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1.
Front Endocrinol (Lausanne) ; 15: 1368944, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756997

RESUMO

Background: The 2022 World Health Organization (WHO) classification of pituitary neuroendocrine tumour (PitNET) supersedes the previous one in 2017 and further consolidates the role of transcription factors (TF) in the diagnosis of PitNET. Here, we investigated the clinical utility of the 2022 WHO classification, as compared to that of 2017, in a cohort of patients with non-functioning PitNET (NF-PitNET). Methods: A total of 113 NF-PitNET patients who underwent resection between 2010 and 2021, and had follow-up at Queen Mary Hospital, Hong Kong, were recruited. Surgical specimens were re-stained for the three TF: steroidogenic factor (SF-1), T-box family member TBX19 (TPIT) and POU class 1 homeobox 1 (Pit-1). The associations of different NF-PitNET subtypes with tumour-related outcomes were evaluated by logistic and Cox regression analyses. Results: Based on the 2022 WHO classification, the majority of NF-PitNET was SF-1-lineage tumours (58.4%), followed by TPIT-lineage tumours (18.6%), tumours with no distinct lineage (16.8%) and Pit-1-lineage tumours (6.2%). Despite fewer entities than the 2017 classification, significant differences in disease-free survival were present amongst these four subtypes (Log-rank test p=0.003), specifically between SF-1-lineage PitNET and PitNET without distinct lineage (Log-rank test p<0.001). In multivariable Cox regression analysis, the subtype of PitNET without distinct lineage (HR 3.02, 95% CI 1.28-7.16, p=0.012), together with tumour volume (HR 1.04, 95% CI 1.01-1.07, p=0.017), were independent predictors of a composite of residual or recurrent disease. Conclusion: The 2022 WHO classification of PitNET is a clinically useful TF and lineage-based system for subtyping NF-PitNET with different tumour behaviour and prognosis.


Assuntos
Tumores Neuroendócrinos , Neoplasias Hipofisárias , Organização Mundial da Saúde , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/classificação , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/metabolismo , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/classificação , Tumores Neuroendócrinos/metabolismo , Adulto , Idoso , Prognóstico , Adulto Jovem , Seguimentos , Proteínas com Domínio T/metabolismo
2.
Zhongguo Gu Shang ; 37(2): 135-41, 2024 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-38425063

RESUMO

OBJECTIVE: To evaluate the feasibility and accuracy of virtual preoperative planning and 3D-printed templates for pre-contoured plates for the treatment of posterior wall fractures of the acetabulum. METHODS: A retrospective analysis of 29 patients with posterior acetabular wall fractures treated between August 2017 and March 2021 were divided into 2 groups based on whether to use preoperative virtual planning and 3D printed template. In 3D-printing group, there were 14 patients, including 10 males and 4 females; aged from 21 to 53 years old;CT-based virtual surgical planning was done using Mimics and 3-Matic software and 3D-printed templates for pre-contoured plates were adopted. In conventional group, there were 15 patients, including 10 males and 5 females;aged from 19 to 55 years old;conventional method of intra-operative contouring to adapt the plate to the fracture region was adopted. Blood loss, surgical time, radiographic quality of reduction, and hip function were compared between groups. RESULTS: The difference in operation time and intraoperative blood loss was significant(P<0.05). Twenty-three patients were followed up from 12 to 30 months, and the fractures in both groups healed with a healing time of 3 to 6 months. At the last follow-up, the Merle d'Aubign-Postel score of the 3D printed group was lower than that of the conventional group(P<0.05), with no significant differences in walking ability, hip mobility and total score(P>0.05). In 3D printing group, 6 cases were excellent, 5 cases were good, 3 cases were fair;in conventional group, 5 cases were excellent, 5 cases were good, 4 cases were fair, 1 case was worse;no significant difference between two groups(P>0.05). CONCLUSION: Virtual preoperative planning and 3D-printed templates for pre-contoured plates can reduce operative time and the blood loss of surgery, improve the quality of reduction. This method is efficient, accurate and reliable to treat acetabular posterior wall fractures.


Assuntos
Fraturas Ósseas , Fraturas do Quadril , Fraturas da Coluna Vertebral , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Fixação Interna de Fraturas/métodos , Estudos Retrospectivos , Fraturas do Quadril/cirurgia , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Acetábulo/lesões , Impressão Tridimensional , Placas Ósseas , Resultado do Tratamento
3.
iScience ; 27(3): 109116, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38384839

RESUMO

The serine/threonine protein phosphatase family involves series of cellular processes, such as pre-mRNA splicing. The function of one of its members, protein phosphatase, Mg2+/Mn2+ dependent 1G (PPM1G), remains unclear in hepatocellular carcinoma (HCC). Our results demonstrated that PPM1G was significantly overexpressed in HCC cells and tumor tissues compared with the normal liver tissues at both protein and RNA levels. High PPM1G expression is associated with shorter overall survival (p < 0.0001) and disease-free survival (p = 0.004) in HCC patients. Enhanced expression of PPM1G increases the cell proliferation rate, and knockdown of PPM1G led to a significant reduction in tumor volume in vivo. Further experiments illustrated that upregulated-PPM1G expression increased the protein expression of gain-of-function (GOF) mutant p53. Besides, the immunoprecipitation analysis revealed a direct interaction between PPM1G and GOF mutant p53. Collectively, PPM1G can be a powerful prognostic predictor and potential drug-target molecule.

4.
Vox Sang ; 119(4): 383-387, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38245843

RESUMO

BACKGROUND AND OBJECTIVES: B(A) phenotype is usually formed by nucleotide mutations in the ABO*B.01 allele, with their products exhibiting glycosyltransferases (GTs) A and B overlapping functionality. We herein report a B(A) allele found in a Chinese family. MATERIALS AND METHODS: The entire ABO genes of the probands, including flanking regulatory regions, were sequenced through PacBio third-generation long-read single-molecule real-time sequencing. 3D molecular models of the wild-type and mutant GTB were generated using the DynaMut web server. The effect of the mutation on the enzyme function was predicted by PROVEAN and PolyPhen2. The predictions of stability changes were performed using DynaMut and SNPeffect. RESULTS: Based on serological and sequencing features, we concluded the two probands as possible cases of the B(A) phenotype. Crystallization analysis showed that Thr266 substitution does not disrupt the hydrogen bonds. However, some changes in interatomic contacts, such as loss of ionic interactions and hydrophobic contacts, and addition of weak hydrogen bonds, may have affected protein stability to some extent. This mutation was predicted to have a benign effect on enzyme function and slightly reduce protein stability. CONCLUSION: The probands had the same novel B(A) allele with a c.797T>C (p.Met266Thr) mutation on the ABO*B.01 backbone.


Assuntos
Glicosiltransferases , Mutação de Sentido Incorreto , Humanos , Fenótipo , Mutação , Glicosiltransferases/química , Glicosiltransferases/genética , Alelos , China , Sistema ABO de Grupos Sanguíneos/genética , Genótipo
5.
Eur J Med Chem ; 264: 116008, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38056298

RESUMO

Proliferating cancer cells are characterized by the Warburg effect, a metabolic alteration in which ATP is generated from cytoplasmic glycolysis instead of oxidative phosphorylation. The pyruvate dehydrogenase complex/pyruvate dehydrogenase kinase (PDC/PDK) axis plays a crucial role in this effect and has been identified as a potential target for anticancer drug development. Herein, we present the discovery and pharmacological evaluation of potent PDK inhibitors targeting the PDK/PDC axis. We successfully identified 6 compounds from a small molecule library through a structure-based virtual screening campaign and evaluated their enzymatic inhibitory potencies for PDK1-4. Our results indicated that compound 1 exhibited submicromolar inhibitory activities against PDK1-3 (IC50 = 109.3, 135.8, and 458.7 nM, respectively), but is insensitive to PDK4 (IC50 = 8.67 µM). Furthermore, compound 1 inhibited the proliferation of A549 cells with an EC50 value of 10.7 µM. In addition, compound 1 induced cell apoptosis, arrested the cell cycle at the S phase, and reduced cell invasion and migration, while showing low in vivo toxicity at a high dose. Based on these observations, it can be concluded that compound 1 is a promising anti-PDK1-3 lead that merits further investigation.


