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1.
BMC Public Health ; 24(1): 1224, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702746

RESUMO

BACKGROUND: Accumulating evidence suggests a pivotal role of vitamin B2 in the pathogenesis and progression of prostate cancer (PCa). Vitamin B2 intake has been postulated to modulate the screening rate for PCa by altering the concentration of prostate-specific antigen(PSA). However, the relationship between vitamin B2 and PSA remains indeterminate. Hence, we conducted a comprehensive evaluation of the association between vitamin B2 intake and PSA levels, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: From a pool of 20,371 participants in the NHANES survey conducted between 2003 and 2010, a cohort of 2,323 participants was selected for the present study. The male participants were classified into four distinct groups based on their levels of vitamin B2 intake. We employed a multiple linear regression model and a non-parametric regression method to investigate the relationship between vitamin B2 and PSA levels. RESULTS: The study cohort comprised of 2,323 participants with a mean age of 54.95 years (± 11.73). Our findings revealed a statistically significant inverse correlation between vitamin B2 intake (mg) and PSA levels, with a reduction of 0.13 ng/ml PSA concentration for every unit increase in vitamin B2 intake. Furthermore, we employed a fully adjusted model to construct a smooth curve to explore the possible linear relationship between vitamin B2 intake and PSA concentration. CONCLUSIONS: Our study in American men has unveiled a notable inverse association between vitamin B2 intake and PSA levels, potentially posing a challenge for the identification of asymptomatic prostate cancer. Specifically, our findings suggest that individuals with higher vitamin B2 intake may be at a greater risk of being diagnosed with advanced prostate cancer in the future, possibly indicating a detection bias. These results may offer a novel explanation for the observed positive correlation between vitamin B2 intake and prostate cancer.


Assuntos
Inquéritos Nutricionais , Antígeno Prostático Específico , Neoplasias da Próstata , Riboflavina , Humanos , Masculino , Antígeno Prostático Específico/sangue , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Idoso , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Riboflavina/administração & dosagem , Adulto
2.
World J Gastroenterol ; 30(13): 1926-1933, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38659487

RESUMO

Accurate preoperative diagnosis is highly important for the treatment of perivascular epithelioid cell tumors (PEComas) because PEComas are mainly benign tumors and may not require surgical intervention. By analyzing the causes, properties and clinical manifestations of PEComas, we summarize the challenges and solutions in the diagnosis of PEComas.


Assuntos
Neoplasias Hepáticas , Neoplasias de Células Epitelioides Perivasculares , Humanos , Neoplasias de Células Epitelioides Perivasculares/cirurgia , Neoplasias de Células Epitelioides Perivasculares/patologia , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/diagnóstico , Hepatectomia , Cuidados Pré-Operatórios/métodos , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Fígado/patologia , Fígado/cirurgia , Fígado/diagnóstico por imagem
3.
World J Gastrointest Oncol ; 16(3): 945-967, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38577477

RESUMO

BACKGROUND: Gastric cancer (GC) is a highly aggressive malignancy with a heterogeneous nature, which makes prognosis prediction and treatment determination difficult. Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours. Inflammation also affects the prognosis of GC patients. Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis. However, the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear. AIM: To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients. METHODS: In this study, the mRNA expression profiles and corresponding clinical information of GC patients were obtained from the Gene Expression Omnibus (GEO) database (GSE66229). An inflammatory-related gene prognostic signature model was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database. GC patients from the GSE26253 cohort were used for validation. Univariate and multivariate Cox analyses were used to determine the independent prognostic factors, and a prognostic nomogram was established. The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram. The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram. Gene set enrichment analysis was performed to explore the potential regulatory pathways involved. The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT. Finally, we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents. RESULTS: A prognostic model consisting of three inflammatory-related genes (MRPS17, GUF1, and PDK4) was constructed. Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients. According to the risk score, GC patients were stratified into high- and low-risk groups, and patients in the high-risk group had significantly worse prognoses according to age, sex, TNM stage and Lauren type. Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging. Finally, the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group, indicating a link between inflammation-related genes and drug sensitivity. CONCLUSION: In conclusion, we established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.

