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Cardiomiopatia Hipertrófica , Mutação , Linhagem , Humanos , Masculino , Feminino , Cardiomiopatia Hipertrófica/genética , Pessoa de Meia-Idade , AdultoRESUMO
BACKGROUND: Respiratory epithelial adenomatoid hamartoma (REAH) is a benign lesion commonly occurring in the nasal cavity and sinuses. It is often accompanied by nasal polyps (NP). While the histological features of these two conditions have been studied, there is limited knowledge about their differences in the underlying immunopathology. METHODS: Nasal tissue specimens were collected from 8 patients with concurrent REAH and NP and 10 controls. The expression levels of inflammatory cytokines, tight junctions (TJ), and epithelial-mesenchymal transition (EMT)-related factors in the tissues were analyzed. The mRNA expression of the aforementioned factors was measured using qRT-PCR, while the expression of TJ and EMT-related proteins was analyzed through Western blotting and immunohistochemistry. RESULTS: Compared to the control group, levels of inflammatory cytokines (IFN-α, IL-5, IL-17A, IL-31, IL-33, and TNF-α) and EMT-related factors (α-SMA, COL1A1, MMP9, TGF-ß1, and Vimentin) were significantly increased in both REAH and NP tissues. Conversely, E-Cadherin and TJ-related factors (Claudin-4 and Occludin) significantly decreased. When comparing REAH with NP, it was observed that the expression of IL-4, IL-5, and IL-33 was lower in REAH, while TNF-É; was higher. Regarding TJ-related factors, the expression of Occludin was lower in REAH. Furthermore, in terms of EMT-related factors, except for E-Cadherin, the expressions of É-SMA, COL1A1, CTGF, MMP9, TGF-ß11, and Vimentin were higher in REAH. CONCLUSION: REAH and NP exhibit different immunopathological mechanisms. NP demonstrates a more severe inflammatory response, whereas REAH is characterized by a more pronounced TJ and EMT breakdown than NP.
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Transição Epitelial-Mesenquimal , Hamartoma , Pólipos Nasais , Humanos , Pólipos Nasais/patologia , Pólipos Nasais/metabolismo , Pólipos Nasais/imunologia , Hamartoma/patologia , Hamartoma/metabolismo , Hamartoma/genética , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Citocinas/metabolismo , Mucosa Respiratória/patologia , Mucosa Respiratória/metabolismo , Imuno-HistoquímicaRESUMO
Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.
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Dasatinibe , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva , Inibidores de Proteínas Quinases , Humanos , Estudos Retrospectivos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Inibidores de Proteínas Quinases/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Dasatinibe/uso terapêutico , China , Resultado do Tratamento , Masculino , Feminino , Pirimidinas/uso terapêutico , Adulto , Pessoa de Meia-IdadeRESUMO
Gyrokinetic simulations of the fishbone instability in DIII-D tokamak plasmas find that self-generated zonal flows can dominate the nonlinear saturation by preventing coherent structures from persisting or drifting in the energetic particle phase space when the mode frequency down-chirps. Results from the simulation with zonal flows agree quantitatively, for the first time, with experimental measurements of the fishbone saturation amplitude and energetic particle transport. Moreover, the fishbone-induced zonal flows are likely responsible for the formation of an internal transport barrier that was observed after fishbone bursts in this DIII-D experiment. Finally, gyrokinetic simulations of a related ITER baseline scenario show that the fishbone induces insignificant energetic particle redistribution and may enable high performance scenarios in ITER burning plasma experiments.
