6-diazo-5-oxonorleucine (DON), an agent that blocks the production of UDP-GlcNAc and inhibits O-GlcNAcylation, markedly attenuated the removal of HSV-1 in wild type C57BL/6 mice, leading to an increased viral retention, elevated infiltration of inflammatory cells, and worsened tissue damages to those displayed in STING gene knockout mice. Together, our data suggest that STING is O-GlcNAcylated in HSV-1, which is crucial for an effective antiviral innate immune response. CONCLUSION: HSV-1 infection activates the generation of UDP-Glc-NAc by upregulating the HBP metabolism. Elevated UDP-Glc-NAc promotes the O-GlcNAcylation of STING, which mediates the anti-viral function of STING. Targeting O-GlcNAcylation of STING could be a useful strategy for antiviral innate immunity.
Subject(s)
Herpesvirus 1, Human , Membrane Proteins , Animals , Mice , Herpesvirus 1, Human/metabolism , Immunity, Innate , Interferons , Membrane Proteins/metabolism , Mice, Inbred C57BL , Uridine DiphosphateABSTRACT
Different from accounting supervision and audit supervision,financial supervision pays more attention to the standardization of economic behavior from the management and governance level,financial supervision has the characteristics of comprehensiveness,foresightedness and guidance,which is very important for the healthy development of public hospital.By analyzing the main problems and challenges faced by the internal financial supervision in public hospitals,it discusses the construction of supervision system,the perfection of working mechanism,the optimization of supervision means and the construction of supervision environment,to explore the concrete ways and suggestions of improving the efficiency of internal financial supervision in public hospitals.
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Bronchiectasis has the characteristics of long course,gradual aggravation,easy recurrence and difficult to treat.The characteristics are similar to those arouse by incubative pathogenic factors.Based on the theory of incubative pathogenic factors,this disease is often related to the incubative pathogenic factors in the body's areas with deficient healthy qi,which occur at regular times.The etiology can be external,congenital,or internal.Treatment should focus on different characteristics of incubative pathogenic factors.Attention should be paid to clearing and dispersing in external pathogenic factors,while attention should be paid to supporting and promoting healthy qi in congenital pathogenic factors,and do not forget to remove internal pathogenic factors.
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Objective:To investigate the effects of ubiquitin-specific protease (USP) 7/47 inhibitor (Cat. No. 1247825-37-1) on the proliferation and apoptosis of acute myeloid leukemia (AML) cells with or without internal tandem duplications of the Flt3 gene (Flt3-ITD). Methods:ATP assay was used to detect the effects of 1247825-37-1 on the cell viability of two AML cell lines (MOLM13 and MV4-11) harboring Flt3-ITD mutation and one AML cell line (THP-1) without Flt3-ITD mutation as well as the primary Flt3-ITD-mutant and non-mutant AML cells from patient samples. Flow cytometry was used to detect the apoptosis of AML cell lines treated by different concentrations of 1247825-37-1.Results:Compared with the control group, 1247825-37-1 was able to significantly inhibit the proliferation of MOLM13, MV4-11 and THP-1 cells ( P<0.000 1). Besides, the cell viability of primary AML cells was also inhibited by 1247825-37-1, and a stronger inhibitory effect on non-mutant AML cells was observed. The USP7/USP47 inhibitor 1247825-37-1 could inhibit the proliferation of AML cells in a dose-dependent manner and a low dose (2 or 4 μmol/L) of 1247825-37-1 would be effective. Moreover, 1247825-37-1 was also able to efficiently induce the apoptosis of above AML cell lines in a dose-dependent manner. Conclusions:The USP7/USP47 inhibitor 1247825-37-1 significantly inhibits the proliferation of AML cells with or without Flt3-ITD mutation.
