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Purpose: To investigate potential differences in pregnancy outcomes among patients with regular menstruation who underwent frozen-thawed embryo transfer using natural cycle (NC) or hormone replacement therapy (HRT). Methods: This study retrospectively analyzed 2672 patients with regular menstruation who underwent FET from November 2015 to June 2021 at the single reproductive medical center. A one-to-one match was performed applying a 0.02 caliper with propensity score matching. Independent factors influencing the live birth and clinical pregnancy rates were screened and developed in the nomogram by logistic regression analysis. The efficacy of live birth rate and clinical pregnancy rate prediction models was assessed with the area under the ROC curve, and the live birth rate prediction model was internally validated within the bootstrap method. Results: The NC protocol outperformed the HRT protocol in terms of clinical pregnancy and live birth rates. The stratified analysis revealed consistently higher live birth and clinical pregnancy rates with the NC protocol across different variable strata compared to the HRT protocol. However, compared to the HRT treatment, perinatal outcomes indicated that the NC protocol was related to a higher probability of gestational diabetes. Multifactorial logistic regression analysis demonstrated independent risk factors for live birth rate and clinical pregnancy rate. To predict the two rates, nomogram prediction models were constructed based on these influencing factors. The receiver operating characteristic curve demonstrated moderate predictive ability with an area under curve (AUC) of 0.646 and 0.656 respectively. The internal validation of the model for live birth rate yielded an average AUC of 0.646 implying the stability of the nomogram model. Conclusion: This study highlighted that NC yielded higher live birth and clinical pregnancy rates in comparison to HRT in women with regular menstruation who achieved successful pregnancies through frozen-thawed embryo transfer. However, it might incur a higher risk of developing gestational diabetes.
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Criopreservação , Transferência Embrionária , Terapia de Reposição Hormonal , Resultado da Gravidez , Pontuação de Propensão , Humanos , Feminino , Gravidez , Transferência Embrionária/métodos , Adulto , Estudos Retrospectivos , Terapia de Reposição Hormonal/métodos , Resultado da Gravidez/epidemiologia , Taxa de Gravidez , Menstruação , Nascido Vivo/epidemiologia , Fertilização in vitro/métodos , Ciclo Menstrual/fisiologiaRESUMO
INTRODUCTION: The risk of surgery and postoperative complications increases greatly in frail older patients with sarcopenia. The purpose of this study is to explore the correlation between myostatin (MSTN) levels and cognitive function and postoperative pulmonary complications (PPCs) in older patients undergoing thoracoscopic lobectomy and to determine whether MSTN could be used to predict the risk of postoperative complications and cognitive impairment. METHODS: A prospective observational study was conducted at the First Affiliated Hospital of Bengbu Medical College, China, between January 2023 and June 2023. The risk factors of PPCs and postoperative cognitive impairment were studied using backward stepwise logistic regression analysis. The independent factors were formed into a linear regression equation to construct a risk score model for each patient. The 122 patients who participated in the study were divided into two groups, a low-level group and a high-level group, based on an MSTN level cut-off; the preoperative MSTN cut-off values was 25.55 ng/mL for cognitive dysfunction and 22.29 ng/mL for PPCs. The PPCs and cognitive function of the groups were compared. RESULTS: Preoperative MSTN was confirmed as a risk factor for postoperative cognitive dysfunction and PPCs. After surgery, the proportion of patients with cognitive impairment in the high-level group was significantly higher than in the low-level group (P < 0.001). In the high-level group, the incidence of respiratory tract infections was 17.9% higher (P = 0.021), hypoxaemia was 20.5% higher (P = 0.001) and respiratory failure was 14.4% higher (P = 0.012) than in the low-level group. In addition, a high level of MSTN increased the length of hospital stay (P < 0.001) and decreased the Barthel Index score (P < 0.001). CONCLUSIONS: The study findings suggest that MSTN could be used as an index to predict complications and cognitive impairment after thoracoscopic lobectomy in older patients with sarcopenia and to provide evidence for reducing postoperative cognitive impairment and PPCs.
