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BACKGROUND: 13-15% of breast cancer/BC patients diagnosed as pathological complete response/pCR after neoadjuvant systemic therapy/NST suffer from recurrence. This study aims to estimate the rationality of organoid forming potential/OFP for more accurate evaluation of NST efficacy. METHODS: OFPs of post-NST residual disease/RD were checked and compared with clinical approaches to estimate the recurrence risk. The phenotypes of organoids were classified via HE staining and ER, PR, HER2, Ki67 and CD133 immuno-labeling. The active growing organoids were subjected to drug sensitivity tests. RESULTS: Of 62 post-NST BC specimens, 24 were classified as OFP-I with long-term active organoid growth, 19 as OFP-II with stable organoid growth within 3 weeks, and 19 as OFP-III without organoid formation. Residual tumors were overall correlated with OFP grades (P < 0.001), while 3 of the 18 patients (16.67%) pathologically diagnosed as tumor-free (ypT0N0M0) showed tumor derived-organoid formation. The disease-free survival/DFS of OFP-I cases was worse than other two groups (Log-rank P < 0.05). Organoids of OFP-I/-II groups well maintained the biological features of their parental tumors and were resistant to the drugs used in NST. CONCLUSIONS: The OFP would be a complementary parameter to improve the evaluation accuracy of NST efficacy of breast cancers.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Terapia Neoadjuvante , Intervalo Livre de Doença , Receptor ErbB-2 , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
The current standard second-line treatment is immune checkpoint inhibitors monotherapy for nonsmall cell lung cancer (NSCLC) patients. The objective of this phase 2 study was to evaluate the efficacy and safety of nivolumab plus docetaxel compared with nivolumab monotherapy for second-line therapy in immunotherapy-naive patients with advanced NSCLC. Progression-free survival (PFS) was the primary endpoint of this phase 2 study. Patients were randomized to receive nivolumab plus docetaxel or nivolumab monotherapy. From July 2019 to June 2022, a total of 22 patients were recruited, with significantly longer median PFS observed in the nivolumab plus docetaxel group (4.0 months) compared to the nivolumab group (2.0 months), P â =â 0.0019. The study was closed in June 2022 due to slow recruitment. The objective response rate was 10.0% [95% confidence interval (CI), 0-28.6] in the nivolumab group and 25% (95% CI, 0.5-49.5) in the nivolumab + docetaxel group ( P â =â 0.346). Disease control was significantly higher in the nivolumab plus docetaxel arm (40.0% versus 83.3%, P â =â 0.035). There was also an improvement in overall survival (OS) in the nivolumab + docetaxel arm, but this was not statistically significant (10.0 months versus 7.2 months, P â =â 0.129). The addition of docetaxel to nivolumab was well-tolerated, with adverse events more common in the combination group. Despite the small sample size, the results suggest that the addition of docetaxel to nivolumab may be a promising treatment option for NSCLC patients progressing on platinum-based chemotherapy, with trends towards improved OS observed.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Docetaxel/uso terapêutico , Nivolumabe/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Taxoides/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Photocuring 3D printing of hydrogels, with sophisticated, delicate structures and biocompatibility, attracts significant attention by researchers and possesses promising application in the fields of tissue engineering and flexible devices. After years of development, photocuring 3D printing technologies and hydrogel inks make great progress. Herein, the techniques of photocuring 3D printing of hydrogels, including direct ink writing (DIW), stereolithography (SLA), digital light processing (DLP), continuous liquid interface production (CLIP), volumetric additive manufacturing (VAM), and two photon polymerization (TPP) are reviewed. Further, the raw materials for hydrogel inks (photocurable polymers, monomers, photoinitiators, and additives) and applications in tissue engineering and flexible devices are also reviewed. At last, the current challenges and future perspectives of photocuring 3D printing of hydrogels are discussed.