4.
Anal Methods ; 16(19): 3058-3066, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38682943

RESUMO

NH3 gas sensors operating at room temperature, consisting of Ag nanoparticles decorated ß-AgVO3 nanorods (Ag/ß-AgVO3 NRs), were fabricated via a facile hydrothermal method without the need for a template. The surface characteristics and compositions of Ag/ß-AgVO3 NRs were analyzed using X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Ag nanoparticles, ranging in diameter from approximately 20 to 40 nm, were dispersed on the surface of monoclinic ß-AgVO3 NRs with diameters ranging from 50 to 105 nm and lengths from 0.3 to 1.3 µm. The NH3 gas sensing properties of Ag/ß-AgVO3 NRs were studied under both dry air and humid conditions at room temperature. Comparative analysis demonstrated that the Ag/ß-AgVO3 NRs exhibited a strong response to NH3 gas under 70% relative humidity (RH) at room temperature compared to α-AgVO3 NRs. Specifically, the response of the Ag/ß-AgVO3 NRs to 5 ppm NH3 increased by 2.25 times as the RH varied from 20% to 80% at room temperature. This enhanced response was attributed to the effects of formation of nanoheterojunctions, nano-metallic Ag activity and the conductivity of NH4+ and OH- ions induced by the presence of humidity. The room temperature NH3 gas sensors based on Ag/ß-AgVO3 NRs demonstrated strong responses to low NH3 concentrations, high selectivity, good reproducibility, and long-term stability, and show promise for the development of low-power and cost-effective NH3 gas sensors for practical applications even under high humidity.

5.
Heliyon ; 10(6): e28066, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38524612

RESUMO

Luteolin is a potent anti-colorectal cancer chemical. However, its effectiveness is hindered by its poor solubility in water and fat, and it is easy to degrade by gastrointestinal enzymes. In this study, a nano-composite carrier, NH2-MIL-101(Fe)@GO (MG), based on aminated MIL-101(Fe) and graphene oxide (GO) was developed and evaluated. This carrier co-delivered luteolin and matrine, while marine was used to balance the pH for the nano-preparation. The loading capacities for luteolin and matrine were approximately 9.8% and 14.1%, respectively. Luteolin's release at pH = 5 was significantly higher than at pH = 7.4, indicating it had an acidic pH response release characteristic. Compared to MOF and GO alone, MG and NH2-MIL-101(Fe)@GO@Drugs (MGD) enhanced anti-cancer activity by inhibiting tumor cell migration, increasing ROS generation, and upregulating the expression of Caspase-3 and Caspase-9. In conclusion, this study contributes new ideas and methods to the treatment strategy of multi-component anti-colorectal cancer therapy. It also advances drug delivery systems and supports the development of more effective and targeted treatment approaches for colorectal cancer.

6.
Chin J Dent Res ; 27(1): 17-28, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38546516

RESUMO

The dentine sialophosphoprotein (DSPP) gene is the only identified causative gene for dentinogenesis imperfecta type 2 (DGI-II), dentinogenesis imperfecta type 3 (DGI-III) and dentine dysplasia type 2 (DD-II). These three disorders may have similar molecular mechanisms involved in bridging the DSPP mutations and the resulting abnormal dentine mineralisation. The DSPP encoding proteins DSP (dentine sialoprotein) and DPP (dentine phosphoprotein) are positive regulators of dentine formation and perform a function during dentinogenesis. The present review focused on the recent findings and viewpoints regarding the relationship between DSPP and dentinogenesis as well as mineralisation from multiple perspectives, involving studies relating to spatial structure and tissue localisation of DSPP, DSP and DPP, the biochemical characteristics and biological function of these molecules, and the causative role of the proteins in phenotypes of the knockout mouse model and in hereditary dentine defects.


Assuntos
Calcinose , Dentinogênese Imperfeita , Fosfoproteínas , Sialoglicoproteínas , Animais , Camundongos , Calcificação Fisiológica , Dentina , Dentinogênese Imperfeita/genética , Modelos Animais de Doenças , Camundongos Knockout , Humanos , Sialoglicoproteínas/genética , Fosfoproteínas/genética
7.
Nat Commun ; 15(1): 2484, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509096

