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Phenylarsine oxide (PAO) is a known environmental pollutant and skin keratinocytes are most seriously affected. Baicalin (BCN) was reported to have antioxidant and anti-inflammatory effects, but its protective effect against PAO toxicity is unknown. This study aimed at exploring whether baicalin can reverse the toxicity of human epidermal keratinocytes that are subjected to PAO exposure and underlying mechanisms. In silico analysis from a publicly accessible HaCaT cell transcriptome dataset exposed to chronic Arsenic showed significant differential expression of several genes, including the genes related to DNA replication. Later, we performed in vitro experiments, in which HaCaT cells were exposed to PAO (500 nM) in the existence of BCN (10-50 µM). Treatment of PAO alone induces the JNK, p38 and caspase-3 activation, which were engaged in the apoptosis induction, while the activity of AKT was significantly inhibited, which was engaged in the suppression of apoptosis. PAO suppressed SIRT3 expression and induced intracellular reactive oxygen species (ROS), causing a marked reduce in cell viability and apoptosis. However, BCN treatment restored the PAO-induced suppression of SIRT3 and AKT expression, reduced intracellular ROS generation, and markedly suppressed both caspase-3 activation and apoptosis induction. However, the protective effect of BCN was significantly attenuated after pretreatment with nicotinamide, an inhibitor of SIRT3. These findings indicate that BCN protects against cell death induced by PAO via inhibiting excessive intracellular ROS generation via restoring SIRT3 activity and reactivating downstream AKT pathway. In this study, we firstly shown that BCN is an efficient drug to prevent PAO-induced skin cytotoxicity, and these findings need to be confirmed by in vivo and clinical investigations.
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Apoptosis , Arsenicales , Supervivencia Celular , Flavonoides , Queratinocitos , Humanos , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Flavonoides/farmacología , Flavonoides/química , Arsenicales/farmacología , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Estructura Molecular , Relación Dosis-Respuesta a Droga , Sustancias Protectoras/farmacología , Sustancias Protectoras/química , Relación Estructura-Actividad , Piel/efectos de los fármacos , Piel/patologíaRESUMEN
OBJECTIVES: Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is characterized by vocalizations, jerks, and motor behaviors during REM sleep, often associated with REM-related dream content, which is considered a prodromal stage of α-synucleinopathy. The results of the Reading the Mind in the Eyes (RME) reflecting affective Theory of Mind (ToM) are inconsistent in α-synucleinopathy. The present study tried to investigate the RME in patients with iRBD. METHODS: A total of 35 patients with iRBD and 26 healthy controls were included in the study. All participants were administered the RME and the cognitive assessments according to a standard procedure. The patients with iRBD were further divided into two groups (high or low RME) according to the scores of the RME (> 21, or ≤ 20). RESULTS: The patients with iRBD had worse scores on cognitive tests compared with healthy controls involving global cognitive screening, memory, and visuospatial abilities (p < 0.05), but the scores of the RME were similar between the two groups (20.83 ± 3.38, 20.58 ± 3.43) (p Ë 0.05). Patients with low RME had more obvious cognitive impairments than healthy controls. After applying Bonferroni correction for multiple tests, the low REM group only performed worse on the Sum of trials 1 to 5 and delayed recall of the RAVLT compared with the healthy control group (p < 0.001, = 0.002). The RME correlated with the scores of cognitive tests involving executive function, attention, memory, and visuospatial function. CONCLUSIONS: The changes in RME had a relationship with cognitive impairments, especially memory, in patients with iRBD.
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Trastorno de la Conducta del Sueño REM , Teoría de la Mente , Humanos , Trastorno de la Conducta del Sueño REM/fisiopatología , Trastorno de la Conducta del Sueño REM/psicología , Masculino , Femenino , Anciano , Teoría de la Mente/fisiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/etiologíaRESUMEN
BACKGROUND: Soft-tissue functional reconstruction is important for restoring hip function in proximal femoral replacement for tumor resection. This study evaluated the functional outcome and postoperative complications of a specific synthetic ligament for soft-tissue functional reconstruction in proximal femoral replacement for tumor resection. METHODS: This cohort included 80 patients (40 men and 40 women, mean age, 40 years (range, 10 to 79)) who had benign invasive tumors (n = 13), primary malignant bone tumors (n = 40), or bone metastases (n = 27). Patients' medical records, imaging files, surgical details, and postoperative pathological diagnoses were collected. Tumor staging was performed with the Enneking staging criteria. Lower limb and hip functions were assessed using the Musculoskeletal Tumor Society scoring system and Harris Hip score, respectively. RESULTS: Mean postoperative Musculoskeletal Tumor Society and Harris Hip scores were 27 (range, 24 to 30) and 90 (range, 76 to 97), respectively, indicating satisfactory range of motion and stability. Trendelenburg gait was observed in 3 osteosarcoma patients (3.8%), and 6 patients showed unequal lower-limb lengths. Reoperations occurred in 5 cases, including 3 cases of deep vein thromboses and 1 case each of giant cell granuloma and periprosthetic infection. There were 27 patients who had bone metastases who did not require reoperation. CONCLUSIONS: The synthetic ligament reconstruction of the hip with proximal femoral replacement for tumor resection was associated with improved outcomes. Its implementation exhibits the potential to reduce postoperative incidences of hip dislocation and periprostheses infection, thereby warranting its prospective clinical application.
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Neoplasias Óseas , Masculino , Humanos , Femenino , Adulto , Estudios Prospectivos , Resultado del Tratamiento , Estudios Retrospectivos , Neoplasias Óseas/cirugía , Ligamentos/patologíaRESUMEN
OBJECTIVES: Proximal femur tumor resection often leads to hip joint instability and functional loss. Various methods have been clinically applied to repair hip joint soft tissue function, but deficiencies remain. This study aims to evaluate the advantages and disadvantages of the ligament advanced reinforcement system (LARS) tumor tube in assisting soft tissue function reconstruction in patients undergoing tumor type artificial hip replacement surgery. METHODS: This study included 85 patients (41 males, 44 females) with proximal femoral tumors treated at the Xiangya Bone Tumor Treatment Center from January 2012 to January 2022, aged 10 to 79 (38.5±18.2) years. Among them, 13 cases had benign aggressive tumors, 45 had primary malignant bone tumors, and 27 had bone metastases. Clinical data, imaging data, and intraoperative photos were collected. Patients were followed up and postoperative functional evaluations were conducted using the Musculoskeletal Tumor Society (MSTS) scoring system and Harris hip joint scoring system to assess limb function and hip joint function. RESULTS: Preoperative pathological fractures were present in 37 cases (43.5%), with a lesion length of (9.4±2.9) cm. Among non-metastatic tumor patients, 7 experienced postoperative recurrence, including 6 cases of osteosarcoma and 1 case of fibrosarcoma. Pulmonary metastases occurred in 9 osteosarcoma patients. Five patients required reoperation due to postoperative complications, including 3 cases of deep vein thrombosis, 1 case of giant cell granuloma, and 1 case of prosthesis infection. Postoperatively, 5 patients exhibited Trendelenburg gait, and 6 had leg length discrepancies. The postoperative MSTS score was 26.7±1.4, and the Harris score was 89.6±5.3. CONCLUSIONS: The LARS tumor tube can effectively assist in reconstructing the soft tissue function of the hip joint and greatly reduce postoperative complications, making it an effective technical improvement in joint function reconstruction in tumor type artificial hip replacement surgery.
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Artroplastia de Reemplazo de Cadera , Neoplasias Femorales , Articulación de la Cadera , Humanos , Masculino , Femenino , Artroplastia de Reemplazo de Cadera/métodos , Adulto , Persona de Mediana Edad , Adolescente , Niño , Articulación de la Cadera/cirugía , Anciano , Neoplasias Femorales/cirugía , Adulto Joven , Osteosarcoma/cirugía , Procedimientos de Cirugía Plástica/métodos , Neoplasias Óseas/cirugía , Neoplasias Óseas/secundario , Inestabilidad de la Articulación/cirugía , Inestabilidad de la Articulación/etiología , Fémur/cirugía , Prótesis de CaderaRESUMEN
BACKGROUND: Depression is being increasingly acknowledged as a global public health concern, and following this trend, attention towards eating disorders (EDs) has surged within China's national consciousness. EDs symptoms frequently coexist with various mental health conditions, including depression. However, research focusing on EDs symptoms and depressive symptoms among Tibetan students in China remains scant. This study employs network analysis to estimate the relational network between EDs and depressive symptoms. METHODS: Tibetan (n = 2,582) and Han (n = 1,743) students from two universities in the Xizang Autonomous Region, China, completed the Eating Attitude Test-26 (EAT-26) and the Patient Health Questionnaire-9 (PHQ-9). We estimated the network structure of EDs symptoms and depressive symptoms, identified central and bridge symptoms, and examined whether network characteristics differed by gender and ethnic. RESULTS: The core symptoms identified within this study were Calorie_awareness, Desire_to_thin and Fatigue. Conversely, bridge symptoms included Appetite, Suicide, Anhedonia, Guilty, Body_fat_awareness, and Food_preoccupation. The study also revealed no significant gender differences within the network model. However, disparities among ethnic groups were observed within the network structure. CONCLUSIONS: Our study examined the correlation between EDs symptoms and depressive symptoms in Tibetan college students. Focusing on the individual's quest for the perfect body shape and some Tibetan students' appetite problems - potentially stemming from transitioning to a new university environment, adapting to the school canteen's diet, or being away from their hometown - could aid in the prevention and management of EDs and depression symptoms. It could reduce the incidence of complications by helping students maintain good physical and mental health. Concurrently, our research provides insights into the relatively higher levels of depression triggered by the unique plateau environment.
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Depresión , Trastornos de Alimentación y de la Ingestión de Alimentos , Humanos , Depresión/psicología , Tibet/epidemiología , Universidades , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , China/epidemiología , Estudiantes/psicologíaRESUMEN
BACKGROUND: Shoulder soft tissue function reconstruction during tumor-type hemishoulder replacement is an important step to restore shoulder function. This study evaluates the functional prognosis and postoperative complications of ligament advanced reinforcement system (LARS)-assisted soft tissue functional reconstruction in tumor-type hemi-shoulder replacement. MATERIALS AND METHODS: Twenty-two patients with an average age of 37.5 ± 17.8 years diagnosed with benign invasive tumors, primary malignant bone tumors, or bone metastases were enrolled in this study. The patient's medical records (history and surgical details), histological sections, imaging files, oncological prognosis, functional prognosis, and postoperative complications were collected. The upper limb function and shoulder joint function were evaluated using the Musculoskeletal Tumor Society (MSTS) system and American Shoulder and Elbow Surgeons (ASES) scoring criteria, respectively. RESULTS: Twenty-two patients comprising 12 males and 10 females were enrolled. Overall, 9 patients had preoperative pathological fractures. The mean lesion length was 8.6 ± 3.0 cm. The local recurrence was observed in 3 cases, including 2 cases of osteosarcoma and 1 case of MGCT. A further 4 cases had pulmonary metastasis, including 2 cases with local tumor recurrence. The average postoperative MSTS score was 25.8 ± 1.7, and the score of postoperative ASES was 85.7 ± 6.0, both of which showed satisfactory functional recovery. Two cases experienced postoperative complications requiring surgical intervention, including one periprosthetic fracture and one giant cell granuloma. Prosthesis dislocation occurred in 1 case. None of the cases of periprosthetic infection or postoperative complications resulted in implant failure. CONCLUSIONS: LARS-assisted soft tissue function reconstruction in benign and malignant proximal humerus tumors after a tumor-type hemi-shoulder replacement is an effective technical improvement, which can effectively repair the integrity of the joint capsule to restore joint stability, provide a medium for soft tissue attachment to rebuild the muscular dynamic system, and eliminate residual dead space around the prosthesis, effectively improving limb function and reduce postoperative infection complications.
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Artroplastía de Reemplazo de Hombro , Neoplasias Óseas , Osteosarcoma , Articulación del Hombro , Masculino , Femenino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Articulación del Hombro/cirugía , Osteosarcoma/cirugía , Osteosarcoma/patología , Neoplasias Óseas/patología , Complicaciones Posoperatorias/cirugía , Ligamentos/patologíaRESUMEN
OBJECTIVES: Tenascin-C (TNC) is upregulated in serum and cerebrospinal fluid after subarachnoid hemorrhage (SAH) and the deficiency of TNC could alleviate neuronal apoptosis and neuroinflammation after SAH. However, the specific mechanism of TNC regulating neuronal apoptosis and neuroinflammation after SAH is not well recognized. The aim of this study was to investigate whether PI3K/Akt/ NF-κB signaling pathway is involved in the regulation of TNC on early brain injury after SAH. METHODS: Oxygen hemoglobin (OxyHb) was used to induce SAH models in PC12 cells, and classified into control, SAH, LY294002, SAH+TNC-siRNA and SAH+TNC-siRNA+LY groups. Western blotting was applied to examine the protein expression of TNC, Caspase-3, Bax, Bcl-2, PI3K, p-Akt, and p-NF-κB. Reverse transcription quantitative polymerase chain reaction was applied to examine the TNC mRNA expression. Cholecystokinin (CCK)-8 and flow cytometry were used to examine cell proliferation and apoptosis, respectively. ELISA was applied to examine the content of interleukin 6, interleukin 1ß, and tumor necrosis factor α. We showed that the TNC protein was highly expressed in SAH cell model. RESULTS: OxyHb inhibited cell proliferation, promoted cell apoptosis and the expression of proapoptotic protein, and promoted proinflammatory cytokine secretion in PC12 cells, which were restored following TNC gene silencing. Moreover, OxyHb decreased the expression of PI3K and p-Akt and increased the expression of p-NF-κB p65 in PC12 cells, which were activated following TNC gene silencing. The LY294002 weakened the effect of TNC gene silencing. CONCLUSIONS: The TNC gene silencing relieved neuronal apoptosis and neuroinflammation by activating the PI3K/Akt/ NF-κB signaling pathway. TNC-induced neuroinflammation would be a new target to improve outcome after SAH.
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Apoptosis , Mediadores de Inflamación/metabolismo , Neuronas/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Hemorragia Subaracnoidea/metabolismo , Tenascina/metabolismo , Factor de Transcripción ReIA/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Proliferación Celular , Neuronas/patología , Células PC12 , Fosforilación , Interferencia de ARN , Ratas , Transducción de Señal , Hemorragia Subaracnoidea/genética , Hemorragia Subaracnoidea/patología , Tenascina/genéticaRESUMEN
MYBL2 (MYB proto-oncogene like 2) is an emerging prognostic marker for malignant tumors, and its potential role in osteosarcoma and its relationship with immune infiltration in pan-cancer is yet to be elucidated. We constructed a transcription factor activity profile of osteosarcoma using the single-cell regulatory network inference algorithm based on single-cell RNA sequencing data obtained from the Gene Expression Omnibus. Subsequently, we calculated the extent of MYBL2 activation in malignant proliferative osteoblasts. We also explored the association between MYBL2 and chemotherapy resistance in osteosarcoma. Furthermore, we systematically correlated MYBL2 with immunological signatures in the tumor microenvironment in pan-cancer, including immune cell infiltration, immune checkpoints, and tumor immunotherapy prognosis. Finally, we developed and validated a risk score (MRGS), derived an osteosarcoma risk score nomogram based on MRGS, and tested its ability to predict prognosis. MYBL2 and gene enrichment analyses in osteosarcoma and pan-cancer revealed that MYBL2 was positively correlated with cell proliferation and tumor immune pathways. MYBL2 expression positively correlated with SLC19A1 in pan-cancer and osteosarcoma cell lines. Pan-cancer immune infiltration analysis revealed that MYBL2 was correlated with myeloid-derived suppressor cells, Th2 cell infiltration, CD276, RELT gene expression, and tumor mutation burden. In summary, MYBL2 regulates proliferation, progression, and immune infiltration in osteosarcoma and pan-cancer. Therefore, we found that MYBL2 could be used as a potential marker for predicting the osteosarcoma prognosis. Patients with osteosarcoma and high MYBL2 expression are theoretically more sensitive to methotrexate. An osteosarcoma prognostic nomogram can provide new ideas in the search for osteosarcoma prognostic markers.
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Cisplatin is widely used to treat malignancies. However, its major limitation is the development of dose-dependent nephrotoxicity. The precise mechanisms of cisplatin-induced kidney damage remain unclear, and the renoprotective agents during cisplatin treatment are still lacking. Here, we demonstrated that the expression and activity of cGMP-dependent protein kinase-I (PKG-I) were reduced in cisplatin-treated renal tubular cells in vitro as well as in the kidney tissues from cisplatin-treated mice in vivo. Increasing PKG activity by both pharmacological and genetic approaches attenuated cisplatin-induced kidney cell apoptosis in vitro. This was accompanied by decreased Bax/Bcl2 ratio, caspase 3 activity, and cytochrome c release. Cisplatin-induced mitochondria membrane potential loss in the tubular cells was also prevented by increased PKG activity. All of these data suggest a protective effect of PKG on mitochondria function in renal tubular cells. Importantly, increasing PKG activity pharmacologically or genetically diminished cisplatin-induced tubular damage and preserved renal function during cisplatin treatment in vivo. Mitochondria structural and functional damage in the kidney from cisplatin-treated mice was inhibited by increased PKG activity. In addition, increasing PKG activity enhanced ciaplatin-induced cell death in several cancer cell lines. Taken together, these results suggest that increasing PKG activity may be a novel option for renoprotection during cisplatin-based chemotherapy.
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Cisplatino/efectos adversos , Proteína Quinasa Dependiente de GMP Cíclico Tipo I/metabolismo , Túbulos Renales Proximales/patología , Mitocondrias/fisiología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/patología , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Regulación hacia Abajo , Humanos , Riñón/efectos de los fármacos , Riñón/patología , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/metabolismo , Masculino , Ratones , Ratones Transgénicos , Mitocondrias/efectos de los fármacosRESUMEN
Membrane microdomains consisting of sphingomyelin (SM) and cholesterol appear to be important for signal transduction in T-cell activation. The present study was designed to elucidate the role of membrane SM in vivo and in vitro using sphingomyelin synthase 1 (SMS1) knock out (SMS1(-/-)) mice and Concanavalin A (ConA)-induced hepatitis. After establishing SMS1(-/-) mice, we investigated CD4+ T-cell functions including proliferation, cytokine production and signal transduction in vivo. We also examined severity of hepatitis, cytokine production in serum and liver after ConA injection at a dose of 20 mg kg(-1). CD4+ T cells from SMS1(-/-) mice showed severe deficiency of membrane SM and several profound defects compared with wild-type controls as follows: (i) cellular proliferation and production of IL-2 and IFN-γ by co-cross-linking of CD3 and CD4; (ii) tyrosine phosphorylation of LAT and its association with ZAP-70; (iii) clustering and co-localization of TCR with lipid rafts. Consistent with these impaired CD4+ T-cell functions in vitro, SMS1(-/-) mice showed decreased serum levels of IL-6 and IFN-γ by ConA injection, which renders SMS1(-/-) mice less sensitive to ConA-induced hepatitis. These results indicated that the deficiency of membrane SM caused the CD4+ T-cell dysfunction through impaired lipid raft function contributed to protection of ConA-induced liver injury, suggesting that the membrane SM is critical for full T-cell activation both in vitro and in vivo.
