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Abstract Historically, it takes an average of 17 years for new treatments to move from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. Now is the time to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions are diagnosed worldwide, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because it is often silent in the early stages. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from the patient to the clinician to the health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.
Resumo Historicamente, são necessários, em média, 17 anos para que novos tratamentos passem da evidência clínica para a prática diária. Considerando os tratamentos altamente eficazes disponíveis atualmente para prevenir ou retardar o início e a progressão da doença renal, esse período é demasiadamente longo. Agora é o momento de reduzir a lacuna entre o que sabemos e aquilo que fazemos. Existem diretrizes claras para a prevenção e o manejo dos fatores de risco comuns para doenças renais, como hipertensão e diabetes, mas apenas uma fração das pessoas com essas condições é diagnosticada mundialmente, e um número ainda menor recebe tratamento adequado. Da mesma forma, a grande maioria das pessoas que sofrem de doença renal não têm conhecimento de sua condição, pois ela costuma ser silenciosa nos estágios iniciais. Mesmo entre pacientes que foram diagnosticados, muitos não recebem tratamento adequado para a doença renal. Levando em consideração as graves consequências da progressão da doença renal, insuficiência renal ou óbito, é imperativo que os tratamentos sejam iniciados precocemente e de maneira adequada. As oportunidades para diagnosticar e tratar precocemente a doença renal devem ser maximizadas, começando no nível da atenção primária. Existem muitas barreiras sistemáticas, que vão desde o paciente até o médico, passando pelos sistemas de saúde e por fatores sociais. Para preservar e melhorar a saúde renal para todos em qualquer lugar, cada uma dessas barreiras deve ser reconhecida para que soluções sustentáveis sejam desenvolvidas e implementadas sem mais demora.
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Cyclosporine is an immunosuppressant used to prevent organ rejection in kidney, liver, and heart allogeneic transplants. This study aimed to assess the safety of cyclosporine through the analysis of adverse events (AEs) related to cyclosporine in the US Food and Drug Administration Adverse Event Reporting System (FAERS). To detect AEs associated with cyclosporine, a pharmacovigilance analysis was conducted using four algorithms on the FAERS database: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM). A statistical analysis was performed on data extracted from the FAERS database, covering 19,582 case reports spanning from 2013 to 2022. Among these cases, 3,911 AEs were identified, with 476 linked to cyclosporine as the primary suspected drug. Cyclosporin-induced AEs targeted 27 System Organ Classes (SOCs). Notably, the highest case at the SOC level included eye disorders, injury, poisoning, and procedural complications, as well as immune system disorders, all of which are listed on the cyclosporine label. Furthermore, we discovered novel potential AEs associated with hepatobiliary disorders, among others. Moreover, unexpected adverse drug reactions (ADRs), such as biliary anastomosis complication and spermatozoa progressive motility decrease, were identified. Importantly, these newly identified ADRs were not mentioned on the cyclosporine label, which were involved in injury, poisoning, and procedural complications, and investigations at the SOC level. The study used pharmacovigilance analysis of FAERS database to identify new and unexpected potential ADRs relating to cyclosporine, which can provide safety tips for the safe use of cyclosporine.
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OBJECTIVE To establish HPLC fingerprint of Shuangdong capsules， and to study the spectral effect relationship of its anti-inflammatory effect. METHODS The fingerprints of 15 batches of Shuangdong capsules were established by HPLC，and the similarity evaluation was carried out； the foot swelling model was established to investigate the anti-inflammatory activity of Shuangdong capsules. The gray correlation analysis method was used to construct the spectral effect relationship for the anti- inflammatory effect of Shuangdong capsules using the swelling rate of rat foot and the levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， prostaglandin E2 （PGE2）， interleukin-6 （IL-6）， IL-8， IL-1β and tumor necrosis factor-α （TNF-α） in right hindfoot tissues as the pharmacodynamic indexes of anti-inflammatory effects. RESULTS Overall 15 batches of Shuangdong capsules identified 20 common peaks， the similarities were all greater than 0.97， and a total of 8 chromatographic peaks were identified. According to the gray correlation analysis， the correlation degrees between the peak area and the foot swelling rate and the levels of MDA， SOD， PGE2， IL-6， IL-8， IL-1β and TNF-α in 15 batches of Shuangdong capsules were 0.621 1- 0.783 5， 0.564 3-0.827 9， 0.581 0-0.845 3， 0.564 9-0.855 0， 0.583 1-0.856 4， 0.576 5-0.863 5， 0.564 1-0.838 0 and 0.572 5- 0.851 3， respectively. Among them， the chemical components represented by peak 4 （geniposidic acid）， peak 10 （chlorogenic acid） and the chemical composition represented by peak 2 were strongly correlated with anti-inflammatory efficacy indicators. CONCLUSIONS In this study， HPLC fingerprints of 15 batches of Shuangdong capsules were successfully established. Among them， geniposidic acid， chlorogenic acid may be its anti-inflammatory ingredients.