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【Objective】 To explore the effects of breastfeeding on the immune response of CD4+T lymphocytes in infants in non-inflammatory state, and to analyze the immunomodulatory significance of the whole composition of breast milk. 【Methods】 A retrospective cohort study was conducted. From January to September 2022, six-month-old infants who took physical examination in the Child Healthcare Department of Changzhou Children′s Hospital Affiliated to Nantong University, were selected based on inclusion criteria, and were divided into breastfeeding group (n=33) and formula feeding group (n=27) based on their feeding patterns. Flow cytometry was used to detect the percentage of CD4+ T cells, including helper T cell (Th) 1, Th2, Th17, regulatory T cell (Treg), and the levels of related cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-17 in peripheral blood. The differences in these indicators between the two groups were compared. 【Results】 Compared with the formula feeding group, the breastfeeding group showed significantly higher percentages of Th1(t=3.038), Treg (t=2.088). The ratio of Th1 to Th2(Z=2.756), IL-10(Z=2.297) and IFN-γ (Z=2.076) in the peripheral blood of the breastfeeding group were also significantly higher. Conversely, the breastfeeding group had significantly lower percentage of Th17(Z=2.704) and IL-17A (t=2.187) (P<0.05). There was no significant difference the percentage of Th2, as well as in the levels of IL-2, IL-4, IL-6 and TNF-α between the two groups (P>0.05). 【Conclusions】 Breastfeeding has a regulatory effect on the immune response of infant CD4+ T lymphocytes. It promotes the development of Th1/Th2 towards Th1 and the immunomodulatory effect of Treg. Moreover, it inhibits the Th17 type immune response. These findings suggest that the complete composition of breast milk contributes to the development and maturation of infant immune system, enhancing immune defense and immune tolerance.
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Objective:To discuss dominant symptoms and compatibility rules of Dazhui(GV14) based on data mining.Methods:Literature related to Dazhui (GV14) was retrieved from CNKI, Wangfang, VIP, China Biomedical Literature Database (CBM) and Pubmed databases from January 1, 2012 to August 15, 2022, and the main symptoms of Dazhi (GV14) and the compatibility of acupoints were summarized. Gephi 0.9.5 software was used for complex network analysis to compare the treatment for dominant symptoms with single acupoint of Dazhi (GV14) and the compatibility of the acupoint. SPSS Modeler 18.0 software was used to analyze the association rules of acupoint combination based on Apriori algorithm. The clustering analysis of high frequency acupoints was carried out by SPSS Statistics 26.0 software.Results:A total of 722 articles were included, involving 732 prescriptions. The dominant symptoms of single acupoint were cervical spondylosis, acne, and cold; the treatment for dominant symptoms with compatibility included 14 types, such as cervical spondylosis, allergic rhinitis, ischemic stroke sequelae. The meridian compatibility was dominated by bladder meridian, and the frequency of yang meridians was higher than yin meridians. The compatibility of specific acupoints such as Xiahe acupoint, Beishu acupoint and Bahui acupoint were the main acupoints, and the high frequency acupoints were 33 acupoints such as Feishu (BL13), Baihui (GV20), Fengchi (GB20) and Zusanli (ST36), obtaining 4 series and 8 types of compatible combinations of Dazhui (GV14).Conclusions:Dazhui (GV14) is widely used in the treatment of internal diseases, such as respiratory diseases, nervous system diseases and vertebral artery type of cervical spondylosis. It tends to be flexibly used with multiple compatibility and clustering combination of specific acupoints.
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With the development of medical technology, tumor vaccines as a novel precise immunotherapy approach have gradually received attention in clinical applications. Against the backdrop of the global corona virus disease 2019 (COVID-19) outbreak, vaccine technology has further advanced. Depending on the types of antigens, tumor vaccines can be divided into whole-cell vaccines, peptide vaccines, messenger ribonucleic acid (mRNA) vaccines, recombinant virus vaccines, etc. Although some tumor vaccines have been marketed and achieved certain therapeutic effects, the results of tumor vaccines in clinical trials have been unsatisfactory in the past period. With the maturation of next-generation sequencing (NGS) technology and the continuous development of bioinformatics, dynamic monitoring of the entire process of tumor subpopulation development has become a reality, which has laid a solid foundation for personalized, neoantigen-centered therapeutic tumor vaccines. This article reviews the recent developments of tumor vaccines of different types, starts with lung cancer and summarizes the achievements of tumor vaccines in clinical applications, and provides an outlook for the future development of antigen-centered tumor vaccines. .
