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To achieve food security in a contaminated agricultural land, the remediation areas usually need more samples to obtain accurate contamination information and implement appropriate measures. In this study, we propose an optimal encryption sampling design to instead of the detailed survey, which is determined by the variation of heavy metals and the technology capability of remediation, to guide soil sampling for accurately remediation in the potential remediation-effective areas (PRA). The coefficient of screening variation threshold (CSVT), considering spatial variation, technology capacity and acceptable error of sampling, together with the spatial cyclic statistics method of neighbourhood analysis, is introduced to identify and delineate the PRA. Both of the hypothetical analysis and application case studies are conducted to illustrate the advantages and disadvantages of the optimization. The results show that, compared with the detailed survey, the optimal design shows a lower overall accuracy due to its sparsely sampling at the clean area, but it exhibits a similar effect of accurately prediction in boundary delineation and further classification in the PRA in both simulation and application studies. This work provides an effective method for subsequent accurate remediation at the investigation stage and valuable insights into application combination of technology capacity and contaminated agricultural land investigation.
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Agricultura , Monitoramento Ambiental , Recuperação e Remediação Ambiental , Poluentes do Solo , Poluentes do Solo/análise , Recuperação e Remediação Ambiental/métodos , Monitoramento Ambiental/métodos , Solo/química , Metais Pesados/análiseRESUMO
The dorsal root ganglion (DRG) is the primary neuron responsible for transmitting peripheral pain signals to the central nervous system and plays a crucial role in pain transduction. Modulation of DRG excitability is considered a viable approach for pain management. Neuronal excitability is intricately linked to the ion channels on the neurons. The small and medium-sized DRG neurons are chiefly engaged in pain conduction and have high levels of TTX-S sodium channels, with Nav1.7 accounting for approximately 80% of the current. Voltage-gated sodium channel (VGSC or Nav) blockers are vital targets for the management of central nervous system diseases, particularly chronic pain. VGSCs play a key role in controlling cellular excitability. Clinical research has shown that Nav1.7 plays a crucial role in pain sensation, and there is strong genetic evidence linking Nav1.7 and its encoding gene SCN9A gene to painful disorders in humans. Many studies have shown that Nav1.7 plays an important role in pain management. The role of Nav1.7 in pain signaling pathways makes it an attractive target for the potential development of new pain drugs. Meanwhile, understanding the architecture of Nav1.7 may help to develop the next generation of painkillers. This review provides updates on the recently reported molecular inhibitors targeting the Nav1.7 pathway, summarizes their structure-activity relationships (SARs), and discusses their therapeutic effects on painful diseases. Pharmaceutical chemists are working to improve the therapeutic index of Nav1.7 inhibitors, achieve better analgesic effects, and reduce side effects. We hope that this review will contribute to the development of novel Nav1.7 inhibitors as potential drugs.
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Canal de Sódio Disparado por Voltagem NAV1.7 , Bloqueadores do Canal de Sódio Disparado por Voltagem , Humanos , Canal de Sódio Disparado por Voltagem NAV1.7/metabolismo , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/química , Bloqueadores do Canal de Sódio Disparado por Voltagem/uso terapêutico , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/uso terapêutico , Dor do Câncer/tratamento farmacológico , Dor do Câncer/metabolismo , Analgésicos/química , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Relação Estrutura-Atividade , Manejo da Dor/métodos , Estrutura Molecular , Neoplasias/tratamento farmacológico , Bloqueadores dos Canais de Sódio/farmacologia , Bloqueadores dos Canais de Sódio/química , Bloqueadores dos Canais de Sódio/uso terapêuticoRESUMO
Background: All available methods for reconstruction after proximal humerus tumor resection have disadvantages, and the optimal reconstruction method remains uncertain. This study aimed to design a novel 3D-printed glenohumeral fusion prosthesis and verify its feasibility and safety using biomechanical methods. Methods: We verified the feasibility and safety of the 3D-printed glenohumeral fusion prosthesis by finite element analysis and biomechanical experimentation. In the finite element analysis, three reconstruction methods were used, and displacement and von Mises stress were observed; on this basis, in the biomechanical experiment, models constructed with sawbones were classified into two groups. The forceâdisplacement curve of the 3D-printed prosthesis was evaluated. Results: In terms of displacement, the finite element analysis showed greater overall stability for the novel prosthesis than traditional glenohumeral joint arthrodesis. There was no obvious stress concentration in the internal part of the 3D-printed glenohumeral fusion prosthesis; the stable structure bore most of the stress, and the force was well distributed. Adding lateral plate fixation improved the stability and mechanical properties of the prosthesis. Furthermore, the biomechanical results showed that without lateral plate fixation, the total displacement of the prosthesis doubled; adding lateral plate fixation could reduce and disperse strain on the glenoid. Conclusion: The design of the 3D-printed glenohumeral fusion prosthesis was rational, and its stability and mechanical properties were better than those of traditional glenohumeral joint arthrodesis. Biomechanical verification demonstrated the feasibility and safety of this prosthesis, indicating its potential for proximal humerus bone defect reconstruction after tumor resection.