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Hidrogéis , Engenharia Tecidual , Engenharia Tecidual/métodos , Hidrogéis/química , Polímeros , Impressão Tridimensional , EstereolitografiaRESUMO
BACKGROUND: Type A aortic dissection is a fatal disease. However, the role of endoplasmic reticulum stress-related genes (ERSRGs) in type A aortic dissection has not yet been fully clarified. METHODS: Differentially expressed genes in the aorta of type A aortic dissection patients were analyzed based on the GSE52093 database. The ERSRGs were downloaded from the GeneCards website. Functional enrichment analysis and protein-protein interaction analysis were performed on the acquired differentially expressed ERSRGs. The mRNA expression of the 5 top key differentially expressed ERSRGs was further explored in GSE153434 and clinical samples. Immune infiltration correlation analysis was performed on the validated key genes. Finally, we constructed regulatory networks of transcription factors, miRNAs, and chemicals. RESULTS: Twelve differentially expressed ERSRGs were identified, of which 8 genes were downregulated and 4 genes were upregulated. GeneMANIA was adopted to analyze these genes and their interacting proteins, and the results showed that the main function was calcium ion transport. Four key genes, ACTC1, CASQ2, SPP1, and REEP1, were validated in GSE153434 and clinical samples. The area under the ROC curve values for ACTC1, CASQ2, SPP1, and REEP1 were 0.92, 0.96, 0.89, and 1.00, respectively. ACTC1 and REEP1 correlated with multiple immune cells. Many transcription factors, microRNAs, and chemicals were identified with the potential to regulate these 4 key genes. CONCLUSION: In this study, we identified 12 differentially expressed ERSRGs by analyzing the Gene Expression Omnibus database. Four key genes may influence the development of type A aortic dissection by regulating endoplasmic reticulum stress. These results expand our understanding of type A aortic dissection, and the 4 key genes are expected to be diagnostic markers and potential therapeutic targets.
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With the fast economic development and accelerating urbanization, more and more skyscrapers made entirely of concrete and glass are being constructed. To keep a comfortable indoor environment, massive energy for air conditioning or heating appliances is consumed. A huge amount of heat (>30%) is gained or released through glass windows. Using smart windows with the capability to modulate light is an effective way to reduce building energy consumption. Thermochromic hydrogel is one of the potential smart window materials due to its excellent thermal response, high radiation-blocking efficiency, cost-effectiveness, biocompatibility, and good uniformity. In this work, polyhydroxypropyl acrylate (PHPA) hydrogels with controllable lower critical solution temperature (LCST) were prepared by photopolymerization. The transition temperature and transition rate under "static transition" conditions were investigated. Unlike "static" conditions in which the transition temperature was not affected by the initial and final temperature and heating/cooling ramp, the transition temperature varied with the rate of temperature change under dynamic conditions. The "dynamic" transition temperature of the PHPA hydrogel gradually increased with the increase of the heating rate. It was the result of the movement of the molecular chains lagging behind the temperature change when the temperature change was too fast. The results of the solar irradiation experiment by filling PHPA hydrogels into double glazing windows showed that the indoor temperature was about 15 °C lower than that of ordinary glass windows, indicating that it can significantly reduce the energy consumption of air conditioning. In addition, a wide range of adjustable transition temperatures and fast optical response make PHPA hydrogels potentially applicable to smart windows.
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Environmental bisphenols (BPs) pose a global threat to human health because of their extensive use as additives in plastic products. BP residues are increasing in various environmental media (i.e., water, soil, and indoor dust) and biological and human samples (i.e., serum and brain). Both epidemiological and animal studies have determined an association between exposure to BPs and an increased risk of neurodegenerative diseases (e.g., Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis), including cognitive abnormalities and behavioral disturbances. Hence, understanding the biological responses to different BPs is essential for prevention, and treatment. This study provides an overview of the underlying pathogenic molecular mechanisms as a valuable basis for understanding neurodegenerative disease responses to BPs, including accumulation of misfolded proteins, reduction of tyrosine hydroxylase and dopamine, abnormal hormone signaling, neuronal death, oxidative stress, calcium homeostasis, and inflammation. These findings provide new insights into the neurotoxic potential of BPs and ultimately contribute to a comprehensive health risk evaluation.