Subject(s)
Humans , Cancer Vaccines/therapeutic use , Antigens, Neoplasm , Lung Neoplasms/drug therapy , Neoplasms/genetics , Computational Biology , Immunotherapy/methods , LungABSTRACT
With the progress of science and technology and the increase of clinical demand, medical robots have developed rapidly and played a important role in promoting the medical cause. Service robot is a branch of medical robot, which is mainly oriented to medical service and assistance needs, and has been applied in many medical scenarios and achieved demonstration effects. This research first describes the development of medical service robots, and then summarizes the key technologies and clinical applications of robots. Finally, it points out the challenges and directions that medical service robots face at present, and puts forward prospects for their further development in the medical field.
Subject(s)
Robotics , TechnologyABSTRACT
【Objective:】 To investigate the current situation of attitudes and training needs of hospice care among nursing staff in Hainan Province, and analyze the influencing factors, so as to provide basis for formulating scientific and standardized hospice care training programs for nursing staff. 【Methods:】 From October to December in 2021, a total of 1 819 nursing staff from 45 general hospitals, specialized hospitals and nursing homes in 14 cities and counties of Hainan province were selected by convenience sampling method to conduct the questionnaire on hospice care attitude and training needs. 【Results:】 1 789 valid questionnaires were collected with effective recovery of 98.35%. Nursing staff hospice care attitude score was (88.13±12.10) points, the standard score was 70.4 points, hospice care attitude was at medium level. Nursing staff training needs score was (26.96±5.16) points, the standard score was 89.87, the needs of each dimension and item were higher than 75.1%, the training needs were at high level. Professional title, currently engaged in hospice care services, and willingness to engage in hospice care services were the influencing factors of hospice care training needs (P<0.05), and the hospital, have witnessed the death of dying patients or relatives, willingness to engage in hospice care services were the main influencing factors of nurses’ attitude toward hospice care (P<0.05). 【Conclusion:】 At present, nursing staff in Hainan Province held a moderate attitude towards hospice care, and had a high demand for training. The major obstacles for nursing staff to engage in hospice care at present were high stress in the face of dying patients and symptom management. Nursing managers should combine the current situation, pay attention to stimulate nurses’ intrinsic motivation, strengthen the training of nursing staff’s concept of hospice nursing, construct a diversified training system, and carry out specialized and modular skill practice and theoretical training to improve nursing staff’s hospice care ability.
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Considering the surgical risk stratification for patients with severe calcific aortic stenosis (AS), transcatheter aortic valve replacement (TAVR) is a reliable alternative to surgical aortic valve replacement (SAVR) (Fan et al., 2020, 2021; Lee et al., 2021). Despite the favorable clinical benefits of TAVR, stroke remains a dreaded perioperative complication (Auffret et al., 2016; Kapadia et al., 2016; Kleiman et al., 2016; Huded et al., 2019). Ischemic overt stroke, identified in 1.4% to 4.3% of patients in TAVR clinical practice, has been associated with prolonged disability and increased mortality (Auffret et al., 2016; Kapadia et al., 2016; Levi et al., 2022). The prevalence of hyperintensity cerebral ischemic lesions detected by diffusion-weighted magnetic resonance imaging (DW-MRI) was reported to be about 80%, which is associated with impaired neurocognitive function and vascular dementia (Vermeer et al., 2003; Barber et al., 2008; Kahlert et al., 2010).
