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1.
World J Surg Oncol ; 22(1): 168, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918829

RESUMO

BACKGROUND: To investigate the prognosis of patients with Multiple Myeloma (MM) after surgery, analyze the risk factors leading to adverse postoperative outcomes, and establish a nomogram. METHODS: Clinical data from 154 patients with MM who underwent surgery at our institution between 2007 and 2019 were retrospectively analyzed. Assessing and comparing patients' pain levels, quality of life, and functional status before and after surgery (P < 0.05) were considered statistically significant. The Kaplan-Meier survival curve was used to estimate the median survival time. Adverse postoperative outcomes were defined as worsened symptoms, lesion recurrence, complication grade ≥ 2, or a postoperative survival period < 1 year. Logistic regression analysis was used to determine the prognostic factors. Based on the logistic regression results, a nomogram predictive model was developed and calibrated. RESULTS: Postoperative pain was significantly alleviated in patients with MM, and there were significant improvements in the quality of life and functional status (P < 0.05). The median postoperative survival was 41 months. Forty-nine patients (31.8%) experienced adverse postoperative outcomes. Multivariate logistic regression analysis identified patient age, duration of MM, International Staging System, preoperative Karnofsky Performance Status, and Hb < 90 g/L as independent factors influencing patient prognosis. Based on these results, a nomogram was constructed, with a C-index of 0.812. The calibration curve demonstrated similarity between the predicted and actual survival curves. Decision curve analysis favored the predictive value of the model at high-risk thresholds from 10% to-69%. CONCLUSION: This study developed a nomogram risk prediction model to assist in providing quantifiable assessment indicators for preoperative evaluation of surgical risk.


Assuntos
Mieloma Múltiplo , Nomogramas , Qualidade de Vida , Humanos , Mieloma Múltiplo/cirurgia , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Idoso , Taxa de Sobrevida , Seguimentos , Complicações Pós-Operatórias/etiologia , Adulto , Fatores de Risco , Idoso de 80 Anos ou mais , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/diagnóstico
2.
BMC Pregnancy Childbirth ; 24(1): 432, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886682

RESUMO

BACKGROUND: IgA nephropathy (IgAN) is the most common cause of primary glomerulonephritis, with complex pathogenic mechanisms involving abnormal B-cell activation. As a novel biologic agent, telitacicept inhibits both B-lymphocyte stimulating factor and a proliferation-inducing ligand. It also inhibits both B cells and plasma cells and the production of galactose-deficient IgA1 (Gd-IgA1) and its autoantibodies, thus exerting an immunosuppressive effect. Women with IgAN are at a higher risk of adverse pregnancy outcomes such as preeclampsia and miscarriage, especially those with uncontrolled massive proteinuria and advanced chronic kidney disease. Therefore, IgAN disease control before and during pregnancy is essential. Here, we report the case of a woman with IgAN who had a successful pregnancy with significant improvement and long-term remission after treatment with telitacicept. This is the first report of a pregnancy following exposure to telitacicept. CONCLUSION: This report describes the efficacy of telitacicept in patients with IgAN and explores its value in women of childbearing age, suggesting effective and safe treatment options for women who wish to conceive.


Assuntos
Glomerulonefrite por IGA , Complicações na Gravidez , Humanos , Feminino , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/complicações , Gravidez , Adulto , Complicações na Gravidez/tratamento farmacológico , Resultado da Gravidez
3.
ACS Appl Mater Interfaces ; 16(22): 28694-28708, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38768307