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Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Parkinson , Animais , Humanos , Doenças Neurodegenerativas/induzido quimicamente , Doença de Parkinson/etiologia , Doença de Parkinson/metabolismo , Encéfalo/metabolismo , Estresse Oxidativo/fisiologiaRESUMO
Management of diabetic wounds presents a global health challenge due to elevated levels of ROS in the wound microenvironment, persistent dysregulation of inflammation modulation, and limitations in commercially available dressings. Addressing this issue, we have developed a pH-responsive and glucose-sensitive multifunctional hydrogel dressing that dynamically responds to the wound microenvironment and enables on-demand drug release. The dressing incorporates a matrix material based on aminophenylboronic acid-functionalized alginate and a polyhydroxy polymer, alongside an enhancer phase consisting of self-assembled metal-phenol coordination nanospheres formed by tannic acid and iron ions. Using the dynamic borate ester bonds and catechol-metal ion coordination bonds, the dressing exhibits remarkable shape adaptability, self-healing capability, tissue adhesiveness, antioxidant activity, and photothermal responsiveness, without additional curatives or crosslinking agents. As a wound dressing, it elicits macrophage polarization towards an anti-inflammatory phenotype while maintaining long-lasting antimicrobial effects. In a diabetic mouse model of full-thickness wound infections, it effectively mitigated inflammation and vascular damage, significantly expediting the wound healing process with a commendable 97.7% wound closure rate. This work provides a new direction for developing multifunctional smart hydrogel dressings that can accelerate diabetic wound healing for human health.
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Diabetes Mellitus , Nanosferas , Polifenóis , Humanos , Animais , Camundongos , Fenóis , Metais , Alginatos , Inflamação , Hidrogéis/farmacologiaRESUMO
Excessive heavy metals in soils can threaten food security and soil health. New practical technology is urgently needed to remediate cadmium (Cd) contaminated paddies in many parts of the world. Chinese milk vetch (M), rice straw (R), and soil amendments can reduce Cd activity in soil; however, the mechanism underlying this reduction is not well understood. This study explored the impact of co-incorporation of milk vetch, rice straw, and either lime (L), sesbania biochar (B), or sepiolite on soil Cd bioavailability through field experiments. The results indicated that the rice grain Cd concentrations in soil treated with milk vetch + rice straw + fertilizer (MRF, 16.6 %), milk vetch + rice straw + fertilizer + sesbania biochar (MRFB, 50.1 %), and milk vetch + rice straw + fertilizer + lime (MRFL, 48.3 %) were significantly lower than those in soil treated with fertilizer (F). The acid-soluble Cd concentrations influenced rice grain Cd uptake and were 33.9 % and 47.5 % lower for the MRFB and MRFL treatments, respectively, than for F alone. A decrease in acid-soluble Cd (AciCd) was accompanied by a decrease in Eh and increases in pH, Fe2+, cation exchange capacity, and dissolved organic carbon. The MRFB treatment promoted iron plaque (IP) formation on the rice root surface. The relative abundances of Desulfobacterota and Verrucomicrobiota were higher for the MRFB treatment than for the other treatments. A partial least squares path model confirmed that Aci-Cd and low-crystalline IP (IP-Feh) influenced the rice grain Cd concentration.
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Agricultura , Cádmio , Fertilizantes , Oryza , Poluentes do Solo , Solo , Poluentes do Solo/análise , Cádmio/análise , Solo/química , Agricultura/métodos , Microbiologia do Solo , Disponibilidade Biológica , Recuperação e Remediação Ambiental/métodos , Óxidos , Carvão VegetalRESUMO
BACKGROUND: Currently, the diagnosis of postneurosurgical intracranial infection is mainly dependent on cerebrospinal fluid (CSF) bacterial culture, which has the disadvantages of being time-consuming, having a low detection rate, and being easily affected by other factors. These disadvantages bring some difficulties to early diagnosis. Therefore, it is very important to construct a nomogram model to predict the risk of infection and provide a basis for early diagnosis and treatment. METHODS: This retrospective study analyzed postneurosurgical patient data from the Fourth Affiliated Hospital of Harbin Medical University between January 2019 and September 2023. The patients were randomly assigned in an 8:2 ratio into the training cohort and the internal validation cohort. In the training cohort, initial screening of relevant indices was conducted via univariate analysis. Subsequently, the least absolute shrinkage and selection operator logistic regression identified significant potential risk factors for inclusion in the nomogram model. The model's discriminative ability was assessed using the area under the receiver operating characteristic curve, and its calibration was evaluated through calibration plots. The clinical utility of the model was determined using decision curve analysis and further validated by the internal validation cohort. RESULTS: Multivariate logistic regression analysis of the training cohort identified 7 independent risk factors for postoperative intracranial infection: duration of postoperative external drainage (odds ratio [OR] 1.19, P = 0.005), continued fever (OR 2.11, P = 0.036), CSF turbidity (OR 2.73, P = 0.014), CSF pressure (OR 1.01, P = 0.018), CSF total protein level (OR 1.26, P = 0.026), CSF glucose concentration (OR 0.74, P = 0.029), and postoperative serum albumin level (OR 0.84, P < 0.001). Using these variables to construct the final model. The area under the receiver operating characteristic curve value of the model was 0.868 in the training cohort and 0.900 in the internal validation cohort. Calibration and the decision curve analysis indicated high accuracy and clinical benefit of the nomogram, findings that were corroborated in the validation cohort. CONCLUSIONS: This study successfully developed a novel nomogram for predicting postoperative intracranial infection, demonstrating excellent predictive performance. It offers a pragmatic tool for the early diagnosis of intracranial infection.
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Effective utilization of organic resources to activate residual phosphorus (P) in soil and enhance its availability is crucial for mitigating P resource scarcity and assessing the sustainable use of P in agricultural practices. However, the mechanisms through which organic resources affect soil P conversion via microorganisms and functional genes remain unknown, particularly in long-term organic-inorganic agricultural systems. In this study, we examined the impact of combined organic-inorganic fertilizer application on P availability, carbon (C) and P cycling genes, and microbial communities (bacterial and fungal) in reddish paddy soil based on a 42-year field experiment. The results indicated that long-term straw returning and pig manure application significantly augmented soil organic carbon (SOC), Olsen-P, microbial biomass carbon (MBC), microbial biomass phosphorus (MBP), enzyme-P, and CaCl2-P levels in paddy soils. Furthermore, these practices increased the abundance of soil C degradation genes, reduced the abundance of soil P cycling genes, and altered microbial community structure and network complexity. Notably, Module #3 ecological clusters in the fungal ecological co-occurrence network were significantly correlated with P cycling genes. Finally, our study demonstrated that long-term straw returning and pig manure application in paddy fields facilitated two robust and contrasting predictive relationships between C degradation (negative relationship) and P cycling (positive relationship) genes, respectively, and enzyme-P and HCl-P changes to improve soil P availability. This study can enhance our understanding of the role of soil microbial communities and functional genes in mediating P transformation to decipher the enhancement in P application efficiency driven by organic resources in reddish paddy soils.
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Agricultura , Esterco , Fósforo , Microbiologia do Solo , Solo , Fósforo/análise , China , Solo/química , Animais , Agricultura/métodos , Suínos , Fertilizantes , Microbiota , Oryza , Carbono/análiseRESUMO
Hydrogel tubes made of sodium alginate (SA) have potential applications in drug delivery, soft robots, biomimetic blood vessels, tissue stents, and other fields. However, the continuous preparation of hollow SA hydrogel tubes with good stability and size control remains a huge challenge for chemists, material scientists, and medical practitioners. Inspired by the plant apical growth strategy, a new method named soft cap-guided growth was proposed to produce SA hydrogel tubes. Due to the introduction of inert low gravity substances, such as air and heptane, into the extrusion needle in front of calcium chloride solution to form a soft cap, the SA hydrogel tubes with controllable sizes were fabricated rapidly and continuously without using a template through a negative gravitropism mechanism. The SA hydrogel tubes had good tensile strength, high burst pressure, and good cell compatibility. In addition, hydrogel tubes with complex patterns were conveniently created by controlling the motion path of a soft cap, such as a rotating SA bath or magnetic force. Our research provided a simple innovative technique to steer the growth of hydrogel tubes, which made it possible to mass produce hydrogel tubes with controllable sizes and programmable patterns.
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Alginatos , Hidrogéis , Alginatos/química , Hidrogéis/química , Resistência à TraçãoRESUMO
Bacterial invasion hinders the healing process of wound, leading to the formation of chronic infected wound; meanwhile, the misuse of antibiotics has resulted in the emergence of numerous drug-resistant bacteria. The application of conventional antimicrobial methods and wound treatment techniques is not appropriate for wound dressings. In this paper, quaternized poly(vinyl alcohol) (QPVA) and pomegranate-like copper uniformly doped polydopamine nanoparticles (PDA@Cu) were introduced into a gelatin-oxidized carboxymethyl cellulose system to form a multicomponent synergistic antibacterial hydrogel (GOQ3P3). Polydopamine improves the biocompatibility and prevents the detachment of Cu nanoparticles. It can achieve synergistic antibacterial effects through quaternary ammonium salt-inorganic nanoparticle photothermal treatment under 808 nm near-infrared (NIR) irradiation. It exhibits highly efficient and rapid bactericidal properties against Escherichia coli, Staphylococcus aureus, and MRSA (methicillin-resistant Staphylococcus aureus) with an antibacterial rate close to 100%. The gel scaffold composed of macromolecules gives the hydrogel excellent mechanical properties, adhesive capabilities, self-healing characteristics, biocompatibility, and pH degradation and promotes cell adhesion and migration. In a full-thickness wound healing model infected with MRSA, GOQ3P3 controls inflammatory responses, accelerates collagen deposition, promotes angiogenesis, and enhances wound closure in the wound healing cascade reaction. This study provides a feasible strategy for constructing dressings targeting chronic infection wounds caused by drug-resistant bacteria.
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Antibacterianos , Materiais Biocompatíveis , Carboximetilcelulose Sódica , Escherichia coli , Gelatina , Hidrogéis , Teste de Materiais , Testes de Sensibilidade Microbiana , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/química , Gelatina/química , Cicatrização/efeitos dos fármacos , Carboximetilcelulose Sódica/química , Carboximetilcelulose Sódica/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Escherichia coli/efeitos dos fármacos , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Camundongos , Staphylococcus aureus/efeitos dos fármacos , Tamanho da Partícula , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Polímeros/química , Polímeros/farmacologia , Indóis/química , Indóis/farmacologia , Cobre/química , Cobre/farmacologia , HumanosRESUMO
The epidermis of a deep burn wound is entirely absent and the dermal tissue sustains significant damage, accompanied by a substantial amount of tissue exudate. Due to the excessively humid environment, the formation of a scab on the wound becomes challenging, leaving it highly vulnerable to external bacterial invasion. In this work, a core-shell dual-drug-loaded nanofiber dressing was prepared by electrospinning technology for the synergistic treatment of a deep burn. The shell layer consists of polycaprolactone and chitosan encapsulating asiaticoside, with the core layer comprising the clathrate of 2-hydroxypropyl-ß-cyclodextrin and curcumin. Upon application to the wound, the dual-drug-loaded nanofiber dressing exhibited rapid release of asiaticoside, stimulating collagen deposition and promoting tissue repair. The core-shell structure and clathrate configuration ensured sustained release of curcumin, providing antibacterial and anti-inflammatory functions for the wound. The mechanical strength, broad-spectrum antibacterial ability, cell proliferation, and adhesion ability of the nanofiber dressing showed its potential as a medical dressing. This dressing also exhibited excellent wound healing promoting effects in the SD rat burn model. This paper provides a strategy for burn wound healing.