Subject(s)
Humans , Transcatheter Aortic Valve Replacement , Aortic Valve Insufficiency , Diffusion Magnetic Resonance Imaging , Aortic Valve Stenosis , StrokeABSTRACT
The working principle and structural composition of the transcranial magnetic stimulator were introduced.The failures of the transcranial magnetic stimulator in some hospital were summarized from 2018 to 2022.The causes for common failures of the transcranial magnetic stimulator were analyzed with the fishbone diagram,and some suggestions were put forward on its daily utilization management.The maintenance thoughts for two common failures were described in detail including flow control alarm and no magnetic field output.References were provided for daily management and maintenance of the transcranial magnetic stimulator.[Chinese Medical Equipment Journal,2023,44(9):110-113]
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Tu-Xian decoction (TXD), a traditional Chinese medicine (TCM) formula, has been frequently administered to manage diabetic cognitive impairment (DCI). Despite its widespread use, the mechanisms underlying TXD's protective effects on DCI have yet to be fully elucidated. As a significant regulator in neurodegenerative conditions, death-associated protein kinase-1 (DAPK-1) serves as a focus for understanding the action of TXD. This study was designed to whether TXD mediates its beneficial outcomes by inhibiting DAPK-1. To this end, a diabetic model was established using Sprague-Dawley (SD) rats through a high-fat, high-sugar (HFHS) diet regimen, followed by streptozotocin (STZ) injection. The experimental cohort was stratified into six groups: Control, Diabetic, TC-DAPK6, high-dose TXD, medium-dose TXD, and low-dose TXD groups. Following a 12-week treatment period, various assessments-including blood glucose levels, body weight measurements, Morris water maze (MWM) testing for cognitive function, brain magnetic resonance imaging (MRI), and histological analyses using hematoxylin-eosin (H&E), and Nissl staining-were conducted. Protein expression in the hippocampus was quantified through Western blotting analysis. The results revealed that TXD significantly improved spatial learning and memory abilities, and preserved hippocampal structure in diabetic rats. Importantly, TXD administration led to a down-regulation of proteins indicative of neurological damage and suppressed DAPK-1 activity within the hippocampal region. These results underscore TXD's potential in mitigating DCIvia DAPK-1 inhibition, positioning it as a viable therapeutic candidate for addressing this condition. Further investigation into TXD's molecular mechanisms may elucidate new pathways for the treatment of DCI.
Subject(s)
Animals , Rats , Brain/metabolism , Cognitive Dysfunction/drug therapy , Diabetes Mellitus, Experimental/metabolism , Hippocampus , Rats, Sprague-DawleyABSTRACT
Objective:To analyze the clinical characteristics and prognostic value of prostate-specific antigen (PSA) dynamic features in patients with metastatic castration resistant prostate cancer (mCRPC) received abiraterone acetate (AA) therapy.Methods:The data of 89 patients with mCRPC who received AA therapy from January 2017 to June 2021 in Shanghai Tongji Hospital were retrospectively reviewed. The age of patients was (75.7 ± 8.3) years old, median PSA before AA was 56.88 (19.31, 143.75) ng/ml. The PSA dynamic features included PSA nadir (PSAN) and PSAN time. PSAN was defined as the lowest value of PSA after treatment, and PSAN time was defined as time to PSAN after AA treatment. PSAN was divided into 3 groups: PSAN1 (<0.1 ng/ml), PSAN2 (0.1- 4.0 ng/ml) and PSAN3 (>4.0 ng/ml) groups. PSA response was defined as a maximum PSA decline rate ≥50%, and no PSA decline after treatment was defined as primary resistance. Cox regressions adjusted to clinical factors were performed