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ObjectiveTo investigate the changes in cerebral blood perfusion in patients with acute cerebral infarction after taking Tongnaoyin， a traditional Chinese medicine， based on head and neck computed tomography （CT） angiography （CTA） combined with brain CT perfusion imaging （CTP）. MethodA total of 240 patients with cerebral infarction of phlegm and blood stasis syndrome treated in Jiangsu Province Hospital of Traditional Chinese Medicine from March 2018 to September 2023 were randomly divided into a control group （99 cases） and a Tongnaoyin group （141 cases）. Based on the guidelines， the control group was treated with conventional treatment such as anti-aggregation， anticoagulation， lipid-lowering and plaque stabilization， brain protection， and supportive treatment. The Tongnaoyin group was treated with Tongnaoyin of 200 mL in warm conditions in the morning and evening on the basis of the control group. Both groups underwent CTA combined with CTP within 24 hours after admission， and they were reexamined by CTA and CTP in the sixth month after admission. The degree of intracranial artery stenosis was determined according to the North American Symptomatic Carotid Endarterectomy Trial （NASCET） method. The relative cerebral blood volume （rCBV）， relative cerebral blood flow （rCBF）， mean transit time （MTT）， and time to peak （TTP） of the lesion area before and after treatment were compared. The adverse outcomes of the two groups within six months after discharge were compared. ResultCompared with the group before treatment， the degree of vascular stenosis in the Tongnaoyin group was significantly reduced， and the difference was statistically significant （Z=105.369，P<0.05）. Compared with the control group after treatment， the improvement rate of vascular stenosis in the Tongnaoyin group was higher （χ2=84.179，P<0.01）， and the curative effect was better.After treatment， the rCBV and rCBF of patients in the Tongnaoyin group were significantly increased， and the difference was statistically significant （P<0.01）. MTT and TTP showed a trend of shortening， but the difference was not statistically significant. There was no statistically significant difference in rCBV， rCBF， MTT， and TTP in the control group. Compared with those in the control group after treatment， the rCBV and rCBF in the Tongnaoyin group were significantly increased， while MTT and TTP were significantly reduced （P<0.01）. After six months of discharge， the risk of poor prognosis in the Tongnaoyin group was significantly reduced compared with the control group （P<0.05）. ConclusionTongnaoyin has a good effect on improving cerebral blood perfusion in patients with acute cerebral infarction. It can be used as an effective supplement for the conventional treatment of ischemic stroke to improve clinical efficacy.
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Objective To systematically retrieve,evaluate and integrate the best evidences on the early fluid resuscitation management in the patients with acute pancreatitis(AP)at home and abroad to provide ref-erence for clinical decision.Methods The related evidences on the early fluid resuscitation management in the AP patients were retrieved by computer from the databases of BMJ Best Practice,Up To Date,JBI,National Institute for Health and Care Excellence,Registered Nurses Association of Ontario,Guideline International Network,Scottish Intercollegiate Guidelines Network,International Association of Pancreatology,American Pancreatic Association,American College of Gastroenterology,Yimaitong,Cochrane Library,PubMed,Em-bass,CINAHL,The Web of Science,CNKI,Wanfang databases.The retrieval time limit was from the data-base establishment to March 20,2022.The literatures types included thematic evidence summarization,guide-lines,evidence summaries,systematic reviews and expert consensus.The researchers conducted the literature quality evaluation.The literatures meeting the standard conducted the evidence extraction.Results A total of 13 arti-cles were included,including 3 special subject evidence summary,4 guidelines,2 evidence summary,2 systematic evalu-ation and 2 expert consensus.A total of 16 pieces of best evidence were integrated,involving 4 aspects of organization management,evaluation and monitoring,fluid infusion strategy and health education.Conclusion It is recommended to use the target-oriented therapy for early fluid resuscitation management,and perform the fluid resuscitation immediate-ly after diagnosis,according to the patient's underlying disease,disease changes and monitoring indicators,implement precise early fluid resuscitation in order to reverse pancreatic microcirculation disorder,increase tissue perfusion and improve the patient's prognosis.
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Objective To develop nurses'knowledge,attitude and practice questionnaire on medication management for patients with dysphagia,and test its reliability and validity.Methods Based on the evidence-based summary of the best evidence of medication management for patients with dysphagia,guided by the the-ory of knowledge,attitude and practice,the basic dimensions and item pool of the questionnaire were deter-mined through group discussion,Delphi expert consultation and pre-investigation.In order to revise the ques-tionnaire,437 nurses from 10 tertiary hospitals in Jiangsu Province were conveniently selected for investigation,and the reliability and validity of the questionnaire were tested according to the survey results.Results The nurses'knowl-edge,attitude and practice questionnaire on medication management for patients with dysphagia included 43 items in three dimensions.The three dimensions were analyzed by exploratory factors,and six common factors with characteristic roots>1 were extracted.Two factors were extracted from the knowledge dimension,and the cumulative variance contribution rate was 74.958%,One factor was extracted from the attitude dimen-sion,and the cumulative variance contribution rate was 77.655%.Three factors were extracted from the prac-tice dimension,and the cumulative variance contribution rate was 72.274%.The factor load of each item was 0.618-0.902,Cronbach's α coefficient of the total questionnaire was 0.949,and the test-retest reliability was 0.909.The overall content validity coefficient of the questionnaire was 0.922,and the content validity coeffi-cient for each item was 0.800-1.000.Conclusion The nurses'knowledge,attitude and practice questionnaire on medication management for patients with dysphagia developed in this study has good reliability and validi-ty,and could be used as an effective tool to evaluate the status quo of nurses'medication management for pa-tients with dysphagia.