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Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Concanavalina A/inmunología , Hepatitis/inmunología , Microdominios de Membrana/patología , Transferasas (Grupos de Otros Fosfatos Sustitutos)/deficiencia , Animales , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Transferasas (Grupos de Otros Fosfatos Sustitutos)/inmunologíaRESUMEN
Background: Despite great advances in surgical techniques for rotator cuff tear (RCT) over the past decades, the postoperative failure rate of RCT is still high due to the poor healing competence of bone-tendon interface (BTI). The lymphatic vasculature plays a regulatory role in inflammatory disease and affects tissue healing. However, whether lymphangiogenesis and the role of lymphatic vasculature in the physiopathological process of rotator cuff ï¼RCï¼injury remains unknown. Methods: In this study, we constructed a mouse RC injury model and the BTI samples were collected for measurement. Firstly, immunofluorescence was used to investigate the temporal and spatial distribution of lymphangiogenesis in BTI area at different post-injury time points. Subsequently, the mice of experimental group were gavaged with the lymphatic inhibitors (SAR131675) on the first postoperative day to inhibit lymphangiogenesis, while the control group was treated with the vehicle. At postoperative week 2 and 4, the samples were collected for immunofluorescence staining to evaluate lymphatic angiogenesis inhibition. At postoperative week 4 and 8, The supraspinatus (SS) tendon-humeral complexes were collected for bone morphometric, histological and biomechanical tests to assess the healing outcome of the BTI. Results: Immunofluorescence results showed that the lymphatic proliferation in the BTI injury area and increased in consistence with the healing time, and the lymphatic hyperplasia area significantly diminished at postoperative week 4. The lymphatic hyperplasia area in the SAR group was significantly lower than that in the control group both at 2 and 4 weeks postoperatively. Moreover, the administration of SAR131675 significantly impeded RC healing, as evidenced by lower histological scores, lower bone morphometric parameters, and worse biomechanical properties in comparison with that in control group at postoperative weeks 4 and 8. Conclusion: Lymphangiogenesis plays a positive role in RC healing, and targeting the lymphatic drainage at healing site may be a new therapeutic approach to promote RC injury repair. The translational potential of this article: This is the first study to assess the specific role of lymphatic vessels in RC healing, and improving lymphatic drainage may be a potential new therapeutic approach to facilitate repair of BTI. Further, our study provides a reference for possible future treatment of BTI by intervening the lymphatic system.
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Background: The inadequate regeneration of natural tissue (mainly fibrocartilage) between tendon and bone during rotator cuff (RC) repair results in an unsatisfactory quality of RC healing. Cell-free therapy based on stem cell exosomes is a safer and more promising approach for tissue regeneration. Here, we investigated the effect of exosomes from human urine-derived stem cells (USCs) and their subpopulations (CD133+USCs) on RC healing. Methods: USCs were isolated from urine and sorted by flow cytometry to obtain CD133+ urine-derived stem cells (CD133+ USCs). Urine-derived stem cell exosomes (USC-Exos) and CD133+ urine-derived stem cell exosomes (CD133+ USC-Exos) were subsequently isolated from the cell supernatant and identified by transmission electron microscopy (TEM), particle size analysis, and Western blot. We performed in vitro functional assays to evaluate the effects of USC-Exos and CD133+ USC-Exos on human bone marrow mesenchymal stem cells (BMSCs) proliferation, migration, osteogenic differentiation, and chondrogenic differentiation. In vivo experiments were performed by local injection of exosome-hydrogel complexes for the treatment of RC injury. The effects of CD133+ USC-Exos and USC-Exos on RC healing were assessed from imaging, histological, and biomechanical tests. Results: CD133+ USCs were positive for CD29, CD44, CD73, CD90, CD133, but negative for CD34 and CD45. Differentiation ability test results showed that both USCs and CD133+ USCs had the potential for osteogenic, chondrogenic, and adipogenic differentiation, but CD133+ USCs had stronger chondrogenic differentiation ability. CD133+ USC-Exos and USC-Exos could be efficiently taken up by BMSCs and promote their migration, osteogenic and chondrogenic differentiation. However, CD133+ USC-Exos could promote the chondrogenic differentiation of BMSCs more than USC-Exos. Compared with USC-Exos, CD133+ USC-Exos could promote the healing of bone-tendon interface (BTI) more effectively, which might be related to its ability to promote the differentiation of BMSCs into chondroblasts. Although the two exosomes exhibited the same effect in promoting subchondral bone repair in BTI, the CD133+ USC-Exos group had higher histological scores and stronger biomechanical properties. Conclusion: CD133+ USC-Exos hydrogel complex may become a promising therapeutic approach for RC healing based on stem cell exosomes. The translational potential of this article: This is the first study to assess the specific role of CD133+ USC-Exos in RC healing which may be related to the activation of BMSCs by CD133+ USC-Exos towards chondrogenic differentiation. Further, our study provides a reference for possible future treatment of BTI by applying CD133+ USC-Exos hydrogel complex.