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Queimaduras , Curcumina , Nanofibras , Triterpenos , Ratos , Animais , Nanofibras/uso terapêutico , Nanofibras/química , Curcumina/farmacologia , Curcumina/uso terapêutico , Ratos Sprague-Dawley , Queimaduras/tratamento farmacológico , Antibacterianos/uso terapêutico , BandagensRESUMO
The modulus of traditional biomedical hydrogels increases exponentially meditated by dehydration-stiffing mechanism, which leads to the failure of interface matching between hydrogels and soft tissue wounds. It is found in the study that the dual-solvent gels exhibit dehydration-toughening mechanism with the slowly increasing modulus that are always match the soft tissue wounds. Therefore, dual-solvent glycerol hydrogels (GCFen-gly DGHs) are prepared with hydrophobically modified catechol chitosan (hmCSC) and gelatin based on the supramolecular interactions. GCFen-gly DGHs exhibit excellent water retention capacity with a total solvent content exceeding 80%, permanent skin-like modulus within a range of 0.45 to 4.13 kPa, and stable photothermal antibacterial abilities against S, aureus, E. coli, as well as MRSA. Infectious full-thickness rat skin defect model and tissue section analysis indicate that GCFen-gly DGHs are able to accelerate infectious wound healing by alleviating the inflammatory response, promoting granulation tissue growth, re-epithelialization, collagen deposition, and vascular regeneration. As a result, GCFen-gly DGHs is expected to become the next-generation biological gel materials for infectious wound treatment.
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Antibacterianos , Quitosana , Hidrogéis , Cicatrização , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Ratos , Cicatrização/efeitos dos fármacos , Quitosana/química , Antibacterianos/química , Antibacterianos/farmacologia , Ratos Sprague-Dawley , Staphylococcus aureus/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Gelatina/química , Masculino , Glicerol/química , Glicerol/farmacologia , Pele/efeitos dos fármacos , ViscosidadeRESUMO
Endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux-en-Y gastrectomy and an intact major duodenal papilla is challenging and difficult, with unsatisfactory outcomes using various endoscopes. Limited data are available regarding the outcomes of ERCP using a pediatric colonoscope in such patients. To evaluate the efficacy of a pediatric colonoscope in patients with Roux-en-Y gastrectomy and an major duodenal intact papilla, 93 consecutive patients with Roux-en-Y gastrectomy and an intact major duodenal papilla who underwent ERCP using a pediatric colonoscope at the Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, (Nanjing, China) between January 2018 and December 2022 were retrospectively reviewed. Following the failure of bile duct cannulation, a double-guidewire or precut technique was utilized for advanced cannulation. Interventions were performed using standard ERCP therapeutic accessories. The results indicated that distal gastrectomy with Roux-en-Y reconstruction was performed in 38 out of 93 patients, while 55 patients underwent total gastrectomy with Roux-en-Y reconstruction. The success rates associated with endoscope insertion, endoscopic cannulation and therapeutic ERCP were 88.17% (82/93), 85.37% (70/82) and 95.71% (67/70), respectively, while the clinical intervention success and complication rates were 72.04% (67/93) and 7.53% (7/93), respectively. The endoscope insertion time was 40.78±10.04 min, and the ERCP procedure time was 88.55±16.38 min. Student's t-test showed that the endoscope insertion time and the ERCP procedure time in patients undergoing distal gastrectomy were longer than those in patients undergoing total gastrectomy (P<0.05). Binary logistic regression analysis showed that age and number of previous abdominal surgeries were independent risk factors associated with endoscope insertion failure. In conclusion, the present study demonstrated that the use of a pediatric colonoscope is efficacious and safe for patients with Roux-en-Y gastrectomy and an intact major duodenal papilla undergoing ERCP.