to evaluate the influence of PSA dynamic features on patients' radiographic progression-free survival (rPFS) and overall survival (OS). Log-rank test was used to evaluate the survival time of patients in different PSAN groups. Receiver operator characteristic (ROC) curve and area under the curve (AUC) were performed to analyze the predictive value of PSA dynamic features on survival outcomes of patients.Results:The follow-up time was 17 (12, 23) months, and 75 (84.3%) patients showed PSA responses. The median PSAN was 1.82 (0.01, 11.70) ng/ml, median PSAN time was 5.0(3.0, 9.5)months. Multivariate Cox regression indicated that PSAN was an independent risk factor for rPFS ( PSAN2: HR=5.308, P=0.017; PSAN3: HR=13.209, P<0.001), and PSAN time ≥ 5 months( HR=0.309, P<0.001)was an independent protective factor for rPFS. Also, the PSAN3 was an independent risk factor for OS( HR=9.459, P=0.048). Log-rank test indicated that the rPFS of PSAN1 group (median not reached) was significantly longer than PSAN2 [median 13.0(95% CI 8.2-17.8) months, P=0.001] and PSAN3 [8.0 (95% CI 4.1-11.9) months, P<0.001] groups. ROC curve and AUC showed that PSAN had a higher predictive value in rPFS outcomes compared with T stage, metastatic disease volume, and Eastern Cooperative Oncology Group (ECOG) score (0.82 vs. 0.69, 0.68, 0.53, P<0.05). PSAN had a higher predictive value in OS outcomes than metastatic disease volume and ECOG(0.83 vs. 0.63, 0.58, P<0.05). Conclusions:Lower PSAN needs longer PSAN time. PSAN is an independent risk factor for rPFS and OS, and PSAN time is an independent protective factor for rPFS.
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Jingjin (muscle region of meridian) is a distal diagnosis and treatment system of the sinew/fascia disorders on the base of the concept of jin in TCM. Jin should be a particular palpable structure rather than a single anatomic structure with a specific distributing course. Yizhi weishu refers to a idea running through the whole process of diagnosis and treatment of sinew/fascia disorders, in which, the results, obtained by the overall observation and palpation of patient's sinew/fascia structure, are taken as the criteria of treatment. Yitong weishu (taking the sites of sensitivity or tenderness as the points) verifies this idea in practice. Under the guidance of yizhi weishu, through identifying the primary from the secondary, and regulating yin and yang, the spasticity and flaccidity of sinews/fascia can be cured and the induced diseases treated. The diagnosis and treatment system of jingjin, based on yizhi weishu, develops the original jingjin theory with vague concept involved, formulates a systematic thinking of treatment for sinew/fascia disorders and provides a new approach to clinical treatment.
Subject(s)
Humans , Meridians , Acupuncture Therapy , Muscle SpasticityABSTRACT
There are few reports on the use of Allium stents in the treatment of membranous urethral stricture in China. Its safety and effectiveness need to be observed. This study retrospectively analyzed the data of 5 patients admitted to our hospital for the treatment of membranous urethral stricture using Allium-covered metal urethral stents in the past 5 years. The preoperative International Prostatic Symptom Score (IPSS) score was 8.80±1.30, quality of life(QOL)score was 4.20 ±0.84, and the International Index of Erectile Function-5(IIEF-5) score was 20.20 ± 1.92, respectively. Six months after the operation, the IPSS score was 3.60±1.52, the QOL score was 1, and the IIEF-5 score was 19.80±1.48. This operation is easy with little invasion. It can alleviate the dysuria of patients with membranous urethral stricture and has little impact on the sexual function of patients. It is generally safe and controllable, but the appropriate time for implantation still needs to be explored.