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OBJECTIVE: To construct and internally validate a nomogram that predicts the likelihood of postoperative delirium in a cohort of elderly individuals undergoing hip arthroplasty. METHODS: Data for a total of 681 elderly patients underwent hip arthroplasty were retrospectively collected and divided into a model (n = 477) and a validation cohort (n = 204) according to the principle of 7:3 distribution temporally. The assessment of postoperative cognitive function was conducted through the utilization of The Confusion Assessment Method (CAM). The nomogram model for postoperative cognitive impairments was established by a combination of Lasso regression and logistic regression. The receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA) were used to evaluate the performance. RESULTS: The nomogram utilized various predictors, including age, body mass index (BMI), education, preoperative Barthel Index, preoperative hemoglobin level, history of diabetes, and history of cerebrovascular disease, to forecast the likelihood of postoperative delirium in patients. The area under the ROC curves (AUC) for the nomogram, incorporating the aforementioned predictors, was 0.836 (95% CI: 0.797-0.875) for the training set and 0.817 (95% CI: 0.755-0.880) for the validation set. The calibration curves for both sets indicated a good agreement between the nomogram's predictions and the actual probabilities. CONCLUSION: The use of this novel nomogram can help clinicians predict the likelihood of delirium after hip arthroplasty in elderly patients and help prevent and manage it in advance.
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Artroplastia de Quadril , Delírio , Nomogramas , Humanos , Artroplastia de Quadril/efeitos adversos , Idoso , Feminino , Masculino , Estudos Retrospectivos , Delírio/etiologia , Delírio/diagnóstico , Delírio/epidemiologia , Idoso de 80 Anos ou mais , Fatores de Risco , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/diagnóstico , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Curva ROCRESUMO
Radiation therapy is a primary treatment for hepatocellular carcinoma (HCC), but its effectiveness can be diminished by various factors. The over-expression of PD-L1 has been identified as a critical reason for radiotherapy resistance. Previous studies have demonstrated that nifuroxazide exerts antitumor activity by damaging the Stat3 pathway, but its efficacy against PD-L1 has remained unclear. In this study, we investigated whether nifuroxazide could enhance the efficacy of radiotherapy in HCC by reducing PD-L1 expression. Our results showed that nifuroxazide significantly increased the sensitivity of tumor cells to radiation therapy by inhibiting cell proliferation and migration while increasing apoptosis in vitro. Additionally, nifuroxazide attenuated the up-regulation of PD-L1 expression induced by irradiation, which may be associated with increased degradation of PD-L1 through the ubiquitination-proteasome pathway. Furthermore, nifuroxazide greatly enhanced the efficacy of radiation therapy in H22-bearing mice by inhibiting tumor growth, improving survival, boosting the activation of T lymphocytes, and decelerating the ratios of Treg cells in spleens. Importantly, nifuroxazide limited the increased expression of PD-L1 in tumor tissues induced by radiation therapy. This study confirms, for the first time, that nifuroxazide can augment PD-L1 degradation to improve the efficacy of radiation therapy in HCC-bearing mice.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Nitrofuranos , Animais , Camundongos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/radioterapia , Antígeno B7-H1 , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , HidroxibenzoatosRESUMO
INTRODUCTION AND OBJECTIVES: To evaluate the impact of dexmedetomidine impact on cardiac surgery-associated acute kidney injury (CSA-AKI), kidney function, and metabolic and oxidative stress in patients undergoing coronary artery bypass grafting with heart-lung machine support. METHODS: A randomized double-masked trial with 238 participants (50-75 years) undergoing coronary artery bypass grafting was conducted from January 2021 to December 2022. The participants were divided into Dex (n=119) and NS (n = 119) groups. Dex was administered at 0.5 mcg/kg over 10minutes, then 0.4 mcg/kg/h until the end of surgery; the NS group received equivalent saline. Blood and urine were sampled at various time points pre- and postsurgery. The primary outcome measure was the incidence of CSA-AKI, defined as the occurrence of AKI within 96hours after surgery. RESULTS: The incidence of CSA-AKI was significantly lower in the Dex group than in the NS group (18.26% vs 32.46%; P=.014). Substantial increases were found in estimated glomerular filtration rate value at T4-T6 (P<.05) and urine volume 24hours after surgery (P<.01). Marked decreases were found in serum creatinine level, blood glucose level at T1-T2 (P<.01), blood urea nitrogen level at T3-T6 (P<.01), free fatty acid level at T2-T3 (P<.01), and lactate level at T3-T4 (P<.01). CONCLUSIONS: Dex reduces CSA-AKI, potentially by regulating metabolic disorders and reducing oxidative stress. Registered with the Chinese Clinical Study Registry (No. ChiCTR2100051804).
