Enhancing precision medicine: a nomogram for predicting platinum resistance in epithelial ovarian cancer.

BACKGROUND: This study aimed to develop a novel nomogram that can accurately estimate platinum resistance to enhance precision medicine in epithelial ovarian cancer(EOC). METHODS: EOC patients who received primary therapy at the General Hospital of Ningxia Medical University between January 31, 2019, and June 30, 2021 were included. The LASSO analysis was utilized to screen the variables which contained clinical features and platinum-resistance gene immunohistochemistry scores. A nomogram was created after the logistic regression analysis to develop the prediction model. The consistency index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to assess the nomogram's performance. RESULTS: The logistic regression analysis created a prediction model based on 11 factors filtered down by LASSO regression. As predictors, the immunohistochemical scores of CXLC1, CXCL2, IL6, ABCC1, LRP, BCL2, vascular tumor thrombus, ascites cancer cells, maximum tumor diameter, neoadjuvant chemotherapy, and HE4 were employed. The C-index of the nomogram was found to be 0.975. The nomogram's specificity is 95.35% and its sensitivity, with a cut-off value of 165.6, is 92.59%, as seen by the ROC curve. After the nomogram was externally validated in the test cohort, the coincidence rate was determined to be 84%, and the ROC curve indicated that the nomogram's AUC was 0.949. CONCLUSION: A nomogram containing clinical characteristics and platinum gene IHC scores was developed and validated to predict the risk of EOC platinum resistance.

Related Clinical Factors of Platinum-Based Chemotherapy Resistance in Patients with Epithelial Ovarian Cancer.

OBJECTIVE: Ovarian cancer is the second most common malignancy in women, but it is a fatal gynecological tumor. Although it has a standard treatment regimen, resistance to chemotherapy makes patients more prone to early recurrence, leading to poor survival rates. Therefore, this study investigated factors related to platinum resistance through a complete analysis of clinical data. DESIGN: Clinical data of patients with ovarian cancer were collected, and the patients were categorized into platinum-sensitive and platinum-resistant groups. By comparing the differences in clinical data between the groups, the key factors affecting platinum resistance were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected the clinical data of patients with epithelial ovarian cancer (EOC) who were admitted to the Department of Oncology of the General Hospital of Ningxia Medical University between January 1, 2019, and December 31, 2020. We conducted univariate and multivariate analyses and evaluated overall survival and progression-free survival using the Kaplan-Meier method. RESULTS: We enrolled 161 patients with EOC, of whom 124 demonstrated platinum sensitivity and 37 demonstrated platinum resistance after the initial platinum-based chemotherapy. Univariate analyses revealed that the International Federation of Gynecology and Obstetrics (FIGO) stage, neoadjuvant chemotherapy, and Fagotti score were associated with an increased risk of platinum resistance for the first recurrence. In multivariate logistic regression analysis, only Fagotti score and neoadjuvant chemotherapy were associated with an increased risk of platinum resistance (odds ratio: 0.372 and 0.328, 95% confidence interval: 0.160-0.863 and 0.141-0.762, p = 0.021 and 0.010, respectively). LIMITATIONS: The sample size of this study was relatively small because of nonstandard treatment of some patients, the absence of clinical data, and failure of follow-up. CONCLUSIONS: Patients with EOC exhibiting platinum resistance had a very poor prognosis. The Fagotti score and neoadjuvant chemotherapy appeared to increase the risk of platinum resistance at first recurrence.

Automatic retinoblastoma screening and surveillance using deep learning.