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Objective:To predict the molecular mechanism of Biminkang Granules in the treatment of allergic rhinitis using network pharmacological methods combined with animal experiments.Methods:Active component targets and allergic rhinitis targets were screened from TCMSP, OMIM, GeneCards, TTD, DrugBank and PharmGKB databases; R language software was used to map the intersection of drug and disease targets; Cytoscape software and String platform were used to construct intersection target PPI network and conduct network topology analysis; DAVID platform was used to perform GO enrichment and KEGG pathway analysis, and perform molecular docking verification on the main active components and key targets. 32 rats were divided into a blank group of 8 and a model group of 24 using a random number table method. Model rats were induced by ovalbumin to establish an allergic rhinitis model. 24 SD rats that were successfully modeled and were randomly divided into model group, Western medicine group, and Biminkang Granules group using a random number table method, with 8 rats in each group. The Western medicine group was gavaged with 1 mg/kg of loratadine solution, the Biminkang Granules group was gavaged with 4.1 g/kg of Biminkang Granules solution, and the blank group and model group rats were gavaged with the same volume of physiological saline once a day for 2 consecutive weeks. The symptoms of rhinitis in each group of rats for 30 minutes were observed and recorded, and the pathological changes of the rat nasal mucosa were observed using HE staining. ELISA method was used to detect the levels of IL-17 and IL-6 in rat serum, and Western blot method was used to determine the expressions of TNF and STAT3 proteins in rat tissues.Results:A total of 41 target proteins of BiMinKang Dranule in the treatment of allergic rhinitis were predicted, and TNF, STAT3 and other core target proteins were obtained by PPI network topology analysis. The biological process of GO involved drug response, inflammatory response, cytokine response, etc.KEGG enrichment is involved in Th17 cell differentiation, lipid and atherosclerosis, IL-17, toll-like receptor and other pathways. Molecular docking results indicated that the main active components had good binding activity to key target proteins.Animal experiments showed that BiMinKang Dranule could improve the inflammatory symptoms of allergic rhinitis rats, down-regulate the expression of IL-17 and IL-6 in blood, and inhibit the expression of TNF and STAT3 proteins.Conclusion:Biminkang Granules can treat allergic rhinitis through multiple active components, multiple target proteins and multiple pathways, and the mechanism may be related to the regulation of Th17 cell differentiation pathway related proteins.
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Objective To investigate the clinical efficacy of Xuanfei Tongluo Pingchuan Decoction in treating patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and to explore its regulatory mechanism on immune function and inflammatory response.Methods A retrospective study was conducted in 122 patients with AECOPD of phlegm-stasis obstructing lung type,and the patients were divided into an observation group and a control group according to the therapy,with 61 patients in each group.The control group was treated with conventional western medicine,and the observation group was treated with Xuanfei Tongluo Pingchuan Decoction on the basis of treatment for the control group.The treatment lasted for 14 days.Before and after treatment,the patients of the two groups were observed in the changes of pulmonary function indicators,6-minute walking distance(6MWD),COPD Assessment Test(CAT)scores,immune function indicators,and serum inflammatory factors.After treatment,the clinical efficacy and the overall occurrence rate of the adverse reactions were compared between the two groups.Results(1)After 14 days of treatment,the total effective rate of the observation group was 95.08%(58/61),and that of the control group was 77.05%(47/61).The intergroup comparison showed that the therapeutic effect of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,pulmonary function indexes such as the forced expiratory volume in one second(FEV1),forced vital capacity(FVC),and peak expiratory flow(PEF)of the two groups were significantly improved compared with those before treatment(P＜0.05),and the effect on improving all pulmonary function indexes in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the 6MWD of the two groups were significantly higher(P＜0.05)and the CAT scores were significantly lower than those before treatment(P＜0.05),and the observation group was significantly superior to the control group in terms of improving the 6MWD and decreasing CAT scores(P＜0.01).(4)After treatment,the levels of immune function indicators of T lymphocyte subsets CD4+ and CD4+/CD8+ in the two groups were significantly higher than those before treatment(P＜0.05),and CD8+ level was significantly lower than that before treatment(P＜0.05),and the observation group had stronger effect on increasing T lymphocyte subsets CD4+ and CD4+/CD8+ levels and on decreasing CD8+ level than the control group(P＜0.01).(5)After treatment,the serum levels of inflammatory factors C-reactive protein(CRP)and tumor necrosis factor alpha(TNF-α)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the effect on lowering the levels of serum CRP and TNF-α in the observation group was significantly superior to that in the control group(P＜0.01).(6)During the trial,the total incidence of adverse reactions in the observation group was 3.28%(2/61)and that in the control group was 6.56%(4/61),and the intergroup comparison showed that the difference was not statistically significant between the two groups(P＞0.05).Conclusion Xuanfei Tongluo Pingchuan Decoction can effectively alleviate the symptoms of cough and expectoration in AECOPD patients,improve the lung function and immune function,and reduce the inflammatory response.During the treatment,no obvious adverse reactions occur and the therapy is safe and effective.
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Objective To investigate the association between body mass index(BMI),sex hormone and single nucleotide polymorphisms(SNPs)of follicle-stimulating hormone receptor(FSHR)gene rs2268361 and rs2349415 and its correlation with the risk of polycystic ovary syndrome(PCOS).Methods Peripheral blood was collected from 213 PCOS patients and 207 healthy controls,attending the Department of Reproductive Medicine at the First Hospital of Shanxi Medical University,and 32 follicular fluids were randomly collected from each of the PCOS and control groups from March to August 2021.Calculation of BMI of the PCOS and control groups;The levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),testosterone(T),progesterone(P)and prolactin(PRL)in peripheral blood of the two groups were detected by immunochemiluminescence method.Polymerase chain reaction(PCR)and high-resolution melting curve(HRM)were used to analyze the polymorphisms of rs2268361 and rs2349415 in FSHR of the two groups.Quantitative real-time PCR was used to detect the expression of FSHR gene mRNA in peripheral blood and ovarian granulosa cells.Results There was a strong positive correlation between LH and LH/FSH(r=0.88,P<0.05);The levels of BMI,E2,LH,LH/FSH and T in PCOS group were significantly higher than those in control group(P<0.05);FSH level was significantly lower than that of control group(P<0.001).HRM analysis showed the frequencies of CC,CT and TT genotypes at rs2349415 were 55.9%,34.3%and 9.8%in PCOS group and 68.6%,23.2%and 8.2%in control group,respectively.The frequencies of C and T alleles were 73.0%and 27.0%in PCOS group and 80.2%and 19.8%in control group,respectively.There were significant differences in genotype frequencies and allele frequencies between the two groups(P<0.05);The expression level of FSHR mRNA was higher in ovarian granulosa cells in PCOS group than in control group(P=0.004),the expression level of FSHR mRNA in rs2349415 TT genotype was higher than that in CC(P=0.002)and CT(P=0.035)genotype.Conclusion High levels of BMI, LH, E2 and T allele of rs2349415 increased the risk of PCOS.
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Objective To evaluate the efficacy of surgery,chemotherapy and surgery combined chemotherapy for retinoblastoma(RB),and analyze the prognostic factors of RB patients.Methods Clinical data of 1188 RB patients registered in the Surveillance,Epidemiology and End Results(SEER)database from January 2000 to December 2019 were retrospectively analyzed.The baseline characteristics of patients treated with surgery,chemotherapy or surgery combined with chemotherapy were balanced by inverse probability of treatment weighting(IPTW).Log-rank test analysis was used to compare the survival probability of patients in the 3 groups,and Cox regression models were used to analyse the factors influencing the prognosis of RB patients.Results A total of 1188 RB cases were included in this study,including 426 cases in surgery group,200 cases in chemotherapy group and 562 cases in surgery combined with chemotherapy group.After IPTW weighting,baseline data such as age,sex and race were balanced(P＞0.05).Log-rank test results showed that the survival curves of the three groups were significantly different before and after weighting(P＜0.05).After weighted,the survival of patients in surgery group was significantly better than that in chemotherapy group and surgery combined chemotherapy group(P＜0.05),and there was no statistical significance between chemotherapy group and surgery combined chemotherapy group(P＞0.05).The weighted patient survival probability at 1st,3rd and 5th years were 99.7%,98.9%and 98.6%in surgery group;97.4%,95.8%and 95.8%in chemotherapy group;and 97.9%,95.8%and 95.0%in surgery combined chemotherapy group.Cox regression analysis showed that compared with surgery group,the specific risk ratio of death was 1.367(95%CI 1.100-1.700)in chemotherapy group and 1.132(95%CI 0.963-1.330)in combined chemotherapy group.Compared with patients with 1 RB lesion,the patient-specific mortality risk ratio for patients with 2 or more RB lesions was 0.399(95%CI 0.268-0.594).Conclusions Patients with RB have higher survival rates probability after treatment.After controlling the influence of age,sex and other factors,the effect of surgery was better among the three treatment methods.Multifocality may be an independent prognostic factor in RB patients.
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Purpose To explore the expression,mechanism and clinical significance of MCM5 in ovarian cancer.Methods The expression of MCM5 mRNA in ovarian cancer and its correlation with patients'survival were analyzed using GEO and TCGA databases.The expression of MCM5 protein in ovarian cancer was detected by immunohistochemistry of SP two-step method,and its relationship with clinicopathological characteris-tics was analyzed.With inhibition of MCM5 by siRNA in ovarian cancer cells.The effects of MCM5 on cell proliferation,migra-tion,invasion,and apoptosis were detected by CCK-8 assay,EDU,plate cloning,Transwell chamber and flow cytometry.Re-sults Immunophenotype:MCM5 does not stain in the fallopian tube epithelium(0/6),with a positivity rate of 48.3％(57/118)in ovarian cancer.The expression of MCM5 in ovarian cancer is significantly higher than in fallopian tube epithelium,showing diffuse strong expression in high-grade serous carcino-ma.MCM5 expression is strongly correlated with ER-negative status and high Ki67 proliferation index.Knocking down MCM5 expression inhibits proliferation(P＜0.05),clonogenicity(P＜0.05),invasion and migration(P＜0.05)of ovarian cancer cells,and promotes apoptosis.Conclusion MCM5 is highly expressed in human ovarian cancer cells and tissues and is asso-ciated with poor prognosis.It is expected to become a new target for the treatment of ovarian cancer.
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Objective To evaluate the gender differences in fat water fraction(FWF)related to fat metabolism in supraclavicular region of neck with iterative decomposition of water and fat with echo asymmetry and least square estimation iron quantification(IDEAL-IQ)sequence quantitatively.Methods Twenty healthy female and twenty healthy male volunteers were selected for a MRI examination with IDEAL-IQ,then the FWF of R2*,brown adipose tissue(BAT)and white adipose tissue(WAT)were obtained by post-processing.The differences of FWF between the two groups were compared by Mann-Whitney U test.Results There was sig-nificant difference in the FWF of BAT and WAT between the two groups(P＜0.05).The FWF of BAT in the female was higher than that the male,and the FWF of WAT in the male was higher than that the female,there was no significant difference in the R2*between the two groups(P＞0.05).Conclusion IDEAL-IQ sequence can be used to evaluate the FWF in supraclavicular region of neck quantitatively,and classify BAT and WAT,then provide clinical according to the quantitative study of fat content.
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Objective:To conduct a scope review on the application of ICU diaries in critically ill patients, laying the foundation for further exploration and construction of ICU diary patterns and frameworks that were in line with the national conditions and tailored to different regions and cultural backgrounds.Methods:The Joanna Briggs Institute Reviewer′s Manual was used as the methodological framework, and a computer search was conducted in nine domestic and international databases, including China National Knowledge Infrastructure, Wanfang Database, China Biomedical Literature Database, Cochrane Library, PubMed, and Embase, etc. The search period was from the inception of the databases until March 13, 2023. The included literature was screened, summarized, and analyzed.Results:A total of 19 articles were included. ICU diaries were commonly recorded using a combination of text and visuals, with the involvement of both healthcare professionals and family members. Most patients received ICU diaries approximately one month after their transfer from the ICU. Out of the 15 studies, ICU diaries were found to be effective, while 4 studies indicated no significant improvement in patients′ psychological issues. However, ICU diaries were still considered acceptable by patients and their families.Conclusions:The application of ICU diaries has shown positive significance in critically ill patients, but further research and exploration are needed to investigate its impact on issues such as post-traumatic stress disorder, anxiety, depression, and quality of life. In the future, a combination of multiple forms and high-quality research designs with large samples, long periods, and structured approaches should be employed to explore its application effects and long-term outcomes on psychological problems.
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Objective:To retrieve, evaluate and summarize the relevant evidence for respiratory management in patients with amyotrophic lateral sclerosis (ALS), and provide reference for clinical nursing.Methods:The best practices, guidelines, expert consensus and other evidence on respiratory management in ALS patients were systematically retrieved from dometic and foreign relevant guide websites, professional associations and databases. The retrieve period was from January 1, 2016 to April 15, 2023. After the literature quality evaluation, the evidence was extracted from the literature that meets the quality standards.Results:A total of 12 references were included, including 3 guidelines, 1 expert consensus, 1 evidence summary, 4 systematic reviews, and 3 randomized controlled trails. The 25 pieces of evidence were summarized from the patients with ALS, including respiratory assessment, mechanical ventilation, secreta management, and respiratory rehabilitation.Conclusions:This study summarizes the best evidence on respiratory tract management in patients with ALS, which is convenient for clinical medical personnel to carry out more targeted and scientific respiratory assessment, intervention and guidance for patients with ALS.
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Objective To explore the influencing factors of non-suicidal self-injury behavior and motivation in adult patients with depression.Methods A simple random sampling method was used to select 120 adult patients with depression admitted to our hospital from January 2023 to June 2023 as the research objects.The clinical information of the patients was collected,and their loneliness,frustration and self-injury motivation were evaluated.The influencing factors of non-suicidal self-injury(NSSI)behavior and motivation were statistically analyzed.Results Age,ULS-8 score,DS score,marital status and employment status were the influencing factors of NSSI in adult patients with depression(P<0.05).ULS-8 score,DS score,marital status(widowed/divorced)and employment status were independent risk factors for NSSI in adult patients with depression(P<0.05).The ULS-8 score was an independent risk factor for patients with'emotion regulation'as NSSI motivation.Age,DS score and employment(unemployment)were independent risk factors for patients with'interpersonal boundary'as NSSI moti-vation(P<0.05).Conclusion There are many influencing factors of NSSI and NSSI motivation in adult depres-sion patients,and the influencing factors of different NSSI motivations are different.Clinically,the main motivation and related influencing factors of patients implementing NSSI should be clarified through detailed investigation,so as to facilitate the development of targeted intervention strategies for patients.
