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Neurogenic lower urinary tract dysfunction (NLUTD) is a frequent consequence of spinal cord injury (SCI), leading to symptoms that significantly impact quality of life. Although many life-saving techniques are available, current treatment strategies for managing NLUTD still exhibit limitations and drawbacks. Here, we introduce a new electrical neuromodulation strategy involving electrical stimulation of the major pelvic ganglion (MPG) to initiate bladder contraction, in conjunction with innovative programmable (IPG) electrical stimulation on the pudendal nerve (PN) to induce external urethral sphincter (EUS) relaxation in freely moving or anesthetized SCI mice. Furthermore, we conducted the void spot assay, and cystometry coupled with EUS electromyography (EMG) recordings to evaluate voiding function, and monitor bladder pressure and EUS activity. Our findings demonstrate that our novel electrical neuromodulation approach effectively triggers coordinated bladder muscle contraction and EUS relaxation, effectively counteracting SCI-induced NLUTD. Additionally, this electrical neuromodulation method enhances voiding efficiency, closely resembling natural reflexive urination in SCI mice. Thus, our study offers a promising electrical neurostimulation approach aimed at restoring physiological coordination and potentially offering personalized treatment for improving voiding efficiency in individuals with SCI-associated NLUTD.
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Modelos Animais de Doenças , Terapia por Estimulação Elétrica , Traumatismos da Medula Espinal , Micção , Animais , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/fisiopatologia , Camundongos , Micção/fisiologia , Terapia por Estimulação Elétrica/métodos , Bexiga Urinária/fisiopatologia , Bexiga Urinária/inervação , Feminino , Contração Muscular , Eletromiografia , Camundongos Endogâmicos C57BL , Nervo Pudendo/fisiopatologia , Estimulação Elétrica/métodos , Bexiga Urinaria Neurogênica/terapia , Bexiga Urinaria Neurogênica/fisiopatologia , Bexiga Urinaria Neurogênica/etiologia , Uretra/fisiopatologiaRESUMO
Lower urinary tract dysfunction (LUTD) is a prevalent condition characterized by symptoms such as urinary frequency, urgency, incontinence, and difficulty in urination, which can significantly impair patient's quality of life and lead to severe physiological complications. Despite the availability of diverse treatment options, including pharmaceutical and behavioral therapies, these approaches are not without challenges. The objective of this study was to enhance treatment options for LUTD by developing a wireless, battery-free device for managing bladder contractions. We designed and validated a compact, fully implantable, battery-free pulse generator using the magnetic induction coupling mechanism of wireless power transmission. Weighing less than 0.2 g and with a volume of less than 0.1 cubic centimeters, this device enables precise stimulation of muscles or neurons at voltages ranging from 0 to 10 V. Wireless technology allows real-time adjustment of key stimulation parameters such as voltage, duration, frequency, pulse width, and pulse interval. Our findings demonstrate that the device effectively controlled bladder contractions in mice when used to stimulate the Major Pelvic Ganglion (MPG). Additionally, the device successfully managed micturition in mice with bilateral transection of the pudendal nerve. In conclusion, the development of this innovative wireless pulse generator provides a safer and more cost-effective alternative to conventional battery-powered neurostimulators for bladder control, addressing the limitations of such devices. We anticipate that this novel technology will play a pivotal role in the future of electrical stimulation therapies for voiding dysfunctions.
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Background: Differentiated thyroid cancer (DTC) has been increasingly common in women of reproductive age. However, the evidence remains mixed regarding the association of DTC with adverse pregnancy outcomes in pregnant women previously diagnosed with DTC. Methods: We conducted a retrospective cohort study in the Peking University Third Hospital in Beijing, China between January 2012 and December 2022. We included singleton-pregnancy women with a pre-pregnancy DTC managed by surgical treatment (after-surgery DTC) or active surveillance (under-surveillance DTC). To reduce the confounding effects, we adopted a propensity score to match the after-surgery and under-surveillance DTC groups with the non-DTC group, respectively, on age, parity, gravidity, pre-pregnancy weight, height, and Hashimoto's thyroiditis. We used conditional logistics regressions, separately for the after-surgery and under-surveillance DTC groups, to estimate the adjusted associations of DTC with both the composite of adverse pregnancy outcomes and the specific mother-, neonate-, and placenta-related pregnancy outcomes. Results: After the propensity-score matching, the DTC and non-DTC groups were comparable in the measured confounders. In the after-surgery DTC group (n = 204), the risk of the composite or specific adverse pregnancy outcomes was not significantly different from that of the matched, non-DTC groups (n = 816; P > 0.05), and the results showed no evidence of difference across different maternal thyroid dysfunctions, gestational thyrotropin levels, and other pre-specified subgroup variables. We observed broadly similar results in the under-surveillance DTC group (n = 37), except that the risk of preterm birth, preeclampsia, and delivering the low-birth-weight births was higher than that of the matched, non-DTC group [n = 148; OR (95% CI): 4.79 (1.31, 17.59); 4.00 (1.16, 13.82); 6.67 (1.59, 27.90)]. Conclusions: DTC was not associated with adverse pregnancy outcomes in pregnant women previously treated for DTC. However, more evidence is urgently needed for pregnant women with under-surveillance DTC, which finding will be clinically significant in individualizing prenatal care.
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BACKGROUND: The incidence of duodenal adenocarcinoma is increasing, with limited studies on this disease published. This multicenter retrospective study aimed to analyze the clinicopathologic features of duodenal adenocarcinoma and identify prognostic factors for postoperative survival. METHODS: Demographic characteristics, clinicopathologic features, treatment outcomes, and survival of patients with duodenal adenocarcinoma undergoing surgical treatment at 16 Chinese medical centers from 2012 to 2023 were retrospectively analyzed. RESULTS: Among the 2,189 patients with duodenal adenocarcinoma included, 50.07% had extra-ampullary duodenal adenocarcinoma and 49.93% had peri-ampullary duodenal adenocarcinoma. The 1-, 3-, and 5-year overall survival rates for patients who underwent radical surgery were 91.78%, 69.30%, and 55.86%, respectively. The median overall survival was 73 months (range, 64-84), and the median progression-free survival was 64 months (range, 52-76). No differences in survival were observed between the laparotomy and minimally invasive surgery groups (log-rank P = .562); furthermore, no significant between-group differences in operation time, lymph node dissection, postoperative complications, or in-hospital mortality were observed (P > .05). The minimally invasive surgery group experienced less intraoperative blood loss (250 mL vs 100 mL, P < .001), fewer intraoperative blood transfusions (24.97% vs 18.84%, P = .002), and shorter hospital stays (28 days vs 23 days, P < .001). Multivariate Cox regression analysis revealed that advanced age, advanced stage, longer operation time, intraoperative blood transfusion, and postoperative hemorrhage were independent risk factors for poor prognosis. CONCLUSION: Radical surgery was associated with favorable overall survival among patients with duodenal adenocarcinoma, and no difference in survival was observed between patients with extra-ampullary duodenal adenocarcinoma and peri-ampullary duodenal adenocarcinoma. Minimally invasive surgery is a reliable alternative for duodenal adenocarcinoma treatment.
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Background: Cancer-associated fibroblasts (CAFs) are the key components of the immune barrier in liver cancer. Therefore, gaining a deeper understanding of the heterogeneity and intercellular communication of CAFs holds utmost importance in boosting immunotherapy effectiveness and improving clinical outcomes. Methods: A comprehensive analysis by combing single-cell, bulk, and spatial transcriptome profiling with multiplexed immunofluorescence was conducted to unravel the complexities of CAFs in liver cancer. Results: Through an integrated approach involving 235 liver cancer scRNA-seq samples encompassing over 1.2 million cells, we found that CAFs were particularly increased in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). FAP + fibroblasts were identified as the dominant subtype of CAFs, and which were mainly involved in extracellular matrix organization and angiogenesis. These CAFs were enriched in the tumor boundary of HCC, but diffusely scattered within ICC. The DAB2 + and SPP1 + tumor-associated macrophages (TAMs) reinforce the function of FAP + CAFs through signals such as TGF-ß, PDGF, and ADM. Notably, the interaction between DAB2 + TAMs and FAP + CAFs promoted the formation of immune barrier and correlated with poorer patient survival, non-response to immunotherapy in HCC. High FAP and DAB2 immunohistochemical scores predicted shorter survival and higher serum AFP concentration in a local clinical cohort of 90 HCC patients. Furthermore, this communication pattern might be applicable to other solid malignancies as well. Conclusions: The interaction between DAB2 + TAMs and FAP + CAFs appears crucial in shaping the immune barrier. Strategies aimed at disrupting this communication or inhibiting the functions of FAP + CAFs could potentially enhance immunotherapy effectiveness and improve clinical outcomes.
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Fibroblastos Associados a Câncer , Carcinoma Hepatocelular , Neoplasias Hepáticas , Microambiente Tumoral , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/imunologia , Fibroblastos Associados a Câncer/metabolismo , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/imunologia , Microambiente Tumoral/imunologia , Macrófagos/metabolismo , Macrófagos/imunologia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Colangiocarcinoma/terapia , Colangiocarcinoma/patologia , Colangiocarcinoma/imunologia , Colangiocarcinoma/metabolismo , Imunoterapia/métodos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Masculino , Feminino , EndopeptidasesRESUMO
Due to the challenge for intratumoral administration, innate agonists have not made it beyond preclinical studies for efficacy testing in most tumor types. Pancreatic ductal adenocarcinoma (PDAC) has a hostile tumor microenvironment that renders T cells dysfunctional. Innate agonist treatments may serve as a T cell priming mechanism to sensitize PDACs to anti-PD-1 antibody (a-PD-1) treatment. Using a transplant mouse model with spontaneously formed liver metastasis, a genetically engineered KPC mouse model that spontaneously develops PDAC, and a human patient-derived xenograft model, we compared the antitumor efficacy between intrahepatic/intratumoral and intramuscular systemic administration of BMS-986301, a next-generation STING agonist. Flow cytometry, Nanostring, and cytokine assays were used to evaluate local and systemic immune responses. This study demonstrated that administration of STING agonist systemically via intramuscular injection is equivalent to its intratumoral injection in inducing both effector T cell response and antitumor efficacy. Compared to intratumoral administration, T cell exhaustion and immunosuppressive signals induced by systemic administration were attenuated. Nonetheless, either intratumoral or systemic treatment of STING agonist was associated with increased expression of CTLA-4 on tumor-infiltrating T cells. However, the combination of a-PD-1 and anti-CTLA-4 antibody with systemic STING agonist demonstrated the antitumor efficacy in the KPC mouse spontaneous PDAC model. The mouse pancreatic and liver orthotopic model of human patient-derived xenograft reconstituted with PBMC also showed that antitumor and abscopal effects of both intratumoral and intramuscular STING agonist are equivalent. Taken together, this study supports the clinical development of innate agonists via systemic administration for treating PDAC.
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Carcinoma Ductal Pancreático , Proteínas de Membrana , Neoplasias Pancreáticas , Animais , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Humanos , Camundongos , Proteínas de Membrana/agonistas , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Injeções Intralesionais , Ensaios Antitumorais Modelo de Xenoenxerto , Microambiente Tumoral/efeitos dos fármacos , Linhagem Celular TumoralRESUMO
MicroRNA (miRNA/miR) represents a category of endogenous, short-chain non-coding RNA molecules comprising ~22 nucleotides. Specifically, miR-325 is situated within the first sub-band of region 2 on the short arm of the X chromosome. Notably, aberrant expression of miR-325 has been observed across various tumor systems, spanning the nervous, endocrine, respiratory, reproductive and digestive systems. miR-325 exhibits the capacity to target a minimum of 20 protein-coding genes, thereby influencing diverse cellular processes, including cell proliferation, epithelial-mesenchymal transition, apoptosis, invasion and migration. Moreover, miR-325 serves a pivotal role in the formation of six competing endogenous RNA (ceRNA) regulatory axes, involving one circular RNA, four long non-coding RNA and one additional miRNA. By participating in various signaling pathways through gene targeting, the abnormal expression of miR-325 has been associated with clinicopathological conditions in diverse patients with cancer, significantly impacting both the clinicopathology and prognosis of affected individuals. Additionally, miR-325 has been associated with the development of resistance to oxaliplatin, cisplatin and doxorubicin in cancer cells. Its involvement in the anticancer molecular mechanisms of these agents underscores its potential significance in therapeutic contexts. However, it is noteworthy that the current study did not specifically address sex-based cell line selection. In conclusion, the present review provides a comprehensive summary of the relevant findings concerning miR-325, offering valuable insights for future research endeavors focused on determining the molecular mechanisms associated with this miRNA.
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Background: Troponin (Tn) is of an important biomarker for the diagnosis and prognosis of myocardial injury and for evaluating the severity of cardiac involvement due to other systemic diseases in children. Unfortunately, high-sensitivity cardiac troponin I (hs-cTnI) specific reference intervals (RIs) are extremely limited. This study aimed to establish a preliminary pediatric hs-cTnI RI for newborns, children, and adolescents in Wuhan, China. Methods: A total of 1,355 healthy participants (1 day to 19 years) were recruited from a cross-sectional study implemented in Wuhan Children's Hospital from September 2022 to August 2023. Serum hs-cTnI levels were detected via the Mindray automated chemiluminescence immunoassay analyzer (CL-6000i). Specific serum hs-cTnI RIs were established according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The RIs were defined by the nonparametric median (P50), and 2.5th, 97.5th [P50 (P2.5-P97.5)] intervals. Results: Of the 1,355 pediatric participants, serum hs-cTnI concentrations of 1,332 children were measured. The serum overall P50 and 95% interval range (P2.5-P97.5) of serum hs-cTnI was 0.41 (0.00, 44.31) ng/L. This was higher in males of 0.47 (0.00, 44.90) ng/L than in females of 0.36 (0.00, 44.17) ng/L (P<0.01). Age- and sex-specific differences in hs-cTnI levels were observed. The levels were highly variable in children under 1 year of age (especially in newborns), deriving a P50 (P2.5-P97.5) of 22.06 (1.04, 154.22) ng/L, and gradually narrowed and decreased with increasing age, with a markedly lower established P50 (P2.5-P97.5) of 0.36 (0.00, 2.16) ng/L. However, the levels began to increase slightly at the age of 9-12 years and reached a small peak at the age range of 15 to 18 years in males with 0.71 (0.03, 3.29) ng/L, while females were less affected by puberty. Sex- and age-specific RIs for hs-cTnI were established: 5 age-specific RIs in males, 1 day-1 month: 30.16 (8.67, 171.81) ng/L; >1-12 months: 13.20 (0.63, 61.91) ng/L; >1-15 years: 0.36 (0.00, 1.86) ng/L; >15-18 years: 0.71 (0.03, 3.29) ng/L; >18-19 years: 0.52 (0.00, 1.92) ng/L; and 4 age-specific RIs in females, 1 day-1 month: 43.93 (18.82, 146.38) ng/L; >1-12 months: 5.22 (0.92, 42.54) ng/L; >1-6 years: 0.54 (0.00, 2.74) ng/L; >6-19 years: 0.23 (0.00, 1.56) ng/L. Conclusions: This study preliminarily established age- and sex-specific serum hs-cTnI RIs using the Mindray CL-6000i system in healthy children in Wuhan, China.
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The accumulation of senescent cells is an important factor in the complex progression of aging, with significant implications for the development of numerous diseases. Thus, understanding the fundamental mechanisms of senescence is paramount for advancing preventive and therapeutic approaches to age-related conditions. Important to this pursuit is the precise identification and examination of senescent cells, contingent upon the recognition of specific biomarkers. Historically, detection methods relied on assessing molecular protein and mRNA levels and various staining techniques. While these conventional approaches have contributed substantially to the field, they possess limitations in capturing the dynamic evolution of cellular aging in real time. The emergence of novel technologies has led to a paradigm shift in senescence research. Gene-edited mouse models and the application of advanced probes have revolutionized our ability to detect senescent cells. These cutting-edge methodologies provide a more detailed and accurate means of dynamically monitoring, characterizing and potentially eliminating senescent cells, thus enhancing our understanding of the complex mechanisms of aging. This review comprehensively explores both traditional and innovative senescent cell detection methods, elucidating their advantages, limitations and implications for future investigations and could serve as a comprehensive guide and catalyst for further advancements in the understanding of aging and associated pathologies.
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Red blood cells (RBCs), which function as material transporters in organisms, are rich in materials that are exchanged with metabolically active tumor cells. Recent studies have demonstrated that tumor cells can regulate biological changes in RBCs, including influencing differentiation, maturation, and morphology. RBCs play an important role in tumor development and immune regulation. Notably, the novel scientific finding that RBCs absorb fragments of tumor-carrying DNA overturns the conventional wisdom that RBCs do not contain nucleic acids. RBC membranes are excellent biomimetic materials with significant advantages in terms of their biocompatibility, non-immunogenicity, non-specific adsorption resistance, and biodegradability. Therefore, RBCs provide a new research perspective for the development of tumor liquid biopsies, molecular imaging, drug delivery, and other tumor precision diagnosis and treatment technologies.
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Eritrócitos , Neoplasias , Humanos , Eritrócitos/metabolismo , Neoplasias/terapia , Neoplasias/diagnóstico , Neoplasias/patologia , Medicina de Precisão , Animais , Sistemas de Liberação de Medicamentos , Membrana Eritrocítica/química , Membrana Eritrocítica/metabolismo , Materiais Biomiméticos/químicaRESUMO
BACKGROUND: Effective labor pain management is crucial for parturient well-being, as it can improve the delivery experience of pregnant women and reduce anxiety and tension. This systematic review and network meta-analysis compared the efficacy and safety of various analgesics, classified by drug category and individual treatment methods, for labor pain control. METHODS: A comprehensive literature search was conducted in Pubmed, EMBASE, Cochrane Library, and Web of Science databases. All searches commenced from the database's inception to the date of the literature search (May 31, 2023). The Cochrane Risk of Bias 2 tool assessed study bias risk. Network meta-analyses using a random-effects model and odds ratios (ORs) with 95% confidence intervals (CIs) were performed. RESULTS: Fifteen randomized controlled trials evaluating analgesic interventions in ASA I or II parturients were included. Combination therapies (OR: 5.81; 95% CI, 3.76-7.84; probability: 60%) and non-opioid analgesics (OR: 5.61; 95% CI, 2.91-8.30; probability: 39.2%) were superior to placebo for labor pain relief. Specifically, dexmedetomidine/ropivacaine/sufentanil (OR: 7.32; 95% CI, 2.73-11.89; probability: 40.6%) and dexmedetomidine/ropivacaine (OR: 6.50; 95% CI, 2.51-10.33; probability: 11.9%) combinations, bupivacaine/fentanyl and ropivacaine/sufentanil combinations, and remifentanil monotherapy showed improved analgesic efficacy versus placebo. Dexmedetomidine/ropivacaine reduced parturient nausea and vomiting versus alternatives. CONCLUSION: Non-opioids, opioids and combinations thereof effectively relieved labor pain. In addition, dexmedetomidine/ropivacaine combination demonstrated analgesic efficacy and lower nausea and vomiting incidence.
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Analgésicos Opioides , Dor do Parto , Metanálise em Rede , Manejo da Dor , Humanos , Gravidez , Feminino , Analgésicos Opioides/uso terapêutico , Dor do Parto/tratamento farmacológico , Manejo da Dor/métodos , Analgésicos não Narcóticos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Dexmedetomidina/uso terapêuticoRESUMO
Non-apoptotic regulated cell death (RCD) of tumor cells profoundly affects tumor progression and plays critical roles in determining response to immune checkpoint inhibitors (ICIs). Prognosis-distinctive HCC subtypes were identified by consensus cluster analysis based on the expressions of 507 non-apoptotic RCD genes obtained from databases and literature. Meanwhile, a set of bioinformatic tools was integrated to analyze the differences of the tumor immune microenvironment infiltration, genetic mutation, copy number variation, and epigenetics alternations within two subtypes. Finally, a non-apoptotic RCDRS signature was constructed and its reliability was evaluated in HCC patients' tissues. The high-RCDRS HCC subgroup showed a significantly lower overall survival and less sensitivity to ICIs compared to low-RCDRS subgroup, but higher sensitivity to cisplatin, paclitaxel, and sorafenib. Overall, we established an RCDRS panel consisting of four non-apoptotic RCD genes, which might be a promising predictor for evaluating HCC prognosis, guiding therapeutic decision-making, and ultimately improving patient outcomes.
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BACKGROUND: Frailty is a common condition among patients with liver cirrhosis. Nonetheless, its role in predicting liver transplant-free survival (TFS) remains unclear. AIM: This systematic review and meta-analysis were conducted to elucidate the relationship between frailty and TFS in patients with cirrhosis. METHODS: Cohort studies addressing the objective of this meta-analysis were extracted from PubMed, Embase, and Web of Science databases. Between-study heterogeneity was assessed with the Cochrane Q test, and the I^2 statistic was estimated. Random-effect models, considering potential heterogeneity, were employed to combine the results. RESULTS: The meta-analysis encompassed 17 cohort studies involving 6273 patients with cirrhosis, of whom 1983 (31.6%) were classified as frail at baseline. The follow-up periods in the included studies ranged from 3 to 29 months, with an average duration of 11.5 months. The analysis revealed that frailty was significantly associated with a poor TFS (risk ratio [RR]: 2.07, 95% confidence interval: 1.72 to 2.50, p<0.001; I2 = 51%). Sensitivity analyses that sequentially omitted one dataset consistently supported these findings (RR: 1.95 to 2.17, p<0.05 in all cases). Subgroup analyses based on variables such as study design, mean age of patients, baseline Model for End-Stage Liver Disease score, tool used for frailty evaluation, follow-up duration, and study quality score also yielded congruent results. CONCLUSIONS: The evidence suggests that frailty may be an independent risk factor for poor TFS in patients with liver cirrhosis, thus emphasizing the importance of early identification and management of frailty in this population.
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Fragilidade , Cirrose Hepática , Transplante de Fígado , Humanos , Fragilidade/complicações , Cirrose Hepática/mortalidade , Cirrose Hepática/complicações , Fatores de RiscoRESUMO
Background Preoperative recognition of irreversible bowel necrosis is important, as it provides valuable guidance for surgical strategy selection but also may inform perioperative risk assessment and communication. Few studies have focused on the association between CT signs and bowel necrosis. Purpose To assess the diagnostic accuracy of CT signs to predict bowel necrosis in patients with closed-loop small bowel obstruction (CL-SBO). Materials and Methods This retrospective single-center study included patients who were surgically confirmed to have CL-SBO caused by adhesion or internal hernia between January 2016 and May 2022. Necrosis was determined based on surgical exploration and postoperative pathologic examination. Two radiologists independently reviewed CT signs by both subjective visual assessment and objective measurement. Disagreements were resolved in consensus with a third gastrointestinal radiologist. Univariable and multivariable analyses were used to assess the association between CT signs and bowel necrosis, and Cohen κ was used to assess interobserver agreement. Sensitivity and specificity were calculated for each CT sign. Results This study included 145 patients: 61 (42.1%) in the necrotic group (median age, 62 years [IQR, 51-71.5 years]; 37 [60.7%] women) and 84 (57.9%) in the nonnecrotic group (median age, 61.5 years [IQR, 51-68.8 years]; 51 [60.7%] women). Univariable analysis and multivariable analysis showed that increased attenuation of intestinal contents and increased attenuation of intestinal wall were independent predictors for bowel necrosis (odds ratio = 45.3 and 15.1; P = .001 and P < .001, respectively). Increased attenuation of intestinal contents and increased attenuation of intestinal wall had similar sensitivity (64% and 67%, respectively) and specificity (99% and 92%, respectively) for predicting bowel necrosis. However, interobserver agreement was better for assessing the contents than the wall (κ = 0.84 and 0.59, respectively). Conclusion Increased attenuation of intestinal contents was a highly specific CT sign with good reproducibility to predict bowel necrosis in CL-SBO. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Taourel and Zins in this issue.
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Conteúdo Gastrointestinal , Obstrução Intestinal , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/cirurgia , Necrose/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Differentiated thyroid cancer (DTC) is commonly diagnosed in women of child-bearing age, but whether pregnancy influences the prognosis of DTC remains controversial. This study aimed to summarize existing evidence regarding the association of pregnancy with recurrence risk in patients previously treated for DTC. METHODS: We searched PubMed, Embase, Web of Science, Cochrane, and Scopus based on the prespecified protocol registered at PROSPERO (CRD42022367896). After study selection, two researchers independently extracted data from the included studies. For quantitative data synthesis, we used random-effects meta-analysis models to pool the proportion of recurrence (for pregnant women only) and odds ratio (OR; comparing the risk of recurrence between the pregnancy group and the nonpregnancy group), respectively. Then we conducted subgroup analyses to explore whether risk of recurrence differed by response to therapy status or duration of follow-up time. We also assessed quality of the included studies. RESULTS: A total of ten studies were included. The sample size ranged from 8 to 235, with participants' age at pregnancy or delivery ranging from 28 to 35 years. The follow-up time varied from 0.1 to 36.0 years. The pooled proportion of recurrence in all pregnant patients was 0.13 (95% confidence intervals [CI]: 0.06-0.25; I2 : 0.58). Among six included studies reporting response to therapy status before pregnancy, we observed a trend for increasingly higher risk of recurrence from excellent, indeterminate, and biochemically incomplete to structurally incomplete response to therapy ( Ptrend <0.05). The pooled risk of recurrence in the pregnancy group showed no evidence of a significant difference from that in the nonpregnancy group (OR: 0.75; 95% CI: 0.45-1.23; I2 : 0). The difference in follow-up time (below/above five years) was not associated with either the proportion of recurrence in all pregnant patients ( P >0.05) or the OR of recurrence in studies with a comparison group ( P >0.05). Two included studies that focused on patients with distant metastasis also did not show a significant difference in disease recurrence between pregnancy and nonpregnancy groups (OR: 0.51 [95% CI: 0.14-1.87; I2 : 59%]). CONCLUSION: In general, pregnancy appears to have a minimal association with the disease recurrence of DTC with initial treatment. Clinicians should pay more attention to progression of DTC among pregnant women with biochemical and/or structural persistence. REGISTRATION: PROSPERO, https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022367896.
