Machine learning framework develops neutrophil extracellular traps model for clinical outcome and immunotherapy response in lung adenocarcinoma.

Neutrophil extracellular traps (NETs) are novel inflammatory cell death in neutrophils. Emerging studies demonstrated NETs contributed to cancer progression and metastases in multiple ways. This study intends to provide a prognostic NETs signature and therapeutic target for lung adenocarcinoma (LUAD) patients. Consensus cluster analysis performed by 38 reported NET-related genes in TCGA-LUAD cohorts. Then, WGCNA network was conducted to investigate characteristics genes in clusters. Seven machine learning algorithms were assessed for training of the model, the optimal model was picked by C-index and 1-, 3-, 5-year ROC value. Then, we constructed a NETs signature to predict the overall survival of LUAD patients. Moreover, multi-omics validation was performed based on NETs signature. Finally, we constructed stable knockdown critical gene LUAD cell lines to verify biological functions of Phospholipid Scramblase 1 (PLSCR1) in vitro and in vivo. Two NETs-related clusters were identified in LUAD patients. Among them, C2 cluster was provided as "hot" tumor phenotype and exhibited a better prognosis. Then, WGCNA network identified 643 characteristic genes in C2 cluster. Then, Coxboost algorithm proved its optimal performance and provided a prognostic NETs signature. Multi-omics revealed that NETs signature was involved in an immunosuppressive microenvironment and predicted immunotherapy efficacy. In vitro and in vivo experiments demonstrated that knockdown of PLSCR1 inhibited tumor growth and EMT ability. Besides, cocultural assay indicated that the knockdown of PLSCR1 impaired the ability of neutrophils to generate NETs. Finally, tissue microarray (TMA) for LUAD patients verified the prognostic value of PLSCR1 expression. In this study, we focus on emerging hot topic NETs in LUAD. We provide a prognostic NETs signature and identify PLSCR1 with multiple roles in LUAD. This work can contribute to risk stratification and screen novel therapeutic targets for LUAD patients.

RNA-seq analysis revealed genes associated with neuropathic pain induced by chronic compressive injury in interferon regulatory factors 4 knockout mice.

OBJECTIVE: To explore the differential expression of genes between wild-type chronic compressive injury (CCI) mice (WT-CCI) and interferon regulatory factors 4 (IRF4) knockout CCI mice (KO-CCI) by RNA-seq analysis of the mouse spinal cord. METHODS: RNA-seq analysis of the spinal cord tissue of the chronic sciatic nerve ligation mice and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used. RESULTS: A total of 104 genes were up-regulated and 116 genes were down-regulated in spinal cord of the mice in IRF4 knockout (KO-CCI) group compared with that in the wild-type CCI (WT-CCI) group. There were 1472 differentially expressed genes in the biological process group, 62 differentially expressed genes in the cellular component group, and 163 differentially expressed genes in the molecular function group in KO-CCI mice. A total of 14 genes related to inflammatory reactions were differentially expressed. Real-time PCR results confirmed that Pparg and Grpr mRNA expression was up-regulated and Arg 1 and Ccl11 mRNA expression was down-regulated in the KO-CCI group. CONCLUSION: IRF4 is involved in neuropathic pain in CCI mice, IRF4 may participate in neuropathic pain by regulating Grpr, Mas1, Galr3, Nos2, Arg1, Ccl11, Ptgs2, S100a8, Pparg, Cd40, Has2, Gpr151, Il123a, Capns2, Ankrd1, Ccnb1, and Nppb genes.

Establishment of an animal model of sciatic nerve injury induced by local anesthetics.

Peripheral neurotoxicity injury caused by local anesthetics is a common complication of clinical anesthesia. The study of its mechanism is helpful to prevent and treat the neurotoxic injury of local anesthetics. Previous studies on peripheral neurotoxicity injury caused by local anesthetics have mainly focused on in vitro cell experiments. Due to the lack of an animal model of peripheral neurotoxicity damage caused by local anesthetics, there are few in vivo experimental studies regarding this topic. Herein, 1% ropivacaine hydrochloride was injected into the sciatic nerve by direct incision and exposure of the sciatic nerve to create a local anesthetic neurotoxic injury model. The results showed that 1% ropivacaine hydrochloride could reduce the lower limb motor score and mechanical paw withdrawal threshold in mice 48 hours after injection. Pathological sections showed that 48 hours after treatment with 1% ropivacaine hydrochloride, the sciatic nerve showed increased axonal edema and degeneration, edema between nerve fiber bundles, increased degeneration of axon and myelin sheath vacuoles, edema of nerve bundle membrane and local degeneration and necrosis, and a large number of inflammatory cells around the nerve adventitia were soaked. The above results show that under open vision, 1% ropivacaine hydrochloride can cause injury to the sciatic nerve after 48 h of treatment, which can simulate the neurotoxic damage of local anesthetics. This animal model provides a research tool for studying the mechanism of neurotoxic injury caused by local anesthetics.

Biomimetic nitrogen-rich photocatalyst based on cadmium sulfide for photocatalytic hydrogen evolution.

A novel N-rich sugarcane-like photocatalyst CdS/C3N5 (CCN) was prepared by a thermal polymerization method and tested for generating H2 and realizing antiphotocorrosive performance. The best photocatalytic H2 evolution is obtained for a CdS to C3N5 mass ratio of 1:1 (CCN3), which is nearly 33 and 3 times higher than that of pure C3N5 and CdS, respectively. CCN3 can be used to effectively reduce CdS photocorrosion and increase stability because of its N-rich performance and sugarcane-like structure, which can affect electron transport and enhance the internal binding force, respectively. CCN3 can maintain a high H2 evolution ability after 5 cycles, while still maintaining the original sugarcane-like shape, which has an anti-photocorrosive ability.

Clinical Observation of NB-UVB Combined with Total Glucosides of White Paeony Capsules and Urea Cream in the Treatment of Psoriasis Vulgaris / 中国药房

OBJECTIVE:To observe therapeutic efficacy and safety of NB-UVB combined with Total glucosides of white paeony(TGP)capsules and Urea cream in the treatment of psoriasis vulgaris. METHODS:A total of 75 patients with psoriasis vulgaris in dermatology department of our hospital during Jan. 2015-Dec. 2016 were divided into control group(37 cases)and observation group(38 cases)according to random number table. Control group was given TGP capsules 0.6 g orally,3 times a day,reducing to 0.3 g,3 times a day if diarrhea or stool increased significantly after taking the medicine+Urea cream,smearing on the skin,day and evening,for consecutive 12 weeks. Observation group was additionally given NB-UVB irradiation with initial dose of 0.36 J/cm2,2 min/time,every other day,adjusted according to skin reaction for consecutive 8 weeks,on the basis of control group. Clinical efficacies of 2 groups were observed,and PASI scores before and after treatment and the occurrence of ADR were observed. RESULTS:One patient of observation group withdrew from therapy after suffering from obvious edematous erythema with pain due to irradiation. All patients of control group completed treatment. Total response rate of observation group (86.49%)was significantly higher than that of control group(56.76%),with statistical significance(P<0.05). Before treatment, there was no statistical significance in PASI scores between 2 groups(P>0.05). After treatment,PASI scores of 2 groups were significantly lower than before treatment,and observation group was significantly lower than control group,with statistical significance(P<0.05). There was no statistical significance in total incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:NB-UVB combined with TGP capsules and Urea cream show good therapeutic efficacy and safety for psoriasis vulgaris,and can significantly decrease PASI score of patients.