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BACKGROUND:Haploidentical hematopoietic stem cell transplantation is associated with a higher rate of graft rejection and therefore often requires a higher CD34+ cell dose,but the findings reported in existing studies regarding the relationship between CD34+ cell dose and study endpoints after allogeneic hematopoietic stem cell transplantation are controversial. OBJECTIVE:To investigate the effect of CD34+ cell dose on clinical outcomes of haploidentical hematopoietic stem cell transplantation for malignant hematological diseases. METHODS:135 patients who underwent haploidentical hematopoietic stem cell transplantation at Hematopoietic Stem Cell Transplantation Center,Department of Hematology,First Affiliated Hospital of Zhengzhou University between January 2019 and December 2021 were included.Combining the results of previous studies and our center's experience,the cohort was divided into two groups using a CD34+ cell count of 5.0×106/kg as the cut-off point.Clinical outcomes related to graft implantation,relapse incidence,non-relapse mortality,overall survival and progression-free survival were evaluated in both groups. RESULTS AND CONCLUSION:(1)CD34+ cell dose correlated with platelet engraftment,with platelets implanted earlier in the high-dose group than in the low-dose group(14 days vs.16 days,P=0.013).(2)There was no significant difference in 3-year overall survival between the two groups(67.5%vs.53.8%,P=0.257);nor was there a significant difference in progression-free survival between the two groups(65.6%vs.44.2%,P=0.106),but stratified analysis based on disease risk index revealed an association with elevated 3-year progression-free survival in the high-dose group among low-risk patients(72.0%vs.49.3%,P=0.036).(3)The cumulative 3-year relapse incidence was smaller in the high-dose group than in the low-dose group(16.0%vs.33.5%,P=0.05).(4)The rate of non-relapse mortality within 100 days was greater in the high-dose group than in the low-dose group,but there was no significant difference(17.3%vs.6.7%,P=0.070);stratified analysis revealed that non-relapse mortality within 100 days was significantly higher in the high-dose group than in the low-dose group(20.0%vs.3.3%,P=0.046).(5)In conclusion,CD34+ cell doses>5.0×106/kg promote early platelet implantation,improve 3-year progression-free survival in low-risk patients at transplantation and reduce the cumulative relapse incidence.However,in high-risk patients,high-dose CD34+ cells result in increased non-relapse mortality within 100 days after transplantation,which is considered to be possibly associated with an increased occurrence of severe acute graft versus host disease in the early post-transplantation period.Therefore,it is considered that graft versus host disease monitoring should be enhanced in patients who transfused high-dose CD34+ cells.
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BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an effective and even the only way to cure various hematological diseases,but the short-term mortality rate is relatively high after transplantation. OBJECTIVE:To investigate the risk factors affecting the overall survival of patients with hematological diseases in the short term(within 100 days)after allogeneic hematopoietic stem cell transplantation,so as to reduce mortality and effectively prevent related risks in the short term(within 100 days)after allogeneic hematopoietic stem cell transplantation. METHODS:Clinical data of 585 patients with hematological diseases who underwent allogeneic hematopoietic stem cell transplantation at the Hematopoietic Stem Cell Transplantation Center of First Affiliated Hospital of Zhengzhou University from January 1,2018 to June 30,2021 were retrospectively analyzed.The risk factors that affected overall survival within 100 days after allogeneic hematopoietic stem cell transplantation were explored. RESULTS AND CONCLUSION:A total of 585 patients with hematologic diseases underwent allogeneic hematopoietic stem cell transplantation.92 patients died within 100 days after transplantation,with a mortality rate of 15.7%(92/585).The median age of death cases was 26.5 years old(1-56 years),and the median survival time of death cases was 48 days(0-97 days).Univariate analysis exhibited that age≥14 years old,acute graft-versus-host disease,grade IV acute graft-versus-host disease,bacterial bloodstream infection,as well as carbapenem-resistant organism bloodstream infection,were risk factors for overall survival within 100 days after allogeneic hematopoietic stem cell transplantation(P<0.05).Multivariate regression analysis showed that age≥14 years old,grades Ⅲ-Ⅳ acute graft-versus-host disease,bacterial bloodstream infection,and carbapenem-resistant organism bloodstream infections were independent risk factors for overall survival(within 100 days)in patients after allogeneic hematopoietic stem cell transplantation.Hazard ratios were 1.77(95%CI 1.047-2.991),7.926(95%CI 3.763-16.695),2.039(95%CI 1.117-3.722),and 3.389(95%CI 1.563-7.347),respectively.In conclusion,all-cause mortality rate after allogeneic hematopoietic stem cell transplantation is relatively high in the short term.A timely diagnosis and effective treatment of bacterial bloodstream infection and acute graft-versus-host disease are essential to improving allogeneic hematopoietic stem cell transplantation outcomes.