BACKGROUND: Retinoblastoma is the most common intraocular malignancy in childhood. With the advanced management strategy, the globe salvage and overall survival have significantly improved, which proposes subsequent challenges regarding long-term surveillance and offspring screening. This study aimed to apply a deep learning algorithm to reduce the burden of follow-up and offspring screening. METHODS: This cohort study includes retinoblastoma patients who visited Beijing Tongren Hospital from March 2018 to January 2022 for deep learning algorism development. Clinical-suspected and treated retinoblastoma patients from February 2022 to June 2022 were prospectively collected for prospective validation. Images from the posterior pole and peripheral retina were collected, and reference standards were made according to the consensus of the multidisciplinary management team. A deep learning algorithm was trained to identify "normal fundus", "stable retinoblastoma" in which specific treatment is not required, and "active retinoblastoma" in which specific treatment is required. The performance of each classifier included sensitivity, specificity, accuracy, and cost-utility. RESULTS: A total of 36,623 images were included for developing the Deep Learning Assistant for Retinoblastoma Monitoring (DLA-RB) algorithm. In internal fivefold cross-validation, DLA-RB achieved an area under curve (AUC) of 0.998 (95% confidence interval [CI] 0.986-1.000) in distinguishing normal fundus and active retinoblastoma, and 0.940 (95% CI 0.851-0.996) in distinguishing stable and active retinoblastoma. From February 2022 to June 2022, 139 eyes of 103 patients were prospectively collected. In identifying active retinoblastoma tumours from all clinical-suspected patients and active retinoblastoma from all treated retinoblastoma patients, the AUC of DLA-RB reached 0.991 (95% CI 0.970-1.000), and 0.962 (95% CI 0.915-1.000), respectively. The combination between ophthalmologists and DLA-RB significantly improved the accuracy of competent ophthalmologists and residents regarding both binary tasks. Cost-utility analysis revealed DLA-RB-based diagnosis mode is cost-effective in both retinoblastoma diagnosis and active retinoblastoma identification. CONCLUSIONS: DLA-RB achieved high accuracy and sensitivity in identifying active retinoblastoma from the normal and stable retinoblastoma fundus. It can be used to surveil the activity of retinoblastoma during follow-up and screen high-risk offspring. Compared with referral procedures to ophthalmologic centres, DLA-RB-based screening and surveillance is cost-effective and can be incorporated within telemedicine programs. CLINICAL TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT05308043).

Design, methodology, and preliminary results of the non-human primates eye study.

PURPOSE: To describe the normative profile of ophthalmic parameters in a healthy cynomolgus monkey colony, and to identify the characteristic of the spontaneous ocular disease non-human primates (NHP) models. METHODS: The NHP eye study was a cross-sectional on-site ocular examination with about 1,000 macaques held in Guangdong Province, southeastern China. The NHPs (Macaca fascicularis, cynomolgus) in this study included middle-aged individuals with a high prevalence of the ocular disease. The NHP eye study (NHPES) performed the information including systematic data and ocular data. Ocular examination included measurement of intraocular pressure (IOP), anterior segment- optical coherence tomography (OCT), slit-lamp examination, fundus photography, autorefraction, electroretinography, etc. Ocular diseases included measurement of refractive error, anisometropia, cataract, pterygium, etc. RESULTS: A total of 1148 subjects were included and completed the ocular examination. The average age was 16.4 ± 4.93 years. Compared to the male participants, the females in the NHPES had shorter axial length and the mean Average retinal nerve fiber layer (RNFL) thickness (except for the nasal quadrants). The mean IOP, anterior chamber depth, lens thickness, axial length, central corneal thickness, choroid thickness and other parameters were similar in each group. CONCLUSION: The NHPES is a unique and high-quality study, this is the first large macaque monkey cohort study focusing on ocular assessment along with comprehensive evaluation. Results from the NHPES will provide important information about the normal range of ophthalmic measurements in NHP.

Effect of Exogenous Plant Growth Regulators and Rejuvenation Measures on the Endogenous Hormone and Enzyme Activity Responses of Acer mono Maxim in Cuttage Rooting.

The cuttage rooting method for Acer species is difficult to achieve a good efficacy as trees maintain good characteristics at the rejuvenation stage, thus improving the rooting of Acer species. The addition of exogenous hormones and rejuvenation can improve the rooting effect of cuttings; however, the specific regulatory mechanism is still unclear. Here, Acer mono Maxim rejuvenation and non-rejuvenation cuttings were used as test subjects, to investigate the effects of exogenous hormones on the activities of endogenous hormones and antioxidant enzymes in the rooting process of young cuttings. The results showed that exogenous growth-regulating substances significantly improved the rooting rate of A. mono. Exogenous hormones naphthylacetic acid (NAA) + indolebutyric acid (IBA) increased the initial levels of the endogenous hormones, indoleacetic acid (IAA) and abscisic acid (ABA), and the enzyme activities of peroxidase (POD) and polyphenol oxidase (PPO). Rejuvenation treatment prolonged the time of increase in ABA content and indoleacetic acid oxidase (IAAO) activity at the root primordium induction stage, while increasing trans-zeatin riboside (ZR) content and decreasing POD enzyme activity in cuttings. These results demonstrate that A. mono cuttings can achieve the purpose of improving the rooting rate by adding the exogenous hormone (NAA + IBA), which is closely related to the changes of endogenous hormone content and enzyme activity, and these changes of A. mono rejuvenation cuttings are different from non-rejuvenation cuttings.

Advances in Polyoxometalates as Electron Mediators for Photocatalytic Dye Degradation.

The increasing concerns over the environment and the growing demand for sustainable water treatment technologies have sparked substantial interest in the field of photocatalytic dye removal. Polyoxometalates (POMs), known for their intricate metal-oxygen anion clusters, have received considerable attention due to their versatile structures, compositions, and efficient facilitation of photo-induced electron transfers. This paper provides an overview of the ongoing research progress in the realm of photocatalytic dye degradation utilizing POMs and their derivatives. The details encompass the compositions of catalysts, catalytic efficacy, and light absorption propensities, and the photocatalytic mechanisms inherent to POM-based materials for dye degradation are exhaustively expounded upon. This review not only contributes to a better understanding of the potential of POM-based materials in photocatalytic dye degradation, but also presents the advancements and future prospects in this domain of environmental remediation.

[A Health Education Program for Home Emergency Management of Acute Complications of Diabetes in the Elderly].

Objective To establish a health education program for home emergency management of acute complications of diabetes in the elderly.Methods The program was drafted by literature review and panel discussion.The final draft was formed after two rounds of correspondence from 13 experts.Results The recovery rate of the two rounds of expert correspondence was 100%,and the expert authority coefficient was 0.98.The Kendall's harmony coefficients of the two rounds of correspondence were 0.263 and 0.212 respectively(both P<0.001).The established health education program included indicators of three categories:early stage of acute complications of diabetes at home(understanding the inducing factors),emergency warning(quick and early identification in case of emergency),and emergency treatment at home.Conclusion The contents of the health education program are systematic and reliable and meet the needs of health education for home emergency management of the elderly with diabetes.

Discovery of new inhibitors against both NF-κB and osteoclastogenesis from in-house library with α, ß-unsaturated-enone fragment.

The α,ß-unsaturated-enone contained natural products have been reported showing NF-κB inhibition effect. It is well known that NF-κB inhibitors can also be used to inhibit osteoclastogenesis. In a continual discovery new agents for anti-osteoclastogenesis, 8 different type compounds with α,ß-unsaturated-enone fragments from our in-house library were evaluated for NF-κB inhibition and anti-osteoclastogenesis. Experimental results indicated five compounds exhibited inhibition of NF-κB signal pathway. Among them, one compound ((E)-2-(4-fluorobenzylidene)-3,4-dihydronaphthalen-1(2H)-one, 6a) simultaneously inhibits both osteoclastogenesis and NF-κB signal pathway. Furthermore, 12 compounds with similar scaffold with 6a were tested for anti-osteoclastogenesis. As a result, 9 compounds inhibited both NF-κB and osteoclastogenesis. Among them, compound 6b is the most potent inhibitor against NF-κB (IC50 = 2.09 µM) and osteoclast differentiation (IC50 = 0.86 µM). Further studies show that compound 6b blocks the phosphorylation of both p65 and IκBα, and suppresses NF-κB targeted gene expression without interfering MAPKs and PI3K/Akt signal transduction pathways. This study demonstrates that we can identify promising synthesized compounds with new scaffolds as therapeutic solutions against osteoclastogenesis inspired by the privileged fragment derived from natural leads.

Astragalus Polysaccharide Protect against Cadmium-Induced Cytotoxicity through the MDA5/NF-κB Pathway in Chicken Peripheral Blood Lymphocytes.