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Recidiva Local de Neoplasia , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Gravidez , Feminino , Complicações Neoplásicas na Gravidez/patologia , Complicações Neoplásicas na Gravidez/terapiaRESUMO
PURPOSE: To assess diagnostic performance and reproducibility of reduced bowel wall enhancement evaluated by quantitative methods using CT to identify bowel necrosis among closed-loop small bowel obstruction (CL-SBO) patients. METHODS: This retrospective single-center study included patients who diagnosed with CL-SBO caused by adhesion or internal hernia during January 2016 and May 2022. Patients were divided into necrotic group (n = 41) and non-necrotic group (n = 67) according to surgical exploration and postoperative pathology. Two doctors independently measured the attenuation of bowel wall and consensus was reached through panel discussion with a third gastrointestinal radiologist. Reduced bowel wall enhancement was assessed by four quantitative methods. Univariate analyses were used to evaluate the association between each method and bowel necrosis, and kappa/intraclass correlation coefficient values were used to assess interobserver agreement. Diagnostic performance parameters were calculated for each method. RESULTS: Reduced bowel wall enhancement in arterial phase (OR 8.98, P < 0.0001), reduced bowel wall enhancement in portal phase (OR 16.84, P < 0.001), adjusted reduced bowel wall enhancement in arterial phase (OR 29.48, P < 0.001), adjusted reduced bowel wall enhancement in portal phase (OR 145.69, P < 0.001) were significantly associated with bowel necrosis. Adjusted reduced bowel wall enhancement in portal phase had the best diagnostic performance (AUC: 0.92; Youden index: 0.84; specificity: 94.03 %) and interobserver agreement (kappa value of 0.59-0.73) to predict bowel necrosis. CONCLUSION: When assessing reduced bowel enhancement to predict bowel necrosis among CL-SBO patients, using unenhanced CT images and proximal dilated loop as standard references in portal phase is the most accurate quantitative method among those tested.
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Traumatismos Abdominais , Obstrução Intestinal , Doenças Vasculares , Humanos , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Intestino Delgado/diagnóstico por imagem , Sensibilidade e Especificidade , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/cirurgia , Doenças Vasculares/patologia , Necrose/diagnóstico por imagem , Necrose/patologia , Traumatismos Abdominais/complicaçõesRESUMO
Cuproptosis, a recently characterized programmed cell death mechanism, has emerged as a potential contributor to tumorigenesis, metastasis, and immune modulation. Long non-coding RNAs (lncRNAs) have demonstrated diverse regulatory roles in cancer and hold promise as biomarkers. However, the involvement and prognostic significance of cuproptosis-related lncRNAs (CRLs) in oral squamous cell carcinoma (OSCC) remain poorly understood. Based on TCGA-OSCC data, we integrated single-sample gene set enrichment analysis (ssGSEA), the LASSO algorithm, and the tumor immune dysfunction and exclusion (TIDE) algorithm. We identified 11 CRLs through differential expression, Spearman correlation, and univariate Cox regression analyses. Two distinct CRL-related subtypes were unveiled, delineating divergent survival patterns, tumor microenvironments (TME), and mutation profiles. A robust CRL-based signature (including AC107027.3, AC008011.2, MYOSLID, AC005785.1, AC019080.5, AC020558.2, AC025265.1, FAM27E3, and LINC02367) prognosticated OSCC outcomes, immunotherapy responses, and anti-tumor strategies. Superior predictive power compared to other lncRNA models was demonstrated. Functional assessments confirmed the influence of FAM27E3, LINC02367, and MYOSLID knockdown on OSCC cell behaviors. Remarkably, the CRLs-based signature maintained stability across OSCC patient subgroups, underscoring its clinical potential for survival prediction. This study elucidates CRLs' roles in TME of OSCC and establishes a potential signature for precision therapy.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , RNA Longo não Codificante , Humanos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , RNA Longo não Codificante/genética , Neoplasias Bucais/genética , Neoplasias Bucais/terapia , Imunoterapia , Apoptose , Microambiente Tumoral/genéticaRESUMO