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Objective: To investigate the biological behavior spectrum of platelet-derived growth factor alpha receptor (PDGFRA)-mutant gastrointestinal stromal tumor (GIST), and to compare the clinical values of the Zhongshan method of benign and malignant evaluation with the modified National Institutes of Health (NIH) risk stratification. Methods: A total of 119 cases of GIST with PDGFRA mutation who underwent surgical resection at Zhongshan Hospital, Fudan University from 2009 to 2020 were collected. The clinicopathological data, follow-up records, and subsequent treatment were reviewed and analyzed statistically. Results: There were 79 males and 40 females. The patients ranged in age from 25 to 80 years, with a median age of 60 years. Among them, 115 patients were followed up for 1-154 months, and 13 patients progressed to disease. The 5-year disease-free survival (DFS) and overall survival (OS) were 90.1% and 94.1%, respectively. According to the modified NIH risk stratification, 8 cases, 32 cases, 38 cases, and 35 cases were very-low risk, low risk, intermediate risk, and high risk, and 5-year DFS were 100.0%, 95.6%, 94.3%, and 80.5%, respectively. There was no significant difference in prognosis among the non-high risk groups, only the difference between high risk and non-high risk groups was significant (P=0.029). However, the 5-year OS was 100.0%, 100.0%, 95.0% and 89.0%, and there was no difference (P=0.221). According to the benign and malignant evaluation Zhongshan method, 43 cases were non-malignant (37.4%), 56 cases were low-grade malignant (48.7%), 9 cases were moderately malignant (7.8%), and 7 cases were highly malignant (6.1%). The 5-year DFS were 100.0%, 91.7%, 77.8%, 38.1%, and the difference was significant (P<0.001). The 5-year OS were 100.0%, 97.5%, 77.8%, 66.7%, the difference was significant (P<0.001). Conclusions: GIST with PDGFRA gene mutation shows a broad range of biological behavior, ranging from benign to highly malignant. According to the Zhongshan method, non-malignant and low-grade malignant tumors are common, the prognosis after surgery is good, while the fewer medium-high malignant tumors showed poor prognosis after surgical resection. The overall biological behavior of this type of GIST is relatively inert, which is due to the low proportion of medium-high malignant GIST. The modified NIH risk stratification may not be effective in risk stratification for PDGFRA mutant GIST.
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Tumores do Estroma Gastrointestinal , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Adulto , Idoso , Idoso de 80 Anos ou mais , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/cirurgia , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Estudos Retrospectivos , Mutação , Prognóstico , Proteínas Proto-Oncogênicas c-kit/genéticaRESUMO
OBJECTIVE: The aim of this study was to research the therapeutic effectiveness of radial nerve damage paired with a humeral shaft fracture and intramedullary nailing. PATIENTS AND METHODS: Retrospective research was performed on the medical records of 58 individuals who had humeral shaft fractures and radial nerve injuries. The admission period was between June 1, 2020, and June 31, 2022. All study subjects that satisfied the requirements for inclusion were separated, using the random number table approach, into two groups: one for internal fixation (group N), which included 29 cases, and one for minimally invasive procedures (group W), which included 29 patients. Group W received minimally invasive intramedullary nail treatment, and group N received internal fixation with compression plates. The changes in the clinical effects, surgery-related indicators, joint function, nerve function, and levels of stress indicators of the two groups of treatment were analyzed. The changes in adverse reactions and satisfaction of patients were compared. RESULTS: The effective rate of group W was 89.66% (26/29), and that of group N was 72.41% (21/29). Although group W's effective rate was higher than group N's, there was no discernible disparity between the two groups (p>0.05). Surgical blood loss and incision length were much smaller in group W than in group N, and overall operation duration and length of stay were considerably shorter in group W than in group N (p<0.05). The excellent and good rate of elbow joint function in group W was 93.10% (27/29), whereas the excellent and good rate of group N was 65.52% (19/29). The excellent and good rate of elbow joint function in group W was considerably greater than that of group N (p<0.05). In group W, the excellent and good rate of shoulder joint was 96.55% (28/29), and that in group N was 68.97% (20/29), and group W had a considerably greater probability of excellent shoulder joint function than group N (p<0.05); the excellent and good rate of neurological function was 82.76% (24/29) in group W and 58.62% (17/29) in group N, and group W had much greater rates of excellent and good neurological function than group N (p<0.05). prostaglandin E-2 (PGE2), C-reactive protein (CRP) and Substance P (SP) levels in the W group and the N group were substantially higher after the surgery than they were prior to it (p<0.05), and in the W group, the aforementioned stress markers were much lower than they were in the N group (p<0.05). Group W experienced a 3.45% (1/29) rate of adverse events, while group N saw a 24.14% (7/29) incidence. The incidence of adverse responses was substantially lower in group W than in group N (p<0.05). The contentment rate of group W was 93.10% (27/29), and that of group N was 72.41% (21/29). Group W had a much greater contentment percentage than group N (p<0.05). CONCLUSIONS: Minimally invasive intramedullary nailing is a successful therapeutic approach for humeral shaft fractures with radial nerve damage, which may successfully enhance patients' shoulder and elbow joint function and nerve function, reduce patients' stress response, and has the characteristics of minimal adverse responses and high contentment, which is worthy of popularization and deployment.