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BACKGROUND:Currently,there have been studies on the regulatory mechanism of lncRNA\miRNA\mRNA co-expression network on the occurrence and development of osteoarthritis.Our research group has screened qualified NONHSAT248596.1 and miR-146a-5p through the database in the previous stage,but the corresponding in vivo experiments to verify the above regulatory mechanisms are still lacking. OBJECTIVE:To explore the role of NONHSAT248596.1 in regulating competitive endogenous RNA of miR-146a-5p in cartilage degeneration mediated by stromal cell derived factor type 1/chemokine receptor 4 axis in vivo. METHODS:The models of osteoarthritis were established in 36 New Zealand rabbits by injecting stromal cell derived factor 1 solution into the knee joint of the right hind limb.According to the random number table method,they were divided into four groups.lncRNA group,miRNA group,ceRNA group and control group were injected with lentivirus vector overexpressing NONHSAT248596.1,lentivirus vector overexpressing miR-146a-5p,lentivirus vector overexpressing miR-146a-5p+NONHSAT248596.1 and empty lentivirus vector into the molded knee joint,respectively.At 4,8 and 12 weeks of modeling,cartilage tissues and subchondral bone tissues of the knee joint were taken for relevant detection. RESULTS AND CONCLUSION:Hematoxylin-eosin staining and safranin fast green staining showed different degrees of degeneration in the four groups.At 4 weeks,the cartilage tissue of the lncRNA group showed swelling of chondrocytes,loss of cell polarity,destruction of extracellular matrix,surface erosion,fracture formation and partial or full layer loss of cartilage tissue.The degree of cartilage injury was gradually aggravated with time.The progression of articular cartilage inflammation in the miRNA group was the slowest among the four groups.qRT-PCR showed that at the same time point,mRNA expression levels of NONHSAT248596.1,chemokine receptor 4,matrix metalloproteinase 3,matrix metalloproteinase 9 and matrix metalloproteinase 13 in cartilage tissue of the lncRNA group were higher than those of the other three groups(P＜0.05).The mRNA expression levels of miR-146a-5p,aggrecan and type Ⅱ collagen were lower than those of the other three groups(P＜0.05).The mRNA expression levels of NONHSAT248596.1,chemokine receptor 4,matrix metalloproteinase 3,matrix metalloproteinase 9 and matrix metalloproteinase 13 in the miRNA group were lower than those in the ceRNA group and control group at 8 and 12 weeks after the model construction(P＜0.05).The mRNA expressions of miR-146a-5p,aggrecan and type Ⅱ collagen were higher than those of the ceRNA group and control group(P＜0.05).Western blot assay showed that at the same time point,the expression levels of aggrecan and type Ⅱ collagen in cartilage tissue of the lncRNA group were always lower than those of the other three groups(P＜0.05).The expression levels of aggrecan and type Ⅱ collagen in cartilage tissue of the miRNA group at 8 and 12 weeks after modeling were higher than those of the ceRNA group and control group(P＜0.05).The results showed that miR-146a-5p,as the target of NONHSAT248596.1,could be inhibited by the effect of its ceRNA.After acting on miR-146a-5p,NONHSAT248596.1 regulates the stromal cell derived factor type 1/chemokine receptor 4 axis to affect the expression of matrix metalloprotein,type Ⅱ collagen,and aggrecan in osteoarthritis chondrocytes,resulting in the degradation of extracellular matrix and the loss of proteoglycan.
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BACKGROUND:Deferoxamine mesylate is a potential anti-osteoporosis drug with iron chelation,vascular regeneration,and antioxidant effects.Recent studies have shown that the application of deferoxamine mesylate can be extended to the field of tissue regeneration engineering. OBJECTIVE:To investigate whether deferoxamine mesylate can promote the repair effect of iron overload osteoporotic rats after bone grafting for mandibular bone defects by simulating the state of iron accumulation in patients with postmenopausal osteoporosis with high iron intervention in osteoporotic rats. METHODS:An iron accumulation ovariectomized osteoporosis model was firstly constructed.The model group underwent bilateral ovariectomy,and the intraperitoneal injection of ferric ammonium citrate(90 mg/kg,twice a week,for 11 weeks)was started in the 2nd week,while the sham-operated group had some fat around the ovaries removed and was given an equal amount of saline for 11 weeks.After the successful modeling,the experimental rats were divided into sham-operated group(n=6),high iron ovariectomtized group(n=6)and high iron ovariectomized deferoxamine mesylate treatment group(deferoxamine mesylate group,n=6).Bone defects of 5 mm in diameter were established in the rat's bilateral mandibles and implanted with Bio-Oss bone powder.Intraperitoneal injection of deferoxamine mesylate(100 mg/kg,3 times a week)was started on postoperative day 4 in the deferoxamine mesylate group,and equal volume of saline was given in the sham-operated and high iron ovariectomized groups.The bone samples of the mandible,liver and blood were taken at 2 and 12 weeks after bone grafting for Prussian blue staining of the jaw and liver and ELISA detection of serum ferritin to detect iron levels in various body tissues;hematoxylin-eosin