RESUMO

Squamous cell carcinomas (SCCs) are common and aggressive malignancies. Immune check point blockade (ICB) therapy using PD-1/PD-L1 antibodies has been approved in several types of advanced SCCs. However, low response rate and treatment resistance are common. Improving the efficacy of ICB therapy requires better understanding of the mechanism of immune evasion. Here, we identify that the SCC-master transcription factor TP63 suppresses interferon-γ (IFNγ) signaling. TP63 inhibition leads to increased CD8+ T cell infiltration and heighten tumor killing in in vivo syngeneic mouse model and ex vivo co-culture system, respectively. Moreover, expression of TP63 is negatively correlated with CD8+ T cell infiltration and activation in patients with SCC. Silencing of TP63 enhances the anti-tumor efficacy of PD-1 blockade by promoting CD8+ T cell infiltration and functionality. Mechanistically, TP63 and STAT1 mutually suppress each other to regulate the IFNγ signaling by co-occupying and co-regulating their own promoters and enhancers. Together, our findings elucidate a tumor-extrinsic function of TP63 in promoting immune evasion of SCC cells. Over-expression of TP63 may serve as a biomarker predicting the outcome of SCC patients treated with ICB therapy, and targeting TP63/STAT/IFNγ axis may enhance the efficacy of ICB therapy for this deadly cancer.


Assuntos
Carcinoma de Células Escamosas , Interferon gama , Animais , Humanos , Camundongos , Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Imunidade , Interferon gama/metabolismo , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Fatores de Transcrição/metabolismo , Microambiente Tumoral , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
8.
Cell Commun Signal ; 22(1): 140, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378560

RESUMO

Hostile microenvironment of cancer cells provoke a stressful condition for endoplasmic reticulum (ER) and stimulate the expression and secretion of ER chaperones, leading to tumorigenic effects. However, the molecular mechanism underlying these effects is largely unknown. In this study, we reveal that the last four residues of ER chaperones, which are recognized by KDEL receptor (KDELR), is required for cell proliferation and migration induced by secreted chaperones. By combining proximity-based mass spectrometry analysis, split venus imaging and membrane yeast two hybrid assay, we present that EGF receptor (EGFR) may be a co-receptor for KDELR on the surface. Prior to ligand addition, KDELR spontaneously oligomerizes and constantly undergoes recycling near the plasma membrane. Upon KDEL ligand binding, the interactions of KDELR with itself and with EGFR increase rapidly, leading to augmented internalization of KDELR and tyrosine phosphorylation in the C-terminus of EGFR. STAT3, which binds the phosphorylated tyrosine motif on EGFR, is subsequently activated by EGFR and mediates cell growth and migration. Taken together, our results suggest that KDELR serves as a bona fide cell surface receptor for secreted ER chaperones and transactivates EGFR-STAT3 signaling pathway.


Assuntos
Receptores ErbB , Receptores de Peptídeos , Transdução de Sinais , Humanos , Ligantes , Receptores ErbB/metabolismo , Chaperonas Moleculares/metabolismo , Proliferação de Células , Tirosina , Fator de Transcrição STAT3/metabolismo
9.
Transl Oncol ; 42: 101888, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38354632

RESUMO

PURPOSE: To establish a prognostic model of esophageal squamous cell carcinoma (ESCC) patients based on tenascin-C (TNC) expression level and clinicopathological characteristics, and to explore the therapeutic potential of TNC inhibition. METHODS: The expression of TNC was detected using immunohistochemistry (IHC) in 326 ESCC specimens and 50 normal esophageal tissues. Prognostic factors were determined by Cox regression analyses and were incorporated to establish the nomogram. The effects of TNC knockdown on ESCC cells were assessed in vitro and in vivo. Transcriptome sequencing (RNA-seq) and gene set enrichment analysis (GSEA) were performed to reveal signaling pathways regulated by TNC knockdown. The therapeutic significance of TNC knockdown combined with small-molecule inhibitors on cell proliferation was examined. RESULTS: TNC protein was highly expressed in 48.77 % of ESCC tissues compared to only 2 % in normal esophageal epithelia (p < 0.001). The established nomogram model, based on TNC expression, pT stage, and lymph node metastasis, showed good performance on prognosis evaluation. More importantly, the reduction of TNC expression inhibited tumor cell proliferation and xenograft growth, and mainly down-regulated signaling pathways involved in tumor growth, hypoxia signaling transduction, metabolism, infection, etc. Knockdown of TNC enhanced the inhibitory effect of inhibitors targeting ErbB, PI3K-Akt, Ras and MAPK signaling pathways. CONCLUSION: The established nomogram may be a promising model for survival prediction in ESCC. Reducing TNC expression enhanced the sensitivity of ESCC cells to inhibitors of Epidermal Growth Factor Receptor (EGFR) and downstream signaling pathways, providing a novel combination therapy strategy.

10.
J Immunother Cancer ; 12(2)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316518

RESUMO

Treatment of hematologic malignancies with patient-derived anti-CD19 chimeric antigen receptor (CAR) T-cells has demonstrated long-term remissions for patients with otherwise treatment-refractory advanced leukemia and lymphoma. Conversely, CAR T-cell treatment of solid tumors, including advanced gastric cancer (GC), has proven more challenging due to on-target off-tumor toxicities, poor tumor T-cell infiltration, inefficient CAR T-cell expansion, immunosuppressive tumor microenvironments, and demanding preconditioning regimens. We report the exceptional results of autologous Claudin18.2-targeted CAR T cells (CT041) in a patient with metastatic GC, who had progressed on four lines of combined systemic chemotherapy and immunotherapy. After two CT041 infusions, the patient had target lesion complete response and sustained an 8-month overall partial response with only minimal ascites. Moreover, tumor-informed circulating tumor DNA (ctDNA) reductions coincided with rapid CAR T-cell expansion and radiologic response. No severe toxicities occurred, and the patient's quality of life significantly improved. This experience supports targeting Claudin18.2-positive GC with CAR T-cell therapy and helps to validate ctDNA as a biomarker in CAR T-cell therapy. Clinical Insight: Claudin18.2-targeted CAR T cells can safely provide complete objective and ctDNA response in salvage metastatic GC.


Assuntos
Leucemia , Receptores de Antígenos Quiméricos , Neoplasias Gástricas , Humanos , Receptores de Antígenos de Linfócitos T , Neoplasias Gástricas/terapia , Qualidade de Vida , Linfócitos T , Resposta Patológica Completa , Antígenos CD19 , Microambiente Tumoral
11.
Asian J Surg ; 47(4): 1734-1739, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38185563

RESUMO

OBJECTIVE: This study compares endoscopic thyroidectomy by gasless unilateral axillary approach (ETGUA) and sternocleidomastoid leading-edge approach (SLEA) with conventional open thyroidectomy (COT) in hemithyroidectomy. The main focus is on the protection of neck muscles (sternocleidomastoid, omohyoid, sternothyroid) and the postoperative function of voice and swallowing yielded through these common approaches. METHODS: A total of 302 patients who underwent hemithyroidectomy were enrolled and divided into three groups: ETGUA (n = 101), SLEA (n = 100), and COT (n = 101). Ultrasound was used to measure the thickness of bilateral neck muscles, including the sternocleidomastoid, omohyoid, and sternothyroid. The changes in thickness on the surgical side compared to the non-surgical side. Analyzed factors included muscle thickness changes, Swallowing Impairment Score (SIS), Voice Handicap Index (VHI), Scar Cosmesis Assessment and Rating (SCAR), Neck Injury Index (NII), surgery duration, drainage volume, hospitalization, and number of lymph nodes. RESULTS: The clinical characteristics among the three groups were consistent except for differences in sex, age, and BMI. Metrics such as sternocleidomastoid muscle, NII, hypocalcemia, postoperative PTH, transient hoarseness, and number of lymph nodes showed no significant differences among the three groups. However, significant differences were found in the duration of surgery, drainage volume, hospitalization period omohyoid muscle, Sternohyoid muscle, VHI, SIS, and SCAR (all p < 0.001). CONCLUSION: In comparison to COT, ETGUA and SLEA demonstrate superiority in protecting neck muscles and preserving voice and swallowing function without compromising surgical safety or radicality.