CONTEXT AND OBJECTIVE: Differentiated thyroid cancer (DTC) is very common in women of reproductive age. However, it remains unclear whether pregnancy is associated with DTC progression before surgical treatment. METHODS: This retrospective cohort study, conducted at the Peking University Third Hospital in Beijing, China between January 2012 and December 2022, included 311 eligible women aged 20 to 45 years. To control for potential confounders, we first used propensity score matching (PSM) to match the pregnant group (n = 48) with the nonpregnant group (n = 154) on age, tumor size, tumor type, and Hashimoto's thyroiditis status at baseline, and then used Cox proportional risk models stratified by the matched pairs to estimate the association of pregnancy with DTC progression. RESULTS: After PSM, the pregnant and nonpregnant groups were well comparable at baseline (standardized difference < 10% and P > .05). Over an average observation period of 2.5 years, we observed no difference between the pregnant group and the matched nonpregnant group in DTC progression-free survival (hazard ratio [HR] = 0.96; 95% CI, 0.56 to 1.65; P = .895), tumor enlargement-free survival (HR = 0.99; 95% CI, 0.56 to 1.76; P = .969) or lymph node metastasis-free survival (LNM) (HR = 0.67; 95% CI, 0.21 to 2.13; P = .498). The postoperative pathological characteristics also showed no significant difference between the pregnant and nonpregnant groups (P > .05). CONCLUSION: Pregnancy seemed to be irrelevant to DTC progression-free survival before surgical treatment. Further prospective cohort studies are needed to translate this finding into clinical practice.
Assuntos
Adenocarcinoma , Doença de Hashimoto , Neoplasias da Glândula Tireoide , Gravidez , Humanos , Feminino , Estudos Retrospectivos , Pontuação de Propensão , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologiaRESUMO
BACKGROUND: Hepatitis B virus (HBV) remains a substantial public health safety concern drawing considerable attention in China and globally. The detection of HBV serological markers can enable the assessment of HBV infection and replication status in vivo and evaluate the body's protection against HBV. Therefore, this study aims to identify the epidemiological and clinical characteristics of HBV infection in children to prevent and control HBV infection in Wuhan areas. METHODS: We conducted an extensive retrospective cohort analysis of 115,029 individuals aged 0-18 years who underwent HBV serological markers detection for HBV infection in hospital between 2018 and 2021 using Electrochemiluminescence immunoassay. We generated descriptive statistics and analysed HBV infection's epidemiological and clinical characteristics between different sex and age groups. RESULTS: The overall positive detection rates of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb in all participants were 0.13%, 79.09%, 0.17%, 2.81%, and 5.82%, respectively. The positive rate of HBeAb and HBcAb in males was significantly lower than that in females (2.64% vs. 3.13%, 5.56% vs. 6.29%) (P < 0.05). Twenty-two distinct HBV serological expression patterns were revealed. Among them, 8 common expression patterns accounted for 99.63%, while the remaining 14 uncommon expression patterns were primarily observed in neonatal patients with HBV infection. There are no significant differences in serological patterns based on sex (P < 0.05). The overall HBV infection detection rate was 5.82% [range 5.68-5.95] and showed a declining yearly trend. The rate in females was higher than that in males 6.29% [6.05, 6.35] vs. 5.56% [5.39, 5.59]. The overall HBV diagnostic rate over 4 years was 0.20% [0.17, 0.22], and the rate declined yearly. The prevalence of acute infection was higher than that of other infection types before 2019, but the incidence of unclassified infection showed a significant upward trend after 2019. CONCLUSIONS: While the overall HBV infection detection rate in children has decreased year by year, the infection rate remains high in children under one year and between 4 and 18 years. This continued prevalence warrants heightened attention and vigilance.