Assuntos
Proteínas Serina-Treonina Quinases , Complexo Piruvato Desidrogenase , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Complexo Piruvato Desidrogenase/metabolismo , Fosforilação Oxidativa , Divisão Celular
6.
Front Med (Lausanne) ; 10: 1246796, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38116038

RESUMO

Here, we report the first adult case of pancreatic yolk sac tumor with ectopic adrenocorticotropic hormone (ACTH) syndrome. The patient was a 27-year-old woman presenting with abdominal distension, Cushingoid features, and hyperpigmentation. Endogenous Cushing's syndrome was biochemically confirmed. The ACTH level was in the normal range, which raised the suspicion of ACTH precursor-dependent disease. Elevated ACTH precursors were detected, supporting the diagnosis of ectopic ACTH syndrome. Functional imaging followed by tissue sampling revealed a pancreatic yolk sac tumor. The final diagnosis was Cushing's syndrome due to a yolk sac tumor. The patient received a steroidogenesis inhibitor and subsequent bilateral adrenalectomy for control of hypercortisolism. Her yolk sac tumor was treated with chemotherapy and targeted therapy. Cushing's syndrome secondary to a yolk sac tumor is extremely rare. This case illustrated the utility of ACTH precursor measurement in confirming an ACTH-related pathology and distinguishing an ectopic from a pituitary source for Cushing's syndrome.

7.
J Cardiothorac Surg ; 18(1): 293, 2023 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-37833733

RESUMO

OBJECTIVE: To present clinical experiences regarding surgical treatment of patients with severe cicatricial tracheal stenosis. PATIENTS AND METHODS: From January 2008 to March 2020, 14 patients underwent tracheal resection and reconstruction under general anesthesia. Nine cases had cervical tracheal stenosis and five cases had thoracic tracheal stenosis. The mean diameter and length of strictured trachea was 0 - 8 mm with a mean of 4.5 ± 2.4 mm and 1 - 3 cm with a mean of 1.67 ± 0.63 cm, respectively. General anesthesia and mechanical ventilation were performed in ten cases and four patients underwent femoral arteriovenous bypass surgery due to severe stenosis. End-to-end anastomosis of trachea was performed in 13 cases and the anastomosis between trachea and cricothyroid membrane was performed in one case. Absorbable and unabsorbable sutures were used for the anterior and posterior anastomoses, respectively. Postoperative neck anteflexion was maintained by a suture between the chin and superior chest wall. The relevant data of the 14 patients were retrospectively reviewed, and the operation time, blood loss, postoperative hospital stay, postoperative complications and follow-up were retrieved. RESULTS: There was no intraoperative death. The length of resected trachea ranged from 1.5 to 4.5 cm with a mean of 1.67 ± 0.63 cm. Operation time ranged from 50 - 450 min with a mean of 142.8 ± 96.6 min and intraoperative hemorrhage ranged from 10 - 300 ml with a mean of 87.8 ± 83.6 ml. Follow-up period ranged from 5 to 43 months with a mean of 17.9 ± 10.6 months. None of the patients had recurrent laryngeal nerve paralysis during postoperative follow-up. Ten cases were discharged uneventfully. Anastomosis stenosis occurred in three cases who received interventional therapies. Bronchopleurocutaneous fistula occurred in one patient after 6 days postoperatively and further treatment was declined. CONCLUSION: The strategies of anesthesia, mechanical ventilation, identification of stenosis lesion, the "hybrid" sutures and postoperative anteflexion are critical to be optimized for successful postoperative recovery.


Assuntos
Laringe , Estenose Traqueal , Humanos , Estenose Traqueal/cirurgia , Estenose Traqueal/etiologia , Constrição Patológica/complicações , Estudos Retrospectivos , Traqueia/cirurgia , Laringe/cirurgia , Anastomose Cirúrgica/efeitos adversos , Resultado do Tratamento
8.
Proc Natl Acad Sci U S A ; 120(43): e2309698120, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37844218

RESUMO

Mutations in Leucine-rich repeat kinase 2 (LRRK2) are responsible for late-onset autosomal dominant Parkinson's disease. LRRK2 has been implicated in a wide range of physiological processes including membrane repair in the endolysosomal system. Here, using cell-free systems, we report that purified LRRK2 directly binds acidic lipid bilayers with a preference for highly curved bilayers. While this binding is nucleotide independent, LRRK2 can also deform low-curvature liposomes into narrow tubules in a guanylnucleotide-dependent but Adenosine 5'-triphosphate-independent way. Moreover, assembly of LRRK2 into scaffolds at the surface of lipid tubules can constrict them. We suggest that an interplay between the membrane remodeling and signaling properties of LRRK2 may be key to its physiological function. LRRK2, via its kinase activity, may achieve its signaling role at sites where membrane remodeling occurs.