Assuntos
Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Deglutição , Músculos do Pescoço/patologia , Endoscopia , Esvaziamento Cervical , Neoplasias da Glândula Tireoide/cirurgia
12.
Sci Rep ; 14(1): 2592, 2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38296998

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, whose severe form is associated with oxidative stress. Vitamin E as an antioxidant has a protective potential in NAFLD. Whether dietary intake of vitamin E, supplementary vitamin E use, and total vitamin E have a preventive effect on NAFLD requires investigation. A cross-sectional study used data from the National Health and Nutrition Examination Survey (2017-2020) was conducted. Vitamin E intake, including dietary vitamin E, supplementary vitamin E use, and total vitamin E, was obtained from the average of two 24-h dietary recall interviews. The extent of hepatic steatosis was measured by liver ultrasound transient elastography and presented as controlled attenuated parameter (CAP) scores. Participants were diagnosed with NAFLD based on CAP threshold values of 288 dB/m and 263 dB/m. The statistical software R and survey-weighted statistical models were used to examine the association between vitamin E intake and hepatic steatosis and NAFLD. Overall, 6122 participants were included for NAFLD analysis. After adjusting for age, gender, race, poverty level index, alcohol consumption, smoking status, vigorous recreational activity, body mass index, abdominal circumference, hyperlipidemia, hypertension, diabetes, and supplementary vitamin E use, dietary vitamin E was inversely associated with NAFLD. The corresponding odds ratios (OR) and 95% confidence intervals (CI) of NAFLD for dietary vitamin E intake as continuous and the highest quartile were 0.9592 (0.9340-0.9851, P = 0.0039) and 0.5983 (0.4136-0.8654, P = 0.0091) (Ptrend = 0.0056). Supplementary vitamin E was significantly inversely associated with NAFLD (fully adjusted model: OR = 0.6565 95% CI 0.4569-0.9432, P = 0.0249). A marginal improvement in total vitamin E for NAFLD was identified. The ORs (95% CIs, P) for the total vitamin E intake as continuous and the highest quartile in the fully adjusted model were 0.9669 (0.9471-0.9871, P = 0.0029) and 0.6743 (0.4515-1.0071, P = 0.0538). Sensitivity analysis indicated these findings were robust. The protective effects of vitamin E significantly differed in the stratum of hyperlipidemia (Pinteraction < 0.05). However, no statistically significant results were identified when the threshold value was set as 263 dB/m. Vitamin E intake, encompassing both dietary and supplemental forms, as well as total vitamin E intake, demonstrated a protective association with NAFLD. Augmenting dietary intake of vitamin E proves advantageous in the prevention of NAFLD, particularly among individuals devoid of hyperlipidemia.


Assuntos
Técnicas de Imagem por Elasticidade , Hiperlipidemias , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Inquéritos Nutricionais , Estudos Transversais , Vitamina E , Hiperlipidemias/complicações
13.
Exp Cell Res ; 435(1): 113910, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38185251

RESUMO

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignant disease with a poor prognosis. We previously found that p62 presented a marked nuclear-cytoplasmic translocation in ESCC cells as compared that in normal esophageal epithelial cells, but its effects on ESCC cells remain unclear. This study aims to clarify the impacts of different cellular localization of p62 on the function of ESCC cells and the underlying molecular mechanisms. We here demonstrated that cytoplasmic p62 enhances the migration and invasion abilities of esophageal cancer cells, whereas nuclear p62 has no effect. We further explored the interaction protein of p62 by using GST pull-down experiment and identified EPLIN as a potential protein interacting with p62. In addition, reducing EPLIN expression significantly inhibited the migration and invasion of ESCC cells, which were rescued when EPLIN expression was restored after the p62 knockdown. At a molecular level, p62 in cytoplasm positively regulated the expression of EPLIN via enhancing its protein stability. Data from the TCGA and GEO database displayed a significant up-regulation of EPLIN mRNA expression in ESCC tissues compared with corresponding paired esophageal epithelial samples. Our findings present evidence that the nuclear-cytoplasmic translocation of p62 protein contributes to an aggressive malignancy phenotype, providing candidate molecular biomarkers and potential molecular targets for the diagnosis and treatment of ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Citoplasma/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica/genética , Invasividade Neoplásica/genética , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo
14.
Hepatobiliary Pancreat Dis Int ; 23(3): 272-287, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37407412

