Objective To establish a machine learning radiomics model that can accurately predict MRI enhancement patterns of glioma based on T2 fluid attenuated inversion recovery(T2-FLAIR)images for optimizing the workflow of magnetic resonance imaging(MRI)examinations of glioma patients.Methods We retrospectively collected preoperative MR T2-FLAIR images from 385 patients with pathologically confirmed glioma,who were divided into enhancing and non-enhancing groups according to the enhancement pattern.Predictive radiomics models were established using Gaussian Process,Linear Regression,Linear Regression-Least absolute shrinkage and selection operator,Support Vector Machine,Linear Discriminant Analysis or Naive Bayes as the classifiers in the training cohort(n=201)and tested both in the internal(n=85)and external validation cohorts(n=99).The receiver-operating characteristic curve was used to assess the predictive performance of the models.Results The predictive model constructed based on 15 radiomics features using Gaussian Process as the classifier had the best predictive performance in both the training cohort and the internal validation cohort,with areas under the curve(AUC)of 0.88(95%CI:0.81-0.94)and 0.80(95%CI:0.71-0.88),respectively.In the external validation cohort,the model showed an AUC of 0.81(95%CI:0.71-0.90)with sensitivity,specificity,positive predictive value and negative predictive value of 0.98,0.61,0.76 and 0.96,respectively.Conclusion The T2-FLAIR-based machine learning radiomics model can accurately predict the enhancement pattern of gliomas on MRI.

Objective To establish a machine learning radiomics model that can accurately predict MRI enhancement patterns of glioma based on T2 fluid attenuated inversion recovery(T2-FLAIR)images for optimizing the workflow of magnetic resonance imaging(MRI)examinations of glioma patients.Methods We retrospectively collected preoperative MR T2-FLAIR images from 385 patients with pathologically confirmed glioma,who were divided into enhancing and non-enhancing groups according to the enhancement pattern.Predictive radiomics models were established using Gaussian Process,Linear Regression,Linear Regression-Least absolute shrinkage and selection operator,Support Vector Machine,Linear Discriminant Analysis or Naive Bayes as the classifiers in the training cohort(n=201)and tested both in the internal(n=85)and external validation cohorts(n=99).The receiver-operating characteristic curve was used to assess the predictive performance of the models.Results The predictive model constructed based on 15 radiomics features using Gaussian Process as the classifier had the best predictive performance in both the training cohort and the internal validation cohort,with areas under the curve(AUC)of 0.88(95%CI:0.81-0.94)and 0.80(95%CI:0.71-0.88),respectively.In the external validation cohort,the model showed an AUC of 0.81(95%CI:0.71-0.90)with sensitivity,specificity,positive predictive value and negative predictive value of 0.98,0.61,0.76 and 0.96,respectively.Conclusion The T2-FLAIR-based machine learning radiomics model can accurately predict the enhancement pattern of gliomas on MRI.

Objective To explore the associations between genetic variations of DNA repair gene RAD52 and response to platinum?based chemotherapy of small cell lung cancer ( SCLC) , and to analyze the influencing factors on survival. Methods Nine haplotype?tagging single nucleotide polymorphisms ( htSNPs) of RAD52 were genotyped by Sequenom Mass ARRAY technology in 939 SCLC patients who received platinum?based chemotherapy, and had different response and survival time. The associations between genotypes and platinum?based chemotherapy response were analyzed by odds ratios ( ORs) and 95%confidence intervals ( CIs) , adjusted for sex, age, smoking, KPS, staging and chemotherapy regimens, by unconditional logistic regression model. The relative ratios ( RRs ) were estimated using Cox proportional hazards regression model. Results Among the 939 cases, 483 ( 51. 4%) cases received cis?platinum and etoposide treatment while others treated with carboplatin and etoposide. Six hundred and eighty two patients were chemotherapy responders in the study with a response rate of 72.6%. Patients were followed up to get their survival information. The median survival time ( MST) of these patients was 25 months. We found that rs10774474 SNP which located in the 5′?flanking region of RAD52 was significantly associated with chemotherapy response. Compared with the TT genotype, patients with TA and AA genotype had a worse chemotherapy response and increased risk of no?response ( P=0. 004 ) . Correlation analysis showed that patients with KPS >80 had a better chemotherapy response than those with KPS≤80 (P=0.001). The patients with extensive?stage had a worse chemotherapy response than those with limited?stage (P<0.001). Cox proportional hazards regression model analysis showed that nine htSNPs of RAD52 were not associated with the overall survival ( OS) of SCLC patients who received platinum?based chemotherapy. Age≤56, KPS>80, limited?stage, chemotherapy response and radiation therapy can remarkably prolong OS ( all P<0.05) . Conclusions These results suggest that RAD52 genetic polymorphism rs10774474 plays an important role in the response to platinum?based chemotherapy, and may be a potential genetic biomarker for SCLC personalized treatment.