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Injúria Renal Aguda , Ponte de Artéria Coronária , Dexmedetomidina , Humanos , Dexmedetomidina/uso terapêutico , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/epidemiologia , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Método Duplo-Cego , Idoso , Estudos Prospectivos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Incidência , Taxa de Filtração Glomerular/efeitos dos fármacos , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Estresse Oxidativo/efeitos dos fármacosRESUMO
OBJECTIVES: Multiple myeloma (MM) is a malignant plasma cell disorder. The most widely accepted staging system for MM is the revised International Staging System based on cytogenetic and clinical biomarkers. The circulating clonal plasma cells (CPCs) were reported to have potential prognostic impact on MM. Among various diagnostic approaches, multiparametric flow cytometry (FCM) offers heightened sensitivity, minimal invasiveness and reproducibility. We conducted a meta-analysis to evaluate the prognostic value of quantifying CPCs via FCM in newly diagnosed symptomatic MM (NDMM) patients. DESIGN: Systematic review and meta-analysis. DATA SOURCE: PubMed, Web of Science, Embase and references of included studies. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included observational studies that evaluated the prognostic value of CPCs detected by FCM in NDMM. DATA EXTRACTION AND SYNTHESIS: Data were screened and extracted independently by two investigators. The pooled results originated from random effects models. The primary endpoint was overall survival (OS). The secondary endpoint was progression-free survival (PFS). To evaluate the prognostic value of CPCs in NDMM, HRs and their 95% CI for both OS and PFS were derived using COX multivariable models. These values were then used to compute the pooled estimated effect. RESULTS: Our meta-analysis encompassed a total of 2704 NDMM patients from 11 studies up to 27 August 2022. The pooled HR for OS and PFS in CPC-positive (CPCs+) group and CPC-negative group were 1.95 (95% CI 1.24 to 3.07) and 2.07 (95% CI 1.79 to 2.39), respectively. The autologous stem cell transplantation (ASCT) failed to eliminate the adverse impact on OS and PFS. The heterogeneity may stem from the use of novel agents or traditional chemotherapy as initial treatment. CONCLUSION: This meta-analysis indicates CPCs+ had an adverse impact on the prognosis of NDMM patients in the total population, and the adverse impact could not be eliminated by ASCT. PROSPERO REGISTRATION NUMBER: CRD42021272381.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Prognóstico , Plasmócitos/patologia , Citometria de Fluxo , Transplante de Células-Tronco Hematopoéticas/métodos , Reprodutibilidade dos Testes , Transplante AutólogoRESUMO
OBJECTIVE: This study was carried out to confirm whether patients with intermediate-risk differentiated thyroid cancer (DTC) could benefit from initial 131 I ablation and to identify the factors that impacted the benefit. METHODS: We retrospectively assessed a cohort of 548 patients with intermediate-risk DTC who were classified into structural incomplete response (SIR), biochemical incomplete response (BIR), indeterminate response (IDR), and excellent response (ER) groups according to the ATA guidelines (version 2015). A downgrade in the classification, such as from initial SIR to final BIR, IDR, or ER, from BIR to IDR or ER, and from initial IDR to final ER, was defined as benefiting from initial 131 I ablation (benefit group). Non-downgraded classification meant non-benefit. RESULTS: 64.78% of patients benefited from the initial 131 I ablation in the final re-evaluation. Gender (ORâ =â 0.038, P â =â 0.002), interval time (ORâ =â 0.038, P â =â 0.002) and serum ps-Tg (ORâ =â 0.961, P â =â 0.001) were independent prognostic factors for benefiting from initial 131 I ablation, with the cutoff value were 5 months and 19.08 ng/ml. CONCLUSION: Patients with intermediate-risk DTC could benefit from initial 131 I ablation. Female patients with intermediate-risk DTC whose interval time <5 months and ps-Tg <19.08 ng/ml were more likely to benefit. Early 131 I ablation for such patients is beneficial for achieving a complete therapeutic response.
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Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Feminino , Tireoglobulina , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Radioisótopos do Iodo/uso terapêutico , Resultado do TratamentoRESUMO
Hematologic malignancies are the most common hematopoietic diseases and a major public health concern. However, the mechanisms underlying myeloid tumors remain unknown owing to the intricate interplay between mutations and diverse clonal evolution patterns, as evidenced by the analysis of bulk cell-derived omics data. Several single-cell omics techniques have been used to characterize the hierarchies and altered immune microenvironments of hematologic malignancies. The comprehensive single-cell atlas of hematologic malignancies provides novel opportunities for personalized combinatorial targeted treatments, avoiding unwanted chemo-toxicity. In the present study, we performed transcriptome sequencing by combining single-cell RNA sequencing (scRNA-seq) with a targeted oncogenic gene panel for acute myeloid leukemia, overcoming the limitations of scRNA-seq in detecting oncogenic mutations. The distribution of oncogenic IDH1, IDH2, and KRAS mutations in each cell type was identified in the bone marrow (BM) samples of each patient. Our findings suggest that ferroptosis and metabolic reprogramming are involved in the tumorigenesis and chemotherapy resistance of oncogenic mutation-carrying cells. Biological progression via IDH1, IDH2, and KRAS mutations arrests hematopoietic maturation. Our study findings provide a rationale for using primary BM cells for personalized treatment in clinical settings.
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Ferroptose , Neoplasias Hematológicas , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/genética , Mutação , Análise de Sequência de RNA , Microambiente TumoralRESUMO
A colon tumor, one of the digestive tract malignant tumors, is harmful to human health. A potential new treatment still deserves attention. The development of a new drug needs more resources, including time and expense. Therefore, the old drug with new targets has become a current research hotspot. Fluvoxamine, as an antidepressant, could play an effect on inhibiting 5-hydroxytryptamine reuptake. In the present research, the antitumor effects and possible mechanisms of fluvoxamine are validated. The results showed that fluvoxamine significantly suppressed the migration and proliferation of tumor cells, and increased the apoptosis in vitro. Additionally, fluvoxamine significantly delays tumor development, and prompts the apoptosis in tumor tissues of mice-burdened colon tumors in vivo. The tumor suppression might be related with that fluvoxamine inhibits the expression of phosphorylated signal transducer and activator of transcription 3, matrix metalloproteinase 2, and cleaved-caspase 3. Importantly, fluvoxamine significantly reduces the expression level of programmed cell death ligand 1. This could be a possible reason that treatment with fluvoxamine drives the infiltration of T lymphocytes and M1-type macrophages in tumor tissues. Taken together, this research suggests that fluvoxamine might be a promising drug to treat colon cancer by inhibiting the proliferation and migration, inducing apoptosis, and even increasing the immune response of antitumor.
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Neoplasias do Colo , Fluvoxamina , Humanos , Animais , Camundongos , Fluvoxamina/farmacologia , Fluvoxamina/uso terapêutico , Metaloproteinase 2 da Matriz , Antígeno B7-H1/metabolismo , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Linhagem Celular TumoralRESUMO
Background: Optimal protocols for frozen-thawed embryo transfer (FET) after preimplantation genetic testing (PGT) remain unclear. This study compared Day 5 (D5) and Day 6 (D6) blastocysts and evaluated predictors of FET success. Methods: A total of 870 patients with genetic diseases or chromosomal translocations who received PGT at the First Affiliated Hospital of Zhengzhou University from January 2015 to December 2019 were recruited. All patients underwent at least one year of follow-up. Patients were divided into groups according to the blastocyst development days and quality. Univariate and multivariate logistic regression were applied to identify risk factors that affect clinical outcomes and to construct a predictive nomogram model. Area under the curve (AUC) of the subject's operating characteristic curve and GiViTI calibration belt were conducted to determine the discrimination and fit of the model. Results: D5 blastocysts, especially high-quality D5, resulted in significantly higher clinical pregnancy (58.4% vs 49.2%) and live birth rates (52.5% vs 45%) compared to D6. Multivariate regression demonstrated the number of blastocysts, endometrial preparation protocol, days of embryonic development and the quality of blastocysts independently affected live birth rates (P<0.05). A nomogram integrating these factors indicated favorable predictive accuracy (AUC=0.598) and fit (GiViTI, P=0.192). Conclusions: Transferring high-quality D5 euploid blastocysts after PGT maximizes pregnancy outcomes. Blastocyst quality, blastocyst development days, endometrial preparation protocols, and number of blastocysts, independently predicted outcomes. An individualized predictive model integrating these factors displayed favorable accuracy for counseling patients and optimizing clinical management.
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Implantação do Embrião , Transferência Embrionária , Gravidez , Feminino , Humanos , Taxa de Gravidez , Estudos Retrospectivos , Transferência Embrionária/métodos , BlastocistoRESUMO
BACKGROUND: The purpose of this study was to investigate the protective effects of dexmedetomidine (DEX) on total body radiation-induced acute liver injury in mice and to explore the possible mechanisms. METHODS: A total of 40 mice were randomly divided into the Control group (Group C), Dexmedetomidine group (Group Dex), Radiation group (Group R), and Group R+Dex. Mice in Group Dex and Group R+Dex were intraperitoneally injected with 10 µg/mL Dex at 50 mg/kg. Both Group C and Group R received normal saline instead of Dex. Mice were treated via continuous administration for 10 days and injection once a day (pre-administration for 3 days and 7 days after radiation). One hour after administration on the third day, the mice in Group R and R+Dex received total body radiation with a total dose of 6 Gy at a rate of 2 Gy/min. Group C received sham radiation. Levels of aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and liver levels of tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA) were measured. HE staining was employed to evaluate the pathological changes in liver tissues, and the expressions of Nrf2 and HO-1 proteins in the liver were measured by western blot. RESULTS: Compared with group C, serum levels of AST and ALT, liver TNF-α, IL-1ß, MDA, and ROS levels increased, and SOD decreased in Group R. Group R mice had higher liver injury scores, and the protein expressions of Nrf2 and HO-1 proteins were lower (p ï¼ 0.05). Compared with Group R, the levels of AST, ALT, TNF-α, IL-1ß, MDA, and ROS decreased, SOD increased, liver injury scores were lower, and the expressions of Nrf2 and HO-1 proteins were higher in the Group R+Dex group (all p ï¼ 0.05). CONCLUSIONS: Dex exhibits a protective effect on reducing acute radiation-induced liver injury and oxidative stress, and the mechanism may be associated with the activation of Nrf2/HO-1 pathways.
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Dexmedetomidina , Fator 2 Relacionado a NF-E2 , Animais , Dexmedetomidina/metabolismo , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Fígado/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/farmacologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase , Fator de Necrose Tumoral alfaRESUMO
The physiological function and prognostic significance of C-type lectin domain family 12 member A (CLEC12A) in acute myeloid leukemia (AML) patients are unclear. CLEC12A transcriptional expression in a variety of tumors from several public databases was collected and compared. We found that CLEC12A was highly expressed in AML cell lines and in tissues from AML patients and a higher CLEC12A expression in leukemia stem cells. CLEC12A low expression was associated with poor prognosis in the chemotherapy-only group and high CLEC12A expression may benefit from autologous or allogeneic hematopoietic stem cell transplantation (HSCT). CLEC12A expression was positively correlated with infiltrating levels of type 2 macrophages and monocytes and negatively associated with NK cells and regulatory T cells in AML. CLEC12A high was positively associated with immune checkpoint genes as well as macrophage associated genes. CLEC12A is an ideal chimeric antigen receptor T-cell (CAR-T) therapy target for AML and its expression level was closely linked to treatment response and patients' survival outcome. CLEC12A plays an important immunomodulatory role in AML.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Receptores de Antígenos Quiméricos , Humanos , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Prognóstico , Receptores Mitogênicos/genética , Receptores Mitogênicos/metabolismoRESUMO
BACKGROUND: To evaluate the value of preablative stimulated thyroglobulin (ps-Tg) before the first radioactive ablation iodine (RAI) treatment to predict the postoperative metastasis of DTC. METHODS: A total of 235 DTC patients, who underwent total thyroidectomy and neck lymph node dissection, were enrolled. On the basis of the presence or absence of metastasis, all patients were divided into metastasis (M1) and non-metastasis (M0) groups. Besides, the patients in the M1 group were further divided into two subgroups according to sites of metastasis. These groups included cervical lymph node metastasis and distant metastasis groups. Subsequently, the level of serum ps-Tg was measured 3 - 4 days before the first RAI ablation treatment, whereas 131I whole-body imaging and SPECT/CT tomography were performed 5 - 7 days after radio ablation. Subsequently, the Mann Whitney U test was used to compare the different levels of ps-Tg between the two groups. Additionally, the relationship between ps-Tg and the metastasis of DTC was analyzed through correlation analysis, regression analysis, and the ROC curve. RESULTS: The ps-Tg level in the M1 group was higher than that in the M0 group. Further analysis discovered that the ps-Tg in the distant metastasis group was higher than that in the cervical lymph node metastasis and non-metastasis groups. Also, the ps-Tg level was positively correlated with distant metastasis (r = 0.599, p = 0.000). Besides, the results of multivariate logistic regression analysis outlined that the level of ps-Tg was an independent risk factor for the development of distant metastasis (OR = 1.008, p = 0.018). Subsequently, the results from the ROC analysis also showed a good diagnostic performance for ps-Tg in treating distant metastasis (AUC = 0.964, p = 0.000), and the optimal cutoff value was 61.87 ng/mL. CONCLUSIONS: The ps-Tg in patients with DTC before the first RAI ablation treatment is an independent risk factor and a meaningful indicator in predicting postoperative distant metastasis.
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Iodo , Neoplasias da Glândula Tireoide , Humanos , Radioisótopos do Iodo/uso terapêutico , Estudos Retrospectivos , Tireoglobulina , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
Recently, a difference between involved and uninvolved free light chains (dFLC) less than 10 mg/L after treatment (stringent dFLC response) was reported to be associated with superior survival in light-chain (AL) amyloidosis. We conducted a retrospective study of AL amyloidosis patients treated with bortezomib to investigate the predictive value of a stringent dFLC response. Two hundred and thirty-five patients were included. The cardiac and renal responses were much higher in patients achieving a stringent dFLC response (86.5% versus 42.7% and 75.9% versus 38.2%, p < .001). Patients with a stringent dFLC response had significantly longer overall survival and time to next treatment (TNT). Among the very good partial response (VGPR) patients, the TNT of stringent dFLC responders was superior to those of the remaining VGPR patients (p = .045) and comparable to those of complete response patients. In conclusion, a stringent dFLC response might be added to current response criteria for AL amyloidosis.
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Amiloidose , Amiloidose de Cadeia Leve de Imunoglobulina , Amiloidose/diagnóstico , Amiloidose/tratamento farmacológico , Bortezomib , Humanos , Cadeias Leves de Imunoglobulina , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Estudos RetrospectivosRESUMO
The aimf of this study was to explore effects of miR-132 and glycogen synthase kinase-3ß (GSK-3ß) on learning and memory in mice. miR-132 inhibitor GSK-3ß overexpression agent (sh-GSK-3ß) and normal saline (negative control group) were injected into the hippocampus of adult mice, and healthy adult mice were taken as the unrelated control group. The expression of miR-132 and GSK-3ß in the hippocampus of adult and elderly mice was detected using reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis. Morris water maze test was employed to detect learning and memory function in mice. The dual luciferase reporter was adopted to determine the relationship between miR-132 and GSK-3ß. Compared with the adult group, the expression of miR-132 was significantly downregulated in the hippocampus in the elderly group, while the expression of GSK-3ß was upregulated. Injecting miR-132 inhibitor into the hippocampus of adult mice led to a significant increase in escape latency and a significant decrease in the number of times of crossing platforms. The injection of GSK-3ß overexpression agent into the hippocampus of adult mice resulted in a marked increase in escape latency and a significant decrease in the number of times of crossing platforms in the water maze test. It was also found that downregulation of GSK-3ß reversed the decline in learning and memory in mice caused by downregulation of miR-132 expression. The dual luciferase report identified a targeted regulatory relationship between miR-132 and GSK-3ß. Overexpression of miR-132 can inhibit the expression of GSK-3ß in mouse learning and memory ability, which provides some inspiration for understanding the occurrence of learning and memory disorders and future treatment methods.
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Polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes (POEMS) syndrome is associated with increased risk for ischemic stroke (IS). Because POEMS syndrome is rare, little is known regarding the underlying mechanism and prognosis for IS in patients in whom it occurs. The medical records of patients with POEMS syndrome were screened between January 2018 and January 2000 at Peking Union Medical College Hospital to identify those with IS. The baseline characteristics, IS features, and patient outcomes were analyzed. Forty-one (8.0%) of 510 POEMS patients were documented to have IS. Patients with IS were older, had a higher percentage of Overall Neuropathy Limitation Scale score >4, and had a higher level of fibrinogen compared with those who did not have IS. Ninety-three percent of IS events occurred before or within 3 months after a diagnosis of POEMS. Of 41 occurrences of IS, 29 (46.3%) were multifocal. Recurrent IS was observed in 13 (31.7%) of 41 patients, but not in patients with successful anti-plasma cell therapy. The 3-year overall survival rate in patients with IS was 71.0% and for those without IS, it was 88.5% (P = .002). We showed that 8.0% of POEMS patients had IS, and most IS events occurred in POEMS patients not being treated effectively. Having IS was a predictor of unfavorable prognosis. Early diagnosis, immediate initiation of treatment for POEMS, and control of POEMS syndrome is key to reducing the occurrence of IS, improving survival, and preventing recurrence of IS.
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Isquemia Encefálica , AVC Isquêmico , Síndrome POEMS , Paraproteinemias , Acidente Vascular Cerebral , Humanos , Síndrome POEMS/complicações , Síndrome POEMS/diagnóstico , Síndrome POEMS/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: Previous cardiac magnetic resonance (CMR) studies have shown that both late gadolinium enhancement (LGE) and left ventricular (LV) strain have prognostic value in amyloid light-chain (AL) amyloidosis, but the right ventricular (RV) strain has not yet been studied. We aim to determine the incremental prognostic value of LV and RV LGE and strain in AL amyloidosis. METHODS: This prospective study recruited 87 patients (age, 56.9±9.1 years; M/F, 56/31) and 20 healthy subjects (age, 52.7±8.1 years; M/F, 11/9) who underwent CMR. The LV LGE was classified into no, patchy and global groups. The RV LGE was classified into negative and positive groups. Myocardial deformation was measured using a dedicated software. Follow-up was performed for all-cause mortality using Cox proportional hazards regression and Kaplan-Meier curves. RESULTS: During a median follow-up of 21 months, 34 deaths occurred. Presence of LV LGE [HR 2.44, 95% confidence interval (CI), 1.10-5.45, P=0.029] and global longitudinal strain (GLS) (HR 1.13 per 1% absolute decrease, 95% CI, 1.02-1.25, P=0.025) were independent LV predictors. RV LGE (HR 4.07, 95% CI, 1.09-15.24, P=0.037) and GLS (HR 1.10 per 1% absolute decrease, 95% CI, 1.00-1.21, P=0.047) were independent RV predictors. Complementary to LV LGE, LV GLS impairment or RV LGE further reduced survival (both log rank P<0.001). CONCLUSIONS: This study confirms the incremental prognostic value of LV GLS and RV LGE in AL amyloidosis, which refines the conventional risk evaluation based on LV LGE. GLS based on non-contrast-enhanced CMR are promising new predictors.
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BACKGROUND: To compare the application value of serum and urinary ß2-microglobulin in immunoglobulin A nephropathy (IgAN). METHODS: Two hundred thirteen patients were hospitalized at the First Affiliated Hospital of Bengbu Medical College in China because of physical abnormalities and diagnosed with IgAN by means of renal biopsy between January 2010 and December 2018. ß2-MG levels in serum and urine were detected through immunoturbidimetric methods. The renal histopathology was quantified according to Katafuchi semi-quantitative standards and Lee's grading. RESULTS: One hundred twenty-four patients were male and 89 cases were female, for a 1.39:1 male to female ratio. The average age was 38.25 ± 12.48 years old when patients received their first renal biopsy. The levels of serum ß2-MG and urine ß2-MG increased gradually with the aggravation of tubulointerstitial lesions. Results of correlation analysis showed that serum ß2-MG had higher application value. Serum ß2-MG levels were positively correlated with SCr and tubulointerstitial lesions (r = 0.840, 0.652, p = 0.000), negatively correlated with CG-eGFR (r = -0.680, p = 0.000). The results of multivariate logistic regression analysis showed that serum ß2-MG was a marker of independent risk factor for the score of tubulointerstitial lesions ≥ 3 (OR = 6.649, p = 0.000). ROC analysis showed better diagnostic performance for serum ß2-MG, with the optimal cutoffs in predicting tubulointerstitial score ≥ 1, score ≥ 4 and score ≥ 7 of 1.905 mg/L, 2.13 mg/L, and 4.49 mg/L, respectively. CONCLUSIONS: Serum ß2-MG is valuable in evaluating renal function and pathological lesions in IgAN patients and has significant predictive value in evaluating tubulointerstitial lesions. Serum ß2-MG may be used as a non-invasive diagnostic indicator for predicting renal function and tubulointerstitial lesions in IgAN.
Assuntos
Glomerulonefrite por IGA , Adulto , Biomarcadores , China , Feminino , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/diagnóstico , Humanos , Rim , Masculino , Pessoa de Meia-IdadeRESUMO
To explore the clinical characteristics and outcomes in Chinese patients with type I cryoglobulinemia (CG), we retrospectively analyzed the clinical data, management, and outcomes of 45 patients diagnosed with type I CG in our hospital from January 2015 to March 2019. In our study, all type I CGs were secondary to hematologic diseases, and monoclonal gammopathy of unknown significance was the most common primary disease, accounting for 48.9% (n = 22). Additionally, B cell non-Hodgkin lymphoma, Waldenström's macroglobulinemia, and multiple myeloma accounted for 24.4% (n = 11), 20.0% (n = 9), and 6.7% (n = 3), respectively. In patients with type I CG, skin damage was the most common symptom, presenting in 57.8% of the patients, followed by peripheral neuropathy (22.2%) and renal involvement (15.6%). Treatment was initiated in 29 patients (64.4%), and the most common choice was a rituximab-based regimen in 13 patients (44.8%), followed by bortezomib-based regimen in 11 patients (37.9%). Clinical symptoms were significantly improved after treatment, and the clinical remission rate was 86.2%, including 34.5% of complete clinical remission, while the laboratory response rate was 88.9%, including 33.3% of complete response and 55.6% of partial response. The expected 1-year overall survival was 97.8%. In conclusion, for patients with multisystemic involvement, such as skin damage, kidney damage, or peripheral neuropathy, the diagnosis of type I CG should be considered, and the underlying disease needs to be explored. Symptoms and primary diseases should be taken into consideration before choosing initial management.
Assuntos
Bortezomib/administração & dosagem , Crioglobulinemia/tratamento farmacológico , Crioglobulinemia/mortalidade , Rituximab/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , China/epidemiologia , Crioglobulinemia/sangue , Crioglobulinemia/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
Background: Amyloid light chain (AL) amyloidosis is characterized by tissue deposition of amyloid fibres derived from immunoglobulin that can lead to irreversible organ damage. Information about genomic profiles of AL amyloidosis is lacking.Methods: In this study, we adopted a two-step strategy to investigate the mutational profile of AL amyloidosis bone marrow plasma cells (PCs) and their clinical implications. In step one, whole-exome sequencing was performed in bone marrow PCs and paired with normal tissue from 10 AL amyloidosis patients, by which we identified 10 significantly mutated genes (SMGs). In step two, we constituted a targeted gene sequencing (TGS) panel covering the frequently mutated genes identified in step one, genes reported in prior AL amyloidosis studies, and known cancer driver mutations. Then, we analysed an expanded cohort of AL amyloidosis patients (N = 48) with this panel comprising 98 genes.Results: Four recurrent mutations were identified by TGS and verified by Sanger sequencing: ASB15 (c. 844 C > T), ASCC3 (c. 1595 A > G), HIST1H1E (c. 311 C > T) and KRAS (c. 35 G > A), among which the first three mutations were associated with inferior overall survival (OS). Additionally, we found that the number of mutations identified by the TGS panel of 98 genes could be a prognostic predictor for OS.Conclusions: In summary, we revealed genomic profiling in AL amyloidosis and found mutation profiles associated with OS.