Development and validation of an inflammatory biomarkers model to predict gastric cancer prognosis: a multi-center cohort study in China.

BACKGROUND: Inflammatory factors have increasingly become a more cost-effective prognostic indicator for gastric cancer (GC). The goal of this study was to develop a prognostic score system for gastric cancer patients based on inflammatory indicators. METHODS: Patients' baseline characteristics and anthropometric measures were used as predictors, and independently screened by multiple machine learning(ML) algorithms. We constructed risk scores to predict overall survival in the training cohort and tested risk scores in the validation. The predictors selected by the model were used in multivariate Cox regression analysis and developed a nomogram to predict the individual survival of GC patients. RESULTS: A 13-variable adaptive boost machine (ADA) model mainly comprising tumor stage and inflammation indices was selected in a wide variety of machine learning models. The ADA model performed well in predicting survival in the validation set (AUC = 0.751; 95% CI: 0.698, 0.803). Patients in the study were split into two sets - "high-risk" and "low-risk" based on 0.42, the cut-off value of the risk score. We plotted the survival curves using Kaplan-Meier analysis. CONCLUSION: The proposed model performed well in predicting the prognosis of GC patients and could help clinicians apply management strategies for better prognostic outcomes for patients.

The effect of massage on patients with chronic fatigue syndrome: A systematic review and meta-analysis.

BACKGROUND: Chronic fatigue syndrome (CFS) is a long-term and complex chronic disease that seriously affects the physical and mental health and quality of life of patients. Massage, as one of the methods in traditional Chinese medicine, can treat both symptoms and root causes and is widely used to treat CFS. The main purpose is to systematically evaluate the impact of massage therapy on the efficacy and safety of CFS patients, providing a reference for clinical practice. METHODS: By searching for literature published in PubMed, Cochrane Library, Web of Science, Embase, Wanfang Database, VIP Database, and China National Knowledge Infrastructure Database until November 2023, randomized controlled trial studies were selected according to the established inclusion and exclusion criteria. The Cochrane system evaluation manual was used to evaluate the quality of the included studies, and RevMan5.4 software was used for meta-analysis. RESULTS: 32 randomized controlled trials were included, with a total of 2594 CFS patients. Meta-analysis showed that the total score of the fatigue scale (FS-14) in the treatment group, MD = -1.59, 95% CI (-1.84, -1.34), P < .00001; Physical fatigue score, MD = -1.30, 95% CI (-1.60, -1.00), P < .00001; Mental fatigue score, MD = -0.84, 95% CI (-0.99, -0.72), P < .0001]; Effective rate [RR = 1.23, 95% CI (1.19,1.28), P < .00001]; all indicators were superior to the control group, Only one study reported adverse reactions, including local swelling, skin bruising, and nausea. CONCLUSION: Our research findings suggest that massage therapy has a significant therapeutic effect on CFS, avoiding adverse reactions and improving fatigue symptoms. Therefore, massage therapy for chronic fatigue syndrome should be further promoted and applied.

Syringaresinol attenuates Tau phosphorylation and ameliorates cognitive dysfunction induced by sevoflurane in aged rats.

Cognitive dysfunction following anesthesia with agents such as sevoflurane is a significant clinical problem, particularly in elderly patients. This study aimed to explore the protective effects of the phytochemical syringaresinol (SYR) against sevoflurane-induced cognitive deficits in aged Sprague-Dawley rats and to determine the underlying mechanisms involved. We assessed the impact of SYR on sevoflurane-induced cognitive impairment, glial activation, and neuronal apoptosis through behavioral tests (Morris water maze), immunofluorescence, Western blotting for key proteins involved in apoptosis and inflammation, and enzyme-linked immunosorbent assays for interleukin-1ß, tumor necrosis factor-α, and interleukin-6. SYR treatment mitigated sevoflurane-induced cognitive decline, reduced microglial and astrocyte activation (decreased Iba-1 and GFAP expression), and countered neuronal apoptosis (reduced Bax, cleaved-caspase3, and cleaved-PARP expression). SYR also enhanced Sirtuin-1 (SIRT1) expression and reduced p-Tau phosphorylation; these effects were reversed by the SIRT1 inhibitor EX527. SYR exerts neuroprotective effects on sevoflurane-induced cognitive dysfunction by modulating glial activity, apoptotic signaling, and Tau phosphorylation through the SIRT1 pathway. These findings could inform clinical strategies to safeguard cognitive function in patients undergoing anesthesia.

Quantitative lipidomics reveals the changes of lipids and antioxidant capacity in egg yolk from laying hens with fatty liver hemorrhagic syndrome.

In laying hens, fatty liver hemorrhagic syndrome (FLHS) is a common metabolic disorder, which can affect egg production and nutritional value. However, the impact of FLHS on the lipid content in egg yolks was not clear. In this study, FLHS model was induced by using high-energy low-protein diet, and the egg quality was evaluated. Egg yolk lipids were quantitatively analyzed by using ultra-performance liquid chromatography-mass spectrometry combined with multivariate statistical analysis. Gene expressions of the lipoprotein were determined by qRT-PCR and antioxidant capacity of the egg yolk were determined by kits. The elevated blood lipids and extensive lipid droplets observed indicated successful establishment of the FLHS model in laying hens. Measurements of egg quality showed that egg yolk weight was increased in the FLHS group. Lipidomics revealed that 1,401 lipids, comprising 27 lipid subclasses in the egg yolk. According to score plots of principal component analysis and orthogonal partial least squares discriminant analysis, different lipid profile was observed between the control and FLHS groups. A total of 97 different lipid species were screen out. Sphingolipid and glycerophospholipid metabolism were identified as key pathways. Free polyunsaturated fatty acids (PUFA) exhibited an increase in the FLHS group (P < 0.05). Notably, the form of PUFAs was changed that the FLHS group showed an increase in triacylglycerol-docosahexenoic acid and triacylglycerol-arachidonic acid in the egg yolk, while triacylglycerol-α-linolenic acid was decreased (P < 0.05). Total superoxide dismutase was decreased in the egg yolks affected by FLHS. Gene expressions of vitellogenin 2 (VTG2), VTG3, very low-density apolipoprotein II and apolipoprotein B were increased in the liver of laying hens with FLHS (P < 0.05). In conclusion, FLHS promoted the lipid transport from the liver to the yolk by upregulating lipoprotein expression, which altered lipid profile, and reduced antioxidant capacity in the yolk. This study provided a foundation for understanding the changes in lipids, lipid transport and lipid antioxidation capacity in egg yolk from laying hens with FLHS.

Rational Design of Amorphous Carbon-Coated Laminar-Structured Wood for Integrating Repeatable Early Fire Detection and High-Temperature Affordable Flexible Pressure Sensing in One System.

High-temperature affordable flexible polymer-based pressure sensors integrated with repeatable early fire warning service are strongly desired for harsh environmental applications, yet their creation remains challenging. This work proposed an approach for preparing such advanced integrated sensors based on silver nanoparticles and an ammonium polyphosphate (APP)-modified laminar-structured bulk wood sponge (APP/Ag@WS). Such integrated sensors demonstrated excellent fire warning performance, including a short response time (minimum of 0.44 s), a long-lasting alarm time (>750 s), and reliable repeatability. Moreover, it achieved high-temperature affordable flexible pressure sensing that exhibited an almost unimpaired working range of 0-7.5 kPa and a higher sensitivity (in the low-pressure range, maximum to 226.03 kPa-1) after fire. The high stability was attributed to reliable structural elasticity, and the wood-derived amorphous carbon is capable of repeatable fire warnings. Finally, a Ag@APP/WS-based wireless fire alarm system that realized reliable house fire accident detection was demonstrated, showing great promise for smart firefighting application.

Integrating network pharmacology, experimental validation and molecular docking to reveal the alleviation of Yinhuang granule on idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by the abnormal proliferation of fibroblast and excessive deposition of extracellular matrix (ECM), accompanied by inflammation and ultimately respiratory failure. Yinhuang granule (YHG), with clinical properties of clearing heat, detoxifying and anti-inflammation, is commonly used to heal upper respiratory diseases in China for decades. PURPOSE: To explore the improvement of YHG on bleomycin (BLM)-induced IPF in mice and its possible engaged mechanism. METHODS: The mortality rate was recorded, lung function was determined and hematoxylin-eosin (H&E) staining was carried out to explore the alleviation of YHG on BLM-caused IPF in mice. Hydroxyproline, collagen I and collagen III contents were detected, and Sirius red and Masson staining were conducted to evaluate YHG's alleviation on lung fibrosis. The underlying mechanism was predicted by network pharmacology, and confirmed by Real-time polymerase chain reaction (RT-PCR), Western-blot (WB) and enzyme linked immunosorbent assay (ELISA). The binding affinity between related key proteins and active compounds in YHG was calculated by using molecular docking, and further validated by cellular thermal shift assay (CESTA). RESULTS: YHG (400, 800 mg/kg) weakened lung damage and pulmonary fibrosis in mice induced by BLM. Network pharmacology and experimental validation displayed that inflammation and angiogenesis participated in the YHG-provided improvement on IPF, and key involved molecules included tumor necrosis factor-α (TNFα), vascular endothelial growth factor-A (VEGFA), interleukine-6 (IL-6), etc. The data of molecular docking presented that some main active compounds from YHG had a high binding affinity with TNFR1 or VEGFR2, and some of them were further validated by CESTA. CONCLUSION: YHG effectively improved the BLM-induced IPF in mice via reducing inflammation and angiogenesis.

Assessing the causal association between dietary vitamin intake and lymphoma risk: a Mendelian randomisation study.

Observational studies of diet-related vitamins and lymphoma risk results were inconsistent. Our study aimed to estimate the causality between dietary vitamin intake and lymphoma through a Mendelian randomisation (MR) study. We enrolled dietary-related retinol, vitamin C, vitamin E, vitamin B6 and vitamin B12 as exposures of interest, with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) as the outcome. The causal effects were estimated using inverse variance weighting (IVW), MR-Egger regression analysis and weighted median, supplemented by sensitivity analyses. The results revealed that genetically predicted dietary vitamin B12 intake was associated with a reduced HL risk (OR = 0.22, 95% CI 0.05-0.91, p = 0.036). The Q test did not reveal heterogeneity, the MR-Egger test showed no significant intercepts, and the leave-one-out (LOO) analysis did not discover any SNP that affect the results. No causal relationship about dietary vitamin intake on the NHL risk was observed.

Two all-biomass cellulose/amino acid spherical nanoadsorbents based on a tri-aldehyde spherical nanocellulose II amino acid premodification platform for the efficient removal of Cr(VI) and Cu(II).

Adsorbents consisting of spherical nanoparticles exhibit superior adsorption performance and hence, have immense potential for various applications. In this study, a tri-aldehyde spherical nanoadsorbent premodification platform (CTNAP), which can be grafted with various amino acids, was synthesized from corn stalk. Subsequently, two all-biomass spherical nanoadsorbents, namely, cellulose/l-lysine (CTNAP-Lys) and cellulose/L-cysteine (CTNAP-Cys), were prepared. The morphologies as well as chemical and crystal structures of the two adsorbents were studied in detail. Notably, the synthesized adsorbents exhibited two important characteristics, namely, a spherical nanoparticle morphology and cellulose II crystal structure, which significantly enhanced their adsorption performance. The mechanism of the adsorption of Cr(VI) onto CTNAP-Lys and that of Cu(II) onto CTNAP-Cys were studied in detail, and the adsorption capacities were determined to be as high as 361.69 (Cr(VI)) and 252.38 mg/g (Cu(II)). Using the proposed strategy, it should be possible to prepare other all-biomass cellulose/amino acid spherical nanomaterials with high functional group density for adsorption, medical, catalytic, analytical chemistry, corrosion, and photochromic applications.

Protocadherin-1 serves as a prognostic biomarker and promotes pancreatic cancer progression by suppressing CD8+ T cell infiltration through CCL5-CCR5 axis.

Previous studies have shown that Protocadherins (PCDHs) enhance tumor proliferation, invasion, and metastasis; yet their role in pancreatic cancer (PC) progression and the tumor immune microenvironment remains unclear. This study aims to elucidate the role of PCDH1 in different cancer types, with a particular focus on its impact on immune suppression in PC. Utilizing data from TCGA, GTEx, and Gent2 databases, we assessed the expression of PCDH1 across various cancer types. The prognostic value of PCDH1 was demonstrated through Cox regression, Kaplan-Meier analysis, and ROC curve, while its relationship with gene mutations, tumor mutational burden (TMB), immune cell infiltration, and other clinical factors was investigated using Spearman correlation. Furthermore, the effect of PCDH1 on PC malignancy was experimentally validated by a series of in vitro and in vivo assays. Our results show a significant upregulation of PCDH1 in various tumor types, which is associated with poor prognosis, suggesting its potential application as an independent prognostic biomarker. Notably, in PC, PCDH1 exhibited significant associations with gene mutations, TMB, and immune cell infiltration. Clinical validations revealed a correlation between high PCDH1 expression and poor prognosis, coupled with a low level of CD8+ T cell infiltration. Furthermore, both in vitro and in vivo experiments confirmed the role of PCDH1 in promoting PC cell proliferation and migration while inhibiting CD8+ T cell recruitment through its modulation of CCL5-CCR5 axis. In conclusion, PCDH1 regulates the proliferation and migration of PC cells as well as CD8+ T cell infiltration in PC. PCDH1 may serve as a prognostic biomarker in multiple tumor types.

Polyphyllins in cancer therapy: A systematic review and meta-analysis of animal studies.

BACKGROUND: Polyphyllins are secondary metabolites that inhibit the growth of various tumours; however, clinical trials on their use are lacking. HYPOTHESIS/PURPOSE: In this study, we aimed to evaluate the antitumour efficacy of polyphyllins in animal models. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Electronic bibliographic databases including PubMed, Web of Science, China Science and Technology Journal Database, Wanfang Data, and China National Knowledge Infrastructure were searched for relevant articles. The Systematic Review Centre for Laboratory Animal Experimentation's Risk of Bias tool was used to assess methodological quality. RevMan V.5.4 (Cochrane) and Stata MP 17 software were used to perform a meta-analysis. RESULTS: Thirty articles were analysed including 33 independent experiments and 452 animals in this paper. Overall, tumour volume (standardised mean difference [SMD]: -3.35; 95 % confidence interval [CI]: -4.27 to -2.43; p < 0.00001) and tumour weight (SMD: -3.79; 95% CI: -4.75 to -2.82; p < 0.00001) were reduced by polyphyllins, which showed a good cancer therapeutic effect; mouse weight (SMD: -0.22; 95% CI: -0.61 to -0.18; p = 0.28) was insignificantly different, which indicated that polyphyllins did not affect the growth of the mice within the test range. Moreover, the molecular mechanisms of the antitumour activity of polyphyllins were explained, including the P53, NF-kB, AMPK, and ERK signalling pathways. CONCLUSION: Polyphyllins inhibit the growth of cancers within the experimental dose. However, due to heterogeneity of the results of the included studies, more studies are needed to support this conclusion.

Multi-Objective Optimal Trajectory Planning for Robotic Arms Using Deep Reinforcement Learning.

This study investigated the trajectory-planning problem of a six-axis robotic arm based on deep reinforcement learning. Taking into account several characteristics of robot motion, a multi-objective optimization approach is proposed, which was based on the motivations of deep reinforcement learning and optimal planning. The optimal trajectory was considered with respect to multiple objectives, aiming to minimize factors such as accuracy, energy consumption, and smoothness. The multiple objectives were integrated into the reinforcement learning environment to achieve the desired trajectory. Based on forward and inverse kinematics, the joint angles and Cartesian coordinates were used as the input parameters, while the joint angle estimation served as the output. To enable the environment to rapidly find more-efficient solutions, the decaying episode mechanism was employed throughout the training process. The distribution of the trajectory points was improved in terms of uniformity and smoothness, which greatly contributed to the optimization of the robotic arm's trajectory. The proposed method demonstrated its effectiveness in comparison with the RRT algorithm, as evidenced by the simulations and physical experiments.

Does the timing of surgery affect outcomes in young and middle-aged patients undergoing surgical stabilization of rib fractures? Feedback was based on real data from physicians, patients, and family caregivers.

BACKGROUND: There is a general clinical consensus that early surgical stabilization of rib fractures (SSRF, ≤ 48-72 h after admission) can benefit patients, and this is only regarding the surgeon's opinions. This study assessed the true outcomes of young and middle-aged patients at different surgical timings. METHODS: This retrospective cohort study was conducted among patients aged 30-55 years who were hospitalized with a diagnosis of isolated rib fractures and underwent SSRF between July 2017 and September 2021. The patients were divided into early (≤ 3 days), mid- (4-7 days) and late (8-14 days) groups, according to the interval (days) between surgery and injury date. The impact of different surgical timings on clinical outcomes, patients, and families was assessed by comparing SSRF-related data during hospitalization and follow-up studies of clinicians, patients themselves, and family caregivers 1-2 months after surgery. RESULTS: In this study, 155 complete patient data were finally included, including 52, 64, and 39 patients in the early, mid, and late groups, respectively. Length of operation, preoperative closed chest drainage rate, length of hospital stay, intensive care unit length of stay, duration of invasive mechanical ventilation in the early group were lower than those in the intermediate and late groups. Additionally, hemothorax and excess pleural fluid incidence after SSRF was lower in the early group than in the intermediate and late groups. Postoperative follow-up results showed that patients in the early group had higher SF-12 physical component summary scores and shorter duration of absence from work. Family caregivers had lower Zarit Burden Interview scores than those in the mid- and late groups. CONCLUSION: From the experience of our institution's SSRF, early surgery is safe and offers additional potential benefits for young and middle-aged patients and families with isolated rib fractures.

Identification of disulfidptosis-related genes with immune infiltration in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant primary tumor that is usually diagnosed at an advanced stage; thus, there is an urgent need for efficient and sensitive novel diagnostic markers to determine the prognosis and halt disease progression in patients with HCC. Disulfidptosis is a recently discovered form of programmed cell death, essentially an abnormal accumulation of intracellular bisulfides. Therefore, our study aimed to investigate the role of disulfidptosis-related genes (DRGs) in the pathogenesis of HCC. Based on public databases, our work demonstrates the relationship between DRG and expression, immunity, mutation/drug sensitivity, and functional enrichment in HCC. We also revealed the significant heterogeneity of HCC in different DRGs sub-clusters and in differentially expressed genes (DEGs), respectively. Subsequently, the most relevant candidate gene, SLC7A11, was screened by machine learning to further validate the significance of SLC7A11 in the clinical features, prognosis, nomogram pattern, and immune infiltration of HCC. Our study, which elucidates the potential mechanisms of DRGs and HCC, reveals that SLC7A11 can serve as a novel prognostic biomarker and provides opportunities and challenges for individualized cancer immunotherapy strategies.

Surgical resection and orbital iodine-125 brachytherapy for orbital malignancy: a novel treatment for orbital lymphoma.

OBJECTIVES: Orbital lymphoma is one of the most common adult orbital malignancies, accounting for approximately 10% of all orbital tumors. This study aimed to analyze the effects of surgical resection and orbital iodine-125 brachytherapy implantation for orbital lymphoma. PATIENTS AND METHODS: This was a retrospective study. Clinical data of 10 patients were collected from October 2016 to November 2018 and followed up to March 2022. Patients underwent the primary surgery for maximal safe removal of the tumor. After a pathologic diagnosis of a primary orbital lymphoma was established, iodine-125 seed tubes were designed based on the tumor size and invasion range, and direct vision was placed into the nasolacrimal canal or/and under the orbital periosteum around the resection cavity during the secondary surgery. Then, follow-up data, including the general situation, ocular condition, and tumor recurrence, were recorded. RESULTS: Of the 10 patients, the pathologic diagnoses included extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (6 cases), small lymphocytic lymphoma (1 case), mantle cell lymphoma (2 cases), and diffuse large B-cell lymphoma (1 case). The number of seeds implanted ranged from 16 to 40. The follow-up period ranged between 40 and 65 months. All patients in this study were alive and well had tumors that were completely controlled. No tumor recurrences or metastases occurred. Three patients had dry eye syndrome and two patients had abnormal facial sensation. No patient had radiodermatitis involving the skin around the eye, and no patient had radiation-related ophthalmopathy. CONCLUSIONS: Based on preliminary observations, iodine-125 brachytherapy implantation appeared to be a reasonable alternative to external irradiation for orbital lymphoma.

Frequent Telomerase Reverse Transcriptase Promoter and Fibroblast Growth Factor Receptor 3 Mutations Support the Precursor Nature of Papillary Urothelial Hyperplasia of the Urinary Bladder.

The precursor nature of papillary urothelial hyperplasia of the urinary bladder is uncertain. In this study, we investigated the telomerase reverse transcriptase (TERT) promoter and fibroblast growth factor receptor 3 (FGFR3) mutations in 82 patients with papillary urothelial hyperplasia lesions. Thirty-eight patients presented with papillary urothelial hyperplasia and concurrent noninvasive papillary urothelial carcinoma, and 44 patients presented with de novo papillary urothelial hyperplasia. The prevalence of the TERT promoter and FGFR3 mutations is compared between de novo papillary urothelial hyperplasia and those with concurrent papillary urothelial carcinoma. Mutational concordance between papillary urothelial hyperplasia and concurrent carcinoma was also compared. The TERT promoter mutations were detected in 44% (36/82) of papillary urothelial hyperplasia, including 23 (23/38, 61%) papillary urothelial hyperplasia with urothelial carcinoma and 13 (13/44, 29%) de novo papillary urothelial hyperplasia. The overall concordance of TERT promoter mutation status between papillary urothelial hyperplasia and concurrent urothelial carcinoma was 76%. The overall FGFR3 mutation rate of papillary urothelial hyperplasia was 23% (19/82). FGFR3 mutations were detected in 11 patients with papillary urothelial hyperplasia and concurrent urothelial carcinoma (11/38, 29%) and 8 patients with de novo papillary urothelial hyperplasia (8/44, 18%). Identical FGFR3 mutation status was detected in both papillary urothelial hyperplasia and urothelial carcinoma components in all 11 patients with FGFR3 mutations. Our findings provide strong evidence of a genetic association between papillary urothelial hyperplasia and urothelial carcinoma. High frequency of TERT promoter and FGFR3 mutations suggests the precursor role of papillary urothelial hyperplasia in urothelial carcinogenesis.

Biological and clinical perspectives of TERT promoter mutation detection on bladder cancer diagnosis and management.

The telomerase reverse transcriptase (TERT) promoter mutations are associated with increased TERT mRNA and TERT protein levels, telomerase activity, and shorter but stable telomere length. TERT promoter mutation is the most common mutation that occurs in approximately 60-80% of patients with bladder cancer. The TERT promoter mutations occur in a wide spectrum of urothelial lesions, including benign urothelial proliferation and tumor-like conditions, benign urothelial tumors, premalignant and putative precursor lesions, urothelial carcinoma and its variants, and nonurothelial malignancies. The prevalence and incidence of TERT promoter mutations in a total of 7259 cases from the urinary tract were systematically reviewed. Different platforms of TERT promoter mutation detection were presented. In this review, we also discussed the significance and clinical implications of TERT promoter mutation detection in urothelial tumorigenesis, surveillance and early detection, diagnosis, differential diagnosis, prognosis, prediction of treatment responses, and clinical outcome. Identification of TERT promoter mutations from urine or plasma cell-free DNA (liquid biopsy) will facilitate bladder cancer screening program and optimal clinical management. A better understanding of TERT promoter mutation and its pathway would open new therapeutic avenues for patients with bladder cancer.

Darinaparsin (ZIO-101) enhances the sensitivity of small-cell lung cancer to PARP inhibitors.

Small-cell lung cancer (SCLC) is an aggressive high-grade neuroendocrine carcinoma of the lung associated with early metastasis and an exceptionally poor prognosis. Little progress has been made in developing efficacious targeted therapy for this recalcitrant disease. Herein, we showed that H3.3, encoded by two genes (H3F3A and H3F3B), was prominently overexpressed in SCLC. Darinaparsin (ZIO-101), a derivative of arsenic trioxide, dose- and time-dependently inhibited the viability of SCLC cells in an H3.3-dependent manner. More importantly, ZIO-101 treatment resulted in substantial accumulation of H3.3 and PARP1 besides induction of G2/M cell cycle arrest and apoptosis in SCLC cells. Through integrative analysis of the RNA-seq data from Cancer Cell Line Encyclopedia dataset, JNCI and Genomics of Drug Sensitivity in Cancer 2 datasets, we found that H3F3A expression was negatively correlated with the IC50 values of PARP inhibitors (PARPi). Furthermore, co-targeting H3.3 and PARP1 by ZIO-101 and BMN673/olaparib achieved synergistic growth inhibition against SCLC in vitro and in vivo. In conclusion, it is feasible to target H3.3 by ZIO-101 to potentiate the response rate of PARPi in SCLC patients.

A novel 3D deep learning model to automatically demonstrate renal artery segmentation and its validation in nephron-sparing surgery.

Purpose: Nephron-sparing surgery (NSS) is a mainstream treatment for localized renal tumors. Segmental renal artery clamping (SRAC) is commonly used in NSS. Automatic and precise segmentations of renal artery trees are required to improve the workflow of SRAC in NSS. In this study, we developed a tridimensional kidney perfusion (TKP) model based on deep learning technique to automatically demonstrate renal artery segmentation, and verified the precision and feasibility during laparoscopic partial nephrectomy (PN). Methods: The TKP model was established based on convolutional neural network (CNN), and the precision was validated in porcine models. From April 2018 to January 2020, TKP model was applied in laparoscopic PN in 131 patients with T1a tumors. Demographics, perioperative variables, and data from the TKP models were assessed. Indocyanine green (ICG) with near-infrared fluorescence (NIRF) imaging was applied after clamping and dice coefficient was used to evaluate the precision of the model. Results: The precision of the TKP model was validated in porcine models with the mean dice coefficient of 0.82. Laparoscopic PN was successfully performed in all cases with segmental renal artery clamping (SRAC) under TKP model's guidance. The mean operation time was 100.8 min; the median estimated blood loss was 110 ml. The ischemic regions recorded in NIRF imaging were highly consistent with the perfusion regions in the TKP models (mean dice coefficient = 0.81). Multivariate analysis revealed that the feeding lobar artery number was strongly correlated with tumor size and contact surface area; the supplying segmental arteries number correlated with tumor size. Conclusions: Using the CNN technique, the TKP model is developed to automatically present the renal artery trees and precisely delineate the perfusion regions of different segmental arteries. The guidance of the TKP model is feasible and effective in nephron-sparing surgery.

Integrating network pharmacology and in vivo experimental validation to reveal the alleviation of mailuoning oral liquid on non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) especially the later stage non-alcoholic steatohepatitis (NASH) seriously endangers human's health and has become a global public health issue in recent years. Mailuoning Oral Liquid (MLN) is a modern traditional Chinese medicine prescription composed by Lonicerae japonicae flos, Achyranthis bidentatae radix, Scrophulariae radix and Dendrobium Caulis. MLN is generally used to treat the syndrome of blood stasis in clinical practice. PURPOSE: To observe the alleviation of MLN on NASH in vivo, and explore the possible underlying mechanism. Furthermore, this study also aims to find which Chinese medicinal drug contained in MLN exerts the main pharmacological activity. METHODS: NASH model was induced in mice by feeding with methionine and choline deficient (MCD) diet. The effects of MLN on hepatic lipids accumulation, liver inflammation, hepatic fibrosis, and the expression of some molecules were investigated by histological observation, biochemical index analysis, quantitative real-time PCR and western blot. Network pharmacology was applied to predict those involved molecular targets and potential mechanisms, which was further validated in vivo. BODIPY fluorescence staining assay was used to detect cellular lipids accumulation. RESULTS: MLN (7.8, 23.4 ml/kg) improved NASH in MCD-fed mice. Network pharmacology results demonstrated that peroxisome proliferator-activated receptor α (PPARα) signaling pathway was crucially involved in the MLN-provided alleviation on NASH. Further experimental validation results showed that MLN increased the expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and restored the decreased expression of nuclear PPARα in MCD-fed mice. Further results displayed that Achyranthis bidentatae radix and Lonicerae japonicae flos contributed greatly to the MLN-provided alleviation on NASH in vivo. BODIPY fluorescence staining assay showed that 25R-inokosterone and cynaroside, two compounds from Achyranthis bidentatae radix and Lonicerae japonicae flos, obviously reduced intracellular lipids accumulation in hepatocytes stimulated by non-esterified fatty acid (NEFA). CONCLUSION: MLN improved NASH in MCD-fed mice, and the PGC-1α-PPARα signaling pathway was involved in this process. Moreover, Lonicerae japonicae flos and Achyranthis bidentatae radix contained in MLN contributed greatly to the MLN-provided improvement on NASH.