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Lichen as mutualistic symbiosis is the dominant organism in various extreme terrestrial environment on Earth, however, the mechanisms of their adaptation to extreme habitats have not been fully elucidated. In this study, we chose the Antarctic dominant lichen species Usnea aurantiacoatra to generate a high-quality genome, carried out phylogenetic analysis using maximum likelihood and identify genes under positive selection. We performed functional enrichment analysis on the positively selected genes (PSGs) and found that most of the PSGs focused on transmembrane transporter activity and vacuole components. This suggest that the genes related to energy storage and transport in Antarctic U. aurantiacoatra were affected by environmental pressure. Inside of the 86 PSGs screened, two protein interaction networks were identified, which were RNA helicase related proteins and regulator of G-protein signaling related proteins. The regulator of the G-protein signaling gene (UaRGS1) was chosen to perform further verification by the lichen genetic manipulation system Umbilicaria muhlenbergii. Given that the absence of UmRgs1 resulted in elevated lethality to cold shock, the role for UaRgs1 in Antarctic U. aurantiacoatra resistance to cold can be inferred. The investigation of lichen adaptation to extreme environments at the molecular level will be opened up.

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Aim: To optimize gastric cancer screening score and reduce screening costs using machine learning models. Methods: This study included 228,634 patients from the Taizhou Gastric Cancer Screening Program. We used three machine learning models to optimize Li's gastric cancer screening score: Gradient Boosting Machine (GBM), Distributed Random Forest (DRF), and Deep Learning (DL). The performance of the binary classification models was evaluated using the area under the curve (AUC) and area under the precision-recall curve (AUCPR). Results: In the binary classification model used to distinguish low-risk and moderate- to high-risk patients, the AUC in the GBM, DRF, and DL full models were 0.9994, 0.9982, and 0.9974, respectively, and the AUCPR was 0.9982, 0.9949, and 0.9918, respectively. Excluding Helicobacter pylori IgG antibody, pepsinogen I, and pepsinogen II, the AUC in the GBM, DRF, and DL models were 0.9932, 0.9879, and 0.9900, respectively, and the AUCPR was 0.9835, 0.9716, and 0.9752, respectively. Remodel after removing variables IgG, PGI, PGII, and G-17, the AUC in GBM, DRF, and DL was 0.8524, 0.8482, 0.8477, and AUCPR was 0.6068, 0.6008, and 0.5890, respectively. When constructing a tri-classification model, we discovered that none of the three machine learning models could effectively distinguish between patients at intermediate and high risk for gastric cancer (F1 scores in the GBM model for the low, medium and high risk: 0.9750, 0.9193, 0.5334, respectively; F1 scores in the DRF model for low, medium, and high risks: 0.9888, 0.9479, 0.6694, respectively; F1 scores in the DL model for low, medium, and high risks: 0.9812, 0.9216, 0.6394, respectively). Conclusion: We concluded that gastric cancer screening indicators could be optimized when distinguishing low-risk and moderate to high-risk populations, and detecting gastrin-17 alone can achieve a good discriminative effect, thus saving huge expenditures.

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Composting is widely applied in recycling ever-increasing sewage sludge. However, the insufficient elimination of antibiotics and antibiotic resistance genes (ARGs) in conventional compost fertilizer poses considerable threat to agriculture safety and human health. Here we investigated the efficacy and potential mechanisms in the removal of antibiotics and ARGs from sludge in hyperthermophilic composting (HTC) plant. Our results demonstrated that the HTC product was of high maturity. HTC led to complete elimination of antibiotics and potential pathogens, as well as removal of 98.8 % of ARGs and 88.1 % of mobile genetic elements (MGEs). The enrichment of antibiotic-degrading candidates and related metabolic functions during HTC suggested that biodegradation played a crucial role in antibiotic removal. Redundancy analysis (RDA) and structural equation modelling (SEM) revealed that the reduction of ARGs was attributed to the decline of ARG-associated bacteria, mainly due to the high-temperature selection. These findings highlight the feasibility of HTC in sludge recycling and provide a deeper understanding of its mechanism in simultaneous removal of antibiotics and ARGs.

