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1.
BMC Ophthalmol ; 24(1): 211, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741093

RESUMO

OBJECTIVE: To investigate the correlation between higher-order aberrations (HOA) after small incision lenticule extraction (SMILE) and the severity of myopia and astigmatism, along with the relevant factors. These findings will provide valuable insights for decreasing the occurrence of HOA after SMILE and enhancing visual quality. METHODS: A total of 75 patients (150 eyes) with myopia and astigmatism who underwent SMILE were categorized into four groups based on the severity of myopia and astigmatism: Myopia Group 1 (Group M1, spherical diopter ranged from -1.00 D to -4.00 D), Myopia Group 2 (Group M2, spherical diopter ranged from -4.10 D to -10.00 D), Astigmatism Group 1 (Group A1, cylindrical diopter ranged from 0 D to -1.00 D), and Astigmatism Group 2 (Group A2, cylindrical diopter ranged from -1.10 D to -3.00 D). A comprehensive assessment was performed to examine the association between HOA and various relevant factors, including a detailed analysis of the subgroups. RESULTS: Group M1 had significantly lower levels of total eye coma aberration (CA), corneal total HOA (tHOA), internal tHOA, and vertical CA ( Z 3 - 1 ) after SMILE than Group M2 (P < 0.05). Similarly, Group A1 had significantly lower levels of total eye tHOA, CA, trefoil aberration (TA), corneal tHOA, TA, and vertical TA ( Z 3 - 3 ) after SMILE than Group A2 (P < 0.05). Pearson correlation analysis indicated a statistically significant positive relationship between the severity of myopia/astigmatism and most HOA (P < 0.05). Subgroup evaluations demonstrated a notable increase in postoperative HOA associated with myopia and astigmatism in Groups M2 and A2 compared with the control group. Lenticule thickness, postoperative central corneal thickness (CCT), postoperative uncorrected distance visual acuity (UDVA), and postoperative corneal Km and Cyl were strongly correlated with most HOA. Age, eyes, and postoperative intraocular pressure (IOP) were only associated with specific HOA. CONCLUSION: HOA positively correlated with the severity of myopia and astigmatism after SMILE. However, this relationship was not linear. HOA after SMILE was influenced by various factors, and additional specialized investigations are required to establish its clinical importance.


Assuntos
Astigmatismo , Cirurgia da Córnea a Laser , Aberrações de Frente de Onda da Córnea , Miopia , Refração Ocular , Acuidade Visual , Humanos , Miopia/cirurgia , Miopia/fisiopatologia , Astigmatismo/fisiopatologia , Astigmatismo/etiologia , Masculino , Feminino , Adulto , Acuidade Visual/fisiologia , Cirurgia da Córnea a Laser/métodos , Cirurgia da Córnea a Laser/efeitos adversos , Aberrações de Frente de Onda da Córnea/fisiopatologia , Aberrações de Frente de Onda da Córnea/etiologia , Adulto Jovem , Refração Ocular/fisiologia , Substância Própria/cirurgia , Estudos Retrospectivos , Lasers de Excimer/uso terapêutico , Complicações Pós-Operatórias , Topografia da Córnea , Adolescente
2.
Front Med (Lausanne) ; 11: 1274101, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601117

RESUMO

Objective: To examine the causes and factors that lead to high order aberration (HOA) during the treatment of myopia using small incision lenticule extraction (SMILE), as well as the differences between SMILE and other corneal refractive surgeries through a systematic review and meta-analysis. Methods: A systematic search was conducted from January 2015 to February 2023 in Pubmed, Embase, Web of Science, and Google Scholar databases to gather relevant studies on SMILE and HOA. Studies meeting specific criteria were chosen, and clinical data was retrieved for analysis. Results: This meta-analysis resulted in the inclusion of 19 studies involving 1,503 eyes. Pooled results showed significant induction of total HOA (tHOA, d = -0.21, p < 0.001), spherical aberration (SA, d = -0.11, p < 0.001) and coma aberration (CA, d = -0.18, p < 0.001) after SMILE compared to pre-SMILE, while no significant change in trefoil aberration (TA) was observed (d = -0.00, p = 0.91). There was a significantly lower induction of tHOA after SMILE compared to femtosecond laser-assisted in situ keratomileusis (FS-LASIK, d = 0.04, p < 0.001), and no significant difference was observed compared to wavefront aberration-guided (WFG) refractive surgery (d = 0.00, p = 0.75). There was also a significant association between different levels of myopia and astigmatism, duration of follow-up, lenticule thickness, and preoperative central corneal thickness (CCT) on the induction of tHOA after SMILE (p < 0.05), while the higher preoperative myopia group (sphere > -5D), lower preoperative astigmatism group (cylinder ≤ -1D), larger lenticule thickness group (lenticule thickness > 100 µm), shorter follow-up group (follow-up 1 month postoperatively) and the thicker CCT group (CCT > 550 µm) brought a significant induction of tHOA compared to the opposite comparison group (p < 0.001). Conclusion: While SMILE can induce HOA significantly, it induces less HOA than FS-LASIK. Postoperative HOA following SMILE can be affected by factors such as myopia, astigmatism, lenticule thickness, CCT, and duration of follow-up. Future research should continue to explore techniques to decrease the induction of HOA by using this methodology. Systematic review registration: https://www.crd.york.ac.uk/prospero/.

3.
Nat Commun ; 15(1): 3175, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609408

RESUMO

Although papillary thyroid cancer (PTC) has a good prognosis, its recurrence rate is high and remains a core concern in the clinic. Molecular factors contributing to different recurrence risks (RRs) remain poorly defined. Here, we perform an integrative proteogenomic and metabolomic characterization of 102 Chinese PTC patients with different RRs. Genomic profiling reveals that mutations in MUC16 and TERT promoter as well as multiple gene fusions like NCOA4-RET are enriched by the high RR. Integrative multi-omics analyses further describe the multi-dimensional characteristics of PTC, especially in metabolism pathways, and delineate dominated molecular patterns of different RRs. Moreover, the PTC patients are clustered into four subtypes (CS1: low RR and BRAF-like; CS2: high RR and metabolism type, worst prognosis; CS3: high RR and immune type, better prognosis; CS4: high RR and BRAF-like) based on the omics data. Notably, the subtypes display significant differences considering BRAF and TERT promoter mutations, metabolism and immune pathway profiles, epithelial cell compositions, and various clinical factors (especially RRs and prognosis) as well as druggable targets. This study can provide insights into the complex molecular characteristics of PTC recurrences and help promote early diagnosis and precision treatment of recurrent PTC.


Assuntos
Proteogenômica , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/genética , Proteínas Proto-Oncogênicas B-raf/genética , Metabolômica , Neoplasias da Glândula Tireoide/genética
4.
Cereb Cortex ; 34(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38642107

RESUMO

Glioma is a systemic disease that can induce micro and macro alternations of whole brain. Isocitrate dehydrogenase and vascular endothelial growth factor are proven prognostic markers and antiangiogenic therapy targets in glioma. The aim of this study was to determine the ability of whole brain morphologic features and radiomics to predict isocitrate dehydrogenase status and vascular endothelial growth factor expression levels. This study recruited 80 glioma patients with isocitrate dehydrogenase wildtype and high vascular endothelial growth factor expression levels, and 102 patients with isocitrate dehydrogenase mutation and low vascular endothelial growth factor expression levels. Virtual brain grafting, combined with Freesurfer, was used to compute morphologic features including cortical thickness, LGI, and subcortical volume in glioma patient. Radiomics features were extracted from multiregional tumor. Pycaret was used to construct the machine learning pipeline. Among the radiomics models, the whole tumor model achieved the best performance (accuracy 0.80, Area Under the Curve 0.86), while, after incorporating whole brain morphologic features, the model had a superior predictive performance (accuracy 0.82, Area Under the Curve 0.88). The features contributed most in predicting model including the right caudate volume, left middle temporal cortical thickness, first-order statistics, shape, and gray-level cooccurrence matrix. Pycaret, based on morphologic features, combined with radiomics, yielded highest accuracy in predicting isocitrate dehydrogenase mutation and vascular endothelial growth factor levels, indicating that morphologic abnormalities induced by glioma were associated with tumor biology.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Fator A de Crescimento do Endotélio Vascular/genética , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Isocitrato Desidrogenase/genética , Imageamento por Ressonância Magnética , Glioma/diagnóstico por imagem , Glioma/genética , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Mutação , Estudos Retrospectivos
5.
Front Oncol ; 14: 1358133, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38651150

RESUMO

Background: Adenocarcinoma of the rete testis (AORT) is an extremely rare and aggressive tumor with a poor prognosis. Its etiology and pathological characteristics have not been extensively studied, making accurate diagnosis and appropriate management challenging. AORT, an invasive testicular tumor with a mortality rate of 46%, treatment typically involves radical orchiectomy, retroperitoneal pelvic lymph node dissection (RPLND), adjuvant chemotherapy, and/or ongoing monitoring, but the response to conventional radiation and chemotherapy is limited. At present, no effective targeted therapy for AORT has been found. Case description: In this case report, we present the clinical scenario of a 50-year-old male patient initially diagnosed with a right testicular hydrocele, who subsequently underwent eversion of the parietal tunica vaginalis. Postoperative pathological analysis revealed metastatic clear cell renal cell carcinoma (ccRCC). PET/CT demonstrated findings suggestive of left renal upper pole carcinoma with involvement of the right scrotum, para-aortic region, bilateral iliac vessels, bilateral inguinal region, and multiple metastases. Sunitinib, a tyrosine kinase inhibitor, is commonly employed in the treatment of ccRCC. The patient underwent treatment with sunitinib for a duration of 20 months, resulting in the inactivation of multiple metastases. Following this, a radical orchiectomy was performed, and the postoperative pathology confirmed the presence of AORT. This article provides a comprehensive account of the patient's medical history, diagnostic process, treatment modalities, and subsequent follow-up observations. Conclusions: This case report highlights the successful use of targeted therapy with sunitinib in a patient with AORT. The patient showed a positive response to targeted therapy. This study not only provides a novel foundation for the treatment of AORT, but also offers valuable insights for future treatment strategies in managing this particular form of testicular cancer.

6.
Sci Rep ; 14(1): 7645, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561361

RESUMO

Remimazolam, a novel intravenous anesthetic, has been proven to be safe and efficacious in the gastroscopy setting among the elderly. However, reports comparing the effectiveness and safety of using equivalent doses of remimazolam with propofol have not been seen. The aim of this study was to compare the sedation efficacy and safety of the 95% effective doses (ED95) of remimazolam versus propofol combined with sufentanil in the gastroscopy setting among the elderly. In the first step of this two-step study, a modified up-and-down method was used to calculate the ED95 of remimazolam and propofol when combined with 0.1 µg/kg sufentanil in inhibiting body movement of elderly patients undergoing gastroscopy. In the second step, ED95 of both agents calculated in the first step were administered, endpoints of efficacy, safety, and incidence of adverse events were compared. A total of 46 individuals completed the first step. The ED95 of remimazolam was 0.163 mg/kg (95% CI 0.160-0.170 mg/kg), and that of propofol was 1.042 mg/kg (95% CI 1.007-1.112 mg/kg). In the second step, 240 patients completed the trial. The anesthetic effective rates of the remimazolam group and the propofol group were 78% and 83%, respectively, with no statistical difference (P = 0.312). Patients in the remimazolam group had more stable circulatory functions (P < 0.0001) and a lower incidence of pain on injection (3.3% vs. 19.5%, P < 0.0001). The incidence of hypotension was low in the remimazolam versus propofol group (15.6% vs. 39.0%, P < 0.0001). Overall adverse event was low in the remimazolam versus propofol group (21.3% vs. 62.7%, P < 0.0001).In this study, we found that when anesthesia was administered to elderly gastroscopy patients based on 95% effective doses of remimazolam and propofol, remimazolam was as effective as propofol, but was safer with a lower incidence of adverse events.Study registration: Chinese Clinical Trial Registry, ChiCTR2000034234. Registered 29/06/2020, https://www.chictr.org.cn .


Assuntos
Anestesia , Propofol , Idoso , Humanos , Benzodiazepinas , Gastroscopia , Propofol/efeitos adversos , Sufentanil
7.
Cancer Lett ; 590: 216839, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38570084

RESUMO

Tissue-resident memory CD8+T cells (CD8+TRMs) are thought to play a crucial role in cancer immunosurveillance. However, the characteristics of CD8+TRMs in the tumor microenvironment (TME) of human non-small cell lung cancer (NSCLC) remain unclear. Here, we report that CD8+TRMs accumulate explicitly and exhibit a unique gene expression profile in the TME of NSCLC. Interestingly, these tumor-associated CD8+TRMs uniquely exhibit an innate-like phenotype. Importantly, we found that junction adhesion molecule-like (JAML) provides an alternative costimulatory signal to activate tumor-associated CD8+TRMs via combination with cancer cell-derived CXADR (CXADR Ig-like cell adhesion molecule). Furthermore, we demonstrated that activating JAML could promote the expression of TLR1/2 on CD8+TRMs, inhibit tumor progression and prolong the survival of tumor-bearing mice. Finally, we found that higher CD8+TRMs and JAML expression in the TME could predict favorable clinical outcomes in NSCLC patients. Our study reveals an intrinsic bias of CD8+TRMs for receiving the tumor-derived costimulatory signal in the TME, which sustains their innate-like function and antitumor role. These findings will shed more light on the biology of CD8+TRMs and aid in the development of potential targeted treatment strategies for NSCLC.


Assuntos
Linfócitos T CD8-Positivos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Microambiente Tumoral , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Linfócitos T CD8-Positivos/imunologia , Animais , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Microambiente Tumoral/imunologia , Camundongos , Imunidade Inata , Linhagem Celular Tumoral , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Células T de Memória/imunologia , Células T de Memória/metabolismo , Feminino
8.
Food Chem ; 447: 139035, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38507951

RESUMO

Excessive sodium intake is a major contributor to the incidence of cardiovascular diseases. The objective of this study was to prepare, isolate, and characterize peptides from bovine bone protein and investigate the salty/salt-enhancing mechanism of peptides. 1032 peptides were identified in the enzymatic hydrolysates of bovine bone protein and were further screened by the composition of amino acid residues and molecular docking analysis. 5 peptides were finally selected for solid-phase synthesis, and KER showed a better salty taste by sensory verification. Moreover, the synergistic effect of KER in NaCl and MSG solution could enhance the salty intensity by 65.26 %. The binding of KER to the salty receptor (TMC4) was driven by hydrogen bonding and electrostatic interactions with a binding energy of -88.0734 kcal/mol. This work may provide a new approach to efficiently screen salty peptides from natural food materials, which were expected as a taste enhancer used in salt-reducing foods.


Assuntos
Cloreto de Sódio , Paladar , Animais , Bovinos , Cloreto de Sódio/farmacologia , Simulação de Acoplamento Molecular , Cloreto de Sódio na Dieta , Peptídeos/farmacologia
9.
Sci Adv ; 10(10): eade6900, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38446877

RESUMO

The accumulation of self-renewed polarized microglia in the penumbra is a critical neuroinflammatory process after ischemic stroke, leading to secondary demyelination and neuronal loss. Although known to regulate tumor cell proliferation and neuroinflammation, HDAC3's role in microgliosis and microglial polarization remains unclear. We demonstrated that microglial HDAC3 knockout (HDAC3-miKO) ameliorated poststroke long-term functional and histological outcomes. RNA-seq analysis revealed mitosis as the primary process affected in HDAC3-deficent microglia following stroke. Notably, HDAC3-miKO specifically inhibited proliferation of proinflammatory microglia without affecting anti-inflammatory microglia, preventing microglial transition to a proinflammatory state. Moreover, ATAC-seq showed that HDAC3-miKO induced closing of accessible regions enriched with PU.1 motifs. Overexpressing microglial PU.1 via an AAV approach reversed HDAC3-miKO-induced proliferation inhibition and protective effects on ischemic stroke, indicating PU.1 as a downstream molecule that mediates HDAC3's effects on stroke. These findings uncovered that HDAC3/PU.1 axis, which mediated differential proliferation-related reprogramming in different microglia populations, drove poststroke inflammatory state transition, and contributed to pathophysiology of ischemic stroke.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Microglia , Acidente Vascular Cerebral/genética , Proliferação de Células , Sementes
10.
Cancer Rep (Hoboken) ; 7(3): e2015, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38488482

