Hydroxychloroquine-induced hyperpigmentation of the skin and bull's-eye maculopathy in rheumatic patients: a case report and literature review.

Hydroxychloroquine (HCQ) is used as a traditional disease-modifying antirheumatic drugs (DMARDs), for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, it can cause serious adverse reactions, including hyperpigmentation of the skin and bull's-eye macular lesions. Here, we present a case of HCQ-induced hyperpigmentation of the skin and bull's-eye macular lesions in a patient who received HCQ for RA. A 65-year-old female patient developed blurred vision and hyperpigmentation of multiple areas of skin over the body for one month after 3 years of HCQ treatment for RA. Based on clinical presentation, ophthalmological examination and dermatopathological biopsy, a diagnosis of drug-induced cutaneous hyperpigmentation and bullous maculopathy of the right eye was made. After discontinuation of HCQ and treatment with iguratimod tablets, the hyperpigmentation of the patient 's skin was gradually reduced, and the symptoms of blurred vision were not significantly improved. We also reviewed the available literature on HCQ-induced cutaneous hyperpigmentation and bull's-eye macular lesions and described the clinical features of HCQ-induced cutaneous hyperpigmentation and bull's-eye macular lesions. In conclusion, clinicians should be aware of early cutaneous symptoms and HCQ-associated ophthalmotoxicity in patients with rheumatic diseases on HCQ sulphate and should actively monitor patients, have them undergo regular ophthalmological examinations and give appropriate treatment to prevent exacerbation of symptoms.

Prognostic utility of blood inflammation biomarkers before and after treatment on the survival of patients with locally advanced non-small cell lung cancer undergoing stereotactic body radiotherapy.

BACKGROUND AND OBJECTIVE: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were significant and succinct indicators of systemic inflammation. We assessed the influence of stereotactic body radiotherapy (SBRT) on NLR and PLR in patients with locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: We reviewed the medical data of patients with LA-NSCLC who underwent SBRT between 1 January 2013 and 31 December 2018. NLR and PLR values recorded at pre- and post-SBRT were examined. We assessed the correlation between pre/post-SBRT NLR and PLR and survival outcomes. The decision tree evaluation was conducted using Chi-square automatic detection. RESULTS: In total, 213 patients were included in the study with a median follow-up duration of 40.00 (ranging from 5.28 to 100.70) months. Upon dichotomization by a median, we identified that post-SBRT NLR > 5.5 and post-SBRT PLR > 382.0 were negatively associated with shorter overall survival (OS). In the multivariate assessment, post-SBRT PLR > 382.0 was the only factor. Based on post-SBRT PLR, tumor locations, and tumor stage, we categorized patients into low, medium, or high-risk groups. CONCLUSIONS: Post-SBRT PLR > 382.0 correlated with survival in patients undergoing SBRT. The decision tree model might play a role in future risk stratification to guide the clinical practice of individualized SBRT for LA-NSCLC.

Ultrasound-guided stellate ganglion block benefits the postoperative recovery of patients undergoing laparoscopic colorectal surgery: a single-center, double-blinded, randomized controlled clinical trial.

BACKGROUND: With the increasing prevalence of colorectal cancer (CRC), optimizing perioperative management is of paramount importance. This study investigates the potential of stellate ganglion block (SGB), known for its stress response-mediating effects, in improving postoperative recovery. We postulate that preoperative SGB may enhance the postoperative recovery of patients undergoing laparoscopic CRC surgery. METHODS: We conducted a randomized controlled trial of 57 patients undergoing laparoscopic colorectal cancer surgery at a single center. Patients, aged 18-70 years, were randomly assigned to receive either preoperative SGB or standard care. SGB group patients received 10 mL of 0.2% ropivacaine under ultrasound guidance prior to surgery. Primary outcome was time to flatus, with secondary outcomes encompassing time to defecation, lying in bed time, visual analog scale (VAS) pain score, hospital stays, patient costs, intraoperative and postoperative complications, and 3-year mortality. A per-protocol analysis was used. RESULTS: Twenty-nine patients in the SGB group and 28 patients in the control group were analyzed. The SGB group exhibited a significantly shorter time to flatus (mean [SD] hour, 20.52 [9.18] vs. 27.93 [11.69]; p = 0.012), accompanied by decreased plasma cortisol levels (mean [SD], postoperatively, 4.01 [3.42] vs 7.75 [3.13], p = 0.02). Notably, postoperative pain was effectively managed, evident by lower VAS scores at 6 h post-surgery in SGB-treated patients (mean [SD], 4.70 [0.91] vs 5.35 [1.32]; p = 0.040). Furthermore, patients in the SGB group experienced reduced hospital stay length (mean [SD], day, 6.61 [1.57] vs 8.72 [5.13], p = 0.042). CONCLUSIONS: Preoperative SGB emerges as a promising approach to enhance the postoperative recovery of patients undergoing laparoscopic CRC surgery. CLINICAL TRIAL REGISTRATION: ChiCTR1900028404, Principal investigator: Xia Feng, Date of registration: 12/20/2019.