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cGMP-dependent protein kinase (PKG) is a multifunctional protein. Whether PKG plays a role in ischemia-reperfusion-induced kidney injury (IRI) is unknown. In this study, using an in vivo mouse model of renal IRI, we determined the effect of renal IRI on kidney PKG-I levels and also evaluated whether overexpression of PKG-I attenuates renal IRI. Our studies demonstrated that PKG-I levels (mRNA and protein) were significantly decreased in the kidney from mice undergoing renal IRI. Moreover, PKG-I transgenic mice had less renal IRI, showing improved renal function and less tubular damage compared with their wild-type littermates. Transgenic mice in the renal IRI group had decreased tubular cell apoptosis accompanied by decreased caspase 3 levels/activity and increased Bcl-2 and Bag-1 levels. In addition, transgenic mice undergoing renal IRI demonstrated reduced macrophage infiltration into the kidney and reduced production of inflammatory cytokines. In vitro studies showed that peritoneal macrophages isolated from transgenic mice had decreased migration compared with control macrophages. Taken together, these results suggest that PKG-I protects against renal IRI, at least in part through inhibiting inflammatory cell infiltration into the kidney, reducing kidney inflammation, and inhibiting tubular cell apoptosis.
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Proteínas Quinasas Dependientes de GMP Cíclico/metabolismo , Riñón/metabolismo , Daño por Reperfusión/metabolismo , Animales , Apoptosis/fisiología , Caspasa 3/genética , Caspasa 3/metabolismo , Proteínas Quinasas Dependientes de GMP Cíclico/genética , Riñón/irrigación sanguínea , Riñón/fisiopatología , Macrófagos/metabolismo , Ratones , Ratones Transgénicos , Daño por Reperfusión/genética , Daño por Reperfusión/fisiopatologíaRESUMEN
Objectives: Dementia with Lewy bodies (DLB) is the second most common type of neurodegenerative dementia following Alzheimer's disease dementia (ADD). This study investigated the diagnostic role of the gesture imitation test in detecting DLB and differentiating DLB from ADD. Methods: A total of 63 patients with DLB, 93 patients with ADD, and 88 healthy controls were included in this study. All participants were administered the gesture imitation test, the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the clock drawing test (CDT), and other neuropsychological tests. Results: The patients with DLB performed worse than the healthy controls in the global scores and on every item of the gesture imitation test (p < 0.001). The area under the curve (AUC) for the global scores was 0.889 (p < 0.001) in differentiating the DLB and control groups. Item 4 was a better discriminator, with a sensitivity of 79.37% and a specificity of 79.55%. The AUC for the global scores decreased to 0.593 and the difference was marginal (p = 0.079) in differentiating the DLB and ADD groups. The patients with DLB performed worse on Items 1 and 4 compared with the patients with ADD (p = 0.040, 0.004). The gesture imitation test was positively correlated with the scores of the MMSE (r = 0.355, p = 0.017), the MoCA (r = 0.382, p = 0.010), and the CDT (r = 0.407, p = 0.005) in patients with DLB. Conclusion: The gesture imitation test is an easy, rapid tool for detecting DLB and has a role in differentiating DLB from ADD, especially in Items 1 and 4.
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BACKGROUND: The diagnosis of phosphaturic mesenchymal tumors (PMT) is easily delayed clinically, and their surgical treatment is unstandardized. This study aimed to evaluate our experience in the diagnosis and treatment of PMT and provide a research basis for the accurate and standardized treatment of PMT. MATERIALS AND METHODS: Twelve patients diagnosed with PMT in our department and who underwent surgical treatment were included in this study. Preoperative demographic and clinical information were recorded. CT, MRI, and technetium-99m (Tc99m)-octreotide PET/CT imaging techniques were used to evaluate the general conditions and lesion boundaries of the tumors. Surgical treatment was performed using radical resection and microwave ablation-assisted extended curettage according to the lesion location and size. Patients were strictly followed up with and evaluated for oncological prognosis, radiological results, bone healing, serum ion levels, limb function, and pain level; the occurrence of complications was also recorded. RESULTS: Three patients underwent radical resection, and nine underwent microwave ablation-assisted extended curettage. The average duration of symptoms in this group was 1.5 years (9-35 months) before diagnosis. Serum phosphate and AKP levels returned to normal one and two weeks postoperatively, respectively. There was no apparent specificity in the pathological findings; however, the immunohistochemistry of FGF-23 was positive, and the original fracture sites were effectively healed during the follow-up. The limb function and pain scores were significantly improved. The MSTS score increased from 15.3 to 29.0, and the VAS score decreased from 5.3 to 0.4. All patients recovered, and 90% resumed their original jobs. CONCLUSIONS: Accurate diagnosis and standardized surgical treatment are crucial to achieving a clinical cure for PMT. Combining clinical manifestations, biochemical examinations, imaging characteristics, and pathological findings is an effective way to diagnose PMT accurately. Radical resection and microwave ablation-assisted extended curettage are reliable surgical treatment methods for PMT.
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Aims: Proximal femoral osteoid osteoma (OO) is extremely easy to be misdiagnosed or missed. The purpose of this study was to retrospectively analyze the clinical data of patients with proximal femoral OO in order to determine the clinical manifestation and imaging characteristics of the disease, so as to provide help for the preoperative diagnosis and clinical treatment of proximal femoral OO. Methods: This was a retrospective study involving 35 patients with proximal femoral OO admitted into our hospital from January 2015 to January 2021. The baseline characteristics of the participants included; 24 males and 11 females, aged between 13 and 25 (mean 16.2) years old, and the course of the disease was 1 to 14 (mean 6.3) months. We used previous medical experience records of the patients to analyze for the causes of misdiagnosis. Moreover, we compared the difference between preoperative and postoperative treatment practices in alleviating pain in OO patients and restoring hip function. Follow-ups were carried out regularly, and patients advised to avoid strenuous exercises for 3 months. Results: We followed up 35 patients (25 intercortical, 4 sub-periosteal, and 6 medullary) for an average of 41.4 months. We found that 15 patients (42.9%) had been misdiagnosed of synovitis, perthes disease, osteomyelitis, intra-articular infection, joint tuberculosis and hip impingement syndrome, whose average time from symptoms to diagnosis were 6.3 months. Postoperative pain score and joint function score improved significantly compared with preoperative, and complications were rare. Conclusion: Open surgical resection constitutes an effective treatment for proximal femoral OO by accurately and completely removing the nidus. Wrong choice of examination, and the complexity and diversity of clinical manifestations constitutes the main reasons for the misdiagnosis of proximal femoral OO.
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BACKGROUND: Soft tissue sarcomas on extremities with regional lymph nodes metastasis (STSE-RLNM) is a devastating situation. Optimizing therapeutic approaches is vital but hampered by a shortage of randomized trials. We used a population-level database to evaluate radiotherapy's impact on sarcoma-specific survival (SSS) and overall survival (OS) for surgery for STSE-RLNM. METHODS: We retrospectively screened data from the SEER database (2004-2015), and 265 patients with STSE-RLNM who received surgery, with (134) or without (131) radiotherapy, were enrolled in this study. A propensity-score-matched analysis with the inverse probability of treatment weighting (IPTW) Kaplan-Meier curve was created. The log-rank test and Cox regression analysis were performed to compare SSS and OS in patients with and without radiotherapy. Further analysis of radiotherapy time was conducted, and the Kaplan-Meier curve and the log-rank test were done. Landmark analysis was introduced to attenuate the immortal bias. RESULTS: In the original unadjusted cohort, the radiotherapy + surgery group is associated with improved SSS [hazard ratio (HR), 0.66; 95% CI, 0.47-0.91; p = 0.011] and OS (HR, 0.64; 95% CI, 0.47-0.88; p = 0.006). This significant treatment effect was also noted in IPTW-adjusted Cox regression either on SSS (HR, 0.65; 95% CI, 0.45-0.93; p = 0.020) or on OS (HR, 0.64; 95% CI, 0.46-0.91; p = 0.013). The Kaplan-Meier curve and log-rank test showed that pre- and postoperative radiotherapy was not related to SSS (p = 0.980 or OS (p = 0.890). CONCLUSION: Radiotherapy and surgery has a significant benefit on the prognosis of patients with STSE-RLNM compared to surgery alone. These findings should be considered when making treatment decisions for them.
