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BACKGROUND: Women with gynecological cancer often experience psychological distress, particularly in response to surgical procedures. The impact of mandala art therapy (MAT) during the perioperative period for gynecological cancer patients remains uncertain. We aimed to examine the effects of the MAT program in women with gynecological cancer. METHODS: Employing a quasi-experimental design, we recruited 126 gynecological cancer patients from a university hospital through convenience sampling. Participants were assigned to either receive the MAT program or standard perioperative care. The interventions comprised a three-session MAT program guided by a team of trained mandala psychologists. Generalized estimating equations (GEE) were employed to analyze the effects of MAT over time. RESULTS: A total of 126 patients were enrolled, and 118 completed the entire study. Over 90% of participants completed the perioperative MAT interventions, reporting relatively high satisfaction with the program (7.70 out of 10). Individuals in the MAT group exhibited improved therapeutic effects on STAI-S, VASS, and vital signs over time. Notably, significant group*time interaction effects were noted in STAI-S scores at both the first evaluation, T1 (ß = -4.220, P < .005) and the third evaluation, T3 (ß = -3.797, P < .05), and VASS scores at T1 (ß = -11.186, P < .005), T2 (ß = -9.915, P < .05) and T3 (ß = -9.831, P < .05). Regarding vital signs, the multivariate GEE model revealed significant interaction effects in systolic blood pressure values at both T1 (ß = -7.102, P < .05) and T3 (ß = -10.051, P < .005), diastolic blood pressure values at T3 (ß = -6.441, P < .005), and pulse values at T1 (ß = -6.085, P < .005). No significant differences were observed between groups for pain, hope, or self-acceptance. CONCLUSION: This study posited that MAT could serve as a valuable complementary approach in perioperative care for addressing the psychological needs of women with gynecological cancer. Subsequent research employing more robust methodologies and larger, more diverse participant samples will be necessary to validate these conclusions.
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Arteterapia , Neoplasias dos Genitais Femininos , Período Perioperatório , Humanos , Feminino , Neoplasias dos Genitais Femininos/psicologia , Neoplasias dos Genitais Femininos/cirurgia , Pessoa de Meia-Idade , Arteterapia/métodos , Período Perioperatório/psicologia , Período Perioperatório/métodos , Adulto , Estresse Psicológico/psicologia , Estresse Psicológico/terapia , Idoso , Qualidade de Vida/psicologia , Bem-Estar PsicológicoRESUMO
AIM: While insulin sensitivity plays an important role in maintaining glucose metabolic homeostasis and cognitive function, its impact on postoperative delirium (POD) remains unclear. This study aimed to investigate the association between POD and indicators of insulin sensitivity, including insulin resistance and osteocalcin. METHODS: A total of 120 elderly patients undergoing joint replacement were recruited and divided into delirium and non-delirium groups. Plasma and cerebrospinal fluid (CSF) samples were collected for the analysis of biomarkers, including insulin, uncarboxylated osteocalcin (ucOC), total osteocalcin (tOC), and glucose. Insulin resistance was assessed through the homeostatic model assessment of insulin resistance (HOMA-IR). MAIN RESULTS: Out of the total, 28 patients (23.3%) experienced POD within 5 days after surgery. Patients with delirium exhibited higher levels of preoperative HOMA-IR and ucOC in CSF and plasma, and of tOC in CSF (P = 0.028, P < 0.001, P = 0.005, P = 0.019). After adjusting for variables, including age, Mini-Mental State Examination score, surgical site and preoperative fracture, only preoperative ucOC in CSF and HOMA-IR were significantly linked to the incidence of delirium (OR = 5.940, P = 0.008; OR = 1.208, P = 0.046, respectively), both of which also correlated with the severity of delirium (P = 0.007, P < 0.001). Receiver operating curve analysis indicated that preoperative HOMA-IR and ucOC in CSF might partly predict POD (area under the curve [AUC] = 0.697, 95% confidence interval [CI] = 0.501-0.775, AUC = 0.745, 95% CI = 0.659-0.860). CONCLUSIONS: We observed that preoperative elevated HOMA-IR and ucOC in CSF were associated with the incidence and severity of POD. While these preliminary results need confirmation, they suggest a potential involvement of insulin resistance and osteocalcin in the pathological mechanism of POD. Geriatr Gerontol Int 2024; 24: 421-429.
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Artroplastia de Substituição , Delírio do Despertar , Resistência à Insulina , Humanos , Idoso , Osteocalcina , Incidência , Glucose , Artroplastia de Substituição/efeitos adversosRESUMO
PURPOSE: Numerous studies have investigated the relationships between nutritional status and the prognosis of ovarian cancer (OC). However, the majority of these studies have focused on pre-chemotherapy malnutrition, with limited attention given to dynamic changes in nutritional status during chemotherapy and the associated risk factors affecting the prognostic nutritional index (PNI) in OC women. This study aims to explore the variation trend in the nutritional status of OC women over time during chemotherapy and assess its predictive factors. METHODS: A prospective longitudinal study was conducted from January 2021 to August 2023. Body mass index (BMI), PNI, Nutritional Risk Screening (NRS) 2002, serum albumin, and prealbumin measurements were utilized to assess the nutritional status of OC women. Data were collected through face-to-face interviews before initial chemotherapy (T0) and during the first (T1), third (T2), and fifth (T3) cycles of chemotherapy. Generalized Estimating Equations (GEE) were employed for the analysis of potential predictive factors. RESULTS: A total of 525 OC women undergoing chemotherapy completed the study. Significantly varied levels of BMI, PNI, and serum concentrations of hemoglobin, albumin, prealbumin, potassium, sodium, magnesium, and calcium were observed in these patients (p < 0.05). The prevalence of nutritional risk decreased over time during chemotherapy (p < 0.05). Nutritional parameters, including BMI, PNI, and the serum concentrations of albumin and prealbumin, exhibited an upward trend in nutritional status throughout the chemotherapy cycles (p < 0.05). Multivariate analysis indicated that higher levels of BMI, serum albumin, prealbumin, absolute lymphocyte count, and hemoglobin ≥ 110 g/L at admission were associated with elevated PNI after chemotherapy (ß = 0.077, p = 0.028; ß = 0.315, p < 0.001; ß = 0.009, p < 0.001; ß = 1.359, p < 0.001; ß = - 0.637, p = 0.005). CONCLUSION: Patients consistently demonstrated improvements in nutritional risk and status from the initiation to the completion of chemotherapy cycles. Nutritional monitoring of OC women, particularly those exhibiting abnormalities at the commencement of chemotherapy, is crucial. Targeted nutritional support programs should be developed to enhance the prognosis of OC women.
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Estado Nutricional , Neoplasias Ovarianas , Humanos , Feminino , Avaliação Nutricional , Pré-Albumina , Prognóstico , Estudos Prospectivos , Estudos Longitudinais , Albumina Sérica/análise , Hemoglobinas/análise , Neoplasias Ovarianas/tratamento farmacológico , Estudos RetrospectivosRESUMO
BACKGROUND: Insulin plays a crucial and multifactorial role in cognitive activity, with insulin resistance appearing in neurodegenerative and metabolic diseases. Insulin resistance contributes to the pathobiology of postoperative cognitive dysfunction (POCD) in experimental models, which can be rescued by intranasal insulin administration. AIMS: To test the effect of intranasal insulin on the incidence of POCD in elderly patients with metabolic syndrome. METHODS: The study was designed as a randomized, double-blind, placebo-controlled clinical trial. 116 elderly participants were randomly assigned to receive either 40 IU insulin (n = 58) or placebo (n = 58) for 7 days. The primary outcome was the incidence of POCD at 7 days and 3 months after surgery. Secondary outcomes included the degree of peripheral insulin resistance postoperatively, changes in peripheral inflammation levels and the safety of interventions. RESULTS: The results showed that POCD occurred in the insulin group on the 7th postoperative day in 11 (20.8%) patients, which was fewer than the 23 (45.1%) patients in the placebo group (P = 0.008). The insulin group indicated better cognitive functional performance on language and memory test than the placebo group (P < 0.05). Mean peripheral plasma concentration of TNF-α (P < 0.05) and CRP (P < 0.001) in the insulin group was significantly declined compared with the placebo group on D3 and D7. CONCLUSIONS: Intranasal insulin administration reduced the incidence of POCD and alleviated peripheral inflammatory levels in elderly patients with metabolic syndrome. TRIAL REGISTRY: Chinese Clinical Trial Registry (ChiCTR1800015502).
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Disfunção Cognitiva , Resistência à Insulina , Síndrome Metabólica , Complicações Cognitivas Pós-Operatórias , Humanos , Idoso , Insulina/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Síndrome Metabólica/complicaçõesRESUMO
BACKGROUND: Platelet-rich fibrin (PRF) is a second-generation platelet concentrate. Although peripheral blood-derived PRF (P-PRF) is commonly applied in biological augmentation, there is no report about the therapeutic effect of bone marrow-derived PRF (BM-PRF) for degenerative rotator cuff tears (RCTs). PURPOSE/HYPOTHESIS: To examine the effects of platelet-rich plasma (PRP), P-PRF, and BM-PRF during rotator cuff repair (RCR) in degenerative RCTs in rabbits. We hypothesized that BM-PRF would accelerate the bone-tendon healing after RCR. STUDY DESIGN: Controlled laboratory study. METHODS: Degenerative RCT models were created 2 weeks before beginning the study, and 68 juvenile rabbits were divided into 4 groups: the control, PRP, P-PRF, and BM-PRF groups. RCR without augmentation was done in the control group. PRP was prepared by centrifuging peripheral blood twice using a plastic tube. P-PRF and BM-PRF were prepared by centrifuging peripheral blood and bone marrow, respectively, using a glass tube. Rabbits from PRP, P-PRF, and BM-PRF groups were administered the augmentation in a similar fashion for RCR, between the rotator cuff and the footprint of the humerus. At 4, 8, and 12 weeks, rabbits were euthanized and histologically assessed using hematoxylin and eosin staining, Alcian blue staining, and immunohistochemical staining for type I and III collagen. The sections were also evaluated with immunofluorescence staining of vascular endothelial growth factor (VEGF) at 4 weeks. RESULTS: The continuity was significantly better in the BM-PRF group at 4 weeks (P < .05). Immunofluorescence staining demonstrated that VEGF-positive stained cells were significantly greater in the BM-PRF group than in the control group (P < .01). The modified tendon maturing score was significantly greater in the BM-PRF group than in the control and PRP groups at 12 weeks (P < .05). There was no significant difference in the modified tendon maturing score of the P-PRF group compared with the control group. CONCLUSION: The rabbit model of degenerative RCTs demonstrated that RCR combined with BM-PRF enhanced tendon-bone continuity and increased the VEGF-positive cells at 4 weeks and obtained preferable tendon-bone maturation at 12 weeks. CLINICAL RELEVANCE: RCR augmented with BM-PRF has the potential to improve clinical outcomes for RCTs.
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Fibrina Rica em Plaquetas , Plasma Rico em Plaquetas , Lesões do Manguito Rotador , Azul Alciano/metabolismo , Animais , Medula Óssea/metabolismo , Colágeno/metabolismo , Amarelo de Eosina-(YS)/metabolismo , Hematoxilina/metabolismo , Plásticos/metabolismo , Fibrina Rica em Plaquetas/metabolismo , Plasma Rico em Plaquetas/metabolismo , Coelhos , Manguito Rotador/patologia , Lesões do Manguito Rotador/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Aspergillus nidulans (A. nidulans) is an ascomycetous fungus that can cause disseminated infection in humans or animals. The present study aimed to explore the pathogenesis and host spleen immune response after infection with A. nidulans. Thirty KM mice were divided into control group (C) and treated group (T). Serum was collected for the detection of inflammatory markers. Spleens were collected for histopathological examination, fungal culture and transcriptomic analysis. Compared with the control group, the concentrations of serum total protein (TP), globulin (GLO) and C-reactive protein (CRP) were significantly increased (P < 0.01), but the concentration of albumin (ALB) and the ratio of albumin/globulin (A/G) were significantly decreased in the treated group (P < 0.01). In addition, the splenic red pulp was hyperemic, and the white pulp was infiltrated by inflammatory cells in treated group. The chromatin was aggregated, and the mitochondria were swollen in the spleen lymphocytes of treated group. Transcriptome sequencing results showed that 47.2 million and 44.9 million clean reads were obtained in the control group and treated group, respectively. 946 differentially expressed genes (DEGs) were obtained, including 372 up-regulated genes and 574 down-regulated genes. GO analysis showed that these DEGs were mainly involved in the immune responses, antigen binding, immunoglobulin receptor binding, bacterial defence responses, endopeptidase activity and so on. Moreover, KEGG analysis showed that these DEGs were mainly enriched in the following pathways: complement and coagulation cascades, retinol metabolism, cytochrome p450, IL-17 signalling pathway and so on. Additionally, 9 DEGs was validated by qRT-PCR approach. In summary, this study revealed the immune response mechanism of spleen in A. nidulan-infected mice. It will benefit for a better understanding of the pathogenic mechanisms of A. nidulans.
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Aspergillus nidulans , Doenças dos Peixes , Albuminas , Animais , Aspergillus nidulans/genética , Doenças dos Peixes/microbiologia , Perfilação da Expressão Gênica , Humanos , Camundongos , Baço , TranscriptomaRESUMO
Using density functional theory (DFT) calculations, we researched the different anions adsorption on the graphene and found that anions can be stably adsorbed on the graphene surface due to the anion-π interaction. The adsorption energy decreased as the order of HPO42- > SO42- > F- > CH3COO- > ClO3- > NO3- > ClO4- > SCN- > Cl- > Br-. The adsorption energy markedly increased as the valence of anion increased from negative monovalence (< -20 kcal/mol) to negative bivalence (> -40 kcal/mol). The energy decomposition analysis (EDA) showed that anion-π interaction is mainly induced by orbital effect. This work provides new insights for understanding Hofmeister effect at graphene interface from the molecular level and indicates that the anion-π interaction cannot be ignored at the interface, especially for the substrate with π-electron-rich carbon-based nanomaterials.
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Testicular germ cell tumor (TGCT) is the most common malignant tumor in young men and is associated with poor prognosis. We assessed the RNA expression profiles of 13 TGCT tissues and 4 adjacent normal tissues by transcriptome sequencing to identify novel prognostic biomarkers. We detected several differentially expressed mRNAs in TGCT that were functionally annotated by GO and KEGG enrichment analyses to tumorigenesis-related processes such as immunity and chemotherapeutic resistance. An mRNA-lncRNA-miRNA regulatory network was constructed using RNA-Seq data and public databases, and integrated with TCGA database to develop a prediction model for metastasis and recurrence. Finally, GRK4, PCYT2 and RGSL1 were identified as predictive markers of survival and therapeutic response. In conclusion, we found several potential predictors for TGCT prognosis and immunotherapeutic response by ceRNA network analysis.
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Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/genética , RNA Mensageiro/análise , RNA Mensageiro/genética , RNA/análise , RNA/genética , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/genética , Adulto , Biomarcadores Tumorais , Biologia Computacional , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , RNA-SeqRESUMO
Objective: To investigate clinical application of day surgery A1 pulley release for pediatric trigger thumb. Methods: We retrospectively analyzed the clinical data of 1,642 children with trigger thumb who were treated with day surgery A1 pulley release at our hospital, including satisfaction surveys, functional recovery, and complications. Results: The operative time for unilateral and bilateral tenolysis was 4.8 ± 3.1 and 9.2 ± 3.8 min, respectively. Three children had postoperative fever and were discharged on the 2nd day after surgery. The rest of the children were discharged on the day of surgery. All incisions healed primarily, and no complications of vascular and nerve injury were reported. The patients' degree of satisfaction with the medical treatment process, diagnosis and treatment workflow, treatment effectiveness, length of hospital stay and hospitalization cost, and discharge guidance were 97.9, 96.1, 99.3, 91.1, and 98.5%, respectively. The follow-up period was between 5 months and 3 years and 1 month. Four children experienced symptom relapse after the operation, and re-tenolysis was performed in one of them. At the final follow-up, the appearance and function of the thumb had recovered well in all cases. Conclusion: Day surgery A1 pulley release can effectively release tendon sheaths and has a short operative time, no complications of vascular and nerve injury, and good recovery of thumb function. It is a safe and reliable procedure with high patient satisfaction, and it is worthy of clinical promotion.
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OBJECTIVES: To evaluate gait characteristics and investigate changes pre- and post- cerebrospinal fluid tap test (CSF TT) in gait parameters in patients with probable idiopathic normal pressure hydrocephalus (iNPH). METHODS: Sixty patients were sequential circuited and diagnosed with possible iNPH according to Japanese second iNPH guidelines at our hospital from December 2016 to March 2021. All patients underwent the CSF TT. Gait parameters, cognitive and urinary function were assessed pre- and post-CSF TT. Patients who were unable to ambulate to take the tests or could not walk independently or walked normally were excluded. RESULTS: Twenty-six patients were diagnosed with probable iNPH using the CSF TT. After CSF TT, the Boon sum score improved from 20.0 ± 7.7-16.6 ± 8.0 (p < 0.001), the Boon walking score improved from 8.9 ± 3.5-7.8 ± 4.4 (p = 0.008), the Boon step score improved from 6.3 ± 2.3-5.2 ± 2.1 (p < 0.001), the Boon time score improved from 4.9 ± 2.4-3.7 ± 2.3 (p < 0.001), tandem walking disturbance improved from 1.7 ± 0.7-1.4 ± 0.9 (p = 0.043), tendency toward falling improved from 1.7 ± 0.7-1.3 ± 1(p = 0.022), 3-meter timed up and go test (3-mTUG) improved from 21.9 ± 7.1-17.6 ± 5.1( p < 0.001), 10-meter walking (10-MWT) step improved from 31.1 ± 13.1-24.6 ± 7.5 (p < 0.001), velocity improved from 0.7 ± 0.2-0.8 ± 0.3 (p < 0.001) and stride length improved from 0.4 ± 0.1-0.46 ± 0.1(p < 0.001), compared with before the CSF TT. CONCLUSION: These results suggest that many parameters in the Boon gait test were responsive to the CSF TT, and the Boon gait test may help objectify response to the CSF TT by combining the 10-MWT and 3-mTUG gait assessments.
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Marcha/fisiologia , Hidrocefalia de Pressão Normal/fisiopatologia , Equilíbrio Postural/fisiologia , Idoso , Cognição/fisiologia , Feminino , Humanos , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Masculino , Punção EspinalRESUMO
Background: The cardiovascular and cerebrovascular risk of postoperative acute kidney injury (AKI) in surgical patients is poorly described, especially in the hypertensive population. Methods: We conducted a retrospective cohort study among all hypertensive patients who underwent elective noncardiac surgery from January 1st, 2012 to August 1st, 2017 at the Third Xiangya Hospital. The primary outcomes were fatal stroke and fatal myocardial infarction (MI). The secondary outcomes were all-cause mortality. Results: The postoperative cumulative mortality within 3 months, 6 months, 1 year, 2 years, and 5 years were 1.27, 1.48, 2.15, 2.15, and 5.36%, for fatal stroke, and 2.05, 2.27, 2.70, 3.37, and 5.61% for fatal MI, respectively, in patients with postoperative AKI. Compared with non-AKI patients, those with postoperative AKI had a significantly higher risk of fatal stroke and fatal MI within 3 months [hazard ratio (HR): 5.49 (95% CI: 1.88-16.00) and 11.82 (95% CI: 4.56-30.62), respectively], 6 months [HR: 3.58 (95% CI: 1.43-8.97) and 9.23 (95% CI: 3.89-21.90), respectively], 1 year [HR: 3.64 (95% CI: 1.63-8.10) and 5.14 (95% CI: 2.50-10.57), respectively], 2 years [HR: 2.21 (95% CI: 1.03-4.72) and 3.06 (95% CI: 1.66-5.64), respectively], and 5 years [HR: 2.27 (95% CI: 1.30-3.98) and 1.98 (95% CI: 1.16-3.20), respectively]. In subgroup analysis of perioperative blood pressure (BP) lowering administration, postoperative AKI was significantly associated with 1-year and 5-year risk of fatal stroke [HR: 9.46 (95% CI: 2.85-31.40) and 3.88 (95% CI: 1.67-9.01), respectively] in patients with ACEI/ARB, and MI [HR: 6.62 (95% CI: 2.23-19.62) and 2.44 (95% CI: 1.22-4.90), respectively] in patients with CCB. Conclusion: Hypertensive patients with postoperative AKI have a significantly higher risk of fatal stroke and fatal MI, as well as all-cause mortality, within 5 years after elective noncardiac surgery. In patients with perioperative administration of ACEI/ARB and CCB, postoperative AKI was significantly associated with higher risk of fatal stroke and MI, respectively.
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Spermatogonial stem cells (SSCs) are the initial cells for the spermatogenesis. Although much progress has been made on uncovering a number of modulators for the SSC fate decisions in rodents, the genes mediating human SSCs remain largely unclear. Here we report, for the first time, that TCF3, a member of the basic helix-loop-helix family of transcriptional modulator proteins, can stimulate proliferation and suppress the apoptosis of human SSCs through targeting podocalyxin-like protein (PODXL). TCF3 was expressed primarily in GFRA1-positive spermatogonia, and EGF (epidermal growth factor) elevated TCF3 expression level. Notably, TCF3 enhanced the growth and DNA synthesis of human SSCs, whereas it repressed the apoptosis of human SSCs. RNA sequencing and chromatin immunoprecipitation (ChIP) assays revealed that TCF3 protein regulated the transcription of several genes, including WNT2B, TGFB3, CCN4, MEGF6, and PODXL, while PODXL silencing compromised the stem cell activity of SSCs. Moreover, the level of TCF3 protein was remarkably lower in patients with spermatogenesis failure when compared to individuals with obstructive azoospermia with normal spermatogenesis. Collectively, these results implicate that TCF3 modulates human SSC proliferation and apoptosis through PODXL. This study is of great significance since it would provide a novel molecular mechanism underlying the fate determinations of human SSCs and it could offer new targets for gene therapy of male infertility.
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BACKGROUND: The basis of individualized treatment should be individualized mortality risk predictive information. The present study aimed to develop an online individual mortality risk predictive tool for acute-on-chronic liver failure (ACLF) patients based on a random survival forest (RSF) algorithm. METHODS: The current study retrospectively enrolled ACLF patients from the Department of Infectious Diseases of The First People's Hospital of Foshan, Shunde Hospital of Southern Medical University, and Jiangmen Central Hospital. Two hundred seventy-six consecutive ACLF patients were included in the present study as a model cohort (nâ=â276). Then the current study constructed a validation cohort by drawing patients from the model dataset based on the resampling method (nâ=â276). The RSF algorithm was used to develop an individual prognostic model for ACLF patients. The Brier score was used to evaluate the diagnostic accuracy of prognostic models. The weighted mean rank estimation method was used to compare the differences between the areas under the time-dependent ROC curves (AUROCs) of prognostic models. RESULTS: Multivariate Cox regression identified hepatic encephalopathy (HE), age, serum sodium level, acute kidney injury (AKI), red cell distribution width (RDW), and international normalization index (INR) as independent risk factors for ACLF patients. A simplified RSF model was developed based on these previous risk factors. The AUROCs for predicting 3-, 6-, and 12-month mortality were 0.916, 0.916, and 0.905 for the RSF model and 0.872, 0.866, and 0.848 for the Cox model in the model cohort, respectively. The Brier scores were 0.119, 0.119, and 0.128 for the RSF model and 0.138, 0.146, and 0.156 for the Cox model, respectively. The nonparametric comparison suggested that the RSF model was superior to the Cox model for predicting the prognosis of ACLF patients. CONCLUSIONS: The current study developed a novel online individual mortality risk predictive tool that could predict individual mortality risk predictive curves for individual patients. Additionally, the current online individual mortality risk predictive tool could further provide predicted mortality percentages and 95% confidence intervals at user-defined time points.
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Insuficiência Hepática Crônica Agudizada , Humanos , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos RetrospectivosRESUMO
A preliminary chemical investigation on 70% MeOH extract of the roots of Asparagus cochinchinensis resulted in the isolation of nine steroids. These isolates comprised of four new C21 (1-4) and one new pregnane (5) glycosides, and four known C27 (6-9) spirostanol steroids. Their structures were identified via analysis of the spectroscopic data and the results of hydrolytic cleavage. The cytotoxic activities of the compounds were tested toward the human tumor cell line Hela (cervical cancer), and compounds 7 and 8 displayed moderate activity with IC50 values of 35.5 and 39.6 µM, respectively.
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Antineoplásicos Fitogênicos/farmacologia , Apocynaceae/química , Glicosídeos/farmacologia , Extratos Vegetais/farmacologia , Pregnanos/farmacologia , Esteroides/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Proliferação de Células , Feminino , Humanos , Estrutura Molecular , Raízes de Plantas/química , Neoplasias do Colo do Útero/patologiaRESUMO
BACKGROUND: Mammalian spermatogenesis is responsible for male fertility and is supported by the self-renewal and differentiation of spermatogonial stem cells (SSCs). Sertoli cells provide a supportive microenvironment for SSCs, in part by the production of stem cell factor (SCF), which is a potent regulator of spermatogonia proliferation and survival. METHODS: We investigated the novel role of ß-estradiol in modulating the proliferation and apoptosis of fetal SSCs via the regulation of SCF secretion in Sertoli cells isolated from human fetal testes. The proliferation of SSCs in the co-culture system was determined by colony formation and BrdU incorporation assays. TUNEL assay was used to measure SSC apoptosis in co-culture in response to treatment with control, ß-estradiol, or the combination of ß-estradiol and the estrogen receptor inhibitor ICI 182780. RESULTS: In the system with purified human fetal Sertoli cells (MIS+/c-Kit-/AP-), ß-estradiol upregulated the production of SCF in a dose- and time-dependent manner. In the co-culture system of primary human fetal SSCs (c-Kit+/SSEA-4+/Oct-4+/AP+) and Sertoli cells (MIS+), ß-estradiol markedly increased the proliferation of SSCs. Moreover, SSC apoptosis was significantly inhibited by ß-estradiol and was completely reversed by the combination of ß-estradiol and ICI 182780. CONCLUSION: Here we report, for the first time, that ß-estradiol can induce the increase of SCF expression in human fetal Sertoli cells and regulates the growth and survival of human fetal SSCs. These novel findings provide new perspectives on the current understanding of the role of estrogen in human spermatogenesis.
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Diferenciação Celular , Estradiol/farmacologia , Feto/citologia , Células de Sertoli/citologia , Espermatogônias/citologia , Fator de Células-Tronco/metabolismo , Células-Tronco/citologia , Técnicas de Cocultura , Estrogênios/farmacologia , Feto/efeitos dos fármacos , Feto/metabolismo , Idade Gestacional , Humanos , Masculino , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Espermatogênese , Espermatogônias/efeitos dos fármacos , Espermatogônias/metabolismo , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismoRESUMO
Caloric restriction (CR) or Dietary restriction (DR) is known to improve health and in many cases increases lifespan. However, its negative effect on reproduction has not been fully studied. Practicing CR/DR without adequate knowledge on its side effect may risk complications such as infertility, birth defect, or malnutrition. In this study, by using several CR strategies in C. elegans, we examine key functions of reproduction including embryonic development and larvae growth. We find that CR significantly decreases the survival of embryos and slows the growth of the offspring. We further determine that defect in oocyte but not sperm is responsible for the compromised reproduction under CR. Interestingly, adding methionine to the medium reverses the reproduction defects, but does not affect the long lifespan resulted from CR. The beneficial effect of methionine on reproduction requires the yolk protein vitellogenin. CR down-regulates vitellogenin expression, which can be reversed by supplementing methionine in the food. Lacking the yolk protein transport due to rme-2 mutation blocks methionine's beneficial effects. Our study has revealed a novel, methionine-mediated genetic pathway linking nutrient sensing to reproduction and suggested methionine as a potential food supplement to mitigate the side effect of CR.
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Caenorhabditis elegans/fisiologia , Suplementos Nutricionais , Gema de Ovo/metabolismo , Ingestão de Energia , Longevidade , Metionina/farmacologia , Animais , Metionina/administração & dosagemRESUMO
This study examines the physiological responses of the Symbiodiniumvoratum (clade E) to two types of phosphates having different chemical bonds-phosphoesters (C-O-P bonds) and phosphonates (C-P bonds) to explore Symbiodinium cell growth and the molecular perspective of the P utilization process. Alkaline phosphatase (AP), PhnX, PhoA and PhoX expression was profiled for different P conditions using the RT-qPCR method. In a sterile system, Symbiodinium could decompose phosphoesters, such as ATP and glucose 6-phosphate (G-6-P), into dissolved inorganic P (DIP) to supplement inorganic phosphorus but could not directly use phosphoesters for growth. The growth rate and photosynthetic efficiency of zooxanthellae in phosphoester-containing media did not significantly differ from those in the DIP group but were significantly inhibited in medium containing phosphonates such as N-(phosphonomethyl)glycine (glyphosate) and 2-aminoethylphosphonic acid (2-AEP), as well as in DIP-poor medium. The phosphonate group DIP concentration did not change remarkably, indicating that phosphonates can neither be directly used by zooxanthellae nor decomposed into DIP. Our RT-qPCR results support our views that the phosphoesters (C-O-P) had been hydrolyzed outside the cell before being absorbed into the Symbiodinium cell, and implies that PhnX, PhoA and PhoX are perhaps responsible for transporting DIP from medium into cells and for storage of DIP.
Assuntos
Dinoflagellida/metabolismo , Organofosfatos/metabolismo , Fósforo/metabolismo , Fosfatase Alcalina/metabolismo , Dinoflagellida/crescimento & desenvolvimento , Glicina/análogos & derivados , Glicina/metabolismo , GlifosatoRESUMO
To develop a vancomycin-loaded superparamagnetic chitosan nanoparticles (Vm-SPMCNs) system for the treatment of chronic pyogenic osteoarthrosis to avoid the critical side effects caused by the systemic administration of vancomycin, the preparation process of Vm-SPMCNs was optimized by the orthogonal array design method; the optimum parameters were 1.2 g of chitosan, 0.2 g of vancomycin, 0.3 g of magnetite (Fe3O4), 12 mL of glutaraldehyde and stirring at 400 rpm. The drug loading and encapsulation efficiencies of the optimum Vm-SPMCNs were 10.30 ± 0.42% and 79.02 ± 1.81%, respectively. The Fourier transform infrared spectra confirmed that vancomycin was successfully bound to the magnetic chitosan nanoparticles. The Vm-SPMCNs were superparamagnetic particles with a diameter of 207.2 nm. The results of in vitro release tests suggested that the Vm-SPMCNs could constantly release vancomycin to maintain the concentration above the minimum inhibitory concentration for ten days, and noninvasive external magnetic stimulation could modulate the release profile according to the actual therapeutic requirements.
Assuntos
Nanopartículas de Magnetita , Quitosana , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , VancomicinaRESUMO
OBJECTIVE: To investigate the transcriptome profile of genital tubercles (GTs) in male SD rats and explore the mechanism of hypospadias induced by Di (2-ethylhexyl) phthalate (DEHP). METHODS: Forty time-pregnant SD rats were randomly divided into 4 equal groups, namely GD16 group and GD19 group (in which the male GTs were collected on gestation day[GD]16 and GD19 for RNA-seq, respectively), control group and DEHP exposure group (with administration of oil and 750 mg/kg DEHP by gavage from GD12 to GD19, respectively).In the control and DEHP exposure groups, the GTs were collected from the male fetuses on GD19.5, and scanning electron microscopy and HE staining were used to observe the morphological changes.The differentially expressed genes (DEGs) in the GTs were screened using lllumina HiSeq 2000 followed by GO and KEGG enrichment analyses to characterize the transcriptome profile.Immunofluorescence assay was performed to verify the DEGs (Mafb) identified by RNA-seq results.Immunofluorescence assay and Western blotting were used to examine the expression levels of Mafb in the penile tissue. RESULTS: A total of 1360 DEGs were detected in the GTs between GD16 group and GD19 group by RNA-seq.Among these genes, 797 were up-regulated and 563 were down-regulated.These DEGs were mainly enriched in the cell adhesion plaque signaling pathway, axon guidance signaling pathway, and extracellular matrix receptor signaling pathway.Compared with that in GD16 group, Mafb was significantly up-regulated in GD19 group, which was consistent with the sequencing results.Mafb and ß-catenin were significantly down-regulated in DEHP-exposed group compared with the control group (P < 0.01). CONCLUSIONS: Mafb expression increases progressively with the development of GTs in male SD rats.DEHP exposure causes significant down-regulation of Mafb and ß-catenin, suggesting that ß-catenin signaling pathway that affects Mafb is related to DEHP-induced hypospadias in SD rats.
Assuntos
Hipospadia , Animais , Dietilexilftalato , Feminino , Perfilação da Expressão Gênica , Humanos , Fator de Transcrição MafB , Masculino , Proteínas Oncogênicas , Ácidos Ftálicos , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: The hand knob area is the cortical representation of motor hand function. The current study aimed to investigate the effects of eloquent area gliomas on the morphometry of the hand motor cortex and preoperative hand motor function. METHODS: A retrospective study of 320 glioma patients was conducted. Seventy-eight patients with gliomas involving motor functional area were finally enrolled. Using axial T2-weight magnetic resonance images, the width and height of the hand knob were measured in both hemispheres, and differences were compared between the affected and unaffected hemispheres. Receiver operating characteristic (ROC) curve and logistic regression analysis were used to estimate the degree of correlation between distance measurements and motor impairment. RESULTS: The width and height of the hand knob in the affected and unaffected hemispheres were significantly different (pâ¯< 0.0001). The width, height and distance from the tumor to hand knob were reduced in the functionally impaired group compared to the unimpaired group (pâ¯= 0.0003, pâ¯< 0.0001, pâ¯= 0.0005, respectively). The three parameters were significantly correlated and remained significant in ROC and logistic regression analysis. The optimal cut-off value of width, height and distance for identifying preoperative hand muscle strength were 5.73â¯mm, 5.80â¯mm and 5.92â¯mm, respectively. CONCLUSION: The morphometry of the hand knob is often changed by the infiltration or extrusion of the tumors that were located in or near the hand knob. The width, height of hand knob and the distance from tumor to hand knob could serve as anatomic biomarkers related to preoperative neurological motor deficits.