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) has a poor long-term prognosis. The competition of circular RNAs (circRNAs) with endogenous RNA is a novel tool for predicting HCC prognosis. Based on the alterations of circRNA regulatory networks, the analysis of gene modules related to HCC is feasible. METHODS: Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in HCC. Gene function, pathway, and protein interaction analyses were performed for the differentially expressed genes (DEGs) in this regulatory network. In the protein-protein interaction network, hub genes were identified and subjected to regression analysis, producing an optimized four-gene signature for prognostic risk stratification in HCC patients. Anti-HCC drugs were excavated by assessing the DEGs between the low- and high-risk groups. A circRNA-microRNA-hub gene subnetwork was constructed, in which three hallmark genes, KIF4A, CCNA2, and PBK, were subjected to functional enrichment analysis. RESULTS: A four-gene signature (KIF4A, CCNA2, PBK, and ZWINT) that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas (TCGA) cohort and International Cancer Genome Consortium (ICGC) cohort was developed. CDK inhibitors, PI3K inhibitors, HDAC inhibitors, and EGFR inhibitors were predicted as four potential mechanisms of drug action (MOA) in high-risk HCC patients. Subsequent analysis has revealed that PBK, CCNA2, and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion, regulating microsatellite instability (MSI), and exerting an impact on HCC progression. CONCLUSIONS: The present study highlights the role of the circRNA-related regulatory network, identifies a four-gene prognostic signature and biomarkers, and further identifies novel therapy for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , RNA Circular/genética , Prognóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , RNA Endógeno Competitivo , Fosfatidilinositol 3-Quinases , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , MicroRNAs/genética , Microambiente Tumoral , Cinesinas
15.
J Bone Joint Surg Am ; 106(6): 492-500, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38109425

RESUMO

BACKGROUND: Many patients experience lower-extremity swelling following total knee arthroplasty (TKA), which impedes recovery. Diosmin is a semisynthetic flavonoid that is often utilized to treat swelling and pain caused by chronic venous insufficiency. We aimed to evaluate the efficacy and safety of diosmin in reducing lower-extremity swelling and pain as well as in improving functional outcomes following TKA. METHODS: This study was designed as a randomized, controlled multicenter trial and conducted in 13 university-affiliated tertiary hospitals. A total of 330 patients undergoing TKA were randomized to either receive or not receive diosmin postoperatively. The diosmin group received 0.9 g of diosmin twice per day for 14 consecutive days starting on the day after surgery, whereas the control group received neither diosmin nor a placebo postoperatively. The primary outcome was lower-extremity swelling 1, 2, 3, and 14 days postoperatively. The secondary outcomes were postoperative pain assessed with use of a visual analogue scale, Hospital for Special Surgery score, range of knee motion, levels of the inflammatory biomarkers C-reactive protein and interleukin-6, and complications. RESULTS: At all postoperative time points, diosmin was associated with significantly less swelling of the calf, thigh, and upper pole of the patella as well as with significantly lower pain scores during motion. However, no significant differences in postoperative pain scores at rest, Hospital for Special Surgery scores, range of motion, levels of inflammatory biomarkers, or complication rates were found between the diosmin and control groups. CONCLUSIONS: The use of diosmin after TKA reduced lower-extremity swelling and pain during motion and was not associated with an increased incidence of short-term complications involving the outcomes studied. However, further studies are needed to continue exploring the efficacy and safety of diosmin use in TKA. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Artroplastia do Joelho , Diosmina , Humanos , Artroplastia do Joelho/efeitos adversos , Diosmina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Coxa da Perna , Biomarcadores , Resultado do Tratamento
16.
Ultrason Imaging ; 46(2): 110-120, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38140769

RESUMO

Henoch-Schönlein purpura nephritis (HSPN) is one of the most common kidney diseases in children. The current diagnosis and classification of HSPN depend on pathological biopsy, which is seriously limited by its invasive and high-risk nature. The aim of the study was to explore the potential of radiomics model for evaluating the histopathological classification of HSPN based on the ultrasound (US) images. A total of 440 patients with Henoch-Schönlein purpura nephritis proved by biopsy were analyzed retrospectively. They were grouped according to two histopathological categories: those without glomerular crescent formation (ISKDC grades I-II) and those with glomerular crescent formation (ISKDC grades III-V). The patients were randomly assigned to either a training cohort (n = 308) or a validation cohort (n = 132) with a ratio of 7:3. The sonologist manually drew the regions of interest (ROI) on the ultrasound images of the right kidney including the cortex and medulla. Then, the ultrasound radiomics features were extracted using the Pyradiomics package. The dimensions of radiomics features were reduced by Spearman correlation coefficients and least absolute shrinkage and selection operator (LASSO) method. Finally, three radiomics models using k-nearest neighbor (KNN), logistic regression (LR), and support vector machine (SVM) were established, respectively. The predictive performance of such classifiers was assessed with receiver operating characteristic (ROC) curve. 105 radiomics features were extracted from derived US images of each patient and 14 features were ultimately selected for the machine learning analysis. Three machine learning models including k-nearest neighbor (KNN), logistic regression (LR), and support vector machine (SVM) were established for HSPN classification. Of the three classifiers, the SVM classifier performed the best in the validation cohort [area under the curve (AUC) =0.870 (95% CI, 0.795-0.944), sensitivity = 0.706, specificity = 0.950]. The US-based radiomics had good predictive value for HSPN classification, which can be served as a noninvasive tool to evaluate the severity of renal pathology and crescentic formation in children with HSPN.


Assuntos
Glomerulonefrite , Vasculite por IgA , Criança , Humanos , Vasculite por IgA/complicações , Vasculite por IgA/diagnóstico por imagem , Estudos Retrospectivos , Radiômica , Glomerulonefrite/diagnóstico , Glomerulonefrite/patologia , Rim/diagnóstico por imagem , Rim/patologia
17.
Ann Vasc Surg ; 100: 39-46, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38104925

RESUMO

BACKGROUND: To evaluate the safety and efficacy of endovascular denervation (EDN) as an adjunct to percutaneous vascular intervention (PVI) for peripheral artery disease (PAD). METHODS: From August 2019 to April 2021, 38 eligible patients with PAD enrolled in this study were randomly and equally assigned into 2 groups: the PVI group and the PVI + EDN group treated with EDN at the iliac and femoral arteries before PVI. The primary endpoint was the improvement in the ankle brachial index at 6 months after the procedure. The secondary endpoints were transcutaneous oxygen pressure (TcPO2), Rutherford category, numerical rating scale score, and safety. RESULTS: The technical success rates of PVI and EDN were 100%, and no device-related or procedure-related major adverse events occurred in either group. Compared with PVI alone, PVI + EDN demonstrated a significant improvement in limb hemodynamics at 6 months (Δ ankle brachial index 0.44 ± 0.31 vs. 0.24 ± 0.15, P = 0.018). Microcirculatory perfusion of PAD was significantly better at 6 months in the PVI + EDN group (ΔTcPO2, 15.68 ± 16.72 vs. 4.95 ± 13.43, P = 0.036). The Rutherford category was significantly improved in the PVI + EDN group in comparison with the PVI group at the 3-month follow-up (100.00% vs. 68.42%, P = 0.02). The decrease in the numerical rating scale score in the PVI + EDN group was greater than that in the PVI group at 1 week following the procedure (3 [2-5] vs. 4 [4-6], P = 0.022). CONCLUSIONS: In this single-center pilot analysis of a heterogeneous cohort of patients with PAD, PVI with EDN demonstrated a significant improvement in limb ischemia at 6 months compared with PVI alone.


Assuntos
Procedimentos Endovasculares , Doença Arterial Periférica , Humanos , Microcirculação , Resultado do Tratamento , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/cirurgia , Isquemia/diagnóstico por imagem , Isquemia/cirurgia , Denervação , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Fatores de Risco
18.
Sci Rep ; 13(1): 22245, 2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-38097726

RESUMO

To identify cognitive function in Chinese breast cancer survivors. Research questions were: is cognitive function was associated with breast cancer and/or chemotherapy treatment and/or psychological functioning:? and did women with breast cancer experience more cognitive and psychological issues than age-matched women without cancer? Breast cancer survivors with chemotherapy (n = 106, mean age = 50.2 ± 9.5), breast cancer survivors without chemotherapy (n = 100, mean age = 50.5 ± 10.0) and matched healthy controls (n = 96, mean age = 47.9 ± 9.1) completed a battery of cognitive and psychosocial functioning. Demographic characteristics were also collected. The Perceived Cognitive Impairment score for cancer groups was significantly higher than for the healthy group (p = 0.04), but not between the cancer groups. Processing speed was significantly slower in the cancer groups than in the healthy group (both p < 0.001), but not between the cancer groups. Age, living status and education were significantly associated with the FACT-Cog (all p < 0.05). The correlations between the FACT-Cog score and BSI score were strong (r = 0.60 p < 0.01), and between the HADS anxiety and depression scales were strong (r = 0.53 and 0.50, p < 0.01) but correlations were weaker between performance based cognitive tests and measures of psychological functioning. Breast cancer groups indicated more cognitive impairment and reduced psychological functioning compared to the healthy group. However, there was no differences between the breast cancer groups. Chinese breast cancer survivors experienced excess cognitive impairment not associated with usual ageing. Assessment and intervention to address cognitive impairment should be made available to breast cancer survivors.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Disfunção Cognitiva , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Sobreviventes de Câncer/psicologia , Neoplasias da Mama/tratamento farmacológico , Disfunção Cognitiva/etiologia , Sobreviventes/psicologia , Cognição , Qualidade de Vida , China
19.
World J Pediatr ; 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37938453