Effective separation of water-in-oil emulsions using an under-medium superlyophilic membrane with hierarchical pores.

Separating water-in-oil emulsions is important in terms of environmental protection and resource recovery. To address the challenges posed by the water-oil interface, superwetting materials have been designed to accomplish separation through filtration and adsorption. Superhydrophobic membranes prevent the permeation of water droplets owing to extreme repellence and their size-sieving abilities. However, their use in remediating water-contaminated oil is limited by high oil viscosities. Meanwhile, in-air superhydrophilic sorbents are rarely employed for the separation of water-in-oil emulsions due to the thermodynamic and kinetic limitations of water adsorption in oil. Herein, the integration of an under-medium superlyophilic membrane with the hierarchical porous structure of wood is presented for filtration-driven selective adsorption of water from surfactant-stabilized (10 g/L) water-in-oil emulsions. Compared to filtration through a natural wood membrane or direct adsorption using an under-oil superhydrophilic wood membrane, the under-medium superlyophilic wood membrane demonstrated high separation efficiencies of > 99.95% even when applied to the regeneration of high-viscosity lubricating (6.3 mPa s) and edible (50.5 mPa s) oils, exhibiting viscosity-dependent fluxes and excellent stability. Moreover, the cost of purifying 200 mL of lubricating oil using the modified wood membrane was much lower than the oil's market price and required a low energy consumption of ca. 1.72 kWh. ENVIRONMENTAL IMPLICATION: The ever-growing use of petroleum and industrial/domestic oil products has led to excessive (estimated at a million tons per year) output of waste oils. Because direct discharge of waste oils into the environment causes serious pollution problems, separating water-in-oil emulsions is important in terms of environmental protection and resource recovery. Here filtration-driven water adsorption has been demonstrated to be a feasible method for the remediation of water-contaminated waste oils, even those that are highly viscous.

Identification of necroptosis-related lncRNAs for prognosis prediction and screening of potential drugs in patients with colorectal cancer.

BACKGROUND: Tumor recurrence and metastasis lead to a poor prognosis in colorectal cancer (CRC). Necroptosis is closely related to the tumor microenvironment (TME) and affects tumor recurrence and metastasis. We aimed to stratify CRC patients according to necroptosis-related long noncoding RNAs (lncRNAs), which can be used to not only evaluate prognosis and improve precision medicine in clinical practice but also screen potential immunotherapy drugs. AIM: To stratify CRC patients according to necroptosis-related lncRNAs (NRLs), which can be used to not only evaluate prognosis and improve precision medicine in clinical practice but also screen potential immunotherapy drugs. METHODS: LncRNA expression profiles were collected from The Cancer Genome Atlas. NRLs were identified by coexpression analysis. Cox regression analysis identified a NRL signature. Then, the value of this signature was comprehensively and multidimensionally evaluated, and its reliability for CRC prognosis prediction was assessed with clinical CRC data and compared with that of six other lncRNA signatures. Gene set enrichment analysis, TME analysis and half-maximal inhibitory concentration (IC50) prediction were also performed according to the risk score (RS) of the signature. RESULTS: An 8-lncRNA signature significantly associated with overall survival (OS) was constructed, and its reliability was validated with clinical CRC data. Most of the areas under the receiver operating characteristic curves (AUCs) values for 1-, 3- and 5-year OS for this signature were higher than those for the other six lncRNA signatures. OS, disease-specific survival and the progression-free interval were all significantly poorer in the high-risk group. The RS of the signature showed good concordance with the predicted prognosis, with AUCs for 1-, 3- and 5-year OS of 0.79, 0.81 and 0.77, respectively. Additionally, the calibration plots for this signature combined with clinical factors showed that this combination could effectively improve the ability to predict OS. The RS was correlated with tumor stage, lymph node metastasis and distant metastasis. Most of the enriched Kyoto Encyclopedia of Genes and Genomes and Gene Ontology terms were tumor metastasis-related pathways in the high-risk group; these patients showed greater infiltration of immunosuppressive cells, such as cancer-associated fibroblasts, hematopoietic stem cells and M2 macrophages, but less infiltration of infiltrating antitumor effector immune cells, such as cluster of differentiation 8+ T cells and regulatory T cells (Tregs). We explored additional potential immune checkpoint genes and potential immunotherapeutic and chemotherapeutic drugs with relatively low IC50 values. CONCLUSION: We identified an NRL signature with strong fidelity that could stably predict prognosis and might be an indicator of the TME of CRC. Furthermore, additional potential immunotherapeutic and chemotherapeutic drugs were explored.

