RESUMEN
Organic color centers (OCCs), generated by the covalent functionalization of single-walled carbon nanotubes, have been exploited for chemical sensing, bioimaging, and quantum technologies. However, monovalent OCCs can assume at least 6 different bonding configurations on the sp2 carbon lattice of a chiral nanotube, resulting in heterogeneous OCC photoluminescence emissions. Herein, we show that a heat-activated [2 + 2] cycloaddition reaction enables the synthesis of divalent OCCs with a reduced number of atomic bonding configurations. The chemistry occurs by simply mixing enophile molecules (e.g., methylmaleimide, maleic anhydride, and 4-cyclopentene-1,3-dione) with an ethylene glycol suspension of SWCNTs at elevated temperature (70-140 °C). Unlike monovalent OCC chemistries, we observe just three OCC emission peaks that can be assigned to the three possible bonding configurations of the divalent OCCs based on density functional theory calculations. Notably, these OCC photoluminescence peaks can be controlled by temperature to decrease the emission heterogeneity even further. This divalent chemistry provides a scalable way to synthesize OCCs with tightly controlled emissions for emerging applications.
RESUMEN
Excessive accumulation of chromium (Cr) causes severe damage to both physiological and biochemical processes and consequently growth repression in plants. Hexavalent chromium [Cr(VI)]-elicited alterations in plants have been widely elucidated at either physiological or molecular level, whereas little is known about trivalent chromium [Cr(III)]. Here, we found that both Cr(III) and Cr(VI) significantly inhibited root growth in rice plants. However, rice plants under Cr(VI) showed significantly less inhibition in root growth than those under Cr(III) at low levels, which might be attributed to the different hormetic effects of Cr(III) and Cr(VI) on rice plants. It was unexpected that Cr(III) could be actively taken up by rice roots similarly to Cr(VI); whereas they exhibited different kinetic uptake patterns. Furthermore, root-to-shoot Cr translocation under Cr(VI) was much lower than that under Cr(III). These results indicate that the uptake, translocation, and toxicity of Cr(III) differed greatly from those of Cr(VI). Transcriptome profiling of rice roots revealed that a series of gene families involved in detoxification, including ATP-binding cassette (ABC) transporters, multidrug and toxic compound extrusion proteins (MATEs), and Tau class glutathione S-transferases (GSTUs), were significantly associated with Cr accumulation and detoxification in rice roots. In addition, much more members of these gene families were upregulated by Cr(VI) compared to Cr(III), suggesting their vital roles in Cr uptake, translocation, and detoxification, especially under Cr(VI) stress. Further comparison of gstu9 and gstu10/50 mutants with their wild type confirmed that GSTUs play complex roles in the intracellular Cr transport and redox homeostasis during Cr(III) or Cr(VI) stress. Taken together, our findings provides new insights into the differential behaviors of Cr(III) and Cr(VI) in rice roots, as well as new candidate genes such as OsABCs and OsGSTUs, to further elucidate the mechanisms of the uptake, translocation, and detoxification of Cr(III) and Cr(VI).
Asunto(s)
Cromo , Oryza , Raíces de Plantas , Contaminantes del Suelo , Oryza/metabolismo , Oryza/genética , Cromo/metabolismo , Cromo/toxicidad , Raíces de Plantas/metabolismo , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/toxicidad , Transporte Biológico , Inactivación MetabólicaRESUMEN
BACKGROUND: Tertiary lymphoid structures (TLSs) exert a crucial role in the tumor microenvironment (TME), impacting tumor development, immune escape, and drug resistance. Nonetheless, the heterogeneity of TLSs in colorectal cancer (CRC) and their impact on prognosis and treatment response remain unclear. METHODS: We collected genome, transcriptome, clinicopathological information, and digital pathology images from multiple sources. An unsupervised clustering algorithm was implemented to determine diverse TLS patterns in CRC based on the expression levels of 39 TLS signature genes (TSGs). Comprehensive explorations of heterogeneity encompassing mutation landscape, TME, biological characteristics, response to immunotherapy, and drug resistance were conducted using multi-omics data. TLSscore was then developed to quantitatively assess TLS patterns of individuals for further clinical applicability. RESULTS: Three distinct TLS patterns were identified in CRC. Cluster 1 exhibited upregulation of proliferation-related pathways, high metabolic activity, and intermediate prognosis, while Cluster 2 displayed activation of stromal and carcinogenic pathways and a worse prognosis. Both Cluster 1 and Cluster 2 may potentially benefit from adjuvant chemotherapy. Cluster 3, characterized by the activation of immune regulation and activation pathways, demonstrated a favorable prognosis and enhanced responsiveness to immunotherapy. We subsequently employed a regularization algorithm to construct the TLSscore based on 9 core genes. Patients with lower TLSscore trended to prolonged prognosis and a more prominent presence of TLSs, which may benefit from immunotherapy. Conversely, those with higher TLSscore exhibited increased benefits from adjuvant chemotherapy. CONCLUSIONS: We identified distinct TLS patterns in CRC and characterized their heterogeneity through multi-omics analyses. The TLSscore held promise for guiding clinical decision-making and further advancing the field of personalized medicine in CRC.
RESUMEN
Generally shortened 3' UTR due to alternative polyadenylation (APA) is widely observed in cancer, but its regulation mechanisms for cancer are not well characterized. Here, with profiling of APA in colorectal cancer tissues and poly(A) signal editing, we firstly identified that the shortened 3' UTR of CTNNIBP1 in colorectal cancer promotes cell proliferation and migration. We found that liquid-liquid phase separation (LLPS) of PABPN1 is reduced albeit with higher expression in cancer, and the reduction of LLPS leads to the shortened 3' UTR of CTNNBIP1 and promotes cell proliferation and migration. Notably, the splicing factor SNRPD2 upregulated in colorectal cancer, can interact with glutamic-proline (EP) domain of PABPN1, and then disrupt LLPS of PABPN1, which attenuates the repression effect of PABPN1 on the proximal poly(A) sites. Our results firstly reveal a new regulation mechanism of APA by disruption of LLPS of PABPN1, suggesting that regulation of APA by interfering LLPS of 3' end processing factor may have the potential as a new way for the treatment of cancer.
Asunto(s)
Regiones no Traducidas 3' , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales , Proteína I de Unión a Poli(A) , Poliadenilación , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Proteína I de Unión a Poli(A)/metabolismo , Proteína I de Unión a Poli(A)/genética , Movimiento Celular/genética , Regiones no Traducidas 3'/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Separación de FasesRESUMEN
Indistinguishable single photons in the telecom-bandwidth of optical fibers are indispensable for long-distance quantum communication. Solid-state single photon emitters have achieved excellent performance in key benchmarks, however, the demonstration of indistinguishability at room-temperature remains a major challenge. Here, we report room-temperature photon indistinguishability at telecom wavelengths from individual nanotube defects in a fiber-based microcavity operated in the regime of incoherent good cavity-coupling. The efficiency of the coupled system outperforms spectral or temporal filtering, and the photon indistinguishability is increased by more than two orders of magnitude compared to the free-space limit. Our results highlight a promising strategy to attain optimized non-classical light sources.
RESUMEN
PURPOSE: The role of neoadjuvant chemotherapy (NAC) in colon cancer remains unclear. This trial investigated whether 3 months of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery. PATIENTS AND METHODS: OPTICAL was a randomized, phase III trial in patients with clinically staged locally advanced colon cancer (T3 with extramural spread into the mesocolic fat ≥5 mm or T4). Patients were randomly assigned 1:1 to receive six preoperative cycles of mFOLFOX6 or four cycles of CAPOX, followed by surgery and adjuvant chemotherapy (NAC group), or immediate surgery and the physician's choice of adjuvant chemotherapy (upfront surgery group). The primary end point was 3-year disease-free survival (DFS) assessed in the modified intention-to-treat (mITT) population. RESULTS: Between January 2016 and April 2021, of the 752 patients enrolled, 744 patients were included in the mITT analysis (371 in the NAC group; 373 in the upfront surgery group). At a median follow-up of 48.0 months (IQR, 46.0-50.1), 3-year DFS rates were 82.1% in the NAC group and 77.5% in the upfront surgery group (stratified hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.03]). The R0 resection was achieved in 98% of patients who underwent surgery in both groups. Compared with upfront surgery, NAC resulted in a 7% pathologic complete response rate (pCR), significantly lower rates of advanced tumor staging (pT3-4: 77% v 94%), lymph node metastasis (pN1-2: 31% v 46%), and potentially improved overall survival (stratified HR, 0.44 [95% CI, 0.25 to 0.77]). CONCLUSION: NAC with mFOLFOX6 or CAPOX did not show a significant DFS benefit. However, this neoadjuvant approach was safe, resulted in substantial pathologic downstaging, and appears to be a viable therapeutic option for locally advanced colon cancer.
RESUMEN
Introduction: Endophytes play a significant role in regulating plant root development and facilitating nutrient solubilization and transportation. This association could improve plant growth. The present study has uncovered a distinct phenotype, which we refer to as "white root", arising from the intricate interactions between endophytic fungi and bacteria with the roots in a sugarcane and bamboo fungus (Dictyophora indusiata) intercropping system. Methods: We investigated the mechanisms underlying the formation of this "white root" phenotype and its impact on sugarcane yield and metabolism by metabarcoding and metabolome analysis. Results and Discussion: Initial analysis revealed that intercropping with D. indusiata increased sugarcane yield by enhancing the number of viable tillers compared with bagasse and no input control. Metabarcoding based on second-generation and third-generation sequencing indicated that D. indusiate and Bacillus aryabhattai dominates the fungal and bacterial composition in the "white root" phenotype of sugarcane root. The coexistence of D. indusiata and B. aryabhattai as endophytes induced plant growth-promoting metabolites in the sugarcane root system, such as lysoPC 18:1 and dihydrobenzofuran, probably contributing to increased sugarcane yield. Furthermore, the association also enhanced the metabolism of compounds, such as naringenin-7-O-glucoside (Prunin), naringenin-7-O-neohesperidoside (Naringin)*, hesperetin-7-O-neohesperidoside (Neohesperidin), epicatechin, and aromadendrin (Dihydrokaempferol), involved in flavonoid metabolism during the formation of the endophytic phenotype in the sugarcane root system. These observations suggest that the "white root" phenotype promotes sugarcane growth by activating flavonoid metabolism. This study reports an interesting phenomenon where D. indusiata, coordinate with the specific bacteria invade, forms a "white root" phenotype with sugarcane root. The study also provides new insights into using D. indusiata as a soil inoculant for promoting sugarcane growth and proposes a new approach for improve sugarcane cultivation.
RESUMEN
Atomic defect color centers in solid-state systems hold immense potential to advance various quantum technologies. However, the fabrication of high-quality, densely packed defects presents a significant challenge. Herein we introduce a DNA-programmable photochemical approach for creating organic color-center quantum defects on semiconducting single-walled carbon nanotubes (SWCNTs). Key to this precision defect chemistry is the strategic substitution of thymine with halogenated uracil in DNA strands that are orderly wrapped around the nanotube. Photochemical activation of the reactive uracil initiates the formation of sp3 defects along the nanotube as deep exciton traps, with a pronounced photoluminescence shift from the nanotube band gap emission (by 191 meV for (6,5)-SWCNTs). Furthermore, by altering the DNA spacers, we achieve systematic control over the defect placements along the nanotube. This method, bridging advanced molecular chemistry with quantum materials science, marks a crucial step in crafting quantum defects for critical applications in quantum information science, imaging, and sensing.
Asunto(s)
Nanotubos de Carbono , Nanotubos de Carbono/química , ADN , Uracilo , TiminaRESUMEN
Gut bacteriome dysbiosis is known to be implicated in the pathogenesis of inflammatory bowel disease (IBD). Crohn's disease (CD) is an IBD subtype with extensive mucosal inflammation, yet the mucosal virome, an empirical modulator of the bacteriome and mucosal immunity, remains largely unclear regarding its composition and role. Here, we exploited trans-cohort CD patients and healthy individuals to compositionally and functionally investigate the small bowel (terminal ileum) virome and bacteriome. The CD ileal virome was characterised by an under-representation of both lytic and temperate bacteriophages (especially those targeting bacterial pathogens), particularly in patients with flare-up. Meanwhile, the virome-bacteriome ecology in CD ileal mucosa was featured by a lack of Bifidobacterium- and Lachnospiraceae-led mutualistic interactions between bacteria and bacteriophages; surprisingly it was more pronounced in CD remission than flare-up, underlining the refractory and recurrent nature of mucosal inflammation in CD. Lastly, we substantiated that ileal virions from CD patients causally exacerbated intestinal inflammation in IBD mouse models, by reshaping a gut virome-bacteriome ecology preceding intestinal inflammation (microbial trigger) and augmenting microbial sensing/defence pathways in the intestine cells (host response). Altogether, our results highlight the significance of mucosal virome in CD pathogenesis and importance of mucosal virome restoration in CD therapeutics.
Asunto(s)
Bacteriófagos , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Animales , Ratones , Enfermedad de Crohn/patología , Viroma , Enfermedades Inflamatorias del Intestino/patología , Mucosa Intestinal/metabolismo , Íleon/patología , Bacterias , Inflamación/patologíaRESUMEN
IMPORTANCE: Patients with pathological complete response (pCR) of rectal cancer following neoadjuvant treatment had better oncological outcomes. However, reliable methods for accurately predicting pCR remain limited. OBJECTIVE: To evaluate whether transrectal ultrasound-guided tru-cut biopsy (TRUS-TCB) adds diagnostic value to conventional modalities for predicting pathological complete response in patients with rectal cancer after neoadjuvant treatment. DESIGN, SETTING, AND PARTICIPANTS: This study evaluated data of patients with rectal cancer who were treated with neoadjuvant treatment and reassessed using TRUS-TCB and conventional modalities before surgery. This study is registered with ClinicalTrials.gov. MAIN OUTCOMES AND MEASURES: The primary outcome was accuracy, along with secondary outcomes including sensitivity, specificity, negative predictive value, and positive predictive value in predicting tumour residues. Final surgical pathology was used as reference standard. RESULTS: Between June 2021 and June 2022, a total of 74 patients were enroled, with 63 patients ultimately evaluated. Among them, 17 patients (28%) exhibited a complete pathological response. TRUS-TCB demonstrated an accuracy of 0.71 (95% CI, 0.58-0.82) in predicting tumour residues. The combined use of TRUS-TCB and conventional modalities significantly improved diagnostic accuracy compared to conventional modalities alone (0.75 vs. 0.59, P =0.02). Furthermore, TRUS-TCB correctly reclassified 52% of patients erroneously classified as having a complete clinical response by conventional methods. The occurrence of only one mild adverse event was observed. CONCLUSIONS AND RELEVANCE: TRUS-TCB proves to be a safe and accessible tool for reevaluation with minimal complications. The incorporation of TRUS-TCB alongside conventional methods leads to enhanced diagnostic performance.
Asunto(s)
Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Neoplasias del Recto/patología , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Biopsia Guiada por Imagen/métodos , Adulto , Ultrasonografía Intervencional , Recto/patología , Recto/cirugía , Recto/diagnóstico por imagen , Valor Predictivo de las Pruebas , Resultado del TratamientoRESUMEN
Resistance to neoadjuvant chemotherapy leads to poor prognosis of locally advanced rectal cancer (LARC), representing an unmet clinical need that demands further exploration of therapeutic strategies to improve clinical outcomes. Here, we identified a noncanonical role of RB1 for modulating chromatin activity that contributes to oxaliplatin resistance in colorectal cancer (CRC). We demonstrate that oxaliplatin induces RB1 phosphorylation, which is associated with the resistance to neoadjuvant oxaliplatin-based chemotherapy in LARC. Inhibition of RB1 phosphorylation by CDK4/6 inhibitor results in vulnerability to oxaliplatin in both intrinsic and acquired chemoresistant CRC. Mechanistically, we show that RB1 modulates chromatin activity through the TEAD4/HDAC1 complex to epigenetically suppress the expression of DNA repair genes. Antagonizing RB1 phosphorylation through CDK4/6 inhibition enforces RB1/TEAD4/HDAC1 repressor activity, leading to DNA repair defects, thus sensitizing oxaliplatin treatment in LARC. Our study identifies a RB1 function in regulating chromatin activity through TEAD4/HDAC1. It also provides the combination of CDK4/6 inhibitor with oxaliplatin as a potential synthetic lethality strategy to mitigate oxaliplatin resistance in LARC, whereby phosphorylated RB1/TEAD4 can serve as potential biomarkers to guide the patient stratification.
Asunto(s)
Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Oxaliplatino/farmacología , Terapia Neoadyuvante/métodos , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/genética , Quimioradioterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cromatina , Resultado del Tratamiento , Factores de Transcripción de Dominio TEA , Ubiquitina-Proteína Ligasas , Proteínas de Unión a RetinoblastomaRESUMEN
BACKGROUND: Stratum corneum (SC) plays a critical role in skin barrier function for protection and defense in nature. The acidic skin pH, which is also known as the acid mantle, is very important in fighting against outer environmental threats, especially, bacteria. Furthermore, recent research has shown that the transient bacteria could potentially penetrate into deeper layer of the SC down to a few micrometers while posing an additional threat to the deeper layers of the skin. AIM: To develop a sequential tape stripping method for assessing the impact of personal cleansing product on the SC surface layers' acid mantle properties and antimicrobial defense against transient bacteria. METHODS: Fifty-five subjects were recruited. High pH soap-based Product 1 and low pH synthetic surfactant-based Product 2 were applied on the left and right forearms of each subject. Sequential tape stripping was performed on the same spots to access multiple layers of the skin SC. Both antimicrobial defense property and skin pH of different skin layers were evaluated at baseline and 12 h after treatment. RESULTS: The skin's antimicrobial defense was significantly higher 12 h after treatment of the low pH Product 2 as compared to the treatment of high pH Product 1. In fact, this trend was consistent across all three skin layers (Layer 1 to Layer 3) as measured in this study (p < 0.01). Furthermore, the skin surface pH of Layer 1 and Layer 3 were also lower 12 h after the treatment of low pH Product 2 as compared to that of the high pH Product 1 (p < 0.01). CONCLUSION: The results of this investigation demonstrated the benefits of 12-h long lasting and deeper protection of SC acid mantle properties and antimicrobial defense using a low pH skin cleansing product as compared to a high pH product.
Asunto(s)
Antiinfecciosos , Epidermis , Humanos , PielRESUMEN
BACKGROUND: Macrophage (Mφ) activation plays a critical role in the inflammatory response. Activated Mφ go through profound reprogramming of cellular metabolism. However, changes in their intracellular energy metabolism and its effect on inflammatory responses in Crohn's disease (CD) remain currently unclear. The aim of this study is to explore metabolic signatures of CD14+ Mφ and their potential role in CD pathogenesis as well as the underlying mechanisms. METHODS: CD14+ Mφ were isolated from peripheral blood or intestinal tissues of CD patients and control subjects. Real-time flux measurements and enzyme-linked immunosorbent assay were used to determine the inflammatory states of Mφ and metabolic signatures. Multiple metabolic routes were suppressed to determine their relevance to cytokine production. RESULTS: Intestinal CD14+ Mφ in CD patients exhibited activated glycolysis compared with those in control patients. Specifically, macrophagic glycolysis in CD largely induced inflammatory cytokine release. The intestinal inflammatory microenvironment in CD elicited abnormal glycolysis in Mφ. Mechanistically, CD14+ Mφ derived exosomes expressed membrane tumor necrosis factor (TNF), which engaged TNFR2 and triggered glycolytic activation via TNF/nuclear factor κB autocrine and paracrine signaling. Importantly, clinically applicable anti-TNF antibodies effectively prevented exosomal membrane TNF-induced glycolytic activation in CD14+ Mφ. CONCLUSIONS: CD14+ Mφ take part in CD pathogenesis by inducing glycolytic activation via membrane TNF-mediated exosomal autocrine and paracrine signaling. These results provide novel insights into pathogenesis of CD and enhance understanding of the mechanisms of anti-TNF agents.
Asunto(s)
Enfermedad de Crohn , Humanos , Enfermedad de Crohn/patología , Inhibidores del Factor de Necrosis Tumoral , Factor de Necrosis Tumoral alfa/metabolismo , Macrófagos/metabolismo , Citocinas/metabolismo , GlucólisisRESUMEN
Background/Aims: Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is widely accepted as a radical surgery for refractory ulcerative colitis (UC). Definite results on the appropriate pouch length for an evaluation of the risk-to-benefit ratio regarding technical complications and long-term quality of life (QOL) are still scarce. Methods: Data on UC patients who underwent IPAA from 2008 to 2022 in four well-established pouch centers affiliated to China UC Pouch Center Union were collected. Results: A total of 208 patients with a median follow-up time of 6.0 years (interquartile range, 2.3 to 9.0 years) were enrolled. The median lengths of the patients' short and long pouches were 14.0 cm (interquartile range, 14.0 to 15.0 cm) and 22.0 cm (interquartile range, 20.0 to 24.0 cm), respectively. Patients with a short J pouch configuration were less likely to achieve significantly improved long-term QOL (p=0.015) and were prone to develop late postoperative complications (p=0.042), such as increased defecation frequency (p=0.003) and pouchitis (p=0.035). A short ileal pouch was an independent risk factor for the development of late postoperative complications (odds ratio, 3.100; 95% confidence interval, 1.519 to 6.329; p=0.002) and impaired longterm QOL improvement (odds ratio, 2.221; 95% confidence interval, 1.218 to 4.050, p=0.009). Conclusions: The length of the J pouch was associated with the improvement in long-term QOL and the development of late post-IPAA complications. A long J pouch configuration could be a considerable surgical option for pouch construction.
Asunto(s)
Colitis Ulcerosa , Reservorios Cólicos , Proctocolectomía Restauradora , Humanos , Proctocolectomía Restauradora/efectos adversos , Proctocolectomía Restauradora/métodos , Reservorios Cólicos/efectos adversos , Colitis Ulcerosa/cirugía , Colitis Ulcerosa/complicaciones , Calidad de Vida , Resultado del Tratamiento , Estudios Retrospectivos , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugíaRESUMEN
Aligned and suspended carbon nanotubes can outperform randomly oriented networks in electronic biosensing and thin-film electronics. However, carbon nanotubes tend to bundle and form random networks. Here, we show that carbon nanotubes spontaneously align in an ammonium deoxycholate surfactant gel even under low shear forces, allowing direct writing and printing of nanotubes into electrically conducting wires and aligned thin layers across trenches. To demonstrate its application potential, we directly printed arrays of disposable electrical biosensors, which show femtomolar sensitivity in the detection of DNA and SARS-CoV-2 RNA.
Asunto(s)
Técnicas Biosensibles , Nanotubos de Carbono , ARN Viral , Electrónica , ElectricidadRESUMEN
Objective: Compare the clinical efficacy of anterior and posterior Calot's triangle approach in laparoscopic cholecystectomy (LC) for chronic atrophic cholecystitis, to find out which approach is much safer and more reliable. Patients and Methods: From June 2020 to June 2022, 102 patients with chronic atrophic cholecystitis underwent LC in our hospital. They were divided into anterior Calot's triangle approach group and posterior Calot's triangle approach group. In addition, their clinical data, intraoperative conditions, surgical results, and postoperative recovery were analyzed. Results: LC was performed in 41 females and 28 males by the anterior Calot's triangle approach, and in 20 females and 13 males by the posterior Calot's triangle approach. There were no differences in age, gender, and body mass index between the two groups (P > .05). The probability of rupture of cystic artery between both groups was not significantly different (P = .549), and the intraoperative blood loss was more in the anterior group (P = .014). The operative time of the posterior approach appeared to be shorter (P = .013). Bile duct injury and conversion to open cholecystectomy revealed no significant difference (P > .05). The recovery time of gastrointestinal function, wound infection, white blood cell count, liver function, and postoperative hospital stay time were found to be not significantly different (P > .05). Conclusion: By the posterior Calot's triangle approach, LC is a convenient and feasible surgical procedure for chronic atrophic cholecystitis with less blood loss and can become easier without increasing the risk of surgery.
Asunto(s)
Colecistectomía Laparoscópica , Colecistitis , Masculino , Femenino , Humanos , Estudios Retrospectivos , Colecistitis/cirugía , Colecistectomía Laparoscópica/métodos , Colecistectomía/métodos , Pérdida de Sangre QuirúrgicaRESUMEN
BACKGROUND: Accurate prediction of response to neoadjuvant chemoradiotherapy is critical for subsequent treatment decisions for patients with locally advanced rectal cancer. OBJECTIVE: To develop and validate a deep learning model based on the comparison of paired MRI before and after neoadjuvant chemoradiotherapy to predict pathological complete response. DESIGN: By capturing the changes from MRI before and after neoadjuvant chemoradiotherapy in 638 patients, we trained a multitask deep learning model for response prediction (DeepRP-RC) that also allowed simultaneous segmentation. Its performance was independently tested in an internal and 3 external validation sets, and its prognostic value was also evaluated. SETTINGS: Multicenter study. PATIENTS: We retrospectively enrolled 1201 patients diagnosed with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy before total mesorectal excision. Patients had been treated at 1 of 4 hospitals in China between January 2013 and December 2020. MAIN OUTCOME MEASURES: The main outcome was the accuracy of predicting pathological complete response, measured as the area under receiver operating curve for the training and validation data sets. RESULTS: DeepRP-RC achieved high performance in predicting pathological complete response after neoadjuvant chemoradiotherapy, with area under the curve values of 0.969 (0.942-0.996), 0.946 (0.915-0.977), 0.943 (0.888-0.998), and 0.919 (0.840-0.997) for the internal and 3 external validation sets, respectively. DeepRP-RC performed similarly well in the subgroups defined by receipt of radiotherapy, tumor location, T/N stages before and after neoadjuvant chemoradiotherapy, and age. Compared with experienced radiologists, the model showed substantially higher performance in pathological complete response prediction. The model was also highly accurate in identifying the patients with poor response. Furthermore, the model was significantly associated with disease-free survival independent of clinicopathological variables. LIMITATIONS: This study was limited by its retrospective design and absence of multiethnic data. CONCLUSIONS: DeepRP-RC could be an accurate preoperative tool for pathological complete response prediction in rectal cancer after neoadjuvant chemoradiotherapy. UN SISTEMA DE IA BASADO EN RESONANCIA MAGNTICA LONGITUDINAL PARA PREDECIR LA RESPUESTA PATOLGICA COMPLETA DESPUS DE LA TERAPIA NEOADYUVANTE EN EL CNCER DE RECTO UN ESTUDIO DE VALIDACIN MULTICNTRICO: ANTECEDENTES:La predicción precisa de la respuesta a la quimiorradioterapia neoadyuvante es fundamental para las decisiones de tratamiento posteriores para los pacientes con cáncer de recto localmente avanzado.OBJETIVO:Desarrollar y validar un modelo de aprendizaje profundo basado en la comparación de resonancias magnéticas pareadas antes y después de la quimiorradioterapia neoadyuvante para predecir la respuesta patológica completa.DISEÑO:Al capturar los cambios de las imágenes de resonancia magnética antes y después de la quimiorradioterapia neoadyuvante en 638 pacientes, entrenamos un modelo de aprendizaje profundo multitarea para la predicción de respuesta (DeepRP-RC) que también permitió la segmentación simultánea. Su rendimiento se probó de forma independiente en un conjunto de validación interna y tres externas, y también se evaluó su valor pronóstico.ESCENARIO:Estudio multicéntrico.PACIENTES:Volvimos a incluir retrospectivamente a 1201 pacientes diagnosticados con cáncer de recto localmente avanzado y sometidos a quimiorradioterapia neoadyuvante antes de la escisión total del mesorrecto. Eran de cuatro hospitales en China en el período entre enero de 2013 y diciembre de 2020.PRINCIPALES MEDIDAS DE RESULTADO:Los principales resultados fueron la precisión de la predicción de la respuesta patológica completa, medida como el área bajo la curva operativa del receptor para los conjuntos de datos de entrenamiento y validación.RESULTADOS:DeepRP-RC logró un alto rendimiento en la predicción de la respuesta patológica completa después de la quimiorradioterapia neoadyuvante, con valores de área bajo la curva de 0,969 (0,942-0,996), 0,946 (0,915-0,977), 0,943 (0,888-0,998), y 0,919 (0,840-0,997) para los conjuntos de validación interna y las tres externas, respectivamente. DeepRP-RC se desempeñó de manera similar en los subgrupos definidos por la recepción de radioterapia, la ubicación del tumor, los estadios T/N antes y después de la quimiorradioterapia neoadyuvante y la edad. En comparación con los radiólogos experimentados, el modelo mostró un rendimiento sustancialmente mayor en la predicción de la respuesta patológica completa. El modelo también fue muy preciso en la identificación de los pacientes con mala respuesta. Además, el modelo se asoció significativamente con la supervivencia libre de enfermedad independientemente de las variables clinicopatológicas.LIMITACIONES:Este estudio estuvo limitado por el diseño retrospectivo y la ausencia de datos multiétnicos.CONCLUSIONES:DeepRP-RC podría servir como una herramienta preoperatoria precisa para la predicción de la respuesta patológica completa en el cáncer de recto después de la quimiorradioterapia neoadyuvante. (Traducción-Dr. Felipe Bellolio ).
Asunto(s)
Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Estudios Retrospectivos , Inteligencia Artificial , Quimioradioterapia/efectos adversos , Neoplasias del Recto/terapia , Neoplasias del Recto/tratamiento farmacológico , Imagen por Resonancia Magnética , Estadificación de NeoplasiasRESUMEN
The human gut microbiome varies substantially across individuals and populations and differentially tames our immunity at steady-state. Hence, we hypothesize that the large heterogeneity of gut microbiomes at steady-state may shape our baseline immunity differentially, and then mediate discrepant immune responses and symptoms when one encounters a viral infection, such as SARS-CoV-2 infection. To validate this hypothesis, we conducted an exploratory, longitudinal microbiome-COVID-19 study involving homogenous young participants from two geographically different regions in China. Subjects were recruited and sampled of fecal specimens before the 3-week surge window of COVID-19 (between December 11 and December 31, 2022) in China, and then were followed up for assessment of COVID-19 and post-COVID-19 manifestations. Our data showed that the baseline gut microbiome composition was intricately associated with different COVID-19 manifestations, particularly gastrointestinal involvement and post-COVID-19 lingering symptoms, in both an individual- and population-dependent manner. Our study intriguingly for the first time highlight that the gut microbiome at steady-state may prepare us differentially for weathering a respiratory viral infection.
Asunto(s)
COVID-19 , Microbioma Gastrointestinal , Microbiota , Humanos , SARS-CoV-2 , China/epidemiologíaRESUMEN
BACKGROUND: Evidence-based practice (EBP) is an essential approach of optimizing patient outcomes and driving progress in clinical practice. As an important reserve talent of medical staff and researchers, the clinical postgraduates are expected to become the backbones of supporting the implementation of EBP in clinical units after graduation. The assessment of their EBP learning outcomes is an important issue, yet few tools have been developed specifically in Mainland China. The purpose of this study is to adapt the Evidence-Based Practice Profile Questionnaire (EBP2Q) to Mainland China's cultural context and to evaluate the psychometric properties of the Chinese EBP2Q in clinical postgraduates. METHODS: Cross-cultural modification, including translating the original EBP2Q into Chinese was implemented according to established guidelines. A pilot study was carried out in Mainland China among 30 clinical postgraduates. A subsequent validation study was conducted among 633 clinical postgraduates majoring in clinical medicine, stomatology and nursing from Mainland China. Construct validity was assessed by exploratory factor analysis (n = 313), together with confirmatory factor analysis (n = 320). Reliability was determined by internal consistency and test-retest reliability. RESULTS: The Chinese EBP2Q consisted of 40 items. The content validity index of the Chinese EBP2Q achieved 0.938 at an acceptable level. Principal component analysis resulted in a four-factor structure explaining 61.586% of the total variance. All fitting indices satisfied the standard based upon confirmatory factor analyses, indicating that the four-factor structure contributed to an ideal model fit. The internal consistency appeared high for the Chinese EBP2Q, reaching a Cronbach's alpha value of 0.926. Test-retest reliability was 0.868 and the split-half coefficient was 0.925. CONCLUSION: Chinese version of EBP2Q possesses adequate validity, test-retest reliability and internal consistency. It is a promising questionnaire to be adopted by Chinese medical educators in designing their course and curriculum, or by clinical postgraduates for self-assessment of EBP learning.