staining and Masson staining were performed to observe inflammatory cell infiltration and early osteogenesis in the bone defect area;tartrate resistant acid phosphatase staining was performed to observe osteoclast differentiation;ELISA was performed to detect serum calcitonin and type I collagen C-terminal peptide levels;and Micro-CT and hematoxylin-eosin staining were performed to observe osteogenesis in the middle and late stages. RESULTS AND CONCLUSION:The number of tibial trabeculae was reduced and the trabeculae were sparsely arranged in the high iron ovariectomized group.Iron levels in the liver,jaw bone and serum were significantly higher in the high iron ovariectomized group than the sham-operated group at 2 weeks after bone grafting,while the iron levels were significantly decreased after deferoxamine mesylate intervention(P＜0.05).In the early stage of bone defect repair,more inflammatory cell infiltration,less new bone matrix and less type I collagen fiber production were observed in the high iron ovariectomized group than in the sham-operated group(P＜0.05);after deferoxamine mesylate treatment,inflammatory cell infiltration was reduced,a small amount of new bone matrix was produced and collagen fibers increased significantly(P＜0.05).In the middle and late stages of bone defect repair,Micro-CT results showed a reduction in new bone production in the high iron ovariectomized group compared with the sham-operated group and increased new bone matrix after deferoxamine mesylate treatment(P＜0.05).Compared with the sham-operated group,the osteoclast number,serum calcitonin level,and serum type I collagen C-terminal peptide level were increased in the high-iron ovariectomized group,while the osteoclast number was decreased and bone metabolic indexes were improved after treatment with deferoxamine mesylate.To conclude,in ovariectomized rats with high iron intervention,elevated iron levels can be seen in multiple tissues,accompanied by reduced new bone production in the mandibular bone defect area.Deferoxamine mesylate can improve bone metabolism and inhibit osteoclast activity by removing iron deposits in tissues,improve bone formation in iron-accumulated osteoporotic rats,and promote bone healing in the mandibular bone defect area.
الملخص
BACKGROUND:Interleukin-4 can promote the osteogenic effect of bone substitute materials,but its molecular mechanism is not yet clear.Further elucidating the mechanism of interleukin-4 promoting osteogenic effect can help find safe,economical,and effective methods for the regeneration treatment of alveolar bone defects in patients. OBJECTIVE:To explore the effect of interleukin-4 intervention on polarization transformation of macrophages and osteogenic differentiation of bone marrow mesenchymal stem cells and its possible mechanism. METHODS:RAW264.7 cells in the M1 group were induced with interferon gamma + lipopolysaccharide for 24 hours.RAW264.7 cells in the interleukin-4+M1 group were induced with interferon gamma + lipopolysaccharide for 24 hours and then interleukin-4 was added for 24 hours.RAW264.7 cells in the interleukin-4+AG+M1 group were induced with interferon gamma + lipopolysaccharide for 24 hours,and then interleukin-4 and AG-490,a JAK/STAT pathway inhibitor,were added for 24 hours.After intervention,immunofluorescence staining was used to analyze the expression of inducible nitric oxide synthase and CD206,the phenotypic marker protein of macrophages.ELISA kit was used to detect the expression of interleukin-10 and tumor necrosis factor-α in the supernatant of cell culture.The gene expressions of nodular receptor protein-3(NLRP3),interleukin-1β,and caspase-1 were detected by RT-qPCR.The expression levels of tyrosine protein kinase 1(JAK1)/phosphorylated tyrosine protein kinase 1(p-JAK1),signal transduction and transcription activator 6(STAT6)/phosphorylated signal transduction and transcription activator 6(p-STAT6),NLRP3,pro-interleukin-1β and pro-caspase-1 were detected by western blot assay.Then,RAW264.7 cells in the above four groups were indirectly co-cultured with bone marrow mesenchymal stem cells by transwell for 24 hours,followed by alkaline phosphatase staining and alizarin red staining.The mRNA expressions of alkaline phosphatase,collagen type I,and osteocalcin were detected by RT-qPCR. RESULTS AND CONCLUSION:(1)Immunofluorescence and ELISA results showed that interleukin-4 intervention could promote the expression of CD206 and interleukin-10 in M2 macrophages,and inhibit the secretion of inducible nitric oxide synthase and tumor necrosis factor-α.(2)RT-qPCR results showed that interleukin-4 could suppress the expression of NLRP3,interleukin-1β,and caspase-1 mRNAs.(3)Western blot assay showed that interleukin-4 could promote the expression of JAK1/p-JAK1,STAT6/p-STAT6 and NLRP3 proteins.(4)The alkaline phosphatase staining and alizarin red staining of bone marrow mesenchymal stem cells co-cultured with the interleukin-4+M1 group were significantly enhanced,and the mRNA expressions of alkaline phosphatase,collagen type I,and osteocalcin were significantly increased.It is concluded that interleukin-4 may inhibit the activation of NLRP3 by up-regulating JAK1/STAT6 pathway,thus promoting the transformation of macrophages from M1 polarization to M2 polarization,and finally enhancing the osteogenic differentiation ability of bone marrow mesenchymal stem cells.