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Objectives: Cerebral small vessel disease (CSVD) is the most common vascular cause of dementia, and mild cognitive impairment (MCI) is an intermediate state between dementia and normal cognitive aging. The present study investigated the main imaging features of CSVD on different MCI subtypes in memory clinics. Methods: A total of 236 patients with MCI and 85 healthy controls were included. One hundred nine amnestic MCI-multiple domains (amMCI), 38 amnestic MCI-single domain (asMCI), 36 non-amnestic MCI-multiple domains (namMCI), and 53 non-amnestic MCI-single domain (nasMCI) patients were diagnosed. All participants were evaluated with the cognitive assessments and imaging features including white matter hyperintensity (WMH), enlarged perivascular spaces (EPVS), cerebral microbleeds (CMBs), and cerebral atrophy according to a standard procedure. Results: The patients with amMCI, namMCI, and nasMCI had more high-grade basal ganglia EPVS compared with healthy controls, while the percentages of high-grade basal ganglia EPVS in the patients with amMCI were also more than those in patients with asMCI, namMCI, and nasMCI. There were more high-grade centrum semiovale EPVS in patients with amMCI in comparison with all other groups. The patients with amMCI and namMCI had more percentages of severe deep and periventricular WMH and deep CMBs compared with healthy controls. All MCI groups had higher scores of the medial temporal lobe atrophy than healthy controls, whereas the scores of the amMCI group were also higher than those of the namMCI and nasMCI groups. Conclusions: There were varied neuroimaging features of CSVD including cerebral atrophy in different MCI groups, which meant that vascular mechanism contributed to the prodromal stage of dementia.
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Gastrointestinal dysfunction is the main nonmotor characteristic of Parkinson disease (PD), manipulation of gastrointestinal function by altering gut-brain axis is a potentially novel entry point for the treatment of PD. Acupuncture has been reported to confer beneficial effects in the gastrointestinal diseases. Therefore, this study aimed to explore the effects and mechanism of acupuncture on the pathophysiology and gastrointestinal function of PD. A PD mouse model was established by rotenone, and electroacupuncture was used to regulate the gastrointestinal function. Rotenone was found to induce the types of brain pathologies and gastrointestinal dysfunction that are similar to those observed with PD. Electroacupuncture significantly increased the spontaneous activity of mice with PD and increased the expression of tyrosine hydroxylase, while reducing the expression of Iba-1 in substantia nigra (SN), suggesting that motor dysfunction and neurological damage was alleviated. In addition, electroacupuncture significantly reduced the deposition of α-synuclein in both colon and SN, reduced intestinal inflammation, and exerted protective effects on enteric nervous system and intestinal barrier. In conclusion, electroacupuncture confers beneficial effects on the gastrointestinal system of mice with PD and can alleviate neuroinflammation and neuropathic injury by inhibiting intestinal inflammation, promoting intestinal barrier repair and reducing α-synuclein deposition in the colon.
Asunto(s)
Electroacupuntura , Actividad Motora/fisiología , Enfermedades Neuroinflamatorias/terapia , Enfermedad de Parkinson/terapia , Animales , Colon/metabolismo , Modelos Animales de Enfermedad , Electroacupuntura/métodos , Sistema Nervioso Entérico/metabolismo , Ratones , Enfermedades Neuroinflamatorias/fisiopatología , Enfermedad de Parkinson/fisiopatología , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
BACKGROUND: Alzheimer's disease dementia (ADD) is an important health problem in the world. OBJECTIVE: The present study investigated the validity and reliability of a new version of the Frontal Assessment Battery (FAB) named the FAB-phonemic (FAB-P). METHODS: A total of 76 patients with ADD, 107 patients with amnestic mild cognitive impairment (aMCI), 37 patients with non-amnestic MCI (naMCI), and 123 healthy controls were included in this study. All participants were evaluated with the FAB-P and the cognitive assessments according to a standard procedure. RESULTS: The global FAB-P scores in patients with ADD were lower than those of patients with aMCI, patients with naMCI, and healthy controls (pâ<â0.001). Patients with aMCI performed worse than healthy controls (pâ<â0.001). The interrater reliability, test-retest reliability, and Cronbach's alpha coefficient for the FAB-P were 0.997, 0.819, and 0.736, respectively. The test could distinguish the patients with mild ADD, aMCI, and naMCI from healthy controls with classification accuracy of 89.4%, 70.9%, and 61.6%, respectively. It could also discriminate between the patients with ADD and aMCI, between those with ADD and naMCI, and between those with aMCI and naMCI with classification accuracy of 73.8%, 83.9%, and 58.0%, respectively. The regression analysis revealed that the Montreal Cognitive Assessment and the Stroop Color Word Test Part C had the greatest contribution to FAB-P score variance. CONCLUSION: The FAB-P is a valid and reliable tool for evaluating frontal lobe function and can effectively discriminate ADD, aMCI, and naMCI.