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Fixação Intramedular de Fraturas , Fraturas do Úmero , Humanos , Fixação Intramedular de Fraturas/métodos , Nervo Radial/cirurgia , Estudos Retrospectivos , Placas Ósseas , Fraturas do Úmero/cirurgia , Fixação Interna de Fraturas/métodos , Úmero/cirurgia , Resultado do Tratamento , Procedimentos Cirúrgicos Minimamente Invasivos/métodosRESUMO
Immune homeostasis is a steady immune state that not only protects the host from pathogens but also prevents the emergence of pathological self-reactive immune cells. The disruption of immune homeostasis leads to the development of various diseases, such as cancer and autoimmune diseases. An emerging paradigm for the treatment of these diseases with dysfunctional immune systems is the restoration and maintenance of immune homeostasis. However, currently available drugs exert a unidirectional influence on immunity whereby they either augment or inhibit it. This strategy is associated with the drawback of potential adverse effects arising from uncontrolled activation or suppression of the immune system. Fortunately, evidence suggests that acupuncture can bidirectionally regulate the immune system to maintain immune homeostasis. In cases of immunosuppressive diseases (e.g. cancer), acupuncture has an enhancing effect on immunity. Conversely, in autoimmune diseases (e.g. rheumatoid arthritis), acupuncture has been observed to have an immunosuppressive effect, which helps restore normal immune tolerance. However, there is no publication systematically summarizing the bidirectional regulatory effects of acupuncture on the immune system in the literature. Here, our review provides a comprehensive overview of the various mechanisms through which acupuncture modulates the immune system in a bidirectional manner. These mechanisms include the augmentation of NK and CD8+ T cell function, as well as the restoration of Th1/Th2, Th17/Treg and M1/M2 balance. Thus, we propose the concept that acupuncture has the potential to alleviate illnesses through the facilitation of immune normalization. Moreover, we further highlight the therapeutic potential of acupuncture.
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Terapia por Acupuntura , Artrite Reumatoide , Doenças Autoimunes , Neoplasias , Humanos , Doenças Autoimunes/terapia , Homeostase , Neoplasias/patologiaRESUMO
Objective: To investigate the association between remnant cholesterol (RC) and the risk of diabetic retinopathy (DR) in middle-aged and older individuals with diabetes. Methods: Based on the Shanghai Nicheng Cohort Study database, the data of 1 255 individuals with diabetes aged 55-70 years at baseline (2013-2014) with complete fundus photographs and serum cholesterol data in Nicheng, Shanghai, were analyzed. Multinomial logistic regression models were used to evaluate risk ratios (RRs) and their 95% confidence intervals (CIs) between baseline RC level and incident DR. Results: The median age of the subjects was 61.9 years, and 60.4% were women. After a 4.6-year follow-up, 79 (6.3%) patients developed DR, including 50 (4.0%) mild non-proliferative DR and 29 (2.3%) referable DR (RDR). Multivariable logistic regression showed that each mmol/L increase of RC was associated with a 40% higher risk of RDR (RR=1.40, 95%CI 1.03-1.90). Compared with the lowest tertile of RC (<0.63 mmol/L), the risk of RDR in the highest tertile (≥0.85 mmol/L) increased by 4.59 times (RR=5.59, 95%CI 1.51-20.73). Conclusion: The RC level may help identify individuals at high risk of incident RDR in middle-aged and older Chinese adults with diabetes.
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Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Adulto , Pessoa de Meia-Idade , Humanos , Feminino , Idoso , Masculino , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Estudos de Coortes , China/epidemiologia , Colesterol , Fatores de RiscoRESUMO
OBJECTIVE: Shoulder dislocation represents a prevalent category within joint dislocation, accounting for about 40% of all joint dislocations, and anterior dislocation stands out as the prevailing type. It has been reported that in 1.6% of patients, the Latarjet procedure performed under arthroscopy involves transferring the coracoid process to the anterior-inferior aspect of the glenoid and fixing it with two bicortical screws. The tip of the screws may impinge the suprascapular nerve located behind the scapula, resulting in shoulder pain and weakness. This study was performed to analyze the risk of suprascapular nerve (SSN) injury caused by bicortical screws during arthroscopic Latarjet surgery and to identify reliable anatomical landmarks for Latarjet surgery. MATERIALS AND METHODS: Dissection was conducted on 23 fresh adult intact shoulder joint specimens, and the experimental protocol complied with the hospital's ethical requirements for research. Using the glenoid clock face as a reference, the distances between the suprascapular nerve and the anterior edge of the glenoid were measured at the 12:00, 11:00, 10:00, and 9:00 positions, as well as at the level of the suprascapular notch and the level of the spinoglenoid notch. The distances between the suprascapular nerve and the narrowest point of the glenoid rim and the clock scale were recorded. The scapula was divided into three zones, and the number of nerve branches in each zone was recorded. The collected data were subjected to statistical analysis. The suprascapular nerve trunk and branches were marked using radiopaque lines, and measurements were taken at three positions in computed tomography horizontal scans: the suprascapular foramen, the spinoglenoid notch, and the point of entry of the outermost nerve branch into the muscle. RESULTS: The suprascapular nerve originates from the brachial plexus, passes downward and backward through the suprascapular foramen, closely adheres to the bone surface, and runs outward and downward deep to the supraspinatus muscle. The distances between the suprascapular nerve and the glenoid rim at the 12:00, 11:00, 10:00, and 9:00 positions were 335.18±2.31 mm, 28.23±3.47 mm, 22.32±2.78 mm, and 22.12±2.07 mm, respectively. There was a mean of 1.12 nerve branches in zone 1, 2.86 in zone 2, and 3.64 in zone 3. In the neutral position of the shoulder joint, the horizontal distance between point A and the axillary nerve was 27.37 (19.80, 34.55) mm, and the vertical distance was 16.67 (12.85, 20.35) mm. CONCLUSIONS: The use of bicortical screws, especially upper screws, for Latarjet fixation at the level of the spinoglenoid notch, is associated with the risk of suprascapular nerve injury. The narrowest distance between the glenoid rim and the suprascapular nerve was found between 9:00 and 9:30 at the glenoid clock surface. Therefore, caution should be exercised when performing any procedure related to this area. Overall, the Latarjet procedure is a reliable and effective surgical technique, providing benefits such as favorable positioning of the coracoid graft and low bone absorption rate, while also avoiding the potential for suprascapular nerve injury.
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Traumatismos dos Nervos Periféricos , Articulação do Ombro , Adulto , Humanos , Ombro/cirurgia , Articulação do Ombro/cirurgia , Articulação do Ombro/inervação , Escápula/cirurgia , Traumatismos dos Nervos Periféricos/etiologia , Artroscopia/efeitos adversos , Parafusos Ósseos/efeitos adversosRESUMO
Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥â ¢) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
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Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide de Fase Crônica , Adulto , Humanos , Adolescente , Mesilato de Imatinib/efeitos adversos , Incidência , Antineoplásicos/efeitos adversos , Estudos Retrospectivos , Pirimidinas/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Resultado do Tratamento , Benzamidas/efeitos adversos , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Aminopiridinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
In 2020, the prevalence of abnormal spinal curvature among 54 079 students in Shandong Province was 1.54%. The multivariate logistic regression model analysis showed that, compared with those in primary school, economically underdeveloped areas, and non-residential schools, students in middle and high schools, economically average areas, and residential schools had a higher risk of abnormal spinal curvature, with OR (95%CI) values of 2.029 (1.662-2.476), 2.746 (2.208-3.416), 2.237 (1.740-2.875) and 2.057 (1.705-2.483), respectively. Compared with those in economically underdeveloped areas, who were underweight, who had seat adjustments≤1 time per academic year, and who had physical education classes≤1 per week, students in economically developed areas, who were normal weight, overweight, and obese, who had seat adjustments≥2 times per academic year, and who had physical education classes 2-3 or≥4 per week, had a lower risk of abnormal spinal curvature, with OR (95%CI) values of 0.690 (0.521-0.915), 0.722 (0.546-0.955), 0.535 (0.389-0.735), 0.383 (0.274-0.535), 0.835 (0.711-0.980), 0.561 (0.474-0.663) and 0.491 (0.315-0.766), respectively.
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Curvaturas da Coluna Vertebral , Humanos , Fatores de Risco , Prevalência , Instituições Acadêmicas , EstudantesRESUMO
Objective: To explore the selection strategy of pedicled axial flaps for repairing high-voltage electric burn wounds in foot and ankle. Methods: The retrospective observational research method was used. From January 2017 to December 2022, 16 patients with skin and soft tissue defects in foot and ankle after high-voltage electric burns were treated in General Hospital of Eastern Theater Command, including 11 cases of unilateral defect and 5 cases of bilateral defect. All patients were male, aged from 25 to 75 years. After thorough debridement, the area of the defect to be repaired with the flap was 5.0 cm×4.0 cm to 12.0 cm×8.0 cm. Before operation, the color Doppler ultrasound, computed tomography angiography, or digital subtraction angiography was used to fully evaluate the degree of vascular injury in the affected limb and to identify the distribution and traffic anastomosis of vascular network. Pedicled axial flaps with reliable blood supply were used to repair the wounds as soon as possible, and the area of flaps ranged from 3.0 cm×2.0 cm to 13.0 cm×8.0 cm. The wound in the donor area of flaps was repaired with split-thickness skin graft from head or medium-thickness skin graft from thigh. The flap repair of wounds in various areas of the ankle and foot was recorded. The postoperative survivals of the flaps and skin grafts were observed after surgery. The postoperative appearance of flaps and walking function of patients were followed up. At the last follow-up, the foot and ankle function was evaluated and rated using the American Association of Foot and Ankle Surgeons Ankle Posterior Foot Scoring System. Results: Two wounds in toe area were repaired with reverse dorsal pedis flaps, 3 wounds in medial ankle area and 2 wounds in heel area were repaired with medial plantar flaps, 2 wounds in anterior plantar area combined with toe area were repaired with reverse medial plantar flaps, 2 wounds in anterior plantar area combined with toe area and 5 wounds in anterior plantar area were repaired with reverse medial pedis flaps, 1 wound in toe area was combined with proper plantar digital artery flap, 1 dorsal pedis wound and 1 lateral malleolus wound were repaired with lateral supramalleolar perforator flaps, and 1 lateral malleolus wound and 1 dorsal pedis wound were repaired with sural neurovascular flap. One flap had venous reflux disorder after surgery and survived after treatment, while the other flaps and skin grafts survived completely after surgery. During the follow-up of 6 to 24 months after operation, the appearance of the flaps was good, and the walking function of patients was normal. At the last follow-up, the functional score of foot and ankle was 76 to 95, which was evaluated as excellent in 11 cases and good in 5 cases. Conclusions: According to the condition of high-voltage electric burn in foot and ankle, early and thorough debridement, preoperative imaging examination to evaluate blood vessels of the affected limb, and selection of pedicled axial flap with reliable blood supply are good methods for wound repair and related functional reconstruction of high-voltage electric burn in foot and ankle.
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Queimaduras por Corrente Elétrica , Queimaduras , Retalho Perfurante , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Feminino , Humanos , Masculino , Tornozelo/cirurgia , Queimaduras/cirurgia , Queimaduras por Corrente Elétrica/cirurgia , Estudos Retrospectivos , Lesões dos Tecidos Moles/cirurgia , Cicatrização , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
Farrerol (FA) is a traditional Chinese herbal medicine known for its anti-inflammatory and anti-oxidative properties in various diseases. Ferroptosis is an iron-dependent oxidative stress-induced cell death. It is characterized by lipid peroxidation and glutathione depletion and is involved in neuronal injury. However, the role of FA in inhibiting ferroptosis in hypoxic-ischemic encephalopathy (HIE) and its underlying mechanisms are not yet completely elucidated. This study aimed to investigate whether FA could mediate ferroptosis and explore its function and molecular mechanism in HIE. A neonatal rat model of HIE was used, and rats were treated with FA, ML385 (a specific inhibitor of nuclear factor erythroid 2-related factor 2 [Nrf2]), or a combination of both. Neurological deficits, infarction volume, brain water content, pathological changes, and iron ion accumulation in the brain tissues were measured using the Zea-Longa scoring system and triphenyl tetrazolium chloride (TTC), hematoxylin-eosin (HE), and Perls' staining. The expression levels of GSH-Px, MDA, SOD, and ROS in brain tissues were also evaluated. Western blot analysis was performed to analyze the expression of the Nrf2 pathway and ferroptosis-related proteins. The results showed that FA administration significantly reduced neuronal damage, infarct volume, cerebral edema, and iron ion accumulation and inhibited MDA and ROS levels while promoting GSH-Px and SOD levels. FA also increased the expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), Nrf2, and HO-1. Moreover, the combination of ML385 and FA in HIE abolished the FA protective effects. Therefore, the study concludes that FA exerts a neuroprotective effect after HIE by inhibiting oxidative stress and ferroptosis via the Nrf2 signaling pathway.