The effect of restrictive vs. liberal fluid protocols on ocular parameters in patients undergoing prone spine surgery: a randomized controlled trial.

BACKGROUND: Elevated intraocular pressure (IOP) and optic nerve edema occurring during prone surgeries may cause ocular and optic nerve ischaemia injury. We hypothesized that a liberal fluid protocol might further increase IOP and optic nerve sheath diameter (ONSD) than a restrictive fluid protocol for patients in the prone position. METHODS: A single-centre, prospective and randomized trial was conducted. Patients were randomly allocated into 2 groups: the liberal fluid infusion group, in which repeated bolus doses of Ringer's lactate solution were given to maintain pulse pressure variation (PPV) within 6~9%, and the restrictive fluid infusion group, where PPV was maintained within 13-16%. IOP and ONSD were measured in both eyes at 10min after the anaesthesia induction in the supine position, 10min after the prone position placement, and 1h and 2h since the prone position was placed, at the conclusion of surgery, and returned to the supine position. RESULTS: A total of 97 patients were recruited and completed the study. IOP increased significantly from 12±3mmHg in the supine position to 31±5 mmHg (p<0.001) at the end of surgery in the liberal fluid infusion group and from 12±2 to 28±4 mmHg (p<0.001) in the restrictive fluid infusion group. There was a statistically significant difference in the change of IOP over time between the two groups (p=0.019). ONSD increased significantly from 5.3±0.3mm in the supine position to 5.5±0.3mm (p<0.001) at the end of surgery in both groups (both p<0.001). There was no statistically significant difference in the change of ONSD over time between the two groups (p>0.05). CONCLUSIONS: Compared to the restrictive fluid protocol, the liberal fluid protocol increased IOP but not ONSD in patients undergoing prone spine surgery. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov ( https://clinicaltrials.gov ) prior to patient enrollment, ID: NCT03890510, on March 26, 2019. The principal investigator was Xiao-Yu Yang.

Effects of linalool on Botrytis cinerea growth and control of tomato gray mold.

We examined the antifungal characteristics of linalool against Botrytis cinerea using plate inhibition assay and spore germination assay, and assessed the capacity of linalool in controlling tomato gray mold disease via tomato pot inoculation assay. The results showed that linalool exhibited strong inhibitive effects on mycelial growth of B. cinerea, with an EC50 value of 0.581 mL·L-1. In the spore germination test, linalool treatment inhibited spore germination in a dose-dependent manner. The electric conductivity and the malondialdehyde (MDA) contents were significantly increased in linalool-treated B. cinerea than that of the control, indicating that linalool induced oxidative damage and destroyed the cell membrane integrity in B. cinerea. The activities of the superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) in the linalool-treated B. cinerea were decreased significantly by 27.4%, 68.9% and 26.0%, respectively, suggesting that linalool inhibited the antioxidant activity of B. cinerea. In the pot experiment, the diameter of lesions in linalool-treated tomatoes was significantly smaller than that of the control. The activities of SOD, POD, CAT, polyphenol oxidase, and phenylalnine ammonialyase in the linalool-treated tomatoes increased, while the MDA content decreased, suggesting that linalool could alleviate the oxidative damage caused by B. cinerea and promote plant disease resistance. In summary, linalool had inhibitory effect on the growth of B. cinerea and could control gray mold disease in tomatoes. These findings could lay the foundation for developing bota-nical antifungal agents for management of tomato gray mold disease.

The action of topical application of Vitamin B12 ointment on radiodermatitis in a porcine model.

Radiodermatitis is an inevitable side effect of radiotherapy in cancer treatment and there is currently no consensus on effective drugs for treating the condition. Vitamin B12 is known to be effective for repairing and regenerating damaged skin. However, there are few studies on the use of Vitamin B12 for treating radiodermatitis. This study explored the therapeutic efficacy and mechanism of action of Vitamin B12 ointment on radiodermatitis. A porcine model of grade IV radiodermatitis was established. The ointment was applied for 12 weeks after which histological staining, transmission electron microscopy, RT-qPCR, western blotting, and gene sequencing were performed for the evaluation of specific indicators in skin samples. After 12 weeks of observation, the Vitamin B12 treatment was found to have significantly alleviated radiodermatitis. The treatment also significantly reduced the expression levels of NF-κB, COX-2, IL-6, and TGF-ß in the skin samples. The pathways involved in the effects of the treatment were identified by analysing gene expression. In conclusion, Vitamin B12 ointment was found to be highly effective for treating radiodermatitis, with strong anti-radiation, anti-inflammatory, and anti-fibrosis effects. It is thus a promising drug candidate for the treatment of severe radiodermatitis.

Multiple roles for cholinergic signaling in pancreatic diseases.

Cholinergic nerves are widely distributed throughout the human body and participate in various physiological activities, including sensory, motor, and visceral activities, through cholinergic signaling. Cholinergic signaling plays an important role in pancreatic exocrine secretion. A large number of studies have found that cholinergic signaling overstimulates pancreatic acinar cells through muscarinic receptors, participates in the onset of pancreatic diseases such as acute pancreatitis and chronic pancreatitis, and can also inhibit the progression of pancreatic cancer. However, cholinergic signaling plays a role in reducing pain and inflammation through nicotinic receptors, but enhances the proliferation and invasion of pancreatic tumor cells. This review focuses on the progression of cholinergic signaling and pancreatic diseases in recent years and reveals the role of cholinergic signaling in pancreatic diseases.

Artificial intelligence using deep neural network learning for automatic location of the interscalene brachial plexus in ultrasound images.

BACKGROUND: Identifying the interscalene brachial plexus can be challenging during ultrasound-guided interscalene block. OBJECTIVE: We hypothesised that an algorithm based on deep learning could locate the interscalene brachial plexus in ultrasound images better than a nonexpert anaesthesiologist, thus possessing the potential to aid anaesthesiologists. DESIGN: Observational study. SETTING: A tertiary hospital in Shanghai, China. PATIENTS: Patients undergoing elective surgery. INTERVENTIONS: Ultrasound images at the interscalene level were collected from patients. Two independent image datasets were prepared to train and evaluate the deep learning model. Three senior anaesthesiologists who were experts in regional anaesthesia annotated the images. A deep convolutional neural network was developed, trained and optimised to locate the interscalene brachial plexus in the ultrasound images. Expert annotations on the datasets were regarded as an accurate baseline (ground truth). The test dataset was also annotated by five nonexpert anaesthesiologists. MAIN OUTCOME MEASURES: The primary outcome of the research was the distance between the lateral midpoints of the nerve sheath contours of the model predictions and ground truth. RESULTS: The data set was obtained from 1126 patients. The training dataset comprised 11 392 images from 1076 patients. The test dataset constituted 100 images from 50 patients. In the test dataset, the median [IQR] distance between the lateral midpoints of the nerve sheath contours of the model predictions and ground truth was 0.8 [0.4 to 2.9] mm: this was significantly shorter than that between nonexpert predictions and ground truth (3.4 mm [2.1 to 4.5] mm; P < 0.001). CONCLUSION: The proposed model was able to locate the interscalene brachial plexus in ultrasound images more accurately than nonexperts. TRIAL REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov) identifier: NCT04183972.

The LINC00261/MiR105-5p/SELL axis is involved in dysfunction of B cell and is associated with overall survival in hepatocellular carcinoma.

Background: Previous studies have been reported the immune dysfunction of various live tissues. However, the potential molecular mechanism of post-transcriptional regulation of immune related genes in hepatocellular carcinoma (HCC) is still not clear. We tried to identify crucial immune related biomarkers associated with HCC patients' outcomes and to reveal the transcriptional regulation. Method: The fractions of 22 immune cells in tumor and adjacent tissues were estimated by CIBERSORT. Kruskal-Wallis test and differentially expressed analyzes were used for comparative studies. Cox proportional hazard regression model, Kaplan-Meier estimates and Log-rank test were used for survival analyses. Results: From The Cancer Genome Atlas (TCGA), the gene, lncRNA and miRNA expression profiles of 379 HCC samples with clinical information were used for comparative studies. Eleven adaptive and innate immune cell types were significantly altered in HCC samples, including B cell memory, regulatory T cells and follicular helper T cells. Differentially expressed competing endogenous RNA (ceRNA) network associated with patients' overall survival was identified. Then, the novel pathway, including LINC00261, MiR105-5p and selectin L(SELL) was found and may be potential novel biomarkers for patients' outcomes and immunotherapy. Furthermore, SELL was significantly positively correlated (correlation coefficients: 0.47-0.69) with 12 known gene signatures of immunotherapy except for programmed cell death 1 (PDCD1). Conclusions: Our findings could provide insights into the selection of novel LINC00261/MiR105-5p/SELL pathway which is associated with overall survival and may impact on efficacy of immunotherapy in HCC.

Clinical characteristics of anti-N-methyl-D-aspartate receptor encephalitis in patients with a long-term history of mental disorders.

BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune disorder characterized by complex neuropsychiatric syndromes during disease onset. Although this disease has been well documented in the last decade, clinical characteristics of anti-NMDA receptor encephalitis in patients with long-term diagnostic history of mental disorders remain unclear. METHODS: Here, we reviewed and analyzed series of anti-NMDA receptor encephalitis patients with a long-term medical history of psychiatric disorders through a review of literature using PubMed, web of science and Embase database. In addition, we described a patient of anti-NMDA receptor encephalitis with a long-term history of major depressive disorder. RESULTS: A total of 14 patients with anti-NMDA receptor encephalitis and a long-term history of mental disorders were included in our study. We found that most patients were adult (92.9%) and female (78.6%). These patients often first visited a psychiatric department (71.43%). The mean disease course of psychiatric disorders was more than 9 years. Speech impairment (71.4%), abnormal behaviors (64.3%), and catatonia (64.3%) were the most common clinical symptoms. Most patients (85.7%) had a satisfactory prognosis after immunotherapy. CONCLUSION: Anti-NMDA receptor encephalitis in individuals with mental disorders is an underestimated condition, yet it presents complex clinical symptoms. Mental and behavioral impairments are more frequently observed in newly diagnosed anti-NMDA receptor encephalitis patients with a long-term history of mental disorders than those without mental illness. A diagnosis of anti-NMDA receptor encephalitis should be considered when patients with mental illness show sudden fluctuations in psychiatric symptoms.

A computed tomography (CT)-derived radiomics approach for predicting primary co-mutations involving TP53 and epidermal growth factor receptor (EGFR) in patients with advanced lung adenocarcinomas (LUAD).

BACKGROUND: Epidermal growth factor receptor (EGFR) co-mutated with TP53 could reduce responsiveness to tyrosine kinase inhibitors (TKIs) and worsen patients' prognosis compared to TP53 wild type patients in. EGFR: mutated lung adenocarcinomas (LUAD). To identify this genetically unique subset prior to treatment through computed tomography (CT) images had not been reported yet. METHODS: Stage III and IV LUAD with known mutation status of EGFR and TP53 from The First Affiliated Hospital of Sun Yat-sen University (May 1, 2017 to June 1, 2020) were collected. Characteristics of pretreatment enhanced-CT images were analyzed. One-versus-one was used as the multiclass classification strategy to distinguish the three subtypes of co-mutations: EGFR + & TP53 +, EGFR + & TP53 -, EGFR -. The clinical model, semantic model, radiomics model and integrated model were built. Area under the receiver-operating characteristic curves (AUCs) were used to evaluate the prediction efficacy. RESULTS: A total of 199 patients were enrolled, including 83 (42%) cases of EGFR -, 55 (28%) cases of EGFR + & TP53 +, 61 (31%) cases of EGFR + & TP53 -. Among the four different models, the integrated model displayed the best performance for all the three subtypes of co-mutations: EGFR - (AUC, 0.857; accuracy, 0.817; sensitivity, 0.998; specificity, 0.663), EGFR + & TP53 + (AUC, 0.791; accuracy, 0.758; sensitivity, 0.762; specificity, 0.783), EGFR + & TP53 - (AUC, 0.761; accuracy, 0.813; sensitivity, 0.594; specificity, 0.977). The radiomics model was slightly inferior to the integrated model. The results for the clinical and the semantic models were dissatisfactory, with AUCs less than 0.700 for all the three subtypes. CONCLUSIONS: CT imaging based artificial intelligence (AI) is expected to distinguish co-mutation status involving TP53 and EGFR. The proposed integrated model may serve as an important alternative marker for preselecting patients who will be adaptable to and sensitive to TKIs.

Development and validation of nomograms to intraoperatively predict metastatic patterns in regional lymph nodes in patients diagnosed with esophageal cancer.

BACKGROUND: An accurate intraoperative prediction of lymph node metastatic risk can help surgeons in choosing precise surgical procedures. We aimed to develop and validate nomograms to intraoperatively predict patterns of regional lymph node (LN) metastasis in patients with esophageal cancer. METHODS: The prediction model was developed in a training cohort consisting of 487 patients diagnosed with esophageal cancer who underwent esophagectomy with complete LN dissection from January 2016 to December 2016. Univariate and multivariable logistic regression were used to identify independent risk factors that were incorporated into a prediction model and used to construct a nomogram. Contrast-enhanced computed tomography reported LN status and was an important comparative factor of clinical usefulness in a validation cohort. Nomogram performance was assessed in terms of calibration, discrimination, and clinical usefulness. An independent validation cohort comprised 206 consecutive patients from January 2017 to December 2017. RESULTS: Univariate analysis and multivariable logistic regression revealed three independent predictors of metastatic regional LNs, three independent predictors of continuous regional LNs, and two independent predictors of skipping regional LNs. Independent predictors were used to build three individualized prediction nomograms. The models showed good calibration and discrimination, with area under the curve (AUC) values of 0.737, 0.738, and 0.707. Application of the nomogram in the validation cohort yielded good calibration and discrimination, with AUC values of 0.728, 0.668, and 0.657. Decision curve analysis demonstrated that the three nomograms were clinically useful in the validation cohort. CONCLUSION: This study presents three nomograms that incorporate clinicopathologic factors, which can be used to facilitate the intraoperative prediction of metastatic regional LN patterns in patients with esophageal cancer.

Antagonistic effect of N-acetyl-L-cysteine against cadmium-induced cytotoxicity and abnormal immune response on chicken peritoneal macrophages.

Cadmium is a highly toxic metal threatening human and animal health. N-acetyl-L-cysteine (NAC) was reported to play a positive role in disease treatment and immune regulation. The present study aimed to explore the effect of NAC administration on Cd-induced cytotoxicity and abnormal immune response on chicken peritoneal macrophages. Peritoneal macrophages isolated from Isa Brown male chickens were exposed to CdCl2 (20 or 50 µM) and/or NAC (500 µM) for different time periods. Results showed that Cd caused dose-dependent damage on chicken peritoneal macrophages characterized by morphologic and ultrastructural alterations, increased cell apoptosis, reactive oxygen species accumulation and mitochondrial injury. Cd exposure inhibited phagocytic activity of chicken peritoneal macrophages, and promoted transcriptional status of pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) in both unactivated macrophages and cells in response to lipopolysaccharide (LPS) stimuli. Pretreatment with 500 µM NAC did not affect growth of normal chicken peritoneal macrophages, while remarkably inhibiting Cd-caused cell death, oxidative stress, and mitochondrial membrane depolarization. NAC pretreatment significantly prevented intracellular Cd2+ accumulation in the Cd-exposed macrophages. Inhibitory effects of NAC on Cd-induced ROS accumulation and mitochondrial injury on chicken macrophages were confirmed in HD-11 macrophage cell line. In addition, NAC pretreatment promoted the phagocytic activity of Cd-exposed chicken peritoneal macrophages, and significantly inhibited expression of pro-inflammatory factors (IL-1ß, IL-6 and TNF-α) in both Cd-exposed macrophages and Cd-treated cells in response to LPS stimuli. In conclusion, the present study firstly demonstrated the antagonistic effect of NAC against Cd-caused damage and abnormal immune response on chicken peritoneal macrophages. Protective effect of NAC on chicken macrophages was highly related to its suppression on Cd-induced ROS overproduction, pro-inflammatory reaction and intracellular Cd2+ accumulation.

A CT-derived deep neural network predicts for programmed death ligand-1 expression status in advanced lung adenocarcinomas.

BACKGROUND: Programmed death ligand-1 (PD-L1) expression remains a crucial predictor in selecting patients for immunotherapy. The current study aimed to non-invasively predict PD-L1 expression based on chest computed tomography (CT) images in advanced lung adenocarcinomas (LUAD), thus help select optimal patients who can potentially benefit from immunotherapy. METHODS: A total of 127 patients with stage III and IV LUAD were enrolled into this study. Pretreatment enhanced thin-section CT images were available for all patients and were analyzed in terms of both morphologic characteristics by radiologists and deep learning (DL), so to further determine the association between CT features and PD-L1 expression status. Univariate analysis and multivariate logical regression analysis were applied to evaluate significant variables. For DL, the 3D DenseNet model was built and validated. The study cohort were grouped by PD-L1 Tumor Proportion Scores (TPS) cutoff value of 1% (positive/negative expression) and 50% respectively. RESULTS: Among 127 LUAD patients, 46 (36.2%) patients were PD-L1-positive and 38 (29.9%) patients expressed PD-L1-TPS ≥50%. For morphologic characteristics, univariate and multivariate analysis revealed that only lung metastasis was significantly associated with PD-L1 expression status despite of different PD-L1 TPS cutoff values, and its Area under the receiver operating characteristic curve (AUC) for predicting PD-L1 expression were less than 0.700. On the other hand, the predictive value of DL-3D DenseNet model was higher than that of the morphologic characteristics, with AUC more than 0.750. CONCLUSIONS: The traditional morphologic CT characteristics analyzed by radiologists show limited prediction efficacy for PD-L1 expression. By contrast, CT-derived deep neural network improves the prediction efficacy, it may serve as an important alternative marker for clinical PD-L1 detection.

[Advances on the role of primary cilia in neurological diseases].

Primary cilium, widely distributed in mammalian central nervous system, is an important extracellular organelle of cells. The primary cilia contain a variety of ion channels, G-protein coupled receptors and different kinds of kinases, which indicates that primary cilia can detect extracellular signals and transduce them into cells to regulate various cellular and physiological processes. In humans, mutations of genes related to structure and function of primary cilia always cause various monogenetic diseases. Moreover, a series of neuropsychiatric diseases and neurodevelopmental dysplasia are caused by abnormal functions of G-protein coupled receptors, kinases and ion channels in primary cilia. This article reviews recent research progress on the role of primary cilia in related neurological diseases.

Nickel nanoparticles supported on a covalent triazine framework as electrocatalyst for oxygen evolution reaction and oxygen reduction reactions.

Covalent triazine frameworks (CTFs) are little investigated, albeit they are promising candidates for electrocatalysis, especially for the oxygen evolution reaction (OER). In this work, nickel nanoparticles (from Ni(COD)2) were supported on CTF-1 materials, which were synthesized from 1,4-dicyanobenzene at 400 °C and 600 °C by the ionothermal method. CTF-1-600 and Ni/CTF-1-600 show high catalytic activity towards OER and a clear activity for the electrochemical oxygen reduction reaction (ORR). Ni/CTF-1-600 requires 374 mV overpotential in OER to reach 10 mA/cm2, which outperforms the benchmark RuO2 catalyst, which requires 403 mV under the same conditions. Ni/CTF-1-600 displays an OER catalytic activity comparable with many nickel-based electrocatalysts and is a potential candidate for OER. The same Ni/CTF-1-600 material shows a half-wave potential of 0.775 V for ORR, which is slightly lower than that of commercial Pt/C (0.890 V). Additionally, after accelerated durability tests of 2000 cycles, the material showed only a slight decrease in activity towards both OER and ORR, demonstrating its superior stability.

Clinicopathologic predictors of metastasis of different regional lymph nodes in patients intraoperatively diagnosed with stage-I non-small cell lung cancer.

BACKGROUND: Selection of the best lymph node for dissection is a controversial topic in clinical stage-I non-small cell lung cancer (NSCLC). Here, we sought to identify the clinicopathologic predictors of regional lymph node metastasis in patients intraoperatively diagnosed with stage-I NSCLC. METHODS: A retrospective review of 595 patients intraoperatively diagnosed as stage I non-small-cell lung cancer who underwent lobectomy with complete lymph node dissection was performed. Univariate and multivariable logistic regression analysis was performed to determine the independent predictors of regional lymph node metastasis. RESULTS: Univariate logistic regression and multivariable analysis revealed three independent predictors of the presence of metastatic hilar lymph nodes, five independent predictors for lobe specific mediastinal lymph nodes, two independent predictors for lobe nonspecific mediastinal lymph nodes and two independent predictors for skipping mediastinal lymph nodes. CONCLUSIONS: A complete mediastinal lymph node dissection may be considered for patients suspected of nerve invasion and albumin (> 43.1 g/L) or nerve and vascular invasions. Lobe-specific lymph node dissection should probably be performed for patients suspected of pulmonary membrane invasion, vascular invasion, CEA (> 2.21 ng/mL), and tumor (> 1.6 cm) in the right lower lobe or mixed lobes. Hilar lymph node dissection should probably be performed for patients suspected of having bronchial mucosa and cartilage invasion, vascular invasion, and CEA (> 2.21 ng/mL).

Intramuscular Injection of Adenoassociated Virus Encoding Human Neurotrophic Factor 3 and Exercise Intervention Contribute to Reduce Spasms after Spinal Cord Injury.

Limb spasms are phenomena of hyperreflexia that occur after spinal cord injury. Currently, the clinical treatment is less than ideal. Our goal is to develop a combination therapy based on individualized medicine to reduce spasticity after spinal cord injury. In this study, rats received a severe contusive injury at the T9 segment of the spinal cord, followed by gene therapy with adenoassociated virus encoding human neurotrophic factor 3 (AAV-NT3) and a 2-week exercise program starting at 4 weeks after injury. We quantified the frequency of spasms during a swimming test at 4 and 6 weeks after injury and confirmed the results of the swimming test by measuring the H-reflex of the plantar muscle. We obtained weekly hind limb exercise scores to assess the effect of the interventions in hind limb motor function improvement. Then, we used immunofluorescence to observe the immunoreactivity of spinal motor neurons, synaptophysin, cholinergic interneurons, and GABAergic interneurons. We also measured the expression of KCC2 in the spinal cord by western blot. We found that AAV-NT3 gene therapy, exercise, and combination therapy all attenuated the frequency of spasms in the swimming test conducted at 6 weeks after spinal cord injury and increased rate-dependent depression of H-reflex. Combination therapy was significantly superior to AAV-NT3 alone in protecting motor neurons. Recovery of KCC2 expression was significantly greater in rats treated with combination therapy than in the exercise group. Combination therapy was also significantly superior to individual therapies in remodeling spinal cord neurons. Our study shows that the combination of AAV-NT3 gene therapy and exercise can alleviate muscle spasm after spinal cord injury by altering the excitability of spinal interneurons and motor neurons. However, combination therapy did not show a significant additive effect, which needs to be improved by adjusting the combined strategy.