RESUMO

Harvesting wind energy from the environment and integrating it with the internet of things and artificial intelligence to enable intelligent ocean environment monitoring are effective approach. There are some challenges that limit the performance of wind energy harvesters, such as the larger start-up torque and the narrow operational wind speed range. To address these issues, this paper proposes a wind energy harvesting system with a self-regulation strategy based on piezoelectric and electromagnetic effects to achieve state monitoring for unmanned surface vehicles (USVs). The proposed energy harvesting system comprises eight rotation units with centrifugal adaptation and four piezoelectric units with a magnetic coupling mechanism, which can further reduce the start-up torque and expand the wind speed range. The dynamic model of the energy harvester with the centrifugal effect is explored, and the corresponding structural parameters are analyzed. The simulation and experimental results show that it can obtain a maximum average power of 23.25 mW at a wind speed of 8 m/s. Furthermore, three different magnet configurations are investigated, and the optimal configuration can effectively decrease the resistance torque by 91.25% compared with the traditional mode. A prototype is manufactured, and the test result shows that it can charge a 2200 µF supercapacitor to 6.2 V within 120 s, which indicates that it has a great potential to achieve the self-powered low-power sensors. Finally, a deep learning algorithm is applied to detect the stability of the operation, and the average accuracy reached 95.33%, which validates the feasibility of the state monitoring of USVs.

4.
Nutrients ; 16(9)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38732641

RESUMO

Numerous studies have investigated the immunomodulatory effects of yogurt, but the underlying mechanism remained elusive. This study aimed to elucidate the alleviating properties of yogurt on immunosuppression and proposed the underlying mechanism was related to the metabolite D-lactate. In the healthy mice, we validated the safety of daily yogurt consumption (600 µL) or D-lactate (300 mg/kg). In immunosuppressed mice induced by cyclophosphamide (CTX), we evaluated the immune regulation of yogurt and D-lactate. The result showed that yogurt restored body weight, boosted immune organ index, repaired splenic tissue, recovered the severity of delayed-type hypersensitivity reactions and increased serum cytokines (IgA, IgG, IL-6, IFN-γ). Additionally, yogurt enhanced intestinal immune function by restoring the intestinal barrier and upregulating the abundance of Bifidobacterium and Lactobacillus. Further studies showed that D-lactate alleviated immunosuppression in mice mainly by promoting cellular immunity. D-lactate recovered body weight and organ development, elevated serum cytokines (IgA, IgG, IL-6, IFN-γ), enhanced splenic lymphocyte proliferation and increased the mRNA level of T-bet in splenic lymphocyte to bolster Th1 differentiation. Finally, CTX is a chemotherapeutic drug, thus, the application of yogurt and D-lactate in the tumor-bearing mouse model was initially explored. The results showed that both yogurt (600 µL) and D-lactate (300 mg/kg) reduced cyclophosphamide-induced immunosuppression without promoting tumor growth. Overall, this study evaluated the safety, immune efficacy and applicability of yogurt and D-lactate in regulating immunosuppression. It emphasized the potential of yogurt as a functional food for immune regulation, with D-lactate playing a crucial role in its immunomodulatory effects.


Assuntos
Ciclofosfamida , Citocinas , Ácido Láctico , Iogurte , Animais , Camundongos , Ácido Láctico/sangue , Citocinas/metabolismo , Masculino , Terapia de Imunossupressão , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/imunologia , Camundongos Endogâmicos BALB C , Hipersensibilidade Tardia/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Lactobacillus , Bifidobacterium
5.
RSC Adv ; 14(15): 10378-10389, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38567344

RESUMO

The smallest Hückel aromatic ring cyclopropenium substituted by electron-donating C-amino groups produced a aminocyclopropenium electron-rich cation. A bifunctional aminocyclopropenium halide catalyst installed with bis-(hydroxyethyl) functions on the amino group was then designed. A typical (diethanolamino)cyclopropenium halide catalyst C5·I was screened optimally for the cycloaddition of carbon disulfide into an epoxide to produce cyclic dithiocarbonate with an excellent conversion (95%) and high selectivity (92%). The electrostatic enhancement of alkyl C-H HBD capability was implemented via vicinal positive charges on the cyclopropenium core, and the acidity of the terminal O-H hydrogen proton increased by intramolecular H-bonding between the two hydroxy groups on the diethanolamino group (O-H⋯O-H). Then, a hybrid H-bond donor comprising enhanced alkyl C-H and hydroxy O-H was formed. The hybrid HBD offered by aminocyclopropenium was vital in activating the epoxide and stabilizing the intermediate, resulting in reduced O/S scrambling. Moreover, weakly coordinated iodide anion served as a nucleophilic reagent to open the ring of the epoxide. The cooperative catalytic mechanism of the HBD cation and halide anion was supported by NMR titrations and control experiments. Eleven epoxides with various substituents were converted into the corresponding cyclic thiocarbonate with high conversion and selectivity under mild conditions (25 °C, 6 h) without a solvent. The cycloaddition of carbon disulfide with epoxides catalyzed by aminocyclopropenium developed a new working model for hydrogen bonding organocatalysis.