Objective To explore the associations between genetic variations of DNA repair gene RAD52 and response to platinum?based chemotherapy of small cell lung cancer ( SCLC) , and to analyze the influencing factors on survival. Methods Nine haplotype?tagging single nucleotide polymorphisms ( htSNPs) of RAD52 were genotyped by Sequenom Mass ARRAY technology in 939 SCLC patients who received platinum?based chemotherapy, and had different response and survival time. The associations between genotypes and platinum?based chemotherapy response were analyzed by odds ratios ( ORs) and 95%confidence intervals ( CIs) , adjusted for sex, age, smoking, KPS, staging and chemotherapy regimens, by unconditional logistic regression model. The relative ratios ( RRs ) were estimated using Cox proportional hazards regression model. Results Among the 939 cases, 483 ( 51. 4%) cases received cis?platinum and etoposide treatment while others treated with carboplatin and etoposide. Six hundred and eighty two patients were chemotherapy responders in the study with a response rate of 72.6%. Patients were followed up to get their survival information. The median survival time ( MST) of these patients was 25 months. We found that rs10774474 SNP which located in the 5′?flanking region of RAD52 was significantly associated with chemotherapy response. Compared with the TT genotype, patients with TA and AA genotype had a worse chemotherapy response and increased risk of no?response ( P=0. 004 ) . Correlation analysis showed that patients with KPS >80 had a better chemotherapy response than those with KPS≤80 (P=0.001). The patients with extensive?stage had a worse chemotherapy response than those with limited?stage (P<0.001). Cox proportional hazards regression model analysis showed that nine htSNPs of RAD52 were not associated with the overall survival ( OS) of SCLC patients who received platinum?based chemotherapy. Age≤56, KPS>80, limited?stage, chemotherapy response and radiation therapy can remarkably prolong OS ( all P<0.05) . Conclusions These results suggest that RAD52 genetic polymorphism rs10774474 plays an important role in the response to platinum?based chemotherapy, and may be a potential genetic biomarker for SCLC personalized treatment.

Objective: Saposhnikoviae Radix (Fangfeng in Chinese), the roots of Saposhnikovia divaricata, lacks commodity specification and grade standardization in the current market. This study investigated the existing specifications and grades of Saposhnikoviae Radix to provide a standardized scientific reference for its market use. Methods: Based on a textual research of Chinese herbal medicine from the Han Dynasty to the present, medicinal materials of different specifications and grades obtained from Saposhnikoviae Radix in the main producing areas of China were collected and the markets for these materials were investigated. Field investigations were performed in the major producing areas such as Northeast China, Hebei Province, and Inner Mongolia. Four major Chinese herbal medicine markets in China were investigated. Sensory indices were used to categorize the two specifications (wild and cultivated) according to the shape, color, texture, and cross-section. High-performance liquid chromatography was performed to determine the active components. Vernier calipers and measuring tape were used to measure the diameter and length, respectively, of 41 samples. Using Excel and the R Language software, cluster analysis and descriptive statistical analysis were performed to assist in the application of new specifications and grades based on physical characteristics, pharmacological activity, and chemical composition. Results: The two specifications (wild and cultivated) of Saposhnikoviae Radix were divided into three grades each based on the length and diameter. Prim-O-glucosylcimifugin, 5-O-methylvisamminoside, and the length of Saposhnikoviae Radix can be used as a basis for classifying the commodity specifications and grades. The specifications and grade standards of Saposhnikoviae Radix were established based on the following eight aspects: shape, surface characteristics, texture, cross section, taste, prim-O-glucosylcimifugin content, 5-O-methylvisamminoside content and length. Conclusion: The formulation of this standard stipulates the commodity specification level of Saposhnikoviae Radix. It is also suitable for the evaluation of commodity specifications in the process of production, circulation and use of Saposhnikoviae Radix.

Abivertinib, a third-generation tyrosine kinase inhibitor, is originally designed to target epidermal growth factor receptor (EGFR)-activating mutations. Previous studies have shown that abivertinib has promising antitumor activity and a well-tolerated safety profile in patients with non-small-cell lung cancer. However, abivertinib also exhibited high inhibitory activity against Bruton's tyrosine kinase and Janus kinase 3. Given that these kinases play some roles in the progression of megakaryopoiesis, we speculate that abivertinib can affect megakaryocyte (MK) differentiation and platelet biogenesis. We treated cord blood CD34⁺ hematopoietic stem cells, Meg-01 cells, and C57BL/6 mice with abivertinib and observed megakaryopoiesis to determine the biological effect of abivertinib on MK differentiation and platelet biogenesis. Our in vitro results showed that abivertinib impaired the CFU-MK formation, proliferation of CD34⁺ HSC-derived MK progenitor cells, and differentiation and functions of MKs and inhibited Meg-01-derived MK differentiation. These results suggested that megakaryopoiesis was inhibited by abivertinib. We also demonstrated in vivo that abivertinib decreased the number of MKs in bone marrow and platelet counts in mice, which suggested that thrombopoiesis was also inhibited. Thus, these preclinical data collectively suggested that abivertinib could inhibit MK differentiation and platelet biogenesis and might be an agent for thrombocythemia.
Acrylamides/pharmacology* ; Animals ; Blood Platelets/drug effects* ; Cell Differentiation ; Megakaryocytes/drug effects* ; Mice ; Mice, Inbred C57BL ; Piperazines/pharmacology* ; Pyrimidines/pharmacology*

Objective: To explore the associations between genetic variations of glutathione synthetase gene (GSS) and response to platinum-based chemotherapy of small cell lung cancer(SCLC), and to analyze the influencing factors on survival. Methods: Four haplotype-tagging single nucleotide polymorphisms (htSNPs) of GSS were genotyped by Sequenom MassARRAY methods in 903 SCLC patients who received platinum-based chemotherapy, and had different response and survival time. The associations between genotypