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Numerous factors can contribute to a difficult colonoscopy, potentially leading to an incomplete procedure and overlooked lesions. Alternative strategies for handling difficult and incomplete colonoscopies should be considered. We present the case of an 85-year-old male who underwent a difficult colonoscopy, during which two expert endoscopists spent 1.5 h attempting various techniques but failed to intubate the cecum. Subsequently, colonic transendoscopic enteral tubing (TET) was performed. Abdominal plain film revealed tortuosity of the TET tube in the left abdomen corresponding to the distribution of the descending colon. Retrograde colon imaging was conducted by injecting a mixture of contrast medium and air into the colon via the TET tube. X-ray demonstrated well-developed visualization of the entire colon and terminal ileum. And evident elongation and tortuosity of the descending colon resembled an N-type folding pattern. The final diagnosis was determined as descending colon redundancy. Colonic TET combined with retrograde colon imaging through the TET tube may serve as an effective supplementary approach for identifying causes of difficult colonoscopy and improving diagnostic accuracy for bowel diseases when complete visualization is not achieved.
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The cancer-associated alternative splicing (AS) events generate cancer-related transcripts which are involved in uncontrolled cell proliferation and drug resistance. However, the key AS variants implicated in tamoxifen (TAM) resistance in breast cancer remain elusive. In the current study, we investigated the landscape of AS events in nine pairs of primary and relapse breast tumors from patients receiving TAM-based therapy. We unrevealed a notable association between the inclusion of exon 7.2 in the 5'untranslated region (5'UTR) of ALDOA mRNA and TAM resistance. Mechanistically, the inclusion of ALDOA exon 7.2 enhances the translation efficiency of the transcript, resulting in increased ALDOA protein expression, mTOR pathway activity, and the promotion of TAM resistance in breast cancer cells. Moreover, the inclusion of exon 7.2 in ALDOA mRNA is mediated by MSI1 via direct interaction. In addition, elevated inclusion of ALDOA exon 7.2 or expression of MSI1 is associated with an unfavorable prognosis in patients undergoing endocrine therapy. Notably, treatment with Aldometanib, an ALDOA inhibitor, effectively restrains the growth of TAM-resistant breast cancer cells in vitro and in vivo. The present study unveils the pivotal role of an AS event in ALDOA, under the regulation of MSI1, in driving TAM resistance in breast cancer. Therefore, this study provides a promising therapeutic avenue targeting ALDOA to combat TAM resistance.
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Combining rare earth elements with the halide perovskite structure offers valuable insights into designing nonlead (Pb) luminescent materials. However, most of these compositions tend to form zero-dimensional (0D) networks of metal-halide polyhedra, with higher-dimensional (1D, 2D, and 3D) structures receiving relatively less exploration. Herein, we present synthesis and optical properties of Cs3CeCl6·3H2O, characterized by its unique 1D crystal structure. The conduction band minimum of Cs3CeCl6·3H2O becomes less localized as a result of the increased structural dimension, making it possible for the materials to achieve an efficient electrical injection. For both Cs3CeCl6·3H2O single crystals and nanocrystals, we also observed remarkable luminescence with near-unity photoluminescence quantum yield and exceptional phase stability. Cs3CeCl6·3H2O single crystals demonstrate an X-ray scintillation light yield of 31900 photons/MeV, higher than that of commercial LuAG:Ce (22000 photons/MeV); electrically driven light-emitting diodes fabricated with Cs3CeCl6·3H2O nanocrystals yield the characteristic emission of Ce3+, indicating their potential use in next-generation violet-light-emitting devices.
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As the contamination and enrichment in food chain of levofloxacin (LV) antibiotics have caused a significant threat to life safety, the instant detection of LV has become an urgent need. Here, a PDI-functionalized imine-based covalent organic framework (PDI-COF300) was prepared by the electrostatic self-assembly method as fluorescent probe for smartphone visual detection of LV, which exhibited excellent fluorescence quantum yield (82.68%), greater stability, high sensitivity with detection limit of 0.303 µM. Based on the results of molecular docking and Stern-Volmer equation, the LV detection by PDI-COF300 was mainly a static quenching process through π-π stacked hydrophobic interactions and fluorescence resonance energy transfer. Besides, PDI-COF300 was applied to LV detection in environmental medium and milk samples with recoveries from 85.56% to 108.34% and relative standard deviations <2.70%. This work also provided a new general strategy for using PDI-COF in smartphone devices and fluorescent papers for LV fluorescence detection and microanalysis.
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Ewing's sarcoma (EWS) is a highly aggressive malignant bone tumor primarily affecting adolescents and young adults. Despite the efficacy of chemoradiotherapy in some cases, the cure rate for patients with metastatic and recurrent disease remains low. Therefore, there is an urgent need for innovative therapeutic approaches to address the challenges associated with EWS treatment. Epigenetic regulation, a crucial factor in physiological processes, plays a significant role in controlling cell proliferation, maintaining gene integrity, and regulating transcription. Recent studies highlight the importance of abnormal epigenetic regulation in the initiation and progression of EWS. A comprehensive understanding of the intricate interactions between EWS and aberrant epigenetic regulation is essential for advancing clinical drug development. This review aims to provide a comprehensive overview of both epigenetic targets implicated in EWS, integrating various therapeutic modalities to offer innovative perspectives for the clinical diagnosis and treatment of EWS.
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Lipid nanoparticles (LNPs) have proven themselves as transformative actors in chimeric antigen receptor (CAR) T cell therapy, surpassing traditional methods and addressing challenges like immunogenicity, reduced toxicity, and improved safety. Promising preclinical results signal a shift toward safer and more effective CAR T cell treatments. Ongoing research aims to validate these findings in clinical trials, marking a new era guided by LNPs utility in CAR therapy. Herein, we explore the preference for LNPs over traditional methods, highlighting the versatility of LNPs and their effective delivery of nucleic acids. Additionally, we address key challenges in clinical considerations, heralding a new era in CAR T cell therapy.
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Imunoterapia Adotiva , Lipídeos , Nanopartículas , Receptores de Antígenos Quiméricos , Nanopartículas/química , Humanos , Imunoterapia Adotiva/métodos , Animais , Lipídeos/química , Linfócitos T/imunologia , Neoplasias/terapia , Neoplasias/imunologia , LipossomosRESUMO
BACKGROUND: Although myotomy is crucial in peroral endoscopic myotomy (POEM) surgeries, its optimum length remains controversial. Herein, we propose a modified POEM with new method of tailoring myotomy length aim to evaluate the safety, efficacy, and clinical outcomes of this modified POEM compared with standard POEM in type I or II achalasia. METHODS: Seventy-five patients with type I or II achalasia who underwent POEM at the First Hospital of Jilin University between January 2018 and December 2022 were retrospectively analyzed. According to the myotomy approach, these patients were divided into the retrograde on-demand myotomy (RDM, n = 34), with myotomy beginning on gastric side and length tailored by determining the degree of lower esophageal sphincter (LES) distention, and standard myotomy (SM, n = 41) groups. The baseline data, myotomy length, operation time, clinical success rate, adverse event rate, and reflux-related adverse events were compared and analyzed. RESULTS: The median myotomy length in the RDM group was significantly shorter than that in the SM group (6 vs. 8 cm, respectively; p < 0.001). Moreover, the median myotomy time in the RDM group was significantly shorter than that in the SM group (10 vs. 16 min, respectively; p < 0.001). POEM was successfully performed in all the patients. At the 2-year follow-up, high clinical success rates were observed in both the RDM and SM groups (92.0% vs. 93.3%, respectively; p = 1.000). The incidence of intraoperative adverse events and postoperative reflux-related adverse events was low and comparable in both groups. CONCLUSIONS: RDM POEM is a safe and effective method for patients with type I or II achalasia. Furthermore, it has a shorter myotomy length and operation time than standard POEM technique.
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Acalasia Esofágica , Miotomia , Cirurgia Endoscópica por Orifício Natural , Humanos , Acalasia Esofágica/cirurgia , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Miotomia/métodos , Cirurgia Endoscópica por Orifício Natural/métodos , Resultado do Tratamento , Duração da Cirurgia , Idoso , Esfíncter Esofágico Inferior/cirurgia , Esofagoscopia/métodosRESUMO
BACKGROUND: Lysine-specific demethylase 1 (LSD1) is highly expressed in a variety of malignant tumors, rendering it a crucial epigenetic target for anti-tumor therapy. Therefore, the inhibition of LSD1 activity has emerged as a promising innovative therapeutic approach for targeted cancer treatment. METHODS: In our study, we employed innovative structure-based drug design methods to meticulously select compounds from the ZINC15 database. Utilizing virtual docking, we evaluated docking scores and binding modes to identify potential inhibitors. To further validate our findings, we harnessed molecular dynamic simulations and conducted meticulous biochemical experiments to deeply analyze the binding interactions between the protein and compounds. RESULTS: Our results showcased that ZINC10039815 exhibits an exquisite binding mode with LSD1, fitting perfectly into the active pocket and forming robust interactions with multiple critical residues of the protein. CONCLUSIONS: With its significant inhibitory effect on LSD1 activity, ZINC10039815 emerges as a highly promising candidate for the development of novel LSD1 inhibitors.
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Inibidores Enzimáticos , Histona Desmetilases , Simulação de Acoplamento Molecular , Histona Desmetilases/antagonistas & inibidores , Histona Desmetilases/metabolismo , Histona Desmetilases/química , Humanos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Simulação de Dinâmica Molecular , Antineoplásicos/farmacologia , Antineoplásicos/química , Desenho de Fármacos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismoRESUMO
OBJECTIVE: To evaluate the risk factors of new osteoporotic vertebral compression fractures (OVCFs) after percutaneous vertebroplasty (PVP). METHODS: From January 2016 to November 2019, patients suffering from OVCFs were retrospectively reviewed. The independent influence factors for new OVCFs after PVP were assessed, from following variables: age, sex, body mass index, bone mineral density (BMD), history of alcoholism, smoking, hypertension, diabetes, glucocorticoid use, and prior vertebral fractures, the number of initial fractures, mean cement volume, method of puncture, D-type of cement leakage, and regular antiosteoporosis treatment. RESULTS: A total of 268 patients with 347 levels met the inclusion criteria and were finally included in this study. Forty-nine levels of new OVCFs among 33 patients (12.31%) were observed during the follow-up period. It indicated that female (adjusted odds ratio [OR]: 6.812, 95% confidence interval {CI}: [1.096, 42.337], P = 0.040), lower BMD (adjusted OR: 0.477, 95% CI: [0.300, 0.759], P = 0.002), prior vertebral fractures (adjusted OR: 16.145, 95% CI: [5.319, 49.005], P = 0.000), and regular antiosteoporosis treatment (adjusted OR: 0.258, 95% CI: [0.086, 0.774], P = 0.016) were independent influence factors for new OVCF. The cut-off value of BMD to reach new OVCF was -3.350, with a sensitivity of 0.660 and a specificity of 0.848. CONCLUSION: Female, lower BMD (T-score of lumbar), prior vertebral fractures, and regular antiosteoporosis treatment were independent influencing factors. BMD (T-score of lumbar) lower than -3.350 would increase risk for new OVCF, and none osteoporotic treatment has detrimental effect on new onset fractures following PVP.
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Fraturas por Compressão , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Humanos , Masculino , Feminino , Vertebroplastia/métodos , Fraturas por Compressão/cirurgia , Fraturas por Osteoporose/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/etiologia , Estudos Retrospectivos , Idoso , Fatores de Risco , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Densidade Óssea , Estudos de CoortesRESUMO
Gastric peroral endoscopic myotomy (G-POME) is an emerging minimally invasive endoscopic technique involving the establishment of a submucosal tunnel around the pyloric sphincter. In 2013, Khashab et al used G-POME for the first time in the treatment of gastroparesis with enhanced therapeutic efficacy, providing a new direction for the treatment of gastroparesis. With the recent and rapid development of G-POME therapy technology, progress has been made in the treatment of gastroparesis and other upper digestive tract diseases, such as congenital hypertrophic pyloric stenosis and gastric sleeve stricture, with G-POME. This article reviews the research progress and future prospects of G-POME for the treatment of upper digestive tract gastrointestinal diseases.
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Transition metal chalcogenides (TMCs) are widely used in photocatalytic fields such as hydrogen evolution, nitrogen fixation, and pollutant degradation due to their suitable bandgaps, tunable electronic and optical properties, and strong reducing ability. The unique 2D malleability structure provides a pre-designed platform for customizable structures. The introduction of vacancy engineering makes up for the shortcomings of photocorrosion and limited light response and provides the greatest support for TMCs in terms of kinetics and thermodynamics in photocatalysis. This work reviews the effect of vacancy engineering on photocatalytic performance based on 2D semiconductor TMCs. The characteristics of vacancy introduction strategies are summarized, and the development of photocatalysis of vacancy engineering TMCs materials in energy conversion, degradation, and biological applications is reviewed. The contribution of vacancies in the optical range and charge transfer kinetics is also discussed from the perspective of structure manipulation. Vacancy engineering not only controls and optimizes the structure of the TMCs, but also improves the optical properties, charge transfer, and surface properties. The synergies between TMCs vacancy engineering and atomic doping, other vacancies, and heterojunction composite techniques are discussed in detail, followed by a summary of current trends and potential for expansion.
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The link between inflammation and cancer is well documented and colonic inflammation caused by inflammatory bowel disease (IBD) is thought to be a high-risk factor for the development of colorectal cancer (CRC). The complex crosstalk between epithelial and inflammatory cells is thought to underlie the progression from inflammation to cancer. The present review collates and summarises recent advances in the understanding of the pathogenesis of IBD-associated CRC (IBD-CRC), including the oncogenic mechanisms of the main inflammatory signalling pathways and genetic alterations induced by oxidative stress during colonic inflammation, and discusses the crosstalk between the tumour microenvironment, intestinal flora and host immune factors during inflammatory oncogenesis in colitis-associated CRC. In addition, the therapeutic implications of anti-inflammatory therapy for IBD-CRC were discussed, intending to provide new insight into improve clinical practice.
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Compared with circular, arched, and pipe-arched soil-steel structures, box-type soil-steel structures (BTSSSs) have the advantages of high cross-section utilization and low cover depth. However, the degree of influence of the crown and haunch radii on the mechanical performance of BTSSSs is still unclear. Therefore, two full-scale BTSSS models with a span of 6.6 m and a rise of 3.7 m but with different crown and haunch radii were established, and the mechanical properties during backfilling and under live load were tested. Afterward, 2D finite element models (FEMs) were established using the ABAQUS 2020 software and verified using the test data. The influence of cross-section geometric parameters on mechanical performance was analyzed by using the FEM, and a more accurate formula for calculating the bending moment during backfilling was proposed. The results show that the BTSSS with a smaller crown radius has a stronger soil-steel interaction, which promotes more uniform stress on the structure and makes the structure have smaller relative deformations, bending moments, and earth pressure. The span and arch height greatly influence the bending moment and deformation of the structure. Based on the CHBDC, the crown and haunch radii were included in the revised calculation formula.
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Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and death in piglets, resulting in significant economic losses for the pork industry. There is an urgent need for new treatment strategies. Here, we focused on optimizing the process of purifying natural hyperoside (nHYP) from hawthorn and evaluating its effectiveness against PEDV both in vitro and in vivo. Our findings demonstrated that nHYP with a purity >98% was successfully isolated from hawthorn with an extraction rate of 0.42 mg/g. Furthermore, nHYP exhibited strong inhibitory effects on PEDV replication in cells, with a selection index of 9.72. nHYP significantly reduced the viral load in the intestines of piglets and protected three of four piglets from death caused by PEDV infection. Mechanistically, nHYP could intervene in the interaction of PEDV N protein and p53. The findings implicate nHYP as having promising therapeutic potential for combating PEDV infections.
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Infecções por Coronavirus , Crataegus , Vírus da Diarreia Epidêmica Suína , Quercetina/análogos & derivados , Doenças dos Suínos , Animais , Suínos , Diarreia , Antivirais/farmacologia , Antivirais/uso terapêutico , Doenças dos Suínos/tratamento farmacológicoRESUMO
Rational predictions on binding kinetics parameters of drugs to targets play significant roles in future drug designs. Full conformational samplings of targets are requisite for accurate predictions of binding kinetic parameters. In this review, we mainly focus on the applications of enhanced sampling technologies in calculations of binding kinetics parameters and residence time of drugs. The methods involved in molecular dynamics simulations are applied to not only probe conformational changes of targets but also reveal calculations of residence time that is significant for drug efficiency. For this review, special attention are paid to accelerated molecular dynamics (aMD) and Gaussian aMD (GaMD) simulations that have been adopted to predict the association or disassociation rate constant. We also expect that this review can provide useful information for future drug design.
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Simulação de Dinâmica Molecular , Cinética , Humanos , Ligação Proteica , Desenho de Fármacos , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismoRESUMO
BACKGROUND: The high incidence of nonunion in osteoporosis vertebral compression fractures (OVCFs) among the elderly population is a significant concern. But the hypothesis about etiopathogenesis of the intravertebral cleft (IVC) is not convincing. This study aims to investigate the association between spinopelvic parameters and IVC. METHODS: Patients with single segment IVC or healed vertebral compression fracture (HVCF) were retrospectively recruited for the study. Patients with IVC were assigned to the IVC group, the others were assigned to the HVCF group. We estimated whether IVC or HVCF locates the vertebra inflection point on lumbar lateral radiography. Distance between the sagittal line passing through the anterosuperior corner of S1and the center of the vertebra of healed fracture or with IVC (DSVA) and sacral slope (SS) were measured on lumbar lateral plain films. Intergroup spinopelvic parameters were analyzed. analysis to identify independent variables associated with IVC incidence. The receiver operating characteristics (ROC) curve was generated to identify the optimal cut-off point for statistically significant variables. RESULTS: Sixty-five patients were included in the study. Thirty patients (mean age: 74 ± 7.16 years) had single-level IVC, and 35 patients (mean age: 67.71 ± 7.30 years) had single-level HVCF. Age, body mass index (BMI), and DSVA were statistically different between the groups (all P < 0.05). The occurrence of IVC was related to the DSVA in the multivariate logistic regression analysis (OR = 0.73, P < 0.05). CONCLUSIONS: According to the results of this study, large DSVA was a risk factor for IVC formation in patients with OVCFs. Patients with global spinal malalignment should be actively observed during conservative treatment.
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Fraturas por Compressão , Osteoporose , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Idoso , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Fraturas por Compressão/complicações , Fraturas da Coluna Vertebral/complicações , Estudos Retrospectivos , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/complicações , Osteoporose/complicações , Osteoporose/diagnóstico por imagemRESUMO
This study was completed to evaluate the relationship between tumor length and the prognosis of patients with pathological stage IA-IC esophageal adenocarcinoma (EAC). Patients were identified from the Surveillance, Epidemiology, and End Results Program database (United States, 2006-2015). X-tile software and ROC analysis were mainly used to explore the best threshold of tumor length for dividing patients into different groups, and then propensity score matching (PSM) was used to balance other variables between groups. The primary outcome assessed was overall survival (OS). A total of 762 patients were identified, and 500 patients were left after PSM. Twenty millimeters were used as the threshold of tumor length. Patients with longer tumor lengths showed worse OS (median: 93 vs. 128 months; P = 0.006). Multivariable Cox regression analysis showed that longer tumor length was an independent risk factor (hazard ratio 1.512, 95% confidence interval, 1.158-1.974, P = 0.002). Tumor length has an impact on patients with pathological stage IA-IC EAC who undergo surgery alone. The prognostic value of the pathological stage group may be improved after combining it with tumor length and age.
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Adenocarcinoma , Neoplasias Esofágicas , Humanos , Estados Unidos , Prognóstico , Estadiamento de Neoplasias , Adenocarcinoma/patologia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Pontuação de PropensãoRESUMO
BACKGROUND: Chemotherapy and chemoradiation have become essential adjuncts to improve the survival of patients with resectable esophageal squamous cell carcinoma (ESCC) in the perioperative period. Although preoperative treatment plus surgery is commonly used, controversy remains regarding the optimal treatment strategy for patients with locally advanced ESCC. METHODS: A retrospective review of clinical stage II and III ESCC patients who underwent esophagectomy at Henan Cancer Hospital between October 2014 and October 2017 was performed. The patients were divided into a neoadjuvant chemotherapy (NAC) group and an adjuvant chemotherapy (AC) group. Propensity score matching (PSM) was used to exclude confounders. Survival was estimated using KaplanâMeier analysis and compared by the log-rank test. The Cox proportional hazards regression model was used for both the univariate and multivariate analyses. RESULTS: A total of 684 patients were enrolled, including 365 (53.4%) patients in the NAC group. After PSM, 294 pairs of patients were left. NAC prolonged the OS (not reached versus 57.3 months, P = 0.002) and DFS (57.2 vs. 36.4 months, P = 0.010) and decreased the total rate of recurrence (50.1% vs. 59.2%, P = 0.025) and local recurrence (27.9% vs. 36.7%, P = 0.022) compared with AC. The multivariable analyses showed that NAC plus surgery modality was an independent predictor for improved OS (HR: 0.582, 95% CI: 0.467-0.786, P = 0.001). CONCLUSION: NAC plus surgery prolonged OS and DFS, and significantly decreased the total rate of recurrence compared with surgery plus AC in patients with clinical stage II and III ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Terapia Neoadjuvante , Quimioterapia Adjuvante , Quimiorradioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Esofagectomia , Estudos Retrospectivos , Estadiamento de NeoplasiasRESUMO
The bacteria that invade the periapical tissue of teeth can directly damage tissue cells such as periapical fibroblasts, leading to an inflammatory response in the periapical tissue and ultimately resulting in bone destruction. We investigated the role of fibroblast activation protein α (FAPα) and integrin α5 (ITGA5) in periapical bone destruction. This study found that FAPα and ITGA5 were highly expressed in human tissues from patients with chronic apical periodontitis. Osteoclast differentiation decreased when FAPα or ITGA5 was silenced and inhibited. The results of protein molecular docking showed that FAPα had good binding affinity to ITGA5, and its free energy was -14.5â¯kcal/mol. Immunofluorescence staining and co-immunoprecipitation showed that FAPα and ITGA5 formed protein complexes in the inflammatory microenvironment. In conclusion, this study proved that FAPα and ITGA5 participate in the regulation of osteoclast differentiation by forming protein complexes in the inflammatory microenvironment, which then regulates the occurrence and development of chronic apical periodontitis.