6.
Eur Spine J ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647604

RESUMO

PURPOSE: To investigate the effectiveness and safety of separation surgery for Epidural Spinal Cord Compression (ESCC) graded ≥ 2 in patients with Multiple Myeloma (MM), analyze factors influencing surgical outcomes, and develop a preliminary treatment decision framework for these patients. METHODS: A retrospective analysis was conducted on clinical data from 35 MM patients who underwent separation surgery for ESCC graded ≥ 2 between 2013 and 2018. Patient data, including baseline information, surgical details, complications, and pre-operative as well as one-month post-operative efficacy evaluation indicators were recorded. Statistical analysis was performed on pre-operative and post-operative efficacy indicators to determine if there were significant improvements (p < 0.05). Ordered logistic regression was utilized to assess factors associated with an unfavorable post-operative quality of life outcome. RESULTS: Compared to pre-operative values, at one-month post-surgery, patients showed significant improvements in Frankel Score Classification (4 vs 5, p < 0.05), Karnofsky Performance Score (30 vs 70, p < 0.05), and Visual Analogue Scale (8 vs 3, p < 0.05). Complications occurred in 7 cases (20%). The number of segments with ESCC (OR = 0.171, p < 0.05) and pre-operative chemotherapy (OR = 5.202, p = 0.05) were identified as independent factors influencing patient outcomes. Patients with more than two vertebral segments with ESCC exhibited significantly worse post-operative conditions. CONCLUSIONS: Separation surgery effectively alleviates pain, improves neurological function, and enhances the quality of life in patients with ESCC graded ≥ 2 due to MM.

7.
Front Endocrinol (Lausanne) ; 15: 1334414, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318295

RESUMO

Background: Diabetic foot ulcers constitute a substantial healthcare burden on a global scale and present challenges in achieving healing. Our objective was to assess the efficacy of modified tibial cortex transverse transport surgery in managing refractory diabetic foot ulcers. Methods: We retrospectively analyzed clinical data from 98 patients suffering from diabetic foot ulcers classified as Wagner grade ≥II who were admitted to our medical facility between January 2020 and June 2022. All the patients were treated by modified tibial cortex transverse transport surgery, wherein the osteotomy scope was reduced to two rectangular bone windows measuring 1.5cm × 1.5cm each. Record the patient's general information and ulcer healing time; ulcer area, ankle-brachial index, WIFi classification, and visual analogue scale before and 3 months following the surgical intervention. Results: The average duration of diabetes of 98 patients with diabetic foot ulcer was 20.22 ± 8.02 years, 52 patients had more than one toe gangrene on admission. The postoperative wound healing rate was 95.83% and the average healing time was 53.18 ± 20.18 days. The patients showed significant improvement in ankle-brachial index, WIFi classification, and visual analogue scale at 3 months postoperatively compared to preoperatively, with statistically significant differences (P< 0.05). Eight patients experienced complications, and the incidence of complications was 8.16%. Throughout the follow-up period, there were no instances of ulcer recurrence noted. Conclusion: Modified tibial cortex transverse transport surgery demonstrates effectiveness in the management of diabetic foot ulcers by enhancing lower limb microcirculation and facilitating the process of wound healing.


Assuntos
Diabetes Mellitus , Pé Diabético , Humanos , Pé Diabético/cirurgia , Estudos Retrospectivos , Tíbia/cirurgia , Extremidade Inferior , Cicatrização
8.
Sci Total Environ ; 912: 169496, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38135085

RESUMO

The effect of long term exposure to low concentrations of environmental pollutants on hepatic disorders is a major public health concern worldwide. Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent organic pollutants. In recent years, an increasing number of studies have focused on the deleterious effects of low concentrations of PAHs in the initiation or exacerbation of the progression of chronic liver disease. However, the underlying molecular mechanisms and effective intervention methods remain unclear. Here, we found that in hepatocytes, a low concentration of benzo(a)pyrene (B[a]P, an indicator of PAHs) chronic exposure continuously activated 14-3-3η via an epigenetic accumulation of DNA demethylation. As a "switch like" factor, 14-3-3η activated its downstream PI3K/Akt signal, which in turn promoted vascular endothelial growth factor (VEGF) production and secretion. As the characteristic fibrogenic paracrine factor regulated by B[a]P/14-3-3η, VEGF significantly induced the neovascularization and activation of hepatic stellate cells, leading to the development of hepatic fibrosis. Importantly, targeted 14-3-3η by using its specific inhibitor invented by our lab could prevent B[a]P-induced hepatic fibrosis, and could even reverse existent hepatic fibrosis caused by B[a]P. The present study not only revealed novel mechanisms, but also proposed an innovative approach for the targeted reversion/prevention of the harmful effects of exposure to PAHs on chronic liver disease.


Assuntos
Hepatopatias , Hidrocarbonetos Policíclicos Aromáticos , Humanos , Benzo(a)pireno/toxicidade , Benzo(a)pireno/metabolismo , Fator A de Crescimento do Endotélio Vascular , Fosfatidilinositol 3-Quinases , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/prevenção & controle
9.
Apoptosis ; 29(5-6): 849-864, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38117373

RESUMO

Sarcopenia manifests as muscle atrophy and loss that is complicated with malignancy. This study explored the mechanism of extracellular vesicles (EVs) in multiple myeloma (MM) with sarcopenia. SP2/0 conditioned medium (CM) was collected to isolate SP2/0-EVs. C2C12 cells were incubated with SP2/0 CM or SP2/0-EVs. ROS, TNF-α, IL-6, MuRF1 and MyHC levels were detected by DCF-DA fluorescent probe, ELISA, and Western blot. GW4869 was used to inhibit EV secretion in SP2/0 to confirm its effect on muscle atrophy. Serum was collected from MM patients with or without sarcopenia to detect RAGE mRNA expression. SP2/0 cells were transfected with RAGE siRNA and C2C12 cells were treated with the isolated si-RAGE-EVs or/and TLR4 agonist. SP2/0 tumor-bearing mouse model was established. Healthy mice and SP2/0-tumor bearing mice were treated with SP2/0-EVs or si-RAGE-EVs. SP2/0 CM or SP2/0-EVs stimulated ROS, inflammatory responses, and myotube atrophy in C2C12 cells. GW4869 blocked EV secretion and the effects of SP2/0 CM. RAGE mRNA expression in serum EVs was increased in MM&Sarcopenia patients and RAGE knockdown in SP2/0-EVs partially nullified SP2/0-EVs' effects. SP2/0-EVs activated the TLR4/NF-κB p65 pathway by translocating RAGE. SP2/0-EVs-derived RAGE elevated ROS production, inflammation, and myotube atrophy in C2C12 cells and caused muscle loss in SP2/0 tumor-bearing mice by activating the TLR4/NF-κB p65 pathway. SP2/0-EVs partially recapitulated muscle loss in healthy mice. SP2/0-EVs-derived RAGE increased ROS production, inflammation, and myotube atrophy in MM through TLR4/NF-κB p65 pathway activation.


Assuntos
Vesículas Extracelulares , Inflamação , Mieloma Múltiplo , Atrofia Muscular , Receptor para Produtos Finais de Glicação Avançada , Transdução de Sinais , Receptor 4 Toll-Like , Fator de Transcrição RelA , Animais , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , Humanos , Mieloma Múltiplo/patologia , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/genética , Camundongos , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Receptor para Produtos Finais de Glicação Avançada/genética , Fator de Transcrição RelA/metabolismo , Fator de Transcrição RelA/genética , Inflamação/metabolismo , Inflamação/patologia , Inflamação/genética , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Atrofia Muscular/genética , Linhagem Celular Tumoral , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Masculino , Feminino
10.
Mol Nutr Food Res ; 67(24): e2300444, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37897323

RESUMO

SCOPE: Epidemiological studies indicate an inverse correlation between yogurt consumption and colorectal cancer (CRC), but whether there is a cause-and-effect relationship has not yet been validated. This study aims to investigate the effects and possible mechanisms of yogurt on colitis-associated colorectal cancer (CAC) in mice. METHODS AND RESULTS: Experimental CAC is induced by azoxymethane (AOM, 10 mg kg-1 , ip) followed by three cycles of dextran sulfate sodium (DSS, 3%) treatment. Colitis is induced by adding DSS (3%) in drinking water for 5 days. Primary mouse macrophages are isolated for mechanistic studies. Data clearly show that yogurt (15 g kg-1 body weight) significantly reduces the multiplicity of colonic neoplasms by 38.83% in mice. Yogurt protects mice from colitis dependent on lactate receptor GPR81. The deficiency of Gpr81 exacerbates colitis and CAC in mice. Further investigation reveals that GPR81 may be dispensable for gut barrier function but essential for colonic mucosal repair. d-lactate in yogurt can activate GPR81 to suppress proinflammatory macrophage polarization, thereby facilitating inflammatory resolution after colonic injury and consequently suppressing CAC progression. CONCLUSION: Yogurt effectively protects against colitis-associated colorectal tumorigenesis in mice, and this study provides a rationale for introducing yogurt supplementation to patients with chronic inflammatory bowel diseases.


Assuntos
Neoplasias Associadas a Colite , Colite , Neoplasias Colorretais , Humanos , Camundongos , Animais , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/prevenção & controle , Iogurte , Colite/induzido quimicamente , Lactatos , Sulfato de Dextrana/toxicidade , Azoximetano/toxicidade , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
11.
Front Neurol ; 14: 1221912, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37840916

RESUMO

Granular cell tumors are extremely uncommon soft tissue neoplasms that mostly occur in the head and neck regions. Granular cell tumors are generally benign, asymptomatic, and rarely involve the median nerve. Due to the lack of awareness about granular cell tumors, they are easily misdiagnosed and mistreated in primary hospitals. Here, we report a giant atypical granular cell tumor located on the median nerve, approximately 12 cm in size, with unusual symptoms of median nerve damage. Magnetic resonance imaging revealed a fusiform mass that was hyperintense on T2-weighted images and iso-hypointense on T1-weighted images. The mass was subsequently biopsied and found to be a granular cell tumor. The tumor was resected, and a pathological examination was performed. Pathological examination revealed necrotic foci, abundant eosinophilic granules, pustular ovoid bodies, and multiple mitoses. Immunohistochemical staining revealed that the tumor cells were positive for S-100, CD68, SMA, SOX-10, Calretinin, and TFE3. The integrated diagnosis was an atypical granular cell tumor. To the best of our knowledge, this is the first report of an atypical granular cell tumor involving the median nerve. Furthermore, we comprehensively reviewed the existing literature to provide a concise summary of the diagnostic criteria, imaging findings, and pathological features of granular cell tumors. Given the high recurrence and metastasis rates of this disease, granular cell tumors of the median nerve should be considered when a patient presents with symptoms of median nerve impairment. The diagnosis of atypical granular cell tumors relies on pathological examination. In addition, extensive resection and long-term follow-up are necessary to improve prognosis.

12.
J Orthop Surg Res ; 18(1): 650, 2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37658426

RESUMO

OBJECTIVE: This study aimed to describe the learning curve of surgeons performing tibial cortex transverse transport (TTT) and explore its safety and effectiveness during the initial stages of surgeon's learning. METHODS: The clinical data of patients with diabetic foot ulcers classified as Wagner grade ≥ 2, who underwent TTT at our hospital from January 2020 to July 2021, were included in this retrospective analysis. The same physician performed all procedures. Patients were numbered according to the chronological order of their surgery dates. The cumulative sum and piecewise linear regression were used to evaluate the surgeon's learning curve, identify the cut-off point, and divide the patients into learning and mastery groups. A minimum follow-up period of 3 months was ensured for all patients. Baseline data, perioperative parameters, complications, and efficacy evaluation indicators were recorded and compared between the two groups. RESULTS: Sixty patients were included in this study based on the inclusion and exclusion criteria. After completing 20 TTT surgeries, the surgeon reached the cut-off point of the learning curve. Compared to the learning group, the mastery group demonstrated a significant reduction in the average duration of the surgical procedure (34.88 min vs. 54.20 min, P < 0.05) along with a notable decrease in intraoperative fluoroscopy (9.75 times vs. 16.9 times, P < 0.05) frequency, while no significant difference was found regarding intraoperative blood loss (P = 0.318). Of the patients, seven (11.7%) experienced complications, with three (15%) and four cases (10%) occurring during the learning phase and the mastery phase, respectively. The postoperative ulcer area was significantly reduced, and the overall healing rate was 94.8%. Significant improvements were observed in postoperative VAS, ABI, and WIFI classification (P < 0.05). There were no significant differences in the occurrence of complications or efficacy indicators between the learning and mastery groups (P > 0.05). CONCLUSION: Surgeons can master TTT after completing approximately 20 procedures. TTT is easy, secure, and highly efficient for treating foot ulcers. Furthermore, TTT's application by surgeons can achieve almost consistent clinical outcomes in the initial implementation stages, comparable to the mastery phase.


Assuntos
Curva de Aprendizado , Cirurgiões , Humanos , Estudos Retrospectivos , Perda Sanguínea Cirúrgica , Córtex Cerebral
13.
Eur J Med Res ; 28(1): 369, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37737205

RESUMO

IgA nephropathy (IgAN) is the most common primary glomerular disease in the world, and up to 40% of patients with IgAN develop end-stage renal disease (ESRD). At present, an increasing amount of evidence indicates that the pathogenesis of IgAN is related to autoimmunity. In recent years, several studies have shown that B cell activating factors (BAFF), also known as B lymphocyte stimulators (BLyS), and proliferation-inducing ligand APRIL are extremely important for the activation of autoimmune signalling pathways, which have become key targets for the treatment of IgAN. As a dual-target biological agent, telitacicept can inhibit both BLyS and APRIL cytokines, improve the function of renal immune complexes, and reduce haematuria and proteinuria, which play important roles in IgAN pathogenesis and long-term prognosis. This article reviews the role of telitacicept in IgA nephropathy and discusses its potential for use in the treatment of IgAN and other autoimmune diseases where pathogenesis is driven by B cells.


Assuntos
Doenças Autoimunes , Glomerulonefrite por IGA , Humanos , Glomerulonefrite por IGA/tratamento farmacológico , Rim , Glomérulos Renais
14.
Immun Inflamm Dis ; 11(5): e850, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37249283

RESUMO

INTRODUCTION: To review the pathogenesis and treatment of multiple myeloma (MM). MM is a hematological malignancy with abnormal plasma cell proliferation in bone marrow. Due to the emergence of drug resistance, MM is still an incurable malignancy, which requires further exploration of pathogenesis and effective therapeutic targets. METHODS: In this paper, the method of literature review is adopted to obtain the information about MM. Based on the literature, comprehensive and systematic review is made. RESULTS: MM is a complex pathophysiological process with great heterogeneity, mainly reflected in genomic instability and bone marrow microenvironment. At present, the treatment of MM has made great progress, proteasome inhibitors and immunomodulatory drugs are widely used in clinic. Allogeneic stem cell transplantation may be the only promising cure for MM, and its high transplant-related mortality limits its clinical application. CONCLUSIONS: The future of MM treatment lies in the development of more targeted therapies, novel immunotherapies, and a better understanding of the disease's molecular and genetic basis.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Imunoterapia , Mieloma Múltiplo/terapia , Mieloma Múltiplo/tratamento farmacológico , Microambiente Tumoral
15.
J Inflamm Res ; 16: 563-578, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36818195

RESUMO

Objective: To explore the role of sclerosteosis (SOST) gene expression in the occurrence and development of multiple myeloma (MM) complicated with sarcopenia. Methods: Analysis of the SOST expression in skeletal muscle tissue of patients with MM using high-throughput sequencing combined with transcriptomics; observation of morphological changes of the mouse C2C12 myoblasts co-cultured with SP2/0 myeloma cells in Transwell; observation of the SOST expression in the C2C12 myoblasts using the immunofluorescence labeling method; and assessment of the changes in exercise capacity of mice with MM using ethology; and the measurement of the SOST expression in muscles of mice using immunohistochemistry. Results: The transcription level of the SOST gene in the muscle tissue was significantly higher in patients with MM and sarcopenia than in patients with MM without sarcopenia and elderly patients with sarcopenia; the area of C2C12 mouse myoblasts co-cultured with SP2/0 myeloma cells was 167,904 ± 8653.7 pix; this was significantly lower than the area of 402,994 ± 13,575.0 pix in the control group (CG); the fluorescence intensity of SOST in the cells of the experimental group (EG) was 159,389 ± 10,534 AU; this was significantly higher than the intensity of 26,338 ± 6059 AU in the CG; the differences in results of the coat-hanger test, the tail suspension test, the weight-bearing forced swimming test, and the grip strength test between the tumor-bearing mice in the EG and the CG were statistically significant; and the quantitative result of SOST expression in the muscle tissue of the EG mice was 11,515 ± 1573 pix; this was significantly higher than the result of 3399 ± 798.8 pix in the CG. Conclusion: The SOST gene expression was significantly higher in muscle of mice in EG than in CG; and increased SOST gene expression might be a pathogenesis of MM complicated with sarcopenia.

16.
Clin Exp Med ; 23(1): 45-54, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34989932

RESUMO

Multiple myeloma (MM) is a monoclonal malignancy characterized by abnormal proliferation of plasma cells. The disease clinically manifests as anemia, hypercalcemia, renal insufficiencies, and osteolytic damage. Osteolytic damage goes with severe bone pain, spinal instability, and pathological fracture, symptoms that are collectively referred to as multiple myeloma bone disease (MMBD). Polymethylmethacrylate (PMMA) bone cement is widely used for bone repair after MMBD surgery, owing to its excellent biomechanical properties and fast curing. To date, however, efficacy of drug-loading PMMA in inhibition of tumor growth and angiogenesis remains unknown. Here, we report that 17-AAG-loaded PMMA bone cement inhibits MM growth in vivo and suppresses tumor diffusion to peripheral tissues. In addition, 17-AAG-loaded PMMA promotes MM apoptosis by downregulating Bax and active Caspase-3.


Assuntos
Mieloma Múltiplo , Polimetil Metacrilato , Humanos , Camundongos , Animais , Polimetil Metacrilato/farmacologia , Cimentos Ósseos/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Xenoenxertos , Modelos Animais de Doenças
17.
World J Clin Cases ; 10(14): 4380-4394, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35663088

RESUMO

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is often used to predict a poor prognosis in patients with tumors. This study investigated the preoperative peripheral blood NLR in predicting postoperative survival (POS) in patients with multiple myeloma bone disease (MMBD). AIM: To evaluate whether NLR can be used to predict the prognosis of MMBD patients after surgery. METHODS: The clinical data of 82 MMBD patients who underwent surgical treatments in Beijing Chao-yang Hospital were collected. The NLR was obtained from the absolute number of neutrophils and lymphocytes, calculated by the number of neutrophils and divided by the number of lymphocytes. The peripheral blood lymphocyte percentage was used as the major marker to analyze the change in characteristics of the immune statuses of multiple myeloma patients. RESULTS: The NLR cut-off values of NLR ≥ 3 patients and NLR ≥ 4 patients were significantly correlated with POS. The 3- and 5-year cumulative survival rates of the high NLR group (NLR ≥ 3 patients) were 19.1% and 0.0%, respectively, which were lower than those of the low NLR group (NLR < 3 patients) (67.2% and 48.3%) (P = 0.000). In the high NLR group, POS (14.86 ± 14.28) was significantly shorter than that in the low NLR group (32.68 ± 21.76). Univariate analysis showed that the lymphocyte percentage 1 wk after the operation (19.33 ± 9.08) was significantly lower than that before the operation (25.72 ± 11.02). Survival analysis showed that postoperative chemotherapy, preoperative performance status and preoperative peripheral blood NLR ≥ 3 were independent risk factors for POS. CONCLUSION: The preoperative peripheral blood NLR can predict POS in MMBD patients. MMBD patients with a high preoperative NLR (NLR ≥ 3) showed poor prognosis.

18.
BMC Infect Dis ; 22(1): 405, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468738

RESUMO

BACKGROUND: We report a case of spine infection with mucormycosis that manifested signs of paraplegia in a patient suffering from disseminated mucormycosis. Timely and effective surgery was performed. A review of the literature is included. CASE PRESENTATION: A patient with diabetic ketoacidosis complained of back pain and fatigue for one month, and his right lower extremity activity had been limited for 10 days. T4-T6 vertebral and paravertebral soft tissue-involved infections were identified by MRI, which were derived from right lung pneumonia. He underwent abscess debridement, spinal canal decompression, pedicle screw fixation and amphotericin B liposome injection. Histopathological examination revealed broad aseptate hyphae suggestive of invasive mucormycosis. There was improvement in neurological function after surgical and medical treatment. Three months after the surgery, the patient died of uncontrollable massive bleeding of the urinary system. Mucormycosis is characterized by rapid development and a high mortality rate. This case shows the significance of a multidisciplinary team in the diagnosis and treatment of patients with mucormycosis. In addition, orthopedic surgeons should design appropriate surgery plans for spine-involved mucormycosis patients. CONCLUSION: This case present a patient with paraplegia caused by the spread of pulmonary mucormycosis to the vertebral and paravertebral soft tissue of levels T4-T6. After medical treatment, surgical debridement and internal fixation, the patient recovered well but later patient died of possible disease dissemination to the renal or urinary tract which resulted in massive haemorrhage.


Assuntos
Mucormicose , Antifúngicos/uso terapêutico , Humanos , Imageamento por Ressonância Magnética , Masculino , Mucormicose/complicações , Mucormicose/diagnóstico , Mucormicose/terapia , Paraplegia/etiologia
20.
Clin Rheumatol ; 41(7): 2225-2231, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35192086

RESUMO

Psoriasis is a systemic inflammatory disease that is associated with increased risk of several diseases, such as psoriatic arthritis (PsA), inflammatory bowel disease, and cardiovascular diseases. About 20 to 30% patients with psoriasis subsequently develop PsA. IgA nephropathy is the most common primary glomerular disease world-wide. Psoriasis and IgA nephropathy appear to be associated, but the mechanism underlying this connection is unclear. Tofacitinib and leflunomide are common treatments for psoriatic arthritis. We administered tofacitinib combined with leflunomide to a 38-year-old female patient who presented with PsA and IgA nephropathy. After treatment, she experienced significant reductions in the psoriatic lesions, pain in the right knee joint, and proteinuria. Administration of tofacitinib combined with leflunomide for treatment of a patient who had PsA complicated with IgA nephropathy led to significant resolution of the symptoms of both conditions. These results suggest similarities in the pathogenesis of PsA and IgA nephropathy and a possible new treatment for IgA nephropathy.


Assuntos
Artrite Psoriásica , Glomerulonefrite por IGA , Psoríase , Adulto , Artrite Psoriásica/complicações , Artrite Psoriásica/tratamento farmacológico , Feminino , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/tratamento farmacológico , Humanos , Leflunomida/uso terapêutico , Piperidinas , Pirimidinas
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