RESUMO

BACKGROUND: Radiation therapy plays a pivotal role as the primary adjuvant treatment for esophageal cancer (EPC), emphasizing the critical importance of carefully balancing radiation doses to the target area and organs at risk in the radiotherapeutic management of esophageal cancer. AIMS: This study aimed to explore the correlation between morphological parameters and dosimetric parameters of the heart and spinal cord in intermediate- and advanced-stage esophagus cancer to provide a reference for clinical treatment. METHODS AND RESULTS: A total of 105 patients with intermediate- and advanced-stage EPC, who received treatment in our hospital from 2019 to 2021, were included. The morphological parameters were calculated by imaging. Intensity-modulated radiation therapy plan was executed at Raystation4.7. The PTV-G stood for the externally expanded planning target volume (PTV) of the gross tumor volume (GTV) and PTV-C for the externally expanded volume of the clinical target volume (CTV). The prescription dose of PTV-G and PTV-C was set as 60Gy/30F and 54Gy/30F, respectively. The linear regression model was used to analyze the correlation between morphologic parameters of EPC and dosimetric parameters of the heart and spinal cord. In 105 cases, the total lung length was correlated with the spinal cord maximum dose (D2 ). The heart mean doses (Dmean ) and heart V40 (the relative volume that receives 40 Gy or more) was correlated with PTV-G volume, PTV-G length; In middle- and upper-segment EPC cases, only the total lung volume was correlated with the spinal cord Dmean , spinal cord D2 , heart Dmean , and heart V40 ; In middle-stage EPC cases, the heart Dmean was correlated with the PTV-G volume, PTV-G length. The total lung length was correlated with the spinal cord D2 ; In middle- and lower-segment EPC, only the PTV-G volume and PTV-G length were correlated with the heart Dmean . All the aforementioned values were statistically significant. CONCLUSIONS: Combined with the unsegmented tumor and different locations, the organ at risk dose was comprehensively considered.


Assuntos
Neoplasias Esofágicas , Radioterapia de Intensidade Modulada , Humanos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/métodos , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/patologia , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia
11.
Mater Horiz ; 11(8): 1934-1943, 2024 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-38345761

RESUMO

The development of flexible synaptic devices with multicolor signal response is important to exploit advanced artificial visual perception systems. The Sn vacancy-dominant memory and narrow gap characteristics of PEA2SnI4 make it suitable as a functional layer in ultraviolet-visible (UV-Vis) light-stimulated synaptic devices. However, such device tends to have high dark current and poor sensitivity, which is not conducive to subsequent information processing. Here, we proposed a self-powered flexible optoelectronic synapse based on PEA2SnI4 films. By introducing the electron transport layer (ETL), the dark current of the device is decreased by 5 orders of magnitude as compared to the Au/PEA2SnI4/ITO device, and the sensitivity is increased from 10.3% to 99.2% at 1.25 mW cm-2 light illumination (520 nm), indicating the vital role of the introduced ETL in promoting the separation of excitons in the interface and inhibiting the free carrier transfer. On this basis, the optoelectronic synaptic functions with integrated sensing, recognition, and memory features were realized. The array device exhibits UV-Vis light sensitivity and tunable synaptic plasticity, enabling its application for multicolor visual sensing and skin sunburn warning. This work provides an effective strategy for fabricating multicolor intelligent sensors and artificial vision systems, which facilitate the practical application of artificial optoelectronic synapses.


Assuntos
Queimadura Solar , Queimadura Solar/prevenção & controle , Humanos , Raios Ultravioleta/efeitos adversos , Percepção Visual/fisiologia
12.
Atherosclerosis ; 391: 117478, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38417185

RESUMO

BACKGROUND AND AIMS: Atherosclerosis (AS) is a chronic inflammatory disease characterized by lipid infiltration and plaque formation in blood vessel walls. Ganoderic acids (GA), a class of major bioactive compounds isolated from the Chinese traditional medicine Ganoderma lucidum, have multiple pharmacological activities. This study aimed to determine the anti-atherosclerotic effect of GA and reveal the pharmacological mechanism. METHODS: ApoE-/- mice were fed a high-cholesterol diet and treated with GA for 16 weeks to induce AS and identify the effect of GA. Network pharmacological analysis was performed to predict the anti-atherosclerotic mechanisms. An invitro cell model was used to explore the effect of GA on macrophage polarization and the possible mechanism involved in bone marrow dereived macrophages (BMDMs) and RAW264.7 cells stimulated with lipopolysaccharide or oxidized low-density lipoprotein. RESULTS: It was found that GA at 5 and 25 mg/kg/d significantly inhibited the development of AS and increased plaque stability, as evidenced by decreased plaque in the aorta, reduced necrotic core size and increased collagen/lipid ratio in lesions. GA reduced the proportion of M1 macrophages in plaques, but had no effect on M2 macrophages. In vitro experiments showed that GA (1, 5, 25 µg/mL) significantly decreased the proportion of CD86+ macrophages and the mRNA levels of IL-6, IL-1ß, and MCP-1 in macrophages. Experimental results showed that GA inhibited M1 macrophage polarization by regulating TLR4/MyD88/NF-κB signaling pathway. CONCLUSIONS: This study demonstrated that GA play an important role in plaque stability and macrophage polarization. GA exert the anti-atherosclerotic effect partly by regulating TLR4/MyD88/NF-κB signaling pathways to inhibit M1 polarization of macrophages. Our study provides theoretical basis and experimental data for the pharmacological activity and mechanisms of GA against AS.