Cadmium (Cd) is a known environmental pollutant that is associated with inflammation, oxidative stress, and cell apoptosis. Astragalus polysaccharide (APS) is a major component of Astragalus membranaceus, a vital qi-reinforcing herb medicine with favorable immuneregulation properties. To study the effect of APS on the inhibition of the cadmium-induced injury of peripheral blood lymphocytes (PBLs) in chickens through the MDA5/NF-κB signaling pathway, PLBs acquired from 15-day-old chickens were divided into control group, Cd group, APS + Cd group, anti-MDA5 mAb + Cd group, BAY 11-7082 (a nuclear factor kappa-light chain-enhancer of activated B cells [NF-κB] inhibitor) +Cd group, APS group, anti-MDA5 mAb group, and BAY 11-7082 group. The transcription levels of melanoma differentiation-associated gene 5 (MDA5), interferon promoter-stimulating factor 1 (IPS-1), NF-κB, and inflammatory factors tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 were measured by quantitative real-time PCR. MDA5 protein expression was measured by western blotting. Levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were measured by corresponding antioxidant kit. The morphological change of PBLs was measured by transmission electron microscopy. The results showed that Cd significantly increased the expression of MDA5, IPS-1, NF-κB, and their downstream cytokines, IL-1ß and TNF-α, IL-6 in PLBs. In addition, a high level of MDA was observed in the Cd treatment group; the activities of GSH-Px and SOD were significantly lower in the Cd treatment group than those in controls (p < 0.05). Ultrastructural changes of PBLs showed that Cd promoted autophagy, apoptosis, and necrosis in PBLs. However, APS can efficiently improve Cd-induced cell damage by decreasing the activation of the MDA5 signaling pathway. The effect is consistent with that of anti-MDA5 mAb or/and BAY. The results indicated that APS inhibited Cd-induced cytotoxicity through the regulation of MDA5/NF-κB signaling.

Global tendency and research trends of minimally invasive surgery for glaucoma from 1992 to 2023: A visual bibliometric analysis.

Background: Minimally invasive glaucoma surgery has become a popular research topic over the past decade. However, no published studies have provided a systematic overview for this field. A bibliometric analysis is urgently required to characterise current international trends and provide an intuitive description of past and emerging trends. Methods: This study analysed minimally invasive glaucoma surgery-related studies by searching the Web of Science for relevant articles published between 1992 and 2023. All the retrieved titles and abstracts were screened for eligibility, and only articles and reviews written in English were included in the analysis. CiteSpace (version 6.1.6), VOSviewer (version 1.6.19), and the bibliometric package in RStudio were used to construct and visualise the results. Results: A total of 1533 publications were included in the analysis with 26072 citations. A total of 4482 authors from 1191 organizations in 57 countries and regions published papers in 139 journals. After 2010, the number of publications increased significantly, with the highest annual productivity occurring in 2022 (n = 229, 15 %). Most of these studies were published in ophthalmology journals. The journal "Ophthalmology" ranked first with 30 papers and 5275 citations. Among the 10 most productive countries, the United States had the largest share of publications (n = 423, 36 %) and Switzerland had the highest proportion of multiple-country publications (70 %). Neodymium was the first keyword discovered, appearing in 1992 and continuing for 21 years. Kahook dual-blade, progression, gonioscopy-assisted transluminal trabeculotomy, efficacy, minimally invasive glaucoma surgery, cataract extraction, and primary open-angle glaucoma were the most recent keywords since 2020. Conclusions: This was the first bibliometric analysis of minimally invasive glaucoma surgery and provides an overview of the developments in this field. Our results identified outstanding studies, countries, institutions, journals, and authors in the field to point the way forward for scientific research and clinical applications of minimally invasive glaucoma surgery.

Discovery of Novel Antiosteoporosis Leads with Bone Resorption Inhibition and Anabolic Promotion through a Chemotype-Assembly Approach.

Developing a dual-efficiency agent with antiresorptive and anabolic applications is a promising strategy for treating osteoporosis. This study reports the discovery of dual antiosteoporosis agents via a chemotype-assembly approach. Chemotype analysis identified 12 antiresorptive and 12 anabolic chemotypes and 7 dual-function chemotype-assembly rules. Based on these assembly rules, a dual-functional compound S24 was discovered. S24 exhibits osteoclastogenesis inhibition with an IC50 value of 10.28 µM and osteoblast differentiation stimulation at 10 µM. S24 derivatives were designed and synthesized based on the activity relationship of the chemotypes. This yielded a more active compound, S24-14, with an osteoclastogenesis inhibition IC50 value of 0.40 µM and osteoblast differentiation stimulation at 1.0 µM; compound S24-14 also suppressed bone loss in vivo. These results prove that S24-14 can be a potential lead for antiosteoporosis drug development.

[Prediction Model of Groundwater Sulphate Based on Combined Multi-source Spatio-temporal Data].

The accurate prediction of spatial variation trends in groundwater SO42- is of great significance for improving groundwater quality and regional groundwater management level. The multi-source spatio-temporal data such as land cover data, soil parameter data, digital elevation data, and groundwater pH value in the plain area of the Yarkant River Basin in 2011, 2014, 2017, and 2020 were used as characteristic variables to analyze their correlation with groundwater SO42- concentration. To enhance the prediction accuracy, the Bayesian optimization algorithm (BOA) was used to optimize the random forest regression (RFR). Based on the BOA-RFR model, the importance of the characteristic variables was analyzed, the prediction accuracy of the model was evaluated, and the groundwater SO42- prediction map was generated. The results showed that pH value, ground elevation (GE), and percentage of bare land (BAR) in the contribution area were important parameters influencing groundwater hydrochemical composition, which were significantly negatively correlated with groundwater SO42- concentration, and the importance of impact factors for predicting groundwater SO42- concentration exceeded 25 %. The geostatistical interpolation method was used as an auxiliary tool for the predictive modeling of spatial distribution. After adding auxiliary samples, the R2 of groundwater SO42- concentration prediction of the BOA-RFR model was greater than 0.96, and the maximum values of RMSE and MAE were reduced by 4.7 % and 23.8 %, respectively, compared with the minimum values of the model with fewer samples. The SO42- concentration prediction map showed that high SO42- groundwater was enriched in the northeast of the plain area of the Yarkand River Basin, an area that was expanding.

Identification of a G-protein coupled receptor-related gene signature through bioinformatics analysis to construct a risk model for ovarian cancer prognosis.

BACKGROUND: Ovarian cancer (OV) is a common malignant tumor of the female reproductive system with a 5-year survival rate of ∼30 %. Inefficient early diagnosis and prognosis leads to poor survival in most patients. G protein-coupled receptors (GPCRs, the largest family of human cell surface receptors) are associated with OV. We aimed to identify GPCR-related gene (GPCRRG) signatures and develop a novel model to predict OV prognosis. METHOD: We downloaded data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Prognostic GPCRRGs were screened using least absolute shrinkage and selection operator (LASSO) Cox regression analysis, and a prognostic model was constructed. The predictive ability of the model was evaluated by Kaplan-Meier (K-M) survival analysis. The levels of GPCRRGs were examined in normal and OV cell lines using quantitative reverse-Etranscription polymerase chain reaction. The immunological characteristics of the high- and low-risk groups were analyzed using single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. RESULTS: Based on the risks scores, 17 GPCRRGs were associated with OV prognosis. CXCR4, GPR34, LGR6, LPAR3, and RGS2 were significantly expressed in three OV datasets and enabled accurate OV diagnosis. K-M analysis of the prognostic model showed that it could differentiate high- and low-risk patients, which correspond to poorer and better prognoses, respectively. GPCRRG expression was correlated with immune infiltration rates. CONCLUSIONS: Our prognostic model elaborates on the roles of GPCRRGs in OV and provides a new tool for prognosis and immune response prediction in patients with OV.

A novel pH-sensitive hemi-cyanine containing tetrahydropyridine ring near-infrared fluorescence probe with lysosome-targeting ability.

In recent years, hemi-cyanine dyes have been widely used as biological probes due to their red-light emission characteristics and high fluorescence quantum yield. In this study, we synthesized a novel hemi-cyanine dye containing a tetrahydropyridine ring. A lysosomal target was introduced into its structure to create a new pH-sensitive near-infrared fluorescent probe that successfully targeted lysosomes. The results showed that when the probe solution was excited at the absorption wavelength of 650 nm, its fluorescence emission wavelength was about 700 nm, and the peak intensity changed with different pH values in a wide range. Therefore, this probe enabled non-invasive detection of changes in the acidic environment of lysosomes in living organisms and showed good imaging capabilities. Moreover, the probe displays high sensitivity and good stability. The theoretical calculation of a probe structure has also been completed to discuss the relationship between structure and property.

Treatment options for tumor progression after initial immunotherapy in advanced non-small cell lung cancer: A real-world study.

OBJECTIVE: Whether to continue administering immunotherapy to patients with advanced non-small cell lung cancer (NSCLC) who have experienced tumor progression remains controversial after immunotherapy. The aims were to explore survival outcomes after further immunotherapy post-progression and to determine the optimal combination therapy in such cases. METHODS: Overall, 507 patients with NSCLC who underwent immunotherapy and experienced tumor progression were retrospectively divided into Immuno-combination and No-immuno groups according to whether additional combination therapy involving immunotherapy was administered post-progression. Progression-free survival (PFS) and overall survival (OS) were evaluated. Subgroup analyses were performed according to the different treatment regimens for patients in the Immuno-combination group. RESULTS: After propensity score matching, there were 150 patients in the No-immuno group and 300 patients in the Immuno combination group. Superior PFS was observed in the Immuno-combination group compared with those in the No-immuno group (6-month PFS: 25.3 % vs. 60.6 %; 12-month PFS: 6.7 % vs. 24.4 %; P < 0.001). Similar intergroup differences were observed for OS (12-month OS: 22.3 % vs. 69.4 %; 18-month OS: 6.4 % vs. 40.4 %; P < 0.001). Superior PFS outcomes were observed in the Immuno+Antiangiogenic group compared with the Immuno+Chemo group (6-month PFS: 51.3 % vs. 71.5 %; 12-month PFS: 23.1 % vs. 25.7 %; P = 0.017). Similar differences in OS were observed between those same subgroups (12-month OS: 62.1 % vs. 77.9 %; 18-month OS: 33.3 % vs. 48.7 %; P = 0.006). CONCLUSION: Patients with NSCLC experiencing tumor progression post-immunotherapy can still benefit from further treatment, with immunotherapy combined with antiangiogenic therapy the most efficacious option.

Early surveillance of rice bakanae disease using deep learning and hyperspectral imaging.

Bakanae disease, caused by Fusarium fujikuroi, poses a significant threat to rice production and has been observed in most rice-growing regions. The disease symptoms caused by different pathogens may vary, including elongated and weak stems, slender and yellow leaves, and dwarfism, as example. Bakanae disease is likely to cause necrosis of diseased seedlings, and it may cause a large area of infection in the field through the transmission of conidia. Therefore, early disease surveillance plays a crucial role in securing rice production. Traditional monitoring methods are both time-consuming and labor-intensive and cannot be broadly applied. In this study, a combination of hyperspectral imaging technology and deep learning algorithms were used to achieve in situ detection of rice seedlings infected with bakanae disease. Phenotypic data were obtained on the 9th, 15th, and 21st day after rice infection to explore the physiological and biochemical performance, which helps to deepen the research on the disease mechanism. Hyperspectral data were obtained over these same periods of infection, and a deep learning model, named Rice Bakanae Disease-Visual Geometry Group (RBD-VGG), was established by leveraging hyperspectral imaging technology and deep learning algorithms. Based on this model, an average accuracy of 92.2% was achieved on the 21st day of infection. It also achieved an accuracy of 79.4% as early as the 9th day. Universal characteristic wavelengths were extracted to increase the feasibility of using portable spectral equipment for field surveillance. Collectively, the model offers an efficient and non-destructive surveillance methodology for monitoring bakanae disease, thereby providing an efficient avenue for disease prevention and control. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00169-1.

Common endocrine system adverse events associated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs), a novel anti-tumor therapeutic modality, are monoclonal antibodies targeting certain immune checkpoints (ICs) that reactivate T cells to achieve anti-tumor immunity by targeting, binding, and blocking ICs. Targeted inhibitory antibodies against the ICs cytotoxic T-lymphocyte antigen and programmed death receptor-1 have demonstrated efficacy and durable anti-tumor activity in patients with cancer. ICs may prevent autoimmune reactions. However, ICIs may disrupt ICs properties and trigger autoimmune-related adverse reactions involving various organ systems including the cardiovascular, pulmonary, gastrointestinal, renal, musculoskeletal, dermal, and endocrine systems. Approximately 10% of patients with damage to target organs such as the thyroid, pituitary, pancreas, and adrenal glands develop endocrine system immune-related adverse events (irAEs) such as thyroid dysfunction, pituitary gland inflammation, diabetes mellitus, and primary adrenal insufficiency. However, the symptoms of immunotherapy-associated endocrine system irAEs may be nonspecific and similar to those of other treatment-related adverse reactions, and failure to recognize them early may lead to death. Timely detection and treatment of immunotherapy-associated endocrine irAEs is essential to improve the efficacy of immunotherapy, prognosis, and the quality of life of patients. This study aimed to review the mechanisms by which ICIs cause endocrine irAEs providing guidance for the development of appropriate management protocols. Here, we discuss (1) the biological mechanisms of ICs in tumorigenesis and progression, focusing on cytotoxic T-lymphocyte antigen and programmed cell death-1/programmed cell death-ligand 1; and (2) the epidemiology, clinical symptoms, diagnosis, and treatment of four immunotherapy-related endocrine complications.

Nature-Inspired Gelatin-Based Adhesive Hydrogel: A Rapid and User-Friendly Solution for Hemostatic Applications.

Conventional hemostatic agents face challenges in achieving rapid hemostasis and effective tissue repair due to limited hemostatic scenarios, suboptimal efficacy, and inadequate adhesion to wet tissues. Drawing inspiration from nature-sourced materials, a gelatin-based adhesive hydrogel (AOT)  is designed, easily prepared and quick to form, driven by Schiff base and multiple hydrogen bonds for applications in arterial and liver bleeding models. AOT exhibits exceptional adhesion to wet tissues (48.67 ± 0.16 kPa) and displays superior hemostatic properties with reduced blood loss and hemostatic time compared to other hydrogels and conventional hemostatic materials. Moreover, AOT exhibits good biocompatibility and biodegradability. In summary, this easily prepared adhesive hydrogel has the potential to supplant traditional hemostatic agents, offering a novel approach to achieve swift sealing of hemostasis and facilitate wound healing and repair in broader application scenarios, owing to its unique advantages.

Survival benefit of adjuvant chemotherapy after resection of Stage I lung adenocarcinoma containing micropapillary components.

BACKGROUND: The usefulness of postoperative adjuvant chemotherapy (ACT) for patients with stage I lung adenocarcinoma with micropapillary (MIP) components remains unclear. We analyzed whether postoperative ACT could reduce recurrence in patients with stage I lung adenocarcinoma with MIP components, thereby improving their overall survival (OS) and disease-free survival (DFS). METHODS: Data for patients with pathologically confirmed stage I lung adenocarcinoma with MIP components from January 2012 to December 2018 were retrospectively analyzed. OS and DFS were analyzed in groups and subgroups. RESULTS: Overall, 259 patients were enrolled. Patients who received ACT in stage IA showed significantly better survival than did those with no-adjuvant chemotherapy (NACT); (5-year OS 89.4% vs. 73.6%, p < 0.001; 5-year DFS 87.2% vs. 66.0%, p = 0.008). A difference was also observed for in-stage IB patients (5-year OS 82.0% vs. 51.8%, p = 0.001; 5-year DFS 76.0% vs. 41.11 %, p = 0.004). In subgroup analysis based on the proportion of MIP components, patients with 1%-5% MIP components had a significantly better prognosis in the ACT group than in the NACT group (5-year OS 82.4% vs. 66.0%, p = 0.005; 5-year DFS 76.5% vs. 49.1%, p = 0.032). A similar difference was observed for patients with MIP ≥5% (5-year OS 80.7% vs. 47.8%, p = 0.009; 5-year DFS 73.11% vs. 43.5%, p = 0.007). CONCLUSION: Among patients with stage I lung adenocarcinoma with MIP components, those who received ACT showed significant survival benefits compared to those without ACT. Patients with lung adenocarcinoma with MIP components could benefit from ACT when the MIP was ≥1%.