Assuntos
Doença de Parkinson , Proteínas Serina-Treonina Quinases , Humanos , Proteínas Serina-Treonina Quinases/metabolismo , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Fosforilação , Mutação
9.
Chin J Cancer Res ; 35(4): 386-398, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37691890

RESUMO

Objective: The aim of this study was to investigate the prevalence of sarcopenia (SP) and its relationship with gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT). Methods: A total of 108 patients with various hematological disorders were selected from Peking University People's Hospital. SP was screened and diagnosed based on the 2019 Asian Sarcopenia Diagnosis Strategy. Physical measurements and fecal samples were collected, and 16S rRNA gene sequencing was conducted. Alpha and beta diversity analyses were performed to evaluate gut microbiota composition and diversity. Results: After HSCT, significant decreases in calf circumference and body mass index (BMI) were observed, accompanied by a decline in physical function. Gut microbiota analyses revealed significant differences in the relative abundance of Enterococcus, Bacteroides, Blautia and Dorea species before and after HSCT (P<0.05). Before HSCT, sarcopenic patients had lower Dorea levels and higher Phascolarctobacterium levels than non-sarcopenia patients (P<0.01). After HSCT, no significant differences in species abundance were observed. Alpha diversity analysis showed significant differences in species diversity among the groups, with the highest diversity in the post-HSCT 90-day group and the lowest in the post-HSCT 30-day group. Beta diversity analysis revealed significant differences in species composition between pre- and post-HSCT time points but not between SP groups. Linear discriminant analysis effect size (LEfSe) identified Alistipes, Rikenellaceae, Alistipes putredinis, Prevotellaceae defectiva and Blautia coccoides as biomarkers for the pre-HSCT sarcopenia group. Functional predictions showed significant differences in anaerobic, biofilm-forming and oxidative stress-tolerant functions among the groups (P<0.05). Conclusions: This study demonstrated a significant decline in physical function after HSCT and identified potential gut microbiota biomarkers and functional alterations associated with SP in patients with hematological disorders. Further research is needed to explore the underlying mechanisms and potential therapeutic targets.

10.
Fish Shellfish Immunol ; 142: 109130, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37777099

RESUMO

The mitfa gene is a well-known transcription factor associated with microphthalmia and is essential for early melanophore development. However, little is known about how mitfa affects the immune system. Here, we generated a novel mitfa knock-out zebrafish line using the CRISPR/Cas9 system. The mitfa-/- zebrafish exhibited reduced melanin levels compared to the nacre mutant. We investigated the impact on the immune system after exposure to Edwardsiella tarda and bifenazate in zebrafish larvae, and observed that the macrophage numbers were reduced in both treated groups. Remarkably, the expression levels of immune-related genes exhibited significant increases after bacterial challenge or bifenazate exposure in the mitfa-/- zebrafish, except for tlr4 and rela. Furthermore, we conducted xenograft experiments using mouse B16 melanoma cells. Notably, the cancer cells didn't show a high cell migration ratio, implying that the immune system was highly activated after the loss of mifta. Taken together, our findings suggest that mitfa-/- zebrafish serve as a valuable model for investigating the relationship between the immune system and melanocytes, providing new insights into the role of mitfa in immune responses.


Assuntos
Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Camundongos , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Fator de Transcrição Associado à Microftalmia/genética , Carbamatos/metabolismo
11.
Molecules ; 28(16)2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37630305

RESUMO

The irradiation of 176Yb with deuterons offers a promising pathway for the production of the theranostic radionuclide 177Lu. To optimize this process, calculations integrating deuteron transport, isotope production, and decay have been performed. In pure 176Yb, the undesired production of 174g+mLu occurs at higher deuteron energies, corresponding to a distribution slightly shallower than that of 177Lu. Hence, 174g+mLu can be effectively filtered out by employing either a low-energy deuteron beam or stacked foils. The utilization of stacked foils enables the production of 177Lu using a high-energy linear accelerator. Another unwanted isotope, 176mLu, is produced roughly at the same depth as 177Lu, but its concentration can be significantly reduced by selecting an appropriate post-irradiation processing time, owing to its relatively short half-life. The modeling approach extended to the mapping of yields as a function of irradiation time and post-irradiation processing time. An optimized processing time window was identified. The study demonstrates that a high-energy deuteron beam can be employed to produce 177Lu with high specific activity exceeding 3000 GBq/mg. The effect of different purity levels (ranging from 98% to 100%) was also discussed. The impurity levels have a slight impact. The modeling demonstrates the feasibility of obtaining 177Lu with a specific activity > 3000 GBq/mg and radionuclidic purity > 99.5% when using a commercially available 176Yb target of 99.6% purity.

12.
FEBS J ; 290(19): 4792-4809, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37410361

RESUMO

Lung cancer cells often show elevated levels of reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH). However, the connections between deregulated redox homeostasis in different subtypes of lung cancer and acquired drug resistance in lung cancer have not yet been fully established. Herein, we analyzed different subtypes of lung cancer data reported in the Cancer Cell Line Encyclopedia (CCLE) database, the Cancer Genome Atlas program (TCGA), and the sequencing data obtained from a gefitinib-resistant non-small-cell lung cancer (NSCLC) cell line (H1975GR). Using flux balance analysis (FBA) model integrated with multiomics data and gene expression profiles, we identified cytosolic malic enzyme 1 (ME1) and glucose-6-phosphate dehydrogenase as the major contributors to the significantly upregulated NADPH flux in NSCLC tissues as compared with normal lung tissues, and gefitinib-resistant NSCLC cell line as compared with the parental cell line. Silencing the gene expression of either of these two enzymes in two osimertinib-resistant NSCLC cell lines (H1975OR and HCC827OR) exhibited strong antiproliferative effects. Our findings not only underscored the pivotal roles of cytosolic ME1 and glucose-6-phosphate dehydrogenase in regulating redox states in NSCLC cells but also provided novel insights into their potential roles in drug-resistant NSCLC cells with disturbed redox states.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Gefitinibe/farmacologia , NADP/metabolismo , Glucosefosfato Desidrogenase/genética , Resistencia a Medicamentos Antineoplásicos/genética , Oxirredução , Linhagem Celular Tumoral , Proliferação de Células
13.
J Orthop Surg Res ; 18(1): 433, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37312224

RESUMO

BACKGROUND: The present study aimed to evaluate the indications, feasibility, clinical effectiveness and complications of the treatment with microwave in situ inactivation followed by curettage and bone grafting assisted with internal fixation, for the proximal humerus tumors. METHODS: The clinical data of 49 patients with primary or metastatic tumor of the proximal humerus who received intraoperative microwave inactivation in situ with curettage and bone grafting in our hospital from May 2008 to April 2021 were retrospectively analyzed. RESULTS: There were 25 males and 24 females, with an average age of 57.6 ± 19.9 years (range, 20-81). All patients were followed up for 7 to 146 months, with an average period of 69.2 ± 39.8 months. Up to the last follow-up, 14 patients died. The 5-year overall survival was 67.3%, and 5-year tumor-specific survival was 71.4%. The 5-year tumor-specific survival rates were 100% for aggressive benign tumors or low potential malignancy tumors, 70.1% for primary malignancies, and 36.9% for metastatic tumors. The average preoperative MSTS, constant-Murley and VAS scores were 16.81 ± 3.85, 62.71 ± 12.56 and 6.75 ± 2.47, which were all significantly improved at 6 weeks after operation and at the final follow-up (P < 0.05). CONCLUSIONS: Microwave inactivation in situ and curettage and bone grafting are a feasible treatment for tumors of proximal humeral, especially for malignant tumors and metastases, without the necessity of the replacement of the shoulder, with little trauma and good upper limb function, and with low local recurrence and distant metastasis.


Assuntos
Hipertermia Induzida , Neoplasias , Feminino , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Ombro , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Úmero/cirurgia
14.
Cell Tissue Bank ; 24(4): 747-758, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37133795

RESUMO

Decalcified bone matrix (DBM) is a widely used alternative material for bone transplantation. In the DBM production process, an effective particle size and the highest utilization rate of raw materials can be achieved only through multiple high-speed circulating comminution. The rat posterolateral lumbar fusion model (PLF) is the most mature small animal model for the initial evaluation of the efficacy of graft materials for bone regeneration and spinal fusion. To evaluate the differences in the in vivo osteogenic effects of DBM pulverization through 1, 5, 9, and 14 high-speed cycles, sixty athymic rats were divided into six groups: single cycling crushing (CC1), 5 cycles of crushing (CC5), 9 cycles of crushing (CC9), 13 cycles of crushing (CC13), autogenous bone graft (ABG) and negative control (NC). Posterolateral lumbar fusion was performed. Six weeks after surgery, the bilateral lumbar fusion of athymic rats was evaluated through manual palpation, X-ray, micro-CT and histological sections. Rank data were tested by the rank-sum test, and nonparametric data were tested by the Kruskal‒Wallis H test. The manual palpation and X-ray results showed that the fusion rate did not significantly differ between the CC1, CC5, CC9, CC13 and ABG groups. However, cavities appeared in CC9 and CC13 on the micro-CT image. The bone mass (BV/TV) of CC1, CC5, CC9 and CC13 was better than that of the ABG group, while almost no osteogenesis was observed in the NC group. Histologically, there was no obvious difference between the four groups except that the CC9 group and CC13 group had more fibrous tissues in the new bone. In conclusion, DMB with different cycling crushing times has no obvious difference in fusion rate of PLF, but it is slightly better than the ABG group.


Assuntos
Matriz Óssea , Fusão Vertebral , Ratos , Animais , Matriz Óssea/transplante , Ratos Nus , Vértebras Lombares/cirurgia , Osso e Ossos , Fusão Vertebral/métodos , Transplante Ósseo/métodos
15.
J Cardiothorac Surg ; 18(1): 154, 2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-37069699

RESUMO

OBJECTIVE: To evaluate the effect of preoperative pulmonary artery pressure on perioperative outcome of end-stage heart failure patients undergoing heart transplantation. METHODS: Retrospective analysis was undertaken on the clinical data of patients receiving heart transplantation in the Department of Cardiovascular Surgery of our hospital from March 2017 to March 2022. A ROC curve analysis was developed between mean pulmonary artery pressure (mPAP) and postoperative mortality using mPAP as diagnostic criteria. Patients were divided into groups based on this threshold to determine the best mPAP threshold value for predicting postoperative nosocomial mortality, and the differences in preoperative and intraoperative data, postoperative complications, and clinical prognosis of patients in the two groups were compared. Patients were followed up to draw the survival curve of patients in the two groups. RESULTS: The study enlisted the participation of 105 patients. ROC curve research revealed that preoperative pulmonary artery pressure was substantially linked with death following heart transplantation, with mPAP = 30.5mmHg being the best threshold. The group with mPAP ≥ 30.5mmHg had a greater incidence of postoperative ECMO support (28.2% vs. 10.6%, P = 0.021) and a higher incidence of in-hospital mortality (15.4% vs. 1.5%, P = 0.019) than the group with mPAP < 30.5mmHg. The postoperative survival rates of 105 patients were 91.3%, 88.7%, 81.6%, and 77.5% at 1, 2, 3, and 4 years, respectively, however, there was no significant difference between the two groups of patients in the postoperative intermediate-far survival rate (P = 0.431). CONCLUSIONS: Preoperative pulmonary artery pressure in patients with end-stage heart failure is intimately correlated with perioperative prognosis of heart transplant recipients. The optimal cut-off mPAP value in predicting perioperative prognosis of heart transplant recipients is 30.5mmHg. In the high mPAP group, perioperative ECMO support rate and perioperative mortality rate are high, which do not affect the medium and long-term prognosis of the recipients undergoing heart transplantation.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Hipertensão Pulmonar , Humanos , Hipertensão Pulmonar/complicações , Estudos Retrospectivos , Artéria Pulmonar , Prognóstico , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/complicações
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(1): 170-178, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-36765495

RESUMO

OBJECTIVE: To investigate the expression of pyruvate kinase M2 (PKM2) in bone marrow mesenchymal stem cells (BMSCs) in myeloma bone disease (MBD) and its effect on osteogenic and adipogenic differentiation of BMSCs. METHODS: BMSCs were isolated from bone marrow of five patients with multiple myeloma (MM) (MM group) and five with iron deficiency anemia (control group) for culture and identification. The expression of PKM2 protein were compared between the two groups. The differences between osteogenic and adipogenic differentiation of BMSCs were assessed by using alkaline phosphatase (ALP) and oil red O staining, and detecting marker genes of osteogenesis and adipogenesis. The effect of MM cell line (RPMI-8226) and BMSCs co-culture on the expression of PKM2 was explored. Functional analysis was performed to investigate the correlations of PKM2 expression of MM-derived BMSCs with osteogenic and adipogenic differentiation by employing PKM2 activator and inhibitor. The role of orlistat was explored in regulating PKM2 expression, osteogenic and adipogenic differentiation of MM-derived BMSCs. RESULTS: Compared with control, MM-originated BMSCs possessed the ability of increased adipogenic and decreased osteogenic differentiation, and higher level of PKM2 protein. Co-culture of MM cells with BMSCs markedly up-regulated the expression of PKM2 of BMSCs. Up-regulation of PKM2 expression could promote adipogenic differentiation and inhibit osteogenic differentiation of MM-derived BMSCs, while down-regulation of PKM2 showed opposite effect. Orlistat significantly promoted osteogenic differentiation in MM-derived BMSCs via inhibiting the expression of PKM2. CONCLUSION: The overexpression of PKM2 can induce the inhibition of osteogenic differentiation of BMSCs in MBD. Orlistat can promote the osteogenic differentiation of BMSCs via inhibiting the expression of PKM2, indicating a potential novel agent of anti-MBD therapy.


Assuntos
Doenças Ósseas , Células-Tronco Mesenquimais , Mieloma Múltiplo , Humanos , Adipogenia , Doenças Ósseas/metabolismo , Células da Medula Óssea , Diferenciação Celular , Células Cultivadas , Células-Tronco Mesenquimais/fisiologia , Mieloma Múltiplo/metabolismo , Orlistate/metabolismo , Orlistate/farmacologia , Osteogênese/genética , Proteínas de Ligação a Hormônio da Tireoide
17.
Int J Cardiovasc Imaging ; 39(5): 895-906, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36607471

RESUMO

Pediatric patients with ß-thalassemia (ß-TM) with preserved ejection fraction may experience early myocardial damage. This prospective study aimed to investigate left atrial (LA) function restructure in pediatric patients with ß-TM by two-dimensional speckle tracking echocardiography (2D-STE) and evaluate the value of LA strain for predicting myocardial iron overload (MIO). We recruited 50 ß-TM pediatric patients and 30 healthy children aged 3-14 years. The patients were assigned to a normal left ventricular (LV) lesion group (n = 20) and an enlarged LV lesion group (n = 30). Subjects all underwent echocardiography to measure conventional cardiac function parameters and LA strain parameters. The results displayed that LA reservoir strain (LASr), conduit strain (LAScd), contractile strain (LASct) and strain rate were significantly reduced in pediatric patients with ß-TM with preserved ejection fraction. LASr, LAScd, and LASct were negatively correlated with the E/e' ratio, of which LASr had the most significant correlation (r = - 0.69, P < 0.001). LASr and LASct correlated positively with T2* (r = 0.70 and 0.62, respectively, all P < 0.001). In the multiple regression, LASr and LASct were independent predictors for T2*. The areas under the curve for LASr and LASct were 0.87 (P < 0.001) and 0.78 (P = 0.004), respectively. Our results demonstrated that LA strains were dramatically impaired in pediatric patients with ß-TM, and LASr is an efficient indicator for detecting LV early diastolic dysfunction in ß-TM pediatric patients and reflects early myocardial damage. LASr and LASct were independently predictive of MIO, but LASr was a more sensitive predictor.


Assuntos
Fibrilação Atrial , Sobrecarga de Ferro , Disfunção Ventricular Esquerda , Talassemia beta , Humanos , Criança , Volume Sistólico , Estudos Prospectivos , Talassemia beta/complicações , Talassemia beta/diagnóstico por imagem , Valor Preditivo dos Testes , Ecocardiografia/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Átrios do Coração/diagnóstico por imagem , Sobrecarga de Ferro/diagnóstico por imagem , Sobrecarga de Ferro/etiologia
18.
Thorac Cancer ; 14(6): 573-583, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36567443

RESUMO

BACKGROUND: This multi-center study was aimed at retrospectively evaluating the feasibility, safety, clinical outcomes, and surgical learning curve of an optimized procedure for right upper lobectomy (RUL), which is challenging because of the anatomical structures and features of this lobe. METHODS: This study included 45 RUL cases of robot-assisted thoracoscopy (RATS) in a pilot cohort and 187 RUL cases of video-assisted thoracoscopy (VATS) in three cohorts. A total of 121 and 111 patients underwent traditional and optimized RUL, respectively. The optimized surgical procedure was performed to consecutively transect the superior arterial trunk and bronchus, and finally disconnect the pulmonary vein and posterior ascending artery with interlobar fissures. Clinical and radiological data were reviewed retrospectively. RESULTS: Optimized RUL can be performed successfully by RATS or VATS. The optimized procedure yielded better clinical outcomes than the traditional procedure, including shorter operation times, less blood loss, fewer complications, shorter hospital times, lower costs, and a lower likelihood of postoperative intermedius bronchial kinking. Additionally, for calcified interlobar lymph nodes, the optimized VATS group was less likely to be converted to thoracotomy than the traditional group. The skills required to perform optimized VATS RUL can be gained by surgeons after 12 to 15 cases. The two RUL procedures in the pilot cohort showed similar disease-free survival. CONCLUSIONS: The optimized RUL was safe, economical, and feasible, with a short learning curve and satisfactory disease-free survival.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Pneumonectomia/métodos , Brônquios/patologia , Intervalo Livre de Doença , Cirurgia Torácica Vídeoassistida/métodos
19.
Cell Tissue Bank ; 24(1): 203-210, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35831637

RESUMO

At present, the commonly used allogeneic bone powder in the clinic can be divided into nondemineralized bone matrix and demineralized bone matrix (DBM). Commonly used demineralizers include acids and ethylene diamine tetraacetic acid (EDTA). There may be some diversities between them. Also, the size of the bone particle can affects its cell compatibility and osteogenic ability. We produced different particle sizes i.e., < 75, 75-100, 100-315, 315-450, 450-650, and 650-1000 µm, and treated in three ways (nondemineralized, demineralized by EDTA, and demineralized by HCl). Scanning electron microscopy showed that the surface of the samples in each group was relatively smooth without obvious differences. The results of specific surface area and porosity analysis showed that they were significantly higher in demineralized bone powder than in nondemineralized bone powder, however, there was no significant difference between the two decalcification methods. The content of hydroxyproline in nondemineralized bone powder and EDTA-demineralized bone powder had no statistical difference, while HCl-demineralization had statistical significance compared with the former two, and the content increased with the decrease of particle size. The protein and BMP-2 extracted from HCl demineralized bone powder were significantly higher than that from nondemineralized bone powder and EDTA demineralized bone powder, and there were differences among different particle sizes. These results suggested the importance of demineralization mode and particle size of the allogenic bone powder and provided guidance for the choice of the most appropriate particle size and demineralization mode to be used in tissue bioengineering.


Assuntos
Osso e Ossos , Transplante de Células-Tronco Hematopoéticas , Tamanho da Partícula , Pós/análise , Ácido Edético , Matriz Óssea/química , Osteogênese , Técnica de Desmineralização Óssea
20.
J Asian Nat Prod Res ; 25(2): 191-196, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35442135

RESUMO

One new chamigrane sesquiterpene, antroalbol A (1), was isolated from the cultures of the higher fungus Antrodiella albocinnamomea. Its structure was established by means of spectroscopic methods, and the absolute configuration of 1 was confirmed by single crystal x-ray diffraction analysis. The compound was evaluated for its cytotoxicity against five human cancer cell lines, but no significant cytotoxicity was found.


Assuntos
Basidiomycota , Sesquiterpenos , Humanos , Estrutura Molecular , Basidiomycota/química , Sesquiterpenos/química
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