Assuntos
Aterosclerose , Placa Aterosclerótica , Camundongos , Animais , NF-kappa B/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/farmacologia , Receptor 4 Toll-Like/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Aterosclerose/genética , Placa Aterosclerótica/metabolismo , Transdução de Sinais , Macrófagos/metabolismo , Lipídeos
13.
Cell Rep ; 43(2): 113767, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38354085

RESUMO

CD4+ cytotoxic T lymphocytes (CD4+ CTLs) are suggested to play a crucial role in inflammatory diseases, including cancer, but their characteristics in human non-small cell lung cancer (NSCLC) remain unknown. Here, using the cell surface marker CD11b, we identify CD11b+CD4+ CTLs as a cytotoxic subset of CD4+ T cells in multiple tissues of NSCLC patients. In addition, tumor-infiltrating CD11b+CD4+ CTLs show a dysfunctional phenotype with elevated expression of CD200 receptor (CD200R), a negatively immunomodulatory receptor. CD4+ regulatory T (Treg) cells restrain the anti-tumor role of CD11b+CD4+ CTLs via CD200. Mechanistically, inflammatory dendritic cells promote the CD200R expression of CD11b+CD4+ CTLs by secreting interleukin-1ß (IL-1ß). Finally, we demonstrate that CD200 blockade can revive the tumor-killing role of CD11b+CD4+ CTLs and prolong the survival of tumor-bearing mice. Taken together, our study identifies CD11b+CD4+ CTLs in NSCLC with decreased cytotoxicity that can be reinvigorated by CD200 blockade, suggesting that targeting CD200 is a promising immunotherapy strategy in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Humanos , Camundongos , Células Dendríticas , Linfócitos T Citotóxicos , Linfócitos T Reguladores
14.
Chin J Traumatol ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38350782

RESUMO

The treatment strategy for blast injuries is closely linked to the clinical outcome of blast injury casualties. However, the application of military surgery experience to blast injuries caused by production safety accidents is relatively uncommon. In this study, the authors present 2 cases of blast injuries caused by one gas explosion, both cases involved individuals of the same age and gender and experienced similar degree of injury. The authors highlight the importance of using a military surgery treatment strategy, specifically emphasizing the need to understand the concept of damage control and disposal. It is recommended that relevant training in this area should be strengthened to improve the clinical treatment of such injuries. This study provides a valuable reference for healthcare professionals dealing with blast injuries.

15.
J Environ Sci (China) ; 140: 319-330, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38331511

RESUMO

To achieve carbon neutrality, the Chinese government needs to gain a comprehensive understanding of the sources and drivers of greenhouse gas (GHG) emissions, particularly at the county level. Anji County in eastern China is a typical example of an industrial transformation from quarrying to a low-carbon economy. This study analyzed the decoupling types and structural characteristics of GHG emissions and the driving factors of carbon dioxide (CO2) emissions in the Anji from 2006 to 2019, and explored the differences between county-level and provincial-level or city-level results. It was observed that energy-related activities are the main source of GHG emissions in Anji and that economic development is the driving factor behind the increasing CO2 emissions. However, industrial transformation and upgradation coupled with the alternative use of clean energy limit the growth of GHG emissions. This study details the GHG emissions of county during the industrial transformation stage and provides corresponding policy recommendations for county governments.