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Cancer-associated fibroblasts (CAFs) assist in breast cancer (BRCA) invasion and immune resistance by overproduction of extracellular matrix (ECM). Herein, we develop FPC@S, a photodynamic immunomodulator that targets the ECM, to improve the photodynamic immunotherapy for fibrotic BRCA. FPC@S combines a tumor ECM-targeting peptide, a photosensitizer (protoporphyrin IX) and an antifibrotic drug (SIS3). After anchoring to the ECM, FPC@S causes ECM remodeling and BRCA cell death by generating reactive oxygen species (ROS) in situ. Interestingly, the ROS-mediated ECM remodeling can normalize the tumor blood vessel to improve hypoxia and in turn facilitate more ROS production. Besides, upon the acidic tumor microenvironment, FPC@S will release SIS3 for reprograming CAFs to reduce their activity but not kill them, thus inhibiting fibrosis while preventing BRCA metastasis. The natural physical barrier formed by the dense ECM is consequently eliminated in fibrotic BRCA, allowing the drugs and immune cells to penetrate deep into tumors and have better efficacy. Furthermore, FPC@S can stimulate the immune system and effectively suppress primary, distant and metastatic tumors by combining with immune checkpoint blockade therapy. This study provides different insights for the development of fibrotic tumor targeted delivery systems and exploration of synergistic immunotherapeutic mechanisms against aggressive BRCA.
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Neoplasias da Mama , Fibroblastos Associados a Câncer , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Matriz Extracelular/metabolismo , Imunoterapia , Fibrose , Microambiente TumoralRESUMO
Purpose: The purpose of this study is to investigate the efficacy and safety of immune checkpoint inhibitors (ICIs) or plus with chemotherapy in older patients. Methods: We enrolled 110 older patients with non-small cell lung cancer (NSCLC ≥75 years) who received either chemotherapy alone (chemo), ICI plus chemotherapy (ICI + chemo), or ICI alone and ICI plus other therapies, which included anti-angiogenesis drugs or other novel ICI (ICIs). Patient characteristics, treatment response, survival, and toxicity were evaluated. Results: In total population, the ICIs group has the highest disease control rate (DCR 75%). There were no significant differences in progression-free survival (PFS) and overall survival (OS) among older patients between ICI + chemo and ICIs groups (PFS: 5.3 months vs. 5.5 months, p = 0.70, OS: 10.7 months vs. 20.3 months, p = 0.995). Meanwhile, we observed ICIs had a longer PFS and OS than chemo group (PFS: 3.9 months vs. 5.5 months, p = 0.01, OS: 10.9 months vs. 20.3 months, p = 0.05). Subgroup analysis showed that patients with programmed death ligand-1 (PD-L1) ≥ 1% had a distinct longer trend toward OS in ICIs group compared to ICI + chemo group (22.4 months vs. 10.7 months, p = 0.605), even though there was no significant difference. In terms of safety, ICIs was more tolerable and had a lower discontinuation rate than ICI + chemo group. Conclusion: In the real world, ICI + chemo is more likely to be discontinued due to adverse effects and does not significantly improve patient survival compared with ICIs treatment in total population and subgroup. Therefore, ICI alone or ICIs plus other therapies, such as anti-angiogenesis drugs or other novel ICI (ICIs) could be recommended for older cases with PD-L1 positive NSCLC.
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Breeding biology lies at the core of life history research on birds, and it provides important information for avian conservation. We discovered one nest of the Indian Blue Robin (Larvivora brunnea) on 28 May 2021, at the Laojun mountains in Lijiang, northwestern Yunnan, China. Field observation was combined with the use of a GoPro camera for video shooting to quantitatively study the incubation and brooding behavior. We also conducted measurements of the eggs and nestlings on site and inspected the nesting materials used. A bowl-shaped nest with four eggs was located at 2830 m in the evergreen deciduous broad-leaved forest. All eggs were successfully incubated and two nestlings fledged on 22 June 2021, resulting in a total breeding success of 50%. Only the female bird incubated the eggs and brooded the nestlings. The incubation period was at least 13 days and the nestling period was 13 days. As incubation progressed, the incubation bout duration decreased. During the incubation period, the nesting time of the female bird shows a declining trend as incubation progresses. Both parents participated in feeding the nestling, and the frequency of parental supply increased with the maturity of the nestling.