RESUMO

BACKGROUND: Hypothalamus hamartomas (HHs) are rare, congenital, tumor-like, and nonprogressive malformations resulting in drug-resistant epilepsy, mainly affecting children. Gelastic seizures (GS) are an early hallmark of epilepsy with HH. The aim of this study was to explore the disease progression and the underlying physiopathological mechanisms of pathological laughter in HH. METHODS: We obtained clinical information and metabolic images of 56 HH patients and utilized ictal semiology evaluation to stratify the specimens into GS-only, GS-plus, and no-GS subgroups and then applied contrasted trajectories inference (cTI) to calculate the pseudotime value and evaluate GS progression. Ordinal logistic regression was performed to identify neuroimaging-clinical predictors of GS, and then voxelwise lesion network-symptom mapping (LNSM) was applied to explore GS-associated brain regions. RESULTS: cTI inferred the specific metabolism trajectories of GS progression and revealed increased complexity from GS to other seizure types. This was further validated via actual disease duration (Pearson R = 0.532, P = 0.028). Male sex [odds ratio (OR) = 2.611, P = 0.013], low age at seizure onset (OR = 0.361, P = 0.005), high normalized HH metabolism (OR = - 1.971, P = 0.037) and severe seizure burden (OR = - 0.006, P = 0.032) were significant neuroimaging clinical predictors. LNSM revealed that the dysfunctional cortico-subcortico-cerebellar network of GS and the somatosensory cortex (S1) represented a negative correlation. CONCLUSIONS: This study sheds light on the clinical characteristics and progression of GS in children with HH. We identified distinct subtypes of GS and demonstrated the involvement of specific brain regions at the cortical-subcortical-cerebellar level. These valuable results contribute to our understanding of the neural correlates of GS.

20.
J Ultrasound ; 26(4): 891-896, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37792240

RESUMO

OBJECTIVE: This study sought to evaluate the risk factors for recurrent papillary thyroid carcinoma by preoperative ultrasonography. METHODS: A retrospective study enrolled a total of 146 patients with thyroid papillary carcinoma confirmed by postoperative pathology, and divided into a recurrence group (n = 35) and a non-recurrence group (n = 111) to study their preoperative ultrasound report examination, including the presence of thyroiditis, tumor location, the maximum diameter of the primary tumor, tumor number, the presence of focal strong echogenicity within the lesion, the presence of abnormal lymph nodes, the presence of ultrasound imaging manifestations of thyroid invasion, and to explore the risk factors associated with recurrent papillary thyroid cancer. Moreover, the consistency of ultrasound examination and postoperative pathological findings was explored. RESULTS: There were significant differences in the maximum diameter of the primary tumor and thyroid invasion between the recurrent and non-recurrent papillary thyroid carcinoma groups (P < 0.05), and the preoperative tumor diameter diagnostic cutoff value is 13.750 mm. At the same time, ultrasound and pathology have good consistency in the number of papillary thyroid carcinoma tumors, moderate consistency in lymph node metastasis, and excellent consistency in the presence or absence of thyroid invasion. CONCLUSIONS: The maximum diameter of the primary tumor and thyroid invasion can be used as indicators to evaluate the risk of recurrence of thyroid papillary carcinoma by ultrasonic examination. In addition, the number of tumors and the presence of thyroid invasion in ultrasonic and pathological diagnosis showed good consistency.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/complicações , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Estudos Retrospectivos , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/cirurgia , Carcinoma Papilar/complicações , Linfonodos/patologia , Ultrassonografia/métodos
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