Assuntos
Gases de Efeito Estufa , Gases de Efeito Estufa/análise , Dióxido de Carbono/análise , Efeito Estufa , China , Desenvolvimento Econômico
16.
Elife ; 122024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376133

RESUMO

Glucocorticoid-induced osteonecrosis of the femoral head (GONFH) is a common refractory joint disease characterized by bone damage and the collapse of femoral head structure. However, the exact pathological mechanisms of GONFH remain unknown. Here, we observed abnormal osteogenesis and adipogenesis associated with decreased ß-catenin in the necrotic femoral head of GONFH patients. In vivo and in vitro studies further revealed that glucocorticoid exposure disrupted osteogenic/adipogenic differentiation of bone marrow mesenchymal cells (BMSCs) by inhibiting ß-catenin signaling in glucocorticoid-induced GONFH rats. Col2+ lineage largely contributes to BMSCs and was found an osteogenic commitment in the femoral head through 9 mo of lineage trace. Specific deletion of ß-catenin gene (Ctnnb1) in Col2+ cells shifted their commitment from osteoblasts to adipocytes, leading to a full spectrum of disease phenotype of GONFH in adult mice. Overall, we uncover that ß-catenin inhibition disrupting the homeostasis of osteogenic/adipogenic differentiation contributes to the development of GONFH and identify an ideal genetic-modified mouse model of GONFH.


Assuntos
Glucocorticoides , Células-Tronco Mesenquimais , Osteonecrose , beta Catenina , Animais , Humanos , Camundongos , Ratos , Adipogenia/genética , beta Catenina/genética , Diferenciação Celular , Cabeça do Fêmur/patologia , Glucocorticoides/efeitos adversos , Homeostase , Osteogênese/genética , Osteonecrose/patologia
17.
Int J Biol Macromol ; 263(Pt 1): 130076, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38354932

RESUMO

The elucidation of the immunomodulatory molecular mechanisms of polysaccharides has contributed to their further development and application. In this study, the effect of Areca inflorescence polysaccharide (AFP2a) on macrophage activation was confirmed and the detailed mechanisms were investigated based on a comprehensive transcriptional study and specific inhibitors. The results showed that AFP2a induced macrophage activation (M1 polarization), promoting macrophage proliferation, reactive oxygen species production, nitric oxide and cytokine release, and costimulatory molecule expression. RNA-seq analysis identified 5919 differentially expressed genes (DEGs). For DEGs, GO, KEGG, and Reactome enrichment analyses and PPI networks were conducted, elucidating that AFP2a activated macrophages mainly by triggering the Toll-like receptor cascade and corresponding adapter proteins (TIRAP and TRIF), thereby resulting in downstream NF-κB, TNF, and JAK-STAT signaling pathway expression. The inhibition assay revealed that TLR4 and TLR2 were essential for the recognition of AFP2a. This work provides an in-depth understanding of the immunoregulatory mechanism of AFP2a while offering a molecular basis for AFP2a to serve as a potential natural immunomodulator.


Assuntos
Areca , Inflorescência , Inflorescência/metabolismo , Macrófagos , NF-kappa B/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo , RNA-Seq , Ativação de Macrófagos
18.
Technol Cancer Res Treat ; 23: 15330338241229367, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38297814

RESUMO

Objective: To investigate the dosimetric effects of using individualized silicone rubber (SR) bolus on the target area and organs at risk (OARs) during postmastectomy radiotherapy (PMRT), as well as evaluate skin acute radiation dermatitis (ARD). Methods: A retrospective study was performed on 30 patients with breast cancer. Each patient was prepared with an individualized SR bolus of 3 mm thickness. Fan-beam computed tomography (FBCT) was performed at the first and second fractions, and then once a week for a total of 5 times. Dosimetric metrics such as homogeneity index (HI), conformity index (CI), skin dose (SD), and OARs including the heart, lungs, and spinal cord were compared between the original plan and the FBCTs. The acute side effects were recorded. Results: In targets' dosimetric metrics, there were no significant differences in Dmean and V105% between planning computed tomography (CT) and actual treatments (P > .05), while the differences in D95%, V95%, HI, and CI were statistically significant (P < .05). In OARs, there were no significant differences between the Dmean, V5, and V20 of the affected lung, V5 of the heart and Dmax of the spinal cord (P > .05) except the V30 of affected lung, which was slightly lower than the planning CT (P < .05). In SD, both Dmax and Dmean in actual treatments were increased than plan A, and the difference was statistically significant (P < .05), while the skin-V20 and skin-V30 has no difference. Among the 30 patients, only one patient had no skin ARD, and 5 patients developed ARD of grade 2, while the remaining 24 patients were grade 1. Conclusion: The OR bolus showed good anastomoses and high interfraction reproducibility with the chest wall, and did not cause deformation during irradiation. It ensured accurate dose delivery of the target and OARs during the treatment, which may increase SD by over 101%. In this study, no cases of grade 3 skin ARD were observed. However, the potential of using OR bolus to reduce grade 1 and 2 skin ARD warrants further investigation with a larger sample size.


Assuntos
Neoplasias da Mama , Dermatite , Radioterapia de Intensidade Modulada , Humanos , Feminino , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Elastômeros de Silicone , Planejamento da Radioterapia Assistida por Computador/métodos , Dosagem Radioterapêutica , Estudos Retrospectivos , Reprodutibilidade dos Testes , Mastectomia/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Tomografia Computadorizada por Raios X , Dermatite/cirurgia , Órgãos em Risco/efeitos da radiação
19.
Sci Rep ; 14(1): 863, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195676

RESUMO

To evaluate the changes of dry eye parameters after small incision lenticule extraction (SMILE) surgery in patients with different ocular surface disease index (OSDI) scores. Prospective research. Participants were divided into two groups: Group A, OSDI < 13; and Group B, OSDI ≥ 13. The OSDI scores, tear meniscus height (TMH), first non-invasive tear film break-up time (NIBUT-First), and meibomian gland loss (MGL, %) were recorded at postoperative 1 -week and 1-month.113 eyes (57 patients) were enrolled, 70 eyes in Group A, and 43 eyes in Group B. In Group A, the OSDI scores significantly increased at 1-week and 1-month postoperative (all P < 0.001); the TMH, NIBUT-First and lipid layer grade significantly decreased at postoperative 1-week (P = 0.003, 0.005, 0.007, 0.004, respectively), but returned to preoperative level at 1-month postoperative. In Group B, only the lipid layer grade significantly decreased at postoperative 1-week (P < 0.05). Patients with different preoperative OSDI scores may experience different changes early after SMILE surgery. Patients with OSDI scores < 13 may experience more dramatic changes in dry eye symptoms which would resolve, while subjective complains could still exists at 1 month after surgery.


Assuntos
Síndromes do Olho Seco , Ferida Cirúrgica , Humanos , Estudos Prospectivos , Síndromes do Olho Seco/etiologia , Glândulas Tarsais , Lipídeos
20.
Cancer Cell Int ; 24(1): 30, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218909

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) stands as a prevalent malignancy globally, characterized by significant morbidity and mortality. Despite continuous advancements in the treatment of HCC, the prognosis of patients with this cancer remains unsatisfactory. This study aims at constructing a disulfidoptosis­related long noncoding RNA (lncRNA) signature to probe the prognosis and personalized treatment of patients with HCC. METHODS: The data of patients with HCC were extracted from The Cancer Genome Atlas (TCGA) databases. Univariate, multivariate, and least absolute selection operator Cox regression analyses were performed to build a disulfidptosis-related lncRNAs (DRLs) signature. Kaplan-Meier plots were used to evaluate the prognosis of the patients with HCC. Functional enrichment analysis was used to identify key DRLs-associated signaling pathways. Spearman's rank correlation was used to elucidate the association between the DRLs signature and immune microenvironment. The function of TMCC1-AS1 in HCC was validated in two HCC cell lines (HEP3B and HEPG2). RESULTS: We identified 11 prognostic DRLs from the TCGA dataset, three of which were selected to construct the prognostic signature of DRLs. We found that the survival time of low-risk patients was considerably longer than that of high-risk patients. We further observed that the composition and the function of immune cell subpopulations were significantly different between high- and low-risk groups. Additionally, we identified that sorafenib, 5-Fluorouracil, and doxorubicin displayed better responses in the low-score group than those in the high-score group, based on IC50 values. Finally, we confirmed that inhibition of TMCC1-AS1 impeded the proliferation, migration, and invasion of hepatocellular carcinoma cells. CONCLUSIONS: The DRL signatures have been shown to be a reliable prognostic and treatment response indicator in HCC patients. TMCC1-AS1 showed potential as a novel prognostic biomarker and therapeutic target for HCC.

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