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In this study, a microcosm experiment was conducted to investigate the effects of Na2S2O8 preoxidation combined with biostimulation on petroleum-contaminated soil remediation. The response of microbial community during this process was explored using BIOLOG ECO microplate carbon utilization method and 16â¯s rDNA high-throughput sequencing. The results showed that use of 10â¯mg/g Na2S2O8 removed 19.8â¯% of the petroleum hydrocarbons, reduced soil biotoxicity and did not affect soil microbial activity compared to other concentrations. Therefore, sodium persulfate of ca. 10â¯mg/g was used to oxidize petroleum in soil before the biostimulation experiment with organic and inorganic fertilizers. Our finding showed that the content of total petroleum hydrocarbons (TPHs) in soil was reduced by 43.3â¯% in inorganic fertilizer treatment after 60 days. The results of BIOLOG ECO microplate carbon utilization analysis and 16â¯S rDNA high-throughput sequencing further confirmed that biostimulation quickly restored the microbial activities in oxidant treated soil. The main marker bacteria in chemical oxidation combined with biostimulation remediation were Arthrobacter and Paenarthrobacter, and their relative abundances were both significantly negatively correlated with the content of petroleum hydrocarbons in soil.
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Biodegradação Ambiental , Oxirredução , Petróleo , Microbiologia do Solo , Poluentes do Solo , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Fertilizantes/análise , Sulfatos , Hidrocarbonetos , Compostos de Sódio/toxicidade , Solo/química , Arthrobacter , Recuperação e Remediação Ambiental/métodos , Bactérias/efeitos dos fármacos , Bactérias/genéticaRESUMO
The structure of liquid water is primarily composed of three-dimensional networks of water clusters formed by hydrogen bonds, and dissolved oxygen is one of the most important indicators for assessing water quality. In this work, distilled water with different concentration of dissolved oxygen were prepared, and a clear negative correlation between the size of water clusters and dissolved oxygen concentration was observed. Besides, a phenomenon of rapid absorption and release of oxygen at the water interfaces was unveiled, suggesting that oxygen molecules predominantly exist at the interfaces of water clusters. Oxygen molecules can move rapidly through the interfaces among water clusters, allowing dissolved oxygen to quickly reach a saturation level at certain partial pressure of oxygen and temperature. Further exploration into the mechanism by molecular dynamics simulations of oxygen and water clusters found that oxygen molecules can only exist stably at the interfaces among water clusters. A semi-empirical formula relating the average number of water molecules in a cluster (n) to 17O NMR half-peak width (W) was summarized: n = 0.1 W + 0.85. These findings provide a foundation for exploring the structure and properties of water.
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Microbial resource influences the life activities of medicinal plants from several perspectives. Endophytes, rhizosphere microorganisms, and other environmental microorganisms play essential roles in medicinal plant growth and development, plant yield, and clinical efficacy. The microbiota can influence the biosynthesis of active compounds in medicinal plants by stimulating specific metabolic pathways. They induce host plants to improve their resistance to environmental stresses by accumulating secondary metabolites. Microorganisms can interact with their host plants to produce long-term, targeted selection results and improve their ability to adapt to the environment. Due to the interdependence and interaction between microorganisms and medicinal plants, Chinese herbal medicines (CHMs) quality is closely related to the associated microorganisms. This review summarizes the relationship between medicinal plants and their associated microorganisms, including their species, distribution, life activities, and metabolites. Microorganisms can aid in quality control, improve the efficacy of medicinal plants, and provide markers for identifying the origin and storage time of CHMs. Therefore, a comprehensive understanding of the relationship between microorganisms and medicinal plants will help to control the quality of CHMs from different perspectives.
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BACKGROUND: One goal of Anterior Cervical Discectomy and Fusion (ACDF) is to restore the loss of intervertebral disc height (IDH) results from the degenerative process. However, the effects of IDH on postoperative dysphagia after ACDF remain unclear. METHODS: Based on the results of a one-year telephone follow-up, A total of 217 consecutive patients after single-level ACDF were enrolled. They were divided into dysphagia and non-dysphagia groups. The age, BMI, operation time and blood loss of all patients were collected from the medical record system and compared between patients with and without dysphagia. Radiologically, IDH, spinous process distance (SP) of the operated segment, and C2-7 angle (C2-7 A) were measured preoperatively and postoperatively. The relationship between changes in these radiological parameters and the development of dysphagia was analyzed. RESULTS: Sixty-three (29%) cases exhibited postoperative dysphagia. The mean changes in IDH, SP, and C2-7 A were 2.84 mm, -1.54 mm, and 4.82 degrees, respectively. Changes in IDH (P = 0.001) and changes in C2-7 A (P = 0.000) showed significant differences between dysphagia and non-dysphagia patients. Increased IDH and increased C2-7 A (P = 0.037 and 0.003, respectively) significantly and independently influenced the incidence of postoperative dysphagia. When the change in IDH was ≥ 3 mm, the chance of developing postoperative dysphagia for this patient was significantly greater. No significant relationship was observed between the change in spinous process distance (SP) and the incidence of dysphagia. The age, BMI, operation time and blood loss did not significantly influence the incidence of postoperative dysphagia. CONCLUSION: The change in IDH could be regarded as a predictive factor for postoperative dysphagia after single-level ACDF.
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Vértebras Cervicais , Transtornos de Deglutição , Discotomia , Disco Intervertebral , Complicações Pós-Operatórias , Fusão Vertebral , Humanos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Discotomia/efeitos adversos , Vértebras Cervicais/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Fusão Vertebral/efeitos adversos , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Disco Intervertebral/cirurgia , Disco Intervertebral/diagnóstico por imagem , SeguimentosRESUMO
The management of severe full-thickness skin defect wounds remains a challenge due to their irregular shape, uncontrollable bleeding, high risk of infection, and prolonged healing period. Herein, an all-in-one OD/GM/QCS@Exo hydrogel was prepared with catechol-modified oxidized hyaluronic acid (OD), methylacrylylated gelatin (GM), and quaternized chitosan (QCS) and loaded with adipose mesenchymal stem cell-derived exosomes (Exos). Cross-linking of the hydrogel was achieved using visible light instead of ultraviolet light irradiation, providing injectability and good biocompatibility. Notably, the incorporation of catechol groups and multicross-linked networks in the hydrogels conferred strong adhesion properties and mechanical strength against external forces such as tensile and compressive stress. Furthermore, our hydrogel exhibited antibacterial, anti-inflammatory, and antioxidant properties along with wound-healing promotion effects. Our results demonstrated that the hydrogel-mediated release of Exos significantly promotes cellular proliferation, migration, and angiogenesis, thereby accelerating skin structure reconstruction and functional recovery during the wound-healing process. Overall, the all-in-one OD/GM/QCS@Exo hydrogel provided a promising therapeutic strategy for the treatment of full-thickness skin defect wounds through actively participating in the entire process of wound healing.
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Quitosana , Exossomos , Gelatina , Ácido Hialurônico , Hidrogéis , Células-Tronco Mesenquimais , Pele , Cicatrização , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Exossomos/química , Exossomos/metabolismo , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Pele/efeitos dos fármacos , Pele/patologia , Pele/efeitos da radiação , Quitosana/química , Quitosana/farmacologia , Camundongos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Gelatina/química , Gelatina/farmacologia , Luz , Humanos , Antibacterianos/química , Antibacterianos/farmacologia , Proliferação de Células/efeitos dos fármacosRESUMO
BACKGROUND: Ossification of ligamentum flavum (OLF) is a prevalent degenerative spinal disease, typically causing severe neurological dysfunction. Kruppel-like factor 5 (KLF5) plays an essential role in the regulation of skeletal development. However, the mechanism KLF5 plays in OLF remains unclear, necessitating further investigative studies. METHODS: qRT-PCR, immunofluorescent staining and western blot were used to measure the expression of KLF5. Alkaline Phosphatase (ALP) staining, Alizarin red staining (ARS), and the expression of Runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcin (OCN) were used to evaluate the osteogenic differentiation. Luciferase activity assay and ChIP-PCR were performed to investigate the molecular mechanisms. RESULTS: KLF5 was significantly upregulated in OLF fibroblasts in contrast to normal ligamentum flavum (LF) fibroblasts. Silencing KLF5 diminished osteogenic markers and mineralized nodules, while its overexpression had the opposite effect, confirming KLF5's role in promoting ossification. Moreover, KLF5 promotes the ossification of LF by activating the transcription of Connexin 43 (CX43), and overexpressing CX43 could reverse the suppressive impact of KLF5 knockdown on OLF fibroblasts' osteogenesis. CONCLUSION: KLF5 promotes the OLF by transcriptionally activating CX43. This finding contributes significantly to our understanding of OLF and may provide new therapeutic targets.
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Ligamento Amarelo , Ossificação Heterotópica , Humanos , Células Cultivadas , Conexina 43/genética , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Ossificação Heterotópica/genética , Ossificação Heterotópica/metabolismo , Osteogênese/genética , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: A low prognostic nutritional index (PNI) may reflect malnutrition, which has been associated with poor prognosis in patients with various clinical conditions. The aim of the systematic review and meta-analysis was to investigate the association between preoperative PNI and risk of postoperative complications in adult patients after spine surgery. METHODS: An extensive search was conducted on PubMed, Embase, and Web of Science to identify relevant cohort studies. Random-effects models were employed to combine the findings, taking into account the potential influence of heterogeneity. RESULTS: Ten cohort studies involving 3,249 patients receiving spine surgeries were included. Pooled results showed that a low preoperative prognostic nutritional index (PNI) was associated with an increased risk of overall postoperative complications in these patients (odds ratio [OR]: 1.82, 95% confidence interval [CI]: 1.42 to 2.34, P < 0.001; I2 = 49%). Specifically, a preoperative malnutrition as evidenced by a low PNI was associated with a higher incidence of postoperative delirium (OR: 2.36, 95% CI: 1.52 to 3.66, P < 0.001; I2 = 38%) and surgical site infection (OR: 1.41, 95% CI: 1.15 to 1.73, P = 0.001; I2 = 0%). Sensitivity analyses by excluding one study at a time did not significantly change the results (P all <0.05). CONCLUSIONS: A preoperative low prognostic nutritional index (PNI) may be a risk factor of increased incidence of overall postoperative complications, postoperative delirium, and surgical site infection in adult patients after spine surgeries.
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Avaliação Nutricional , Complicações Pós-Operatórias , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Desnutrição , Fatores de Risco , Coluna Vertebral/cirurgiaRESUMO
Veterinary anatomy plays a crucial role in the curriculum for veterinary medicine and surgery. The integration of modern information technology in veterinary education can greatly benefit from innovative tools such as augmented reality (AR) applications. The aim of this study was to develop an accurate and interactive three-dimensional (3D) digital model of an animal skull using AR technology, aiming to enhance the learning of skull anatomy in veterinary anatomy education. In this study, a canine skull specimen was isolated, and the skull bones were scanned using a structured light scanner to create a 3D digital model of the canine skull, which was found to be indistinguishable from the original specimen by measurement of skull proportions. Furthermore, the interactive AR model of the canine skull, displayed using Unity3D, was subjected to testing and evaluation by 60 first-year veterinary medical students attending the gross anatomy of the animal. The students were divided into two groups: the traditional group and AR group. Both groups completed an objective test and a questionnaire. The evaluation of learning effectiveness in the test revealed no significant difference between the traditional group (which learned using textbooks and a canine skull specimen) and AR group (which learned using AR tools). However, in the questionnaire, students displayed high enthusiasm and interest in using the AR tool. Therefore, the application of AR tools can improve students' motivation for learning and enhance the comprehension of anatomical structures in three dimensions. Furthermore, this study exemplifies the use of AR as an auxiliary tool for teaching and learning in veterinary anatomy education.
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Anatomia , Realidade Aumentada , Educação em Veterinária , Estudantes de Medicina , Humanos , Animais , Cães , Educação em Veterinária/métodos , Anatomia/educação , Crânio/diagnóstico por imagemRESUMO
Purpose: Lumbar disc herniation, often treated with surgical decompression when conservative measures fail, presents challenges due to prolonged prone positioning in surgeries. This retrospective study evaluates the benefits of preoperative adaptive training to mitigate post-surgical physiological changes. Patients and Methods: A review of medical records from June 2021 to March 2023 identified 170 patients unresponsive to conservative treatments. Grouped into adaptive training and control groups based on historical data, the former had undergone exercises to prepare for surgery and postoperative changes. Vital signs and VAS scores were extracted from patient records to assess training impact. Results: The adaptive training group demonstrated stabilized vital signs intraoperatively, with a notable improvement in surgical exposure compared to the control group. However, there were no significant differences in operative time or blood loss between the groups. Additionally, postoperative VAS scores showed no significant improvement in the adaptive training group at follow-up intervals of 14 days, 1 month, and 3 months post-operation, compared to the control group. Conclusion: Our study reveals that preoperative adaptive training stabilizes intraoperative blood pressure fluctuations in lumbar disc herniation surgeries. However, this stabilization does not significantly impact long-term postoperative pain management. This highlights the need for further research to explore comprehensive strategies that effectively combine preoperative training with postoperative care.
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Bone metastasis (BM) is one of the most common complications of advanced cancer. Immunotherapy for bone metastasis of lung cancer (LCBM) is not so promising and the immune mechanisms are still unknown. Here, we utilized a model of BM by injecting cancer cells through caudal artery (CA) to screen out a highly bone metastatic derivative (LLC1-BM3) from a murine lung cancer cell line LLC1. Mass spectrometry-based proteomics was performed in LLC1-parental and LLC1-BM3 cells. Combining with prognostic survival information from patients with lung cancer, we identified serpin B9 (SB9) as a key factor in BM. Molecular characterization showed that SB9 overexpression was associated with poor prognosis and high bone metastatic burden in lung cancer. Moreover, SB9 could increase the ability of lung cancer cells to metastasize to the bone. The mechanistic studies revealed that tumor-derived SB9 promoted BM through an immune cell-dependent way by inactivating granzyme B, manifesting with the decreased infiltration of cytotoxic T cells and increased expression level of exhausted markers. A specific SB9-targeting inhibitor [1,3-benzoxazole-6-carboxylic acid (BTCA)] significantly suppressed LCBM in the CA mouse model. This study reveals that SB9 may serve as a therapeutic target and potential prognostic marker for patients with LCBM. IMPLICATIONS: SB9 as a therapeutic target for LCBM.
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Neoplasias Ósseas , Neoplasias Pulmonares , Serpinas , Humanos , Camundongos , Animais , Neoplasias Pulmonares/patologia , Serpinas/genética , Serpinas/metabolismo , Proteômica , Linhagem Celular , Neoplasias Ósseas/genéticaRESUMO
BACKGROUND: The combination of immune checkpoint inhibitors (ICIs) with anti-angiogenic drugs has shown promising anticancer effects. However, ICIs can trigger immune-mediated hepatitis (IMH). We aimed to clarify whether the combined use of anti-angiogenic drugs and ICIs would increase the severity of IMH. METHODS: One hundred IMH patients (ICI monotherapy vs. ICI plus anti-angiogenic therapy 30 vs. 70) were retrospectively enrolled. Clinicopathological parameters were compared between the two groups. RESULTS: IMH mainly showed variable degrees of panlobular hepatitis (84 %), while some cases presented mixed cholangio-hepatitic (14 %) or cholangitic (2 %) pattern. The incidence of moderate-severe injury was not significantly different between the two groups (combination vs. monotherapy 38.6 % vs. 20.0 %, p = 0.109). Specifically, the rates of marked lobular injury and portal inflammation were higher in the combination group than in the monotherapy cohort (p < 0.005), while the frequencies of interface hepatitis, bile duct injury, histiocytosis aggregates, and endothelialitis were comparable between the two groups (p > 0.05). Compared to mild IMH cases, severe IMH cases showed higher immunostaining expression levels of PD-L1 (60.7 % vs. 19.4 %, p < 0.0001). Treatments and outcomes of IMH were not significantly different between the two groups (p > 0.05). CONCLUSIONS: Compared to ICI monotherapy, the administration of anti-angiogenic drugs in combination with ICIs was not associated with increased hepatotoxicity.
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Hepatite , Inibidores de Checkpoint Imunológico , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores da Angiogênese/efeitos adversos , Estudos Retrospectivos , Imunoterapia/efeitos adversosRESUMO
BACKGROUND: The purpose of this study was to analyze p16 expression status and evaluate whether abnormal p16 expression was associated with prognosis in a large-scale esophageal squamous cell carcinoma (ESCC) cohort of patients. METHODS: We retrospectively evaluated p16 expression status of 525 ESCC samples using immunohistochemistry. Associations between abnormal p16 expression and survival were analyzed. RESULTS: P16 negative, focal expression and overexpression were found in 87.6%, 6.9% and 5.5% of ESCC patients. No significant association was observed between abnormal p16 expression and age, sex, tumor site and location, differentiation, vessel and nerve invasion, T stage and lymph node metastasis. In all patients, the survival of p16 focal expression group tended to be better compared with negative group (disease free survival/DFS P=0.040 and overall survival/OS P=0.052) and overexpression group (DFS P=0.201 and OS P=0.258), and there was no survival difference between negative group and overexpression group. The multivariate analysis for OS and DFS found that only clinical stage was a significantly independent prognostic factor (P<0.001). When patients were divided into I-II stage (n=290) and III-IVa stage (n=235), the survival of focal expression group was better compared with negative group (DFS P=0.015 and OS P=0.019), and tended to be better compared with overexpression group (DFS P=0.405 and OS P=0.432) in I-II stage ESCC, which was not found in III-IVa stage ESCC. CONCLUSION: P16 overexpression or negative expression tend to be associated with unfavorable outcomes, especially in I-II stage ESCC. Our study will help to identify a subgroup of ESCC patients with excellent prognosis after surgical therapy.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , Prognóstico , Neoplasias Esofágicas/patologia , Estudos Retrospectivos , Intervalo Livre de Doença , Biomarcadores Tumorais/análiseRESUMO
To rapidly evaluate the quality of complex herbal preparations, a new strategy was proposed based on multi-color scale and efficacy-oriented high-performance thin-layer chromatography (HPTLC) characteristic fingerprint combined with chemometric method. Firstly, effective components were screened through high-performance liquid chromatography with ultraviolet detection and evaporative light-scattering (HPLC-UV-ELSD), using multi-wavelength fusion combined with network pharmacology and molecular docking techniques. Subsequently, guided by the effective components, the targeted HPTLC characteristic fingerprint was established by multi-color scale scanning. Finally, combined with the chemometric method, the consistency of the preparation quality was evaluated, the marker components leading to quality differences were screened, and the quality control limit was established. Sanwujiao Pills (SWJPs) is a herbal preparation composed of six herbs for treating rheumatoid arthritis (RA). Through this strategy, four HPTLC characteristic fingerprints were established, they were derived from five herbs and guided by eight effective components in SWJPs. Through similarity, clustering heatmap, principal component analysis (PCA), and orthogonal partial least squares discriminant analysis (OPLS-DA), the quality distinctions among the 12 batches of SWJPs were determined. These batches were categorized into two groups based on their production time, and eight components affecting the quality of the preparation were identified. Meanwhile, the quality control threshold for SWJPs was determined based on Hotelling's T2 and DModX methods. This strategy aims to rapidly evaluate the quality of complex herbal preparations by HPTLC and extends the application of HPTLC fingerprint chromatography for identifying herbal medicine species and activity-related quality detection. The proposed strategy is also helpful for the quality control of other complex herbal preparations.
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Introduction: Traditional Chinese medicine compound preparations have become an increasingly utilized strategy for tumour treatment. Qidongning Formula (QDN) is a kind of antitumour compound preparation used in hospitals, and it can inhibit the growth of lung cancer cells. However, due to the complexity of botanical drugs, the quality evaluation of QDN is inconsistent, affecting clinical efficacy and posing potential safety risks for clinical application. Additionally, tissue distribution is an integral part of the drug development process. Methods: To study the distribution characteristics of markers in compound preparations and rat tissues, a novel HPLC-QQQ-MS/MS quantitative analytical method was established to determine five markers in QDN simultaneously, and the method was verified. Results and discussion: The analytical results showed that the contents of salidroside (51.6 ± 5.75 µg/g), calycosin-7-O-ß-D-glucoside (94.2 ± 15.4 µg/g), specnuezhenide (371 ± 72.5 µg/g), formononetin (23.8 ± 5.39 µg/g), and polyphyllin I (87.7 ± 10.6 µg/g) were stable in different batches of QDN. After intragastric administration (13.5 g/kg) in rats for 1 h, four markers in the QDN, except polyphyllin I, were distributed in most tissues. QDN was distributed chiefly in the stomach and small intestine, followed by the liver or kidney. The study also found that specnuezhenide had the highest concentration in both QDN and rat tissues (102 ± 22.1 µg/g in the stomach), while formononetin had the highest transfer rate (0.351%) from QDN to rat intestines. The above research lays a quality research foundation for the antitumour application of QDN and provides a scientific reference for the quality control of Chinese medicine compound preparations.
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BACKGROUND: Osteoporosis and obesity are closely related, and the relationships between different types of obesity and osteoporosis are inconsistent. OBJECTIVE: Our objective was to summarize earlier data concerning the association between osteoporosis and obesity (general and central), and to compare the impacts of these two obesity indicators on osteoporosis. METHODS: From inception to May 2021, a comprehensive search in electronic bibliographic databases was conducted, and the search was updated in December 2021, July 2022 and June 2023. The data were independently extracted and evaluated by two investigators from epidemiological studies that reported the impact of obesity on the odds of incident osteoporosis. RESULTS: There were 24 studies included in the final analysis when it came to general obesity measured by body mass index (BMI). Individuals with overweight and obesity had decreased odds of osteoporosis (odds ratio (OR), 0.451, 95% confidence intervals (CIs): 0.366-0.557). Sensitivity analyses showed that both overweight and obesity were decreased odds of osteoporosis, with reductions of 48.6% and 70.1%, respectively (OR, 0.514, 95% CI: 0.407-0.649; OR, 0.299, 95% CI: 0.207-0.433). Conversely, individuals classified as underweight were found to have higher odds of osteoporosis (OR, 2.540, 95% CI: 1.483-4.350). In term of central obesity, the final analysis consisted of 7 studies. No significant association was observed between central obesity and osteoporosis (OR, 0.913, 95% CI: 0.761-1.096). CONCLUSIONS: General overweight and obesity were associated with lower odds of developing osteoporosis, whereas underweight was associated with higher odds. However, central obesity did not show a significant association with osteoporosis. These findings underscore the importance of considering the impact of obesity on osteoporosis. Further research is necessary to reinforce the evidence and validate our findings.
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Sobrepeso , Magreza , Humanos , Sobrepeso/complicações , Sobrepeso/epidemiologia , Obesidade Abdominal , Obesidade/complicações , Obesidade/epidemiologia , Índice de Massa CorporalRESUMO
Background and Aims: Intrahepatic cholangiocarcinoma (ICC) is a subtype of primary liver cancer for which effective therapeutic agents are lacking. Fibroblast growth factor receptor 2 (FGFR2) has become a promising therapeutic target in ICC; however, its incidence and optimum testing method have not been fully assessed. This study investigated the rearrangement of FGFR2 in intrahepatic cholangiocarcinoma using multiple molecular detection methods. Methods: The samples and clinical data of 167 patients who underwent surgical resection of intrahepatic cholangiocarcinoma in Zhongshan hospital, Fudan university were collected. The presence of FGFR2 gene rearrangement was confirmed using fluorescence in situ hybridization (FISH) and targeted next-generation sequencing (NGS). FGFR2 protein expression was determined using immunohistochemistry (IHC). The concordance between the methods was statistically compared. PD-L1 expression was also assessed in this cohort. The clinicopathological characteristics and genomic profile related to FGFR2 rearrangements were also analyzed to assist candidate-screening for targeted therapies. Results: FGFR2 rearrangement was detected in 21 of the 167 ICC cases (12.5%) using FISH. NGS analysis revealed that FGFR2 rearrangement was present in 16 of the 20 FISH-positive cases, which was consistent with the FISH results (kappa value=0.696, p<0.01). IHC showed that 80 of the 167 cases (48%) were positive for FGFR2 expression, which was discordant with both FISH and NGS results. By comparison, FGFR2-positivity tended to correlate with unique clinicopathological subgroups, featuring early clinical stage, histologically small duct subtype, and reduced mucus production (P<0.05), with improved overall survival (p<0.05). FGFR2-positivity was not associated with PD-L1 expression in ICCs. In genome research, we identified eight partner genes fused with FGFR2, among which FGFR2-BICC1 was the most common fusion type. BAP1, CDKN2A, and CDKN2B were the most common concomitant genetic alterations of FGFR2, whereas KRAS and IDH1 mutations were mutually exclusive to FGFR2 rearrangements. Conclusions: FISH achieved satisfactory concordance with NGS, has potential value for FGFR2 screening for targeted therapies. FGFR2 detection should be prioritized for unique clinical subgroups in ICC, which features a histological small duct subtype, early clinical stage, and reduced mucus production.
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BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are new drugs for the treatment of obesity. OBJECTIVE: To assess the weight-loss effects of GLP-1RAs in the treatment of patients with overweight or obesity without diabetes. METHODS: This is a systematic review with meta-analysis and trial sequential analysis. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from their inception to January 1, 2022. Eligible trials report on outcomes including body weight (BW), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), or total body fat (TBF). Mean differences (MDs) and standardized mean differences (SMDs) were summarized using random-effects models. RESULTS: Forty-one trials involving 15,135 participants were included. Compared with controls, GLP-1RAs significantly reduced BW (MD -5.319 kg, 95% CI: -6.465, -4.174), BMI (MD -2.373 kg/m2, 95% CI: -2.821, -1.924), WC (MD -4.302 cm, CI:-5.185 to -3.419), WHR (MD -0.011, CI -0.015 to -0.007), but not TBF (MD -0.320%, CI -1.420 to -0.780). Trial sequential analysis (TSA) supported conclusive evidence of the effects of GLP-1RAs on BW, BMI, and WC for weight loss. GLP-1RAs had nonlinear dose-response relationships with weight loss. Extensive sensitivity analyses demonstrated the robustness of the results, though the GRADE certainty of the evidence ranged from high to very low. High to moderate GRADE certainty of evidence suggested semaglutide as the most effective GLP-1RA agent, with the best efficacy and low to moderate risk of adverse effects. CONCLUSIONS: The present study provides conclusive evidence for the effect of GLP-1RAs on weight loss in a nonlinear dose-response manner in patients with obesity or overweight without diabetes. In terms of changes in BW, BMI, and WC, there is firm evidence for the overall weight-loss effects of GLP-1RAs. Of the GLP-1RAs, semaglutide might be the most effective agent.