Comprehensive assessment of osteoporosis in lumbar spine using compositional MR imaging of trabecular bone.

OBJECTIVES: To comprehensively assess osteoporosis in the lumbar spine, a compositional MR imaging technique is proposed to quantify proton fractions for all the water components as well as fat in lumbar vertebrae measured by a combination of a 3D short repetition time adiabatic inversion recovery prepared ultrashort echo time (STAIR-UTE) MRI and IDEAL-IQ. METHODS: A total of 182 participants underwent MRI, quantitative CT, and DXA. Lumbar collagen-bound water proton fraction (CBWPF), free water proton fraction (FWPF), total water proton fraction (TWPF), bone mineral density (BMD), and T-score were calculated in three vertebrae (L2-L4) for each subject. The correlations of the CBWPF, FWPF, and TWPF with BMD and T-score were investigated respectively. A comprehensive diagnostic model combining all the water components and clinical characteristics was established. The performances of all the water components and the comprehensive diagnostic model to discriminate between normal, osteopenia, and osteoporosis cohorts were also evaluated using receiver operator characteristic (ROC). RESULTS: The CBWPF showed strong correlations with BMD (r = 0.85, p < 0.001) and T-score (r = 0.72, p < 0.001), while the FWPF and TWPF showed moderate correlations with BMD (r = 0.65 and 0.68, p < 0.001) and T-score (r = 0.47 and 0.49, p < 0.001). The high area under the curve values obtained from ROC analysis demonstrated that CBWPF, FWPF, and TWPF have the potential to differentiate the normal, osteopenia, and osteoporosis cohorts. At the same time, the comprehensive diagnostic model shows the best performance. CONCLUSIONS: The compositional MRI technique, which quantifies CBWPF, FWPF, and TWPF in trabecular bone, is promising in the assessment of bone quality. KEY POINTS: • Compositional MR imaging technique is able to quantify proton fractions for all the water components (i.e., collagen-bound water proton fraction (CBWPF), free water proton fraction (FWPF), and total water proton fraction (TWPF)) in the human lumbar spine. • The biomarkers derived from the compositional MR imaging technique showed moderate to high correlations with bone mineral density (BMD) and T-score and showed good performance in distinguishing people with different bone mass. • The comprehensive diagnostic model incorporating CBWPF, FWPF, TWPF, and clinical characteristics showed the highest clinical diagnostic capability for the assessment of osteoporosis.

Competing risk analyses of overall survival and cancer-specific survival in patients with combined hepatocellular cholangiocarcinoma after surgery.

BACKGROUND: Our objective was to identify risk factors affecting overall survival (OS) and cancer-specific survival (CSS) and build nomograms to predict survival based on a large population-based cohort. METHODS: Two hundred and thirty patients diagnosed with CHCC between 2004 and 2015 were retrospectively extracted from the Surveillance, Epidemiology, and End Results (SEER) database as a training cohort. In addition, Ninety-nine patients diagnosed with CHCC between 2000 and 2017 were retrospectively extracted from Sun Yat-Sen University Cancer Center (SYSUCC) as an external validation. Nomograms for predicting probability of OS and CSS were established. Performance of the nomograms was measured by concordance index (C-index) and the area under receiver operating characteristic (ROC) curve (AUC). RESULTS: In training cohort, the 1-, 2 and 3-year OS were 67.7, 46.8 and 37.9%, and the 1-, 2 and 3-year CSS were 73.1, 52.0 and 43.0%, respectively. The established nomograms were well calibrated in both training and validation cohort, with concordance indexes (C-index) of 0.652 and 0.659, respectively for OS prediction; 0.706 and 0.763, respectively for CSS prediction. Nomograms also displayed better discriminatory compared with 8th edition tumor-node-metastasis (TNM) stage system for predicting OS and CSS. CONCLUSION: We constructed nomograms to predict OS and CSS based on a relatively large cohort. The established nomograms were well validated and could serve to improve predictions of survival risks and guide management of patients with CHCC after surgery.

Effect of prior cancer on survival outcomes for patients with pancreatic adenocarcinoma: a propensity score analysis.

BACKGROUND: With the increase in cancer survivors, more pancreatic ductal adenocarcinomas (PDACs) are developing as second primary cancers. Whether a prior cancer has an inferior impact on survival outcomes in patients with PDAC remains unknown, and the validity of criteria used to exclude patients with prior cancers in clinical trials needs to be determined. The aim of this study was to evaluate the prognostic factors and assess the survival impact of a prior cancer in patients with second primary PDAC. METHODS: Patients with PDAC were retrospectively selected from the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific mortality rates were compared between patients with and those without prior cancer. RESULTS: The data of 9235 patients with PDAC from 2004 to 2015 were retrieved from the SEER database, consisting of 438 (4.74%) patients with a prior cancer and 8797 (95.26%) patients without a prior cancer, the patients were then pair-matched using propensity score matching (PSM) analysis. The median OS rates were 7 months for both groups of patients with PDAC with and without prior cancer. These two groups of patients had similar survival rates and cancer-specific mortalities before and after the PSM analysis. In the multivariate analysis, a history of prior cancer was not a significant prognostic factor of OS in patients with PDAC. CONCLUSIONS: Patients with PDAC who had a prior cancer had similar OS and cancer-specific mortality rates as those of patients without a prior cancer. The inclusion of patients with a prior cancer in the clinical trials of PDAC should be considered.

Uni4Eye++: A General Masked Image Modeling Multi-modal Pre-training Framework for Ophthalmic Image Classification and Segmentation.

A large-scale labeled dataset is a key factor for the success of supervised deep learning in most ophthalmic image analysis scenarios. However, limited annotated data is very common in ophthalmic image analysis, since manual annotation is time-consuming and labor-intensive. Self-supervised learning (SSL) methods bring huge opportunities for better utilizing unlabeled data, as they do not require massive annotations. To utilize as many unlabeled ophthalmic images as possible, it is necessary to break the dimension barrier, simultaneously making use of both 2D and 3D images as well as alleviating the issue of catastrophic forgetting. In this paper, we propose a universal self-supervised Transformer framework named Uni4Eye++ to discover the intrinsic image characteristic and capture domain-specific feature embedding in ophthalmic images. Uni4Eye++ can serve as a global feature extractor, which builds its basis on a Masked Image Modeling task with a Vision Transformer architecture. On the basis of our previous work Uni4Eye, we further employ an image entropy guided masking strategy to reconstruct more-informative patches and a dynamic head generator module to alleviate modality confusion. We evaluate the performance of our pre-trained Uni4Eye++ encoder by fine-tuning it on multiple downstream ophthalmic image classification and segmentation tasks. The superiority of Uni4Eye++ is successfully established through comparisons to other state-of-the-art SSL pre-training methods. Our code is available at Github1.

JOINEDTrans: Prior guided multi-task transformer for joint optic disc/cup segmentation and fovea detection.

Deep learning-based image segmentation and detection models have largely improved the efficiency of analyzing retinal landmarks such as optic disc (OD), optic cup (OC), and fovea. However, factors including ophthalmic disease-related lesions and low image quality issues may severely complicate automatic OD/OC segmentation and fovea detection. Most existing works treat the identification of each landmark as a single task, and take into account no prior information. To address these issues, we propose a prior guided multi-task transformer framework for joint OD/OC segmentation and fovea detection, named JOINEDTrans. JOINEDTrans effectively combines various spatial features of the fundus images, relieving the structural distortions induced by lesions and other imaging issues. It contains a segmentation branch and a detection branch. To be noted, we employ an encoder with prior-learning in a vessel segmentation task to effectively exploit the positional relationship among vessel, OD/OC, and fovea, successfully incorporating spatial prior into the proposed JOINEDTrans framework. There are a coarse stage and a fine stage in JOINEDTrans. In the coarse stage, OD/OC coarse segmentation and fovea heatmap localization are obtained through a joint segmentation and detection module. In the fine stage, we crop regions of interest for subsequent refinement and use predictions obtained in the coarse stage to provide additional information for better performance and faster convergence. Experimental results demonstrate that JOINEDTrans outperforms existing state-of-the-art methods on the publicly available GAMMA, REFUGE, and PALM fundus image datasets. We make our code available at https://github.com/HuaqingHe/JOINEDTrans.

Active Passivation of Anion Vacancies in Antimony Selenide Film for Efficient Solar Cells.

Binary antimony selenide (Sb2Se3) is a promising inorganic light-harvesting material with high stability, nontoxicity, and wide light harvesting capability. In this photovoltaic material, it has been recognized that deep energy level defects with large carrier capture cross section, such as VSe (selenium vacancy), lead to serious open-circuit voltage (VOC) deficit and in turn limit the achievable power conversion efficiency (PCE) of Sb2Se3 solar cells. Understanding the nature of deep-level defects and establishing effective method to eliminate the defects are vital to improving VOC. In this study, a novel directed defect passivation strategy is proposed to suppress the formation of VSe and maintain the composition and morphology of Sb2Se3 film. In particular, through systematic study on the evolution of defect properties, the pathway of defect passivation reaction is revealed. Owing to the inhibition of defect-assisted recombination, the VOC increases, resulting in an improvement of PCE from 7.69% to 8.90%, which is the highest efficiency of Sb2Se3 solar cells prepared by thermal evaporation method with superstrate device configuration. This study proposes a new understanding of the nature of deep-level defects and enlightens the fabrication of high quality Sb2Se3 thin film for solar cell applications.

Effect of Energy-driven Molecular Precursor Decomposition on the Crystal Orientation of Antimony Selenide Film and Solar Cell Efficiency.

Antimony selenide (Sb2Se3) consists of 1D (Sb4Se6)n ribbons, along which the carriers exhibit high transport efficiency. By adjusting the deposition parameters of vacuum-deposited methods, such as evaporation temperature, chamber pressure, and vapor concentration, it is possible to grow the (Sb4Se6)n ribbons vertically or highly inclined towards the substrate, resulting in films with [hk1] orientation. However, the specific mechanisms by which these deposition parameters affect the orientation of thin films require a deeper understanding. Herein, a molecular beam epitaxy technique is developed for the preparation of highly [hk1]-oriented Sb2Se3 films, and the effect of evaporation parameters on the film orientation is investigated. It is found that the evaporation temperature can affect the decomposition degree of Sb2Se3, which in turn determines the vapor composition and film orientation. Additionally, the decomposition of Sb2Se3 related to evaporation temperature leads to significant changes in the elemental composition of the film, thereby passivating deep-level defects under Se-rich conditions. Consequently, the Sb2Se3 films with highly [hk1] orientation achieve a power conversion efficiency of 8.42% for the solar cells. This study provides new insights into the control of orientation in antimony-based chalcogenide films and points out new directions for improving the photovoltaic performance of solar cells.

An integrative pan-cancer analysis of the molecular characteristics of dietary restriction in tumour microenvironment.

BACKGROUND: Dietary restriction (DR), a general term for dieting, has been demonstrated as an effective intervention in reducing the occurrence of cancers. Molecular activities associated with DR are crucial in mediating its anti-cancer effects, yet a comprehensive exploration of the landscape of these activities at the pan-cancer level is still lacking. METHODS: We proposed a computational approach for quantifying DR-related molecular activities and delineating the landscape of these activities across 33 cancer types and 30 normal tissues within 27,320 samples. We thoroughly examined the associations between DR-related molecular activities and various factors, including the tumour microenvironment, immunological phenotypes, genomic features, and clinical prognosis. Meanwhile, we identified two DR genes that show potential as prognostic predictors in hepatocellular carcinoma and verified them by immunohistochemical assays in 90 patients. FINDINGS: We found that DR-related molecular activities showed a close association with tumour immunity and hold potential for predicting immunotherapy responses in various cancers. Importantly, a higher level of DR-related molecular activities is associated with improved overall survival and cancer-specific survival. FZD1 and G6PD are two DR genes that serve as biomarkers for predicting the prognosis of patients with hepatocellular carcinoma. INTERPRETATION: This study presents a robust link between DR-related molecular activities and tumour immunity across multiple cancer types. Our research could open the path for further investigation of DR-related molecular processes in cancer treatment. FUNDING: National Natural Science Foundation of China (Grant No. 82000628) and the Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine Foundation of Guangdong Province (Grant No. 2023LSYS001).

Grain Engineering of Sb2 S3 Thin Films to Enable Efficient Planar Solar Cells with High Open-Circuit Voltage.

Sb2 S3 is a promising environmentally friendly semiconductor for high performance solar cells. But, like many other polycrystalline materials, Sb2 S3 is limited by nonradiative recombination and carrier scattering by grain boundaries (GBs). This work shows how the GB density in Sb2 S3 films can be significantly reduced from 1068 ± 40 to 327 ± 23 nm µm-2 by incorporating an appropriate amount of Ce3+ into the precursor solution for Sb2 S3 deposition. Through extensive characterization of structural, morphological, and optoelectronic properties, complemented with computations, it is revealed that a critical factor is the formation of an ultrathin Ce2 S3 layer at the CdS/Sb2 S3 interface, which can reduce the interfacial energy and increase the adhesion work between Sb2 S3 and the substrate to encourage heterogeneous nucleation of Sb2 S3 , as well as promote lateral grain growth. Through reductions in nonradiative recombination at GBs and/or the CdS/Sb2 S3 heterointerface, as well as improved charge-carrier transport properties at the heterojunction, this work achieves high performance Sb2 S3 solar cells with a power conversion efficiency reaching 7.66%. An impressive open-circuit voltage (VOC ) of 796 mV is achieved, which is the highest reported thus far for Sb2 S3 solar cells. This work provides a strategy to simultaneously regulate the nucleation and growth of Sb2 S3 absorber films for enhanced device performance.

Multi-wavelength excitable mid-infrared luminescence and energy transfer in core-shell nanoparticles for nanophotonics.

2 µm mid-infrared (MIR) light sources have shown great potential for broad applications in molecular spectroscopy, eye-safe lasers, biomedical systems and so on. However, previous research studies were mainly focused on conventional materials such as glasses, glass-ceramics and crystals, limiting the luminescence intensity and miniaturization of photonic devices. Here we report a new strategy to realize the multiple excitation wavelength responsive MIR emission in a single nanoparticle by employing an erbium sublattice as the sensitizing host. Intense 2 µm emission of Ho3+ from its 5I7 → 5I8 optical transition was observed under 808, 980 and 1530 nm excitations. The possible energy transfer mechanism between Er3+ and Ho3+ ions was discussed. We also designed a core-shell-shell nanostructure by inserting an NaYF4:Yb interlayer to maximize the absorption of 980 nm photons and enhance the 2 µm emission. The MIR luminescence under 808 nm excitation can be further improved by introducing Nd3+ into the outermost shell and attaching indocyanine green dyes. These results present an efficient way for the development of MIR luminescent nanomaterials with great potential in the fields of MIR gain devices, nanosized MIR light sources, and nanophotonics.

Two plants improve stress response of a subterranean herbivore by downregulating amphetamine addiction pathways.

Introduction: Captivity serves as the primary method for enhancing animal survival and productivity. However, the stress induced by confinement can hinder animal growth and reproduction. The administration of drugs to captive animals can effectively regulate their stress response and can also be used inartificial breeding, reproduction, and experimental animalization of wild species. The plateau zokor (Eospalax baileyi), a subterranean herbivore, experiences significant stress during the captive process owing to its unique habitat. Methods: In our study, we utilized Radix astragali (RA) and Acanthopanax senticosus (AS) extracts to intervene in the stress response of plateau zokors. Results: Our findings demonstrated that RA and AS treatment considerably improved food intake and reduced weight loss, stress-related behavior, and stress hormone levels in plateau zokors. Furthermore, the excitatory pathway of amphetamine addition in the hypothalamus was suppressed by RA and AS treatment, acting through the Grin and Prkc gene families. Notably, after RA treatment, the extracellular matrix-receptor interaction pathway, enriched by the Col1a1/3a1/1a2/6a1 gene, was significantly upregulated, potentially enhancing the immune function of captive plateau zokors. Discussion: In conclusion, our research demonstrates that RA and AS treatment can effectively alleviate the stress response of plateau zokors in captive environments. The downregulation of the excitation pathway and upregulation of the immune pathway offer valuable insights into the response and potential mechanisms of plant-based drugs in mitigating animal stress.

Thermally Driven Point Defect Transformation in Antimony Selenosulfide Photovoltaic Materials.

Thermal treatment of inorganic thin films is a general and necessary step to facilitate crystallization and, in particular, to regulate the formation of point defects. Understanding the dependence of the defect formation mechanism on the annealing process is a critical challenge in terms of designing material synthesis approaches for obtaining desired optoelectronic properties. Herein, a mechanistic understanding of the evolution of defects in emerging Sb2 (S,Se)3 solar cell films is presented. A top-efficiency Sb2 (S,Se)3 solar-cell film is adopted in this study to consolidate this investigation. This study reveals that, under hydrothermal conditions, the as-deposited Sb2 (S,Se)3 film generates defects with a high formation energy, demonstrating kinetically favorable defect formation characteristics. Annealing at elevated temperatures leads to a two-step defect transformation process: 1) formation of sulfur and selenium vacancy defects, followed by 2) migration of antimony ions to fill the vacancy defects. This process finally results in the generation of cation-anion antisite defects, which exhibit low formation energy, suggesting a thermodynamically favorable defect formation feature. This study establishes a new strategy for the fundamental investigation of the evolution of deep-level defects in metal chalcogenide films and provides guidance for designing material synthesis strategies in terms of defect control.

Mechanistic Study of the Transition from Antimony Oxide to Antimony Sulfide in the Hydrothermal Process to Obtain Highly Efficient Solar Cells.

Obtaining high-quality absorber layers is a major task for constructing efficient thin-film solar cells. Hydrothermal deposition is considered a promising method for preparing high-quality antimony sulfide (Sb2 S3 ) films for solar cell applications. In the hydrothermal process, the precursor reactants play an important role in controlling the film formation process and thus the film quality. In this study, Sb2 O3 is applied as a new Sb source to replace the traditional antimony potassium tartrate to modulate the growth process of the Sb2 S3 film. The reaction mechanism of the transition from Sb2 O3 to Sb2 S3 in the hydrothermal process is revealed. Through controlling the nucleation and deposition processes, high-quality Sb2 S3 films are prepared with longer carrier lifetimes and lower deep-level defect densities than those prepared from the traditional Sb source of antimony potassium tartrate. Consequently, a solar cell device based on this improved Sb2 S3 delivers a high power conversion efficiency of 6.51 %, which is in the top tier for Sb2 S3 -based solar devices using hydrothermal methods. This research provides a new and competitive Sb source for hydrothermal growth of high-quality antimony chalcogenide films for solar cell applications.

Metagenomic analysis reveals gut plasmids as diagnosis markers for colorectal cancer.

Background: Colorectal cancer (CRC) is linked to distinct gut microbiome patterns. The efficacy of gut bacteria as diagnostic biomarkers for CRC has been confirmed. Despite the potential to influence microbiome physiology and evolution, the set of plasmids in the gut microbiome remains understudied. Methods: We investigated the essential features of gut plasmid using metagenomic data of 1,242 samples from eight distinct geographic cohorts. We identified 198 plasmid-related sequences that differed in abundance between CRC patients and controls and screened 21 markers for the CRC diagnosis model. We utilize these plasmid markers combined with bacteria to construct a random forest classifier model to diagnose CRC. Results: The plasmid markers were able to distinguish between the CRC patients and controls [mean area under the receiver operating characteristic curve (AUC = 0.70)] and maintained accuracy in two independent cohorts. In comparison to the bacteria-only model, the performance of the composite panel created by combining plasmid and bacteria features was significantly improved in all training cohorts (mean AUCcomposite = 0.804 and mean AUCbacteria = 0.787) and maintained high accuracy in all independent cohorts (mean AUCcomposite = 0.839 and mean AUCbacteria = 0.821). In comparison to controls, we found that the bacteria-plasmid correlation strength was weaker in CRC patients. Additionally, the KEGG orthology (KO) genes in plasmids that are independent of bacteria or plasmids significantly correlated with CRC. Conclusion: We identified plasmid features associated with CRC and showed how plasmid and bacterial markers could be combined to further enhance CRC diagnosis accuracy.

Dopant-free hole-transporting materials for stable Sb2(S,Se)3 solar cells.

Herein, we demonstrate that a thiophene-modified quinoxaline core small molecule can be applied in Sb2(S,Se)3 solar cells. We reveal that the interaction between thiophene and Sb2(S,Se)3 through the Sb-S bond essentially improves the interfacial hole-extraction ability. This study provides a cost-effective dopant-free hole-transporting material for inorganic thin film solar cell applications with excellent stability.

Distinctive Deep-Level Defects in Non-Stoichiometric Sb2 Se3 Photovoltaic Materials.

Characterizing defect levels and identifying the compositional elements in semiconducting materials are important research subject for understanding the mechanism of photogenerated carrier recombination and reducing energy loss during solar energy conversion. Here it shows that deep-level defect in antimony triselenide (Sb2 Se3 ) is sensitively dependent on the stoichiometry. For the first time it experimentally observes the formation of amphoteric SbSe defect in Sb-rich Sb2 Se3 . This amphoteric defect possesses equivalent capability of trapping electron and hole, which plays critical role in charge recombination and device performance. In comparative investigation, it also uncovers the reason why Se-rich Sb2 Se3 is able to deliver high device performance from the defect formation perspective. This study demonstrates the crucial defect types in Sb2 Se3 and provides a guidance toward the fabrication of efficient Sb2 Se3 photovoltaic device and relevant optoelectronic devices.

Comparative Recurrence Analysis of Pancreatic Adenocarcinoma after Resection.

PURPOSE: The relation between tumor sites of pancreatic ductal adenocarcinoma (PDAC) and recurrence was not fully investigated before. We aimed to describe the differences of recurrent patterns in PDAC of head and body/tail after curative surgery. METHODS: The recurrent patterns of PDAC were compared and the associations with clinical characteristics were analyzed in these patients. Prognostic factors of overall survival (OS) and progression-free survival (PFS) were analyzed and validated. Predictive systems were constructed and measured by the area under the AUC curve and concordance index (C-index). RESULTS: A total of 302 PDAC patients were included in this study, including 247 patients with PDAC of head and another 55 patients with PDAC of body/tail. Patients who developed tumor recurrence within 24 months after resection had significantly shorter OS in both groups. Liver metastasis occupied most of the tumor progressions and diminished while local recurrence increased gradually over time. The variation trends were similar for patients in both groups while these changes were more pronounced for patients in the head group. Local recurrence and liver-only metastasis seemed to indicate a better OS. Furthermore, predictive systems for OS and PFS prediction based on independent risk factors were established and showed significant higher values of AUC and C-indexes compared with the TNM stage system. CONCLUSIONS: Different characteristics of progressions for PDAC of head and body/tail suggested biological heterogeneity. The exploration of these variations helps to provide personalized management of recurrence in PDAC.

Survival Comparisons of Hepatic Arterial Infusion Chemotherapy With mFOLFOX and Transarterial Chemoembolization in Patients With Unresectable Intrahepatic Cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis and 40%-60% of patients present with advanced disease at the time of diagnosis. Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have recently been used in unresectable ICC. The aim of this study was to compare the survival differences of unresectable ICC patients after TACE and HAIC treatment. METHODS: Between March 2011 and October 2019, a total of 126 patients with unresectable ICC, as evident from biopsies and imaging, and who had received TACE or HAIC were enrolled in this study. Baseline characteristics and survival differences were compared between the TACE and HAIC treatment groups. RESULTS: ICC Patients had significantly higher survival rates after the HAIC treatment, compared with those after TACE treatment [1-year overall survival (OS) rates: 60.2% vs. 42.9%, 2-year OS rates: 38.7% vs. 29.4%, P=0.028; 1-year progression-free survival (PFS) rates: 15.0% vs. 20.0%, 2-year PFS rates: 0% vs. 0%, P=0.641; 1-year only intrahepatic PFS (OIPFS) rates: 35.0% vs. 24.4%, 2-year OIPFS rates: 13.1% vs. 14.6%, P = 0.026]. Multivariate Cox regression analysis showed that HAIC was a significant and independent factor for OS and OIPFS in the study cohort. CONCLUSIONS: HAIC is superior to TACE for treatment of unresectable ICC. A new tumor response evaluation procedure for HAIC treatment in unresectable ICC patients is needed to provide better therapeutic strategies. A randomized clinical trial comparing the survival benefits of HAIC and TACE is therefore being considered.

Evaluating the efficacy of endoscopic sphincterotomy on biliary-type sphincter of Oddi dysfunction: A retrospective clinical trial.

BACKGROUND: Although endoscopic sphincterotomy (EST) has a positive therapeutic effect on biliary-type sphincter of Oddi dysfunction (SOD), some patients still have little relief after EST, which implies that other functional abdominal pain may also be present with biliary-type SOD and interfere with the diagnosis and treatment of it. AIM: To retrospectively assess EST as a treatment for biliary-type SOD and analyze the importance of functional gastrointestinal disorder (FGID) in guiding endoscopic treatment of SOD. METHODS: Clinical data of 79 patients with biliary-type SOD (type I and type II) treated with EST at Affiliated Hospital of Guizhou Medical University from January 2014 to January 2019 were retrospectively collected to evaluate the clinical therapeutic effect of EST. The significance of relationship between FGID and biliary-type SOD was analyzed. RESULTS: Seventy-nine patients with biliary-type SOD received EST, including 29 type 1 patients and 50 type 2 patients. The verbal rating scale-5 (VRS-5) scores before EST were all 3 or 4 points, and the scores decreased after EST; the difference was statistically significant (P < 0.05). After EST, the serum indexes of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin in biliary-type SOD were significantly lower than before (P < 0.05). After EST, 67 (84.8%) and 8 (10.1%) of the 79 patients with biliary-type SOD had obviously effective (VRS-5 = 0 points) and effective treatment (VRS-5 = 1-2 points), with an overall effectiveness rate of 94.9% (75/79). There was no difference in VRS-5 scores between biliary-type SOD patients with or without FGID before EST (P > 0.05). Of 12 biliary-type SOD (with FGID) patients, 11 had abdominal pain after EST; of 67 biliary-type SOD (without FGID) patients, 0 had abdominal pain after EST. The difference was statistically significant (P <0.05). The 11 biliary-type SOD (with FGID) patients with recurrence of symptoms, the recurrence time was about half a year after the EST, and the symptoms were significantly relieved after regular medical treatment. There were 4 cases of post-endoscopic retrograde cholangiopancreatography pancreatitis (5.1%), and no cholangitis, bleeding or perforation occurred. Patients were followed up for 1 year to 5 years after EST, with an average follow-up time of 2.34 years, and there were no long-term adverse events such as sphincter of Oddi restenosis or cholangitis caused by intestinal bile reflux during the follow-up. CONCLUSION: EST is a safe and effective treatment for SOD. For patients with type I and II SOD combined with FGID, single EST or medical treatment has limited efficacy. It is recommended that EST and medicine be combined to improve the cure rate of such patients.

A tumor-microenvironment-responsive nanomaterial for cancer chemo-photothermal therapy.

Taxol (TAX) is a typical anticancer drug that is widely used in clinical treatment of cancer, while gold nanorods (AuNRs) are a kind of well-known material applied for photothermal therapy (PTT). The therapeutic outcome of TAX in chemotherapy is however limited by drug resistance, while AuNRs often show poor accuracy in PTT. To optimize the functions of TAX and AuNRs, we developed a hydrogen peroxide (H2O2)-triggered nanomaterial (LV-TAX/Au@Ag) for combined chemo-photothermal therapy. In normal tissues, TAX is protected in the lipid bilayer and isolated from the surrounding normal cells, while AuNRs are coated with silver shells and show low photothermal capacity. However, after reaching the tumor tissues, the silver shells can be etched by endogenous H2O2 in the tumor microenvironment, and the photothermal properties of AuNRs are then recovered. Meanwhile, the generated oxygen destabilizes the LV, which makes the 100 nm sized nanosystems disassemble into the smaller sized TAX and AuNRs, leading to the deep penetration and direct interaction with tumor tissues. The related in vitro experiments proved the validity of this "turn off/on" effect. Extensive necrosis and apoptosis were observed in the tumor tissues and the proliferation of solid tumor was greatly suppressed due to this combined chemo-photothermal therapy. In addition, no significant damage was found in normal tissues after the treatment of LV-TAX/Au@Ag. Therefore, the strategy to achieve environmental response by modifying the photothermal agents enhanced the efficiency and safety of nanomedicine, which may help improve cancer treatment.