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Objective:To investigate the clinical characters and prognostic value of PSA flare and bone flare in metastatic castration resistant prostate cancer(mCRPC) patients received Abiterone acetate(AA) therapy.Methods:A retrospective study was conducted for 93 mCRPC patients treated with AA from Jul.2016 to Dec.2020. Mean age was (75.4±8.9)years, median PSA was 58.2 (16.4, 148.6)ng/ml. Patients received at least 6 months of AA treatment. PSA flare was defined as an increase of PSA after AA therapy followed by a decrease. Bone flare was defined as disease progression after 3 months of therapy, typically based on increased lesion intensity or number, and reevaluation 6-9 months later showed improvement in the scan. The clinical characters and prognostic value of the flare phenomenon was evaluated and analyzed respectively.Results:The median follow up time was 16 months(6, 54 months), fourteen patients showed PSA flare at first month after AA treatment, and median time of duration was 2 months(1, 7 months). The serum alkaline phosphatase (ALP) had a similar rising trend along with PSA flare[115.5(98.0, 198.5)U/L vs. 119.0(97.0, 288.8)U/L, P=0.016]. Seven patients showed bone flare and 3 cases co-existed with PSA flare. Multivariate Cox regression analysis indicated bone flare was an independent protective factor for progression free survival(PFS)( HR=0.117, 95% CI 0.015-0.895, P=0.039), PSA flare had no significant influence on PFS ( HR=1.314, 95% CI 0.554-3.121, P=0.536)and overall survival(OS)( HR=1.348, 95% CI 0.393-4.263, P=0.635). Log-rank test showed patients with bone flare had a longer PFS( P=0.016) and OS( P=0.047) compared with patients without bone flare. Conclusions:PSA flare always faded away after 2 months AA therapy and had no influence on PFS and OS. Bone flare maybe an indication for better prognosis.
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Objective:To explore the influencing factors of continuous renal replacement therapy(CRRT)after heart transplantation(HT).Methods:For this retrospective cohort study, the relevant clinical data were retrospectively reviewed for 145 recipients undergoing HT at No.7 Municipal People's Hospital from April 2018 to December 2022.They were assigned into two groups of non-CRRT(n=124)and CRRT(n=21). And t, χ2or rank-sum test was utilized for comparing baseline data, intraoperative and postoperative general conditions of two groups.Variables with P<0.05 in univariate analysis and significant indicators in previous studies were included in multivariate logistic regression analysis to analyze the influencing factors of CRRT post-HT.Receiver operating characteristic curve(ROC)was utilized for selecting the optimal predictive cut-off value. Results:Among them, 66 cases(45.52%)developed AKI and 21(14.48%)required CRRT.Through univariate analysis, preoperative estimated glomerular filtration rate(eGFR), erythrocyte count, platelet, hemoglobin, total bilirubin, intraoperative volume of blood loss, volume of blood transfusion, urine volume, operative duration, cardiopulmonary bypass time, postoperative mechanical ventilation time, ICU stay and postoperative acute kidney injury were compared.The inter-group differences were statistically significant( P<0.05). Further multivariate logistic regression analysis revealed that preoperative hemoglobin level( OR=0.869, 95% CI: 0.770-0.980, P=0.022), preoperative platelet count( OR=0.959, 95% CI: 0.925-0.993, P=0.019), intraoperative volume of hemorrhage( OR=1.004, 95% CI: 1.000-1.009, P=0.049), intraoperative urine volume( OR=0.997, 95% CI: 0.993-1.000, P=0.035), operative duration( OR=1.022, 95% CI: 1.000-1.044, P=0.047)and mechanical ventilation time( OR=1.036, 95% CI: 1.005-1.069, P=0.024)were the independent influencing factors of CRRT post-HT.ROC curve results indicated that area under curve(AUC)of operative duration, mechanical ventilation time and intraoperative volume of hemorrhage were 0.745(95% CI: 0.636-0.855), 0.835(95% CI: 0.735-0.934)and 0.669(95% CI: 0.506-0.830)with a sensitivity of 0.714, 0.857, 0.571 and a specificity of 0.710, 0.685, 0.895.And the cut-off values were 283.5 min, 25.46 h and 825 ml respectively. Conclusions:Hemoglobin level, preoperative platelet count, intraoperative volume of hemorrhage, urine volume, operative duration, mechanical ventilation time and intraoperative urine volume are independent influencing factors of CRRT post-HT.Operative duration >283 min, mechanical ventilation time >25.46 h and intraoperative volume of hemorrhage >825 ml have some predictive values for CRRT post-HT.
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BACKGROUND@#Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated.@*METHODS@#The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry.@*RESULTS@#ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 .@*CONCLUSION@#ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.