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BACKGROUND: To explore the most effective adjuvant chemotherapy regimen for malignant peritoneal mesothelioma (MPM) through patient derived tumor-like cell clusters (PTC) drug sensitivity test. METHODS: PTC were cultured in vitro with intraoperative specimens, and drug sensitivity test was performed to calculate the most effective chemotherapy regimen for MPM. The patients were divided into conventional and individualized chemotherapy group according to whether they received PTC drug testing. Univariate and multivariate analyses were conducted to identify independent prognostic factors. RESULTS: Among 186 MPM patients included, 63 underwent PTC culture and drug sensitivity test. The results showed that the most effective chemotherapy regimen was oxaliplatin + gemcitabine. After propensity score matching, a total of 64 patients were enrolled in the following study, including 32 patients receiving individualized chemotherapy guided by PTC drug results as group 1 and 32 patients receiving conventional chemotherapy as group 2. Survival analysis showed that the median OS of group 1 was not reached, significantly longer than that of group 2 (23.5 months) (p < 0.05). CONCLUSIONS: Compared with conventional chemotherapy, individualized chemotherapy guided by PTC drug sensitivity tests can prolong patient survival, and oxaliplatin + gemcitabine + apatinib could be the optimal adjuvant treatment regimen for MPM.

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BACKGROUND: Atraumatic subarachnoid haemorrhage (SAH) is associated with high morbidity and mortality. Proposed mechanisms for red blood cell (RBC) clearance from the subarachnoid space (SAS) are erythrolysis, erythrophagocytosis or through efflux along cerebrospinal fluid (CSF) drainage routes. We aimed to elucidate the mechanisms of RBC clearance from the SAS to identify targetable efflux pathways. METHODS: Autologous fluorescently-labelled RBCs along with PEGylated 40 kDa near-infrared tracer (P40D800) were infused via the cisterna magna (i.c.m.) in female reporter mice for lymphatics or for resident phagocytes. Drainage pathways for RBCs to extracranial lymphatics were evaluated by in vivo and in situ near-infrared imaging and by immunofluorescent staining on decalcified cranial tissue or dural whole-mounts. FINDINGS: RBCs drained to the deep cervical lymph nodes 15 min post i.c.m. infusion, showing similar dynamics as P40D800 tracer. Postmortem in situ imaging and histology showed perineural accumulations of RBCs around the optic and olfactory nerves. Numerous RBCs cleared through the lymphatics of the cribriform plate, whilst histology showed no relevant fast RBC clearance through dorsal dural lymphatics or by tissue-resident macrophage-mediated phagocytosis. INTERPRETATION: This study provides evidence for rapid RBC drainage through the cribriform plate lymphatic vessels, whilst neither fast RBC clearance through dorsal dural lymphatics nor through spinal CSF efflux or phagocytosis was observed. Similar dynamics of P40D800 and RBCs imply open pathways for clearance that do not impose a barrier for RBCs. This finding suggests further evaluation of the cribriform plate lymphatic function and potential pharmacological targeting in models of SAH. FUNDING: Swiss National Science Foundation (310030_189226), SwissHeart (FF191155).

Asunto(s)

Eritrocitos , Espacio Subaracnoideo , Animales , Femenino , Ratones , Eritrocitos/metabolismo , Espacio Subaracnoideo/metabolismo , Vasos Linfáticos/metabolismo , Fagocitosis , Hemorragia Subaracnoidea/metabolismo

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Guided by a probe-based molecular networking strategy, five undescribed cycloheptapeptides, phakefusins A-E (1-5), were isolated from the marine sponge Phakellia fusca. Compounds 1 and 2 contain the nonproteinogenic amino acid residues of dioxindolyalanine (Dioia) and ß-3-oxindolylalanine (Oia), respectively. Compound 3 possesses a unique methionine sulfoxide, whereas compound 5 includes a glutamic acid ethyl ester unit. Their structures were elucidated through NMR spectroscopy, HR-MS/MS analysis, and the advanced Marfey's method. By synthesizing the (S, S/R)-Oia standard through tryptophan oxidation, we determined the configuration of this amino acid in compound 2 using the advanced Marfey's method. These cycloheptapeptides were evaluated for their antitumor, antibacterial, and antioxidant activities. Compound 1 showed moderate cytotoxicity against MCF-7 and PC9 cells, with IC50 values of 6.8 and 9.6 µM, respectively, while compounds 2-5 demonstrated potential antioxidant effects by upregulating HO-1, NQO1, and SOD2 levels, as well as inducing Nrf2 activation.

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Hospital wastewater is a critical source of antimicrobial resistance (AMR), which facilitates the proliferation and spread of clinically significant antimicrobial resistance genes (ARGs) and pathogenic bacteria. This study utilized metagenomic approaches, including advanced binning techniques, such as MetaBAT2, MaxBin2, and CONCOCT, which offer significant improvements in accuracy and completeness over traditional binning methods. These methods were used to comprehensively assess the dynamics and composition of resistomes and mobilomes in untreated wastewater samples taken from two general hospitals and one cancer hospital. This study revealed a diverse bacterial landscape, largely consisting of Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria, with notable variations in microbial composition among hospitals. Analysis of the top 15 genera showed unique microbial pattern distribution in each hospital: Aeromonas was predominant in 1stHWTS (49.39 %), Acidovorax in the CAHWTS at 16.85 %, and Escherichia and Bacteroides in the 2ndHWTS at 11.44 % and 11.33 %, respectively. A total of 114 pathogenic bacteria were identified, with drug-resistant Aeromonas caviae and Escherichia coli being the most prevalent. The study identified 34 types and 1660 subtypes of ARGs, including important last-resort antibiotic resistance genes (LARGs), such as blaNDM, mcr, and tet(X). Using metagenomic binning, this study uncovered distinct patterns of host-resistance associations, particularly with Proteobacteria and Firmicutes. Network analysis highlighted the complex interactions among ARGs, mobile genetic elements (MGEs), and bacterial species, all contributing to the dissemination of AMR. These findings emphasize the intricate nature of AMR in hospital wastewater and the influence of hospital-specific factors on microbial resistance patterns. This study provides support for implementing integrated management strategies, including robust surveillance, advanced wastewater treatment, and strict antibiotic stewardship, to control the dissemination of AMR. Understanding the interplay among bacterial communities, ARGs, and MGEs is important for developing effective public health measures against AMR.

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Hospitales , Metagenómica , Aguas Residuales , Aguas Residuales/microbiología , Farmacorresistencia Microbiana/genética , Genes Bacterianos , Farmacorresistencia Bacteriana/genética , Antibacterianos/farmacología , Bacterias/genética , Bacterias/efectos de los fármacos , Secuencias Repetitivas Esparcidas , Metagenoma

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The global surge in antibiotic resistance genes (ARGs) presents a serious public health challenge. While methods like metagenomic analysis and qPCR arrays have been instrumental in investigating ARG distributions and dynamics, the vast diversity of ARGs often complicates effective monitoring and risk assessment. Here, we developed a High-Risk ARGs (HRA) chip based on high-capacity quantitative PCR array targeting previously identified high-risk ARGs. These ARGs are known to be prevalent in human-related environments, exhibit gene mobility, and are present in ESKAPE pathogens. The HRA chip include 101 primer sets and the 16S rRNA gene as a reference. These primer sets consist of 34 obtained from previous studies, and 67 newly designed primer sets which were validated in silico and experimentally. Absolute quantification of targeted ARGs is accomplished by generating standard curves for all ARGs with serially ten-fold diluted mixed plasmids containing targeted ARG sequences. The amplification efficiencies of all ARGs exceed 99% via plasmid template dilution tests, suggesting high reliability in quantification. The performance of HRA chip is further evaluated by practical applications in environmental samples from wastewater treatment plants (WWTPs) and soils with various land use types and fertilization regimes. The results indicate the dynamics of high-risk ARGs during wastewater treatment process, and reveal the profiles of soil high-risk ARGs which is distinct from those derived via metagenomic approaches. These findings highlight the potentials of HRA Chip in the evaluation of anthropogenic impacts on the environmental resistome with a more focused spectrum of high-risk ARGs. Overall, the HRA Chip emerges as a powerful and efficient high-throughput tool for rapid detection and quantification of high-risk ARGs, facilitating comprehensive profiling of high-risk resistomes in environmental samples which is essential for human health risk assessment of ARGs.

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Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , ARN Ribosómico 16S/genética , Farmacorresistencia Microbiana/genética , Monitoreo del Ambiente/métodos

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Malignant peritoneal mesothelioma (MPM) is a rare and invasive tumor, and some patients will develop paraneoplastic syndrome (PS) during the course of the disease. This review summarizes PS associated with MPM, focusing on the clinical characteristics and treatment progress in hematological, endocrine, rheumatic, neurological, urinary, and other systems to decrease missed diagnosis and misdiagnosis, help early diagnosis and prompt treatment, and provide guidance for the clinical decision-making of this kind of patients.

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BACKGROUND: Superior mesenteric artery (SMA) injuries rarely occur during blunt abdominal injuries, with an incidence of < 1%. The clinical manifestations mainly include abdominal hemorrhage and peritoneal irritation, which progress rapidly and are easily misdiagnosed. Quick and accurate diagnosis and timely effective treatment are greatly significant in managing emergent cases. This report describes emergency rescue by a multidisciplinary team of a patient with hemorrhagic shock caused by SMA rupture. CASE SUMMARY: A 55-year-old man with hemorrhagic shock presented with SMA rupture. On admission, he showed extremely unstable vital signs and was unconscious with a laceration on his head, heart rate of 143 beats/min, shallow and fast breathing (frequency > 35 beats/min), and blood pressure as low as 20/10 mmHg (1 mmHg = 0.133 kPa). Computed tomography revealed abdominal and pelvic hematocele effusion, suggesting active bleeding. The patient was suspected of partial rupture of the distal SMA branch. The patient underwent emergency mesenteric artery ligation, scalp suture, and liver laceration closure. In view of conditions with acute onset, rapid progression, and high bleeding volume, key points of nursing were conducted, including activating emergency protocol, opening of the green channel, and arranging relevant examinations with various medical staff for quick diagnosis. The seamless collaboration of the multidisciplinary team helped shorten the preoperative preparation time. Emergency laparotomy exploration and mesenteric artery ligation were performed to mitigate hemorrhagic shock while establishing efficient venous accesses and closely monitoring the patient's condition to ensure hemodynamic stability. Strict measures were taken to avoid intraoperative hypothermia and infection. CONCLUSION: After 3.5 h of emergency rescue and medical care, bleeding was successfully controlled, and the patient's condition was stabilized. Subsequently, the patient was transferred to the intensive care unit for continuous monitoring and treatment. On the sixth day, the patient was weaned off the ventilator, extubated, and relocated to a specialized ward. Through diligent medical intervention and attentive nursing, the patient made a full recovery and was discharged on day 22. The follow-up visit confirmed the patient's successful recovery.

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N-nitrosamines are a type of nitrogen-containing organic pollutant with high carcinogenicity and mutagenicity. In the main drinking water sources of small and medium-sized towns in China, the contamination levels of N-nitrosamines remain unclear. In addition, there is still lack of research on the concentration of N-nitrosamines and their precursors in tributary rivers. In this study, eight N-nitrosamines and their formation potentials （FPs） were investigated in the Qingjiang River, which is a primary tributary of the Yangtze River. The sewage discharge sites were also monitored, and the environmental influencing factors, carcinogenic and ecological risks caused by N-nitrosamines, and their precursors were evaluated. The results showed that six N-nitrosamines were detected in water samples of the Qingjiang River, among which NDMA [（10 ±15） ng·L-1], NDEA [（9.3 ±9.3） ng·L-1], and NDBA [（14 ±7.8） ng·L-1] were the dominant N-nitrosamines, whereas seven N-nitrosamines were detected in chloraminated water samples, among which NDMA-FP [（46 ±21） ng·L-1], NDEA-FP [（26 ±8.3） ng·L-1], and NDBA-FP [（22 ±13） ng·L-1] were the dominant N-nitrosamine FPs. The concentrations of N-nitrosamines in the middle reaches of the Qingjiang River were higher than those in the upper and lower reaches. Furthermore, the concentrations of N-nitrosamines in the sample sites of sewage discharge and tributaries were significantly higher than those in other sampling sites. The monitoring results at the direct sewage discharge points indicated that the main source of N-nitrosamines in river water was the sewage carrying N-nitrosamines and their precursors. In addition, the concentrations of the three dominant N-nitrosamines including NDMA, NDBA, and NDEA were positively correlated with each other, mainly because of their similar sewage sources. The average carcinogenic risk to residents due to N-nitrosamine in drinking water sources was 2.4×10-5, indicating a potential carcinogenic risk. Moreover, due to the high concentrations of N-nitrosamine formation potentials in the Qingjiang River, the carcinogenic risk of drinking water may be even higher. The ecological risk assessment showed that the ecological risk quotient values of N-nitrosamines in the Qingjiang River watershed were lower than 0.002, which was negligible.

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Monitoreo del Ambiente , Nitrosaminas , Contaminantes Químicos del Agua , Contaminación Química del Agua , Nitrosaminas/análisis , Medición de Riesgo , Contaminación Química del Agua/estadística & datos numéricos , Contaminantes Químicos del Agua/análisis , China , Exposición a Riesgos Ambientales/estadística & datos numéricos , Agua Potable/análisis , Ríos

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OBJECTIVE: Design and develop a Clinical Care Classification (CCC) nursing information system aligned with nursing terminology CCC, emphasizing standard procedures and a responsibility-based nursing model to enhance efficiency and quality of care. METHODS: Conduct thorough investigation into clinical nursing informatics needs, analyze existing system shortcomings, utilize Microsoft.net for development, integrate standard nursing procedures and clinical operating protocols into system functions. Structure database based on bed characteristics, implant CCC Nursing Terminology and clinical nursing knowledge base. RESULTS: Successfully design and develop CCC Nursing Information System featuring patient list, nurse assignment, nursing evaluation, diagnosis, goals, plan, interventions, special care, shift handover, record query, workload statistics, and intelligent guidance based on patient assessment and nursing elements. CONCLUSION: The CCC Nursing Information System advances standard nursing procedures in clinical practice, promoting standardization and responsibility-based holistic care. It harnesses big data to enhance system intelligence.

Asunto(s)

Informática Aplicada a la Enfermería , Terminología Normalizada de Enfermería , Humanos , Atención de Enfermería/clasificación , Inteligencia Artificial , Registros de Enfermería

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Postoperative cognitive dysfunction (POCD) is a neurological complication associated with surgery and anesthesia that is commonly observed in older patients, and it can significantly affect patient prognosis and survival. Therefore, predicting and preventing POCD is important. Regional cerebral oxygen saturation (rSO2) reflects cerebral perfusion and oxygenation, and decreased intraoperative cerebral oxygen saturation has been reported to increase the risk of POCD. In this review, we elucidated the important relationship between the decline in rSO2 and risk of POCD in older patients. We also emphasized the importance of monitoring rSO2 during surgery to predict and prevent adverse perioperative cognitive outcomes. The findings reveal that incorporating intraoperative rSO2 monitoring into clinical practice has potential benefits, such as protecting cognitive function, reducing perioperative adverse outcomes, and ultimately improving the overall quality of life of older adults.

Asunto(s)

Circulación Cerebrovascular , Complicaciones Cognitivas Postoperatorias , Humanos , Complicaciones Cognitivas Postoperatorias/etiología , Anciano , Saturación de Oxígeno , Encéfalo/metabolismo , Calidad de Vida , Oxígeno/metabolismo , Oxígeno/sangre , Disfunción Cognitiva/etiología

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OBJECTIVE: To explore the perception of good death of patients with end-stage cancer by nurses in the oncology department. METHOD: In the study we used a phenomenological approach and semi-structured interviews. A total of 11 nurses from the oncology department of a Grade A hospital in Taizhou were interviewed on the cognition of good death from July 1 to September 30, 2022. Colaizzi's analysis method was used to analyse the interview data. This study followed the consolidated criteria for reporting qualitative research (COREQ). RESULT: Four themes were identified: a strong sense of responsibility and mission; To sustain hope and faith; The important role of family members; Improve patients' quality of life. CONCLUSION: The nurses in the department of oncology have a low level of knowledge about the "good death", and the correct understanding and view of the "good death" is the premise of the realization of " good death". The ability of nursing staff to improve the "good death", attention, and meet the needs and wishes of individuals and families, is the guarantee of the realization of "good death".

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OBJECTIVE: To understand the prevalence rate of obstructive pulmonary dysfunction in workers exposed to silica dust and analyze its risk factors, so as to provide reference for the formulation of diagnostic criteria for chronic obstructive pulmonary disease caused by occupational dust. METHODS: Data collection and structured questionnaire were used to collect the data of 2064 workers exposed to silica dust who underwent health examination in Hunan Occupational Disease Prevention and Control Hospital and Yuanling Second People's Hospital from January 1, 2021 to June 30, 2022. The prevalence rate of obstructive pulmonary ventilation dysfunction was analyzed and the risk factors were analyzed. RESULTS: The prevalence rate of obstructive pulmonary ventilation dysfunction (FEV1/FVC < 70%) was 2.3% in 2064 silica dust exposed workers. The prevalence of restrictive pulmonary ventilation dysfunction (FVC/Pre < 80%) was 8.1%. The prevalence of obstructive pulmonary ventilation dysfunction in the high level exposure group was higher than that in the low level exposure group, 8.2 vs0.9% (P < 0.05). The rate of obstructive pulmonary ventilation dysfunction in female group was higher than that in male group (5.3% vs. 1.7%, p = 0.00). Workers with obstructive pulmonary dysfunction were older and worked longer than workers without obstructive pulmonary dysfunction, but there was no statistical difference. Multivariate regression analysis showed that high exposure level was a risk factor for obstructive pulmonary ventilation dysfunction in silica dust exposed workers (P < 0.05). Females were the risk factors for obstructive pulmonary ventilation dysfunction (P < 0.05). CONCLUSION: Silica dust exposure can cause obstructive pulmonary ventilation dysfunction and lead to chronic obstructive pulmonary disease. High level of exposure is a risk factor for obstructive pulmonary ventilation dysfunction. Women exposed to dust are more prone to obstructive pulmonary ventilation dysfunction than men. Early diagnosis of chronic obstructive pulmonary disease caused by silica dust and timely intervention measures are very important to delay the decline of lung function and protect the health of workers.

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Polvo , Exposición Profesional , Dióxido de Silicio , Humanos , Femenino , Masculino , Dióxido de Silicio/efectos adversos , Factores de Riesgo , Estudios Transversales , Exposición Profesional/efectos adversos , Prevalencia , Persona de Mediana Edad , Adulto , China/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/etiología , Encuestas y Cuestionarios , Enfermedades Pulmonares Obstructivas/epidemiología , Enfermedades Pulmonares Obstructivas/fisiopatología , Análisis Multivariante

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This study explored the regulatory role of bta-miR-149-3p in the inflammatory response induced by microcystin-leucine arginine (MC-LR) exposure in bovine Sertoli cells. The research endeavored to enhance the comprehension of the epigenetic mechanisms underlying MC-LR-induced cytotoxicity in Sertoli cells and establish a foundation for mitigating these effects in vitro. In this study, we elucidated the regulatory mechanism of bta-miR-149-3p in the MC-LR-induced inflammatory response by verifying the target gene of bta-miR-149-3p through luciferase assays and treating the cells with a bta-miR-149-3p inhibitor for 24 h. The results demonstrate that nuclear factor κB (NF-κB) acts as a downstream target gene of bta-miR-149-3p, which inhibits the MC-LR-induced inflammatory response in bovine Sertoli cells. This inhibition occurs by regulating the downregulation of tight junction constitutive proteins of the blood-testis barrier (BTB) through the suppression of the TLR-4/NF-κB signaling pathway (p < 0.05) and the up-regulation of the adhesion junction protein ß-catenin (p < 0.05). Notably, MC-LR exposure resulted in the up-regulation (p < 0.05) of inflammatory cytokines (IL-6, IL-1ß, and NLRP3) and the down-regulation (p < 0.05) of BTB tight junction constitutive proteins (ZO-1, Occludin) in Sertoli cells. Furthermore, the BTB constitutive protein ZO-1 exhibited significant down-regulation in Sertoli cells pretreated with the bta-miR-149-3p inhibitor compared to controls (p < 0.05), while Occludin showed no significant difference from CTNNB1 (p > 0.05). In summary, our findings suggest that bta-miR-149-3p suppresses the MC-LR-induced inflammatory response and alterations in the expression of BTB proteins in bovine Sertoli cells by inhibiting the TLR-4/NF-κB signaling pathway.

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Toxinas Marinas , MicroARNs , Microcistinas , FN-kappa B , Células de Sertoli , Transducción de Señal , Receptor Toll-Like 4 , Animales , Bovinos , Masculino , Microcistinas/toxicidad , Células de Sertoli/efectos de los fármacos , Células de Sertoli/metabolismo , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , MicroARNs/genética , MicroARNs/metabolismo , Inflamación/inducido químicamente , Leucina/farmacología

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BACKGROUND: Systemic Immune-Inflammation Index (SII), known as an easy, economical and useful marker, correlates with the balance of inflammation and immune response. However, the usefulness of SII in biliary atresia (BA) remains unclear. Therefore, we evaluated the relationship of SII level and postoperative clinical outcomes of BA. METHODS: Retrospective review of 168 patients with BA was conducted with assessments of demographic information, histological findings, laboratory parameters, and clinical outcomes. The LASSO logistic regression analysis was established using the "glmnet" software package to explore the influencing factors related to native liver survival time. Numerical variables were dichotomized based on the receiver operating characteristic (ROC) curve and Youden index yielding the best performance of prediction. R software was used for statistical analysis. RESULTS: Overall, the 24 month native liver survival rate was 43.5% (73 cases) after Kasai portoenterostomy. LASSO logistic regression analysis show that preoperative malnutrition (OR = 0.032, 95%CI 0.001-0.424), gamma-glutamyltransferase (GGT, OR = 0.994, 95%CI 0.987-0.998), lymphocyte count (LY, OR = 2.426, 95%CI 1.467-4.604), SII (OR = 0.977, 95%CI 0.960-0.989), and liver fibrosis grading (LFG, reference: Grade 1, Grade 3, OR = 0.076, 95%CI 0.007-0.614) were the independent influencing factors for 24 month native liver survival. ROC curve analysis showed that the area under the curve of SII level (0.919) was larger than that of preoperative malnutrition (0.690), LFG (0.759), GGT (0.747), and Ly (0.773). A SII < 140.09 was found to be a significant marker in the prediction of 24-month native liver survival, with 90.41% sensitivity and 93.68% specificity. Furthermore, the rates of 24-month native liver survival (33.1% vs. 72.7%), jaundice clearance (46.8% vs. 75.0%), and good liver function recovery (46.8% vs. 65.9%) were lower in the SII ≥ 140.09 group than that in the SII < 140.09 group (all P < 0.05), but there was no difference in the occurrence of cholangitis (P > 0.05). CONCLUSION: Preoperative malnutrition, GGT, Ly, SII, and LFG were independent influencing factors for postoperative 24-month native liver survival of BA. The SII level, as a routine haematological marker, has better universality and simplicity and is related to clinical outcomes after Kasai portoenterostomy.

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Atresia Biliar , Inflamación , Portoenterostomía Hepática , Humanos , Estudios Retrospectivos , Masculino , Femenino , Portoenterostomía Hepática/métodos , Atresia Biliar/cirugía , Lactante , Inflamación/inmunología , Resultado del Tratamiento , Tasa de Supervivencia , Biomarcadores/sangre , Curva ROC

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OBJECTIVE: Intestinal fibrosis is a refractory complication of inflammatory bowel disease (IBD). Tumor necrosis factor ligand-related molecule-1A (TL1A) is important for IBD-related intestinal fibrosis in a dextran sodium sulfate (DSS)-induced experimental colitis model. This study aimed to explore the effects of TL1A on human colonic fibroblasts. METHODS: A trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis model of LCK-CD2-TL1A-GFP transgenic (Tg) or wild-type (WT) mice was established to determine the effect and mechanism of TL1A on intestinal fibrosis. The human colonic fibroblast CCD-18Co cell line was treated concurrently with TL1A and human peripheral blood mononuclear cell (PBMC) supernatant. The proliferation and activation of CCD-18Co cells were detected by BrdU assays, flow cytometry, immunocytochemistry and Western blotting. Collagen metabolism was tested by Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The level of collagen metabolism in the TNBS+ethyl alcohol (EtOH)/Tg group was greater than that in the TNBS+EtOH/WT group. Transforming growth factor-ß1 (TGF-ß1) and p-Smad3 in the TNBS+EtOH/Tg group were upregulated as compared with those in the TNBS+EtOH/WT group. The proliferation of CCD-18Co cells was promoted by the addition of human PBMC supernatant supplemented with 20 ng/mL TL1A, and the addition of human PBMC supernatant and TL1A increased CCD-18Co proliferation by 24.4% at 24 h. TL1A promoted cell activation and increased the levels of COL1A2, COL3A1, and TIMP-1 in CCD-18Co cells. Treatment of CCD-18Co cells with TL1A increased the expression of TGF-ß1 and p-Smad3. CONCLUSION: TL1A promotes TGF-ß1-mediated intestinal fibroblast activation, proliferation, and collagen deposition and is likely related to an increase in the TGF-ß1/Smad3 signaling pathway.

Asunto(s)

Proliferación Celular , Fibroblastos , Fibrosis , Transducción de Señal , Proteína smad3 , Factor de Crecimiento Transformador beta1 , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismo , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/genética , Proteína smad3/metabolismo , Proteína smad3/genética , Humanos , Fibroblastos/metabolismo , Fibroblastos/patología , Animales , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Ratones , Colon/metabolismo , Colon/patología , Colitis/metabolismo , Colitis/inducido químicamente , Colitis/patología , Colitis/genética , Línea Celular , Ratones Transgénicos , Ácido Trinitrobencenosulfónico , Modelos Animales de Enfermedad , Leucocitos Mononucleares/metabolismo

RESUMEN

INTRODUCTION: The safety and efficacy of CRS + HIPEC combined with urinary tract resection and reconstruction are controversial. This study aims to summarize the clinicopathological features and to evaluate the safety and survival prognosis of CRS + HIPEC combined with urinary tract resection and reconstruction. METHODS: The patients who underwent urinary tract resection and reconstruction as part of CRS surgery were retrospectively selected from our disease-specific database for analysis. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were studied using a descriptive approach and the K-M analysis with log-rank comparison. RESULTS: Forty-nine patients were enrolled. Perioperative serious AEs (SAEs) were observed in 11 patients (22.4%), with urinary SAEs occurring in 3 patients (6.1%). Additionally, there were 23 cases (46.8%) involving urinary adverse events (UAEs). The median overall survival (OS) in the entire cohort was 59.2 (95%CI: 42.1-76.4) months. The median OS of the UAE group and No-UAE group were 59.2 months (95%CI not reached), and 50.5 (95%CI: 11.5 to 89.6) months, respectively, with no significant difference (P = 0.475). Furthermore, there were no significant differences in OS based on the grade of UAEs or the number of UAEs (P = 0.562 and P = 0.622, respectively). CONCLUSION: The combination of CRS + HIPEC with urinary tract resection and reconstruction is associated with a high incidence of Grade I-II UAEs, which do not have an impact on OS. The safety profile of this combined technique is acceptable. However, this is a retrospective single-center single-arm analysis, with limitations of generalizability and potential selection bias. The findings need high-level validation.

Asunto(s)

Procedimientos Quirúrgicos de Citorreducción , Hipertermia Inducida , Quimioterapia Intraperitoneal Hipertérmica , Humanos , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Pronóstico , Anciano , Hipertermia Inducida/métodos , Hipertermia Inducida/efectos adversos , Hipertermia Inducida/mortalidad , Quimioterapia Intraperitoneal Hipertérmica/métodos , Estudios de Seguimiento , Adulto , Procedimientos Quirúrgicos de Citorreducción/métodos , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Procedimientos Quirúrgicos de Citorreducción/mortalidad , Terapia Combinada , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/patología , Sistema Urinario/cirugía , Sistema Urinario/patología , Procedimientos Quirúrgicos Urológicos/métodos , Procedimientos de Cirugía Plástica/métodos , Complicaciones Posoperatorias/etiología

RESUMEN

[This retracts the article DOI: 10.3892/etm.2020.8708.].