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Ferroptose , Hipóxia-Isquemia Encefálica , Animais , Ratos , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Animais Recém-Nascidos , Fator 2 Relacionado a NF-E2 , Espécies Reativas de Oxigênio , Glutationa , Ferro , Superóxido DismutaseRESUMO
Objective: Patients with advanced sarcomas have a dismal prognosis with few effective therapies. The purpose of this study was to evaluate the efficacy and safety of anlotinib in the treatment of advanced sarcoma and to explore the relationship between adverse events (AEs) and efficacy. Methods: Data from 45 advanced sarcoma patients who received anlotinib monotherapy at Affiliated Cancer Hospital of Zhengzhou University between June 2018 and August 2021 were retrospectively analyzed. According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1, the objective remission rate (ORR) and disease control rate (DCR) were calculated, and the progression free survival (PFS) and treatment-related AEs were recorded and analyzed. Survival analysis was conducted using the Kaplan-Meier survival rates were compared using the Log rank test. Results: Forty patients were treated for more than 1.5 months and received efficacy evaluation. The ORR and DCR after 3 months were 7.5%(3/40) and 80.0%(32/40), respectively. The overall ORR was 2.5%(1/40), the total DCR was 27.5%(11/40), and the median progression-free survival (m-PFS) was 6.70 months; The m-PFS of alveolar soft tissue sarcoma (ASPS) was 10.27 months, which was significantly longer than that of other subtypes of sarcoma (P=0.048). In addition, the DCR of ASPS and synovial sarcoma (SS) was significantly better than that of osteosarcoma (P<0.05). The most common AEs were elevated thyroid stimulating hormone (17.8%, 8/45), anemia (15.6%, 7/45), fatigue (11.1%, 5/45). Five patients developed grade 3 AEs after treatment; The PFS of patients with hand-foot syndrome after treatment was significantly longer than that of patients without hand-foot syndrome (14.10 vs 6.00, P=0.024). Conclusions: The efficacy of anlotinib in the treatment of ASPS and SS is better than that of other subtypes. The PFS in the group with hand-foot syndrome was significantly longer than that of the group without hand-foot syndrome.
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Neoplasias Ósseas , Síndrome Mão-Pé , Sarcoma Sinovial , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Estudos Retrospectivos , Sarcoma/tratamento farmacológico , Sarcoma Sinovial/tratamento farmacológicoRESUMO
We report the observation of a set of coherent high frequency electromagnetic fluctuations that leads to a turbulence induced self-regulating phenomenon in the DIII-D high bootstrap current fraction plasma. The fluctuations have frequency of 130-220 kHz, the poloidal wavelength and phase velocity are 16-30 m^{-1} and â¼30 km/s, respectively, in the outboard midplane with the estimated toroidal mode number nâ¼5-9. The fluctuations are located in the internal transport barrier (ITB) region at large radius and are experimentally validated to be kinetic ballooning modes (KBM). Quasilinear estimation predicts the KBM to be able to drive experimental particle flux and non-negligible thermal flux, suggesting its significant role in regulating the ITB saturation.
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Objective: Explore the association between atrial fibrillation (AF) reoccurrence and new-onset ischemic stroke (IS) in patients with nonvalvular AF, and explore whether there is a high-risk period of IS after recurrent episodes of AF. Methods: A nested case-control study design was used. A total of 565 nonvalvular AF patients with new-onset IS after a follow-up of at least 2 years in the China-AF cohort were enrolled as the case group, and 1 693 nonvalvular AF patients without new-onset IS were matched as the control group at a ratio of 1â¶3. Frequency and types of recurrent AF in the previous 1 or 2 years were compared between two groups, and the adjusted associations of AF reoccurrence with new onset IS were explored using conditional logistic regression analysis. The proportion of recurrent AF was compared between the case period and control period, and conditional logistic regression analysis was performed to calculate adjusted associations of case-period AF with IS. Results: The nested case-control study design results showed that the proportion of at least one record of recurrent AF in the previous 1 year was higher in the case group than in the control group (72.0% vs. 60.8%, P<0.05), and the recurrent AF was positively correlated with new-onset IS (adjusted OR=1.80, P<0.001). Similar results were also observed in the previous 2 years period. The case-crossover study design analysis showed that among 565 patients with new-onset IS, recurrent AF in the case period was positively correlated with IS (adjusted OR=1.61, P=0.003). Conclusion: Recurrent AF is associated with IS, and there may be a high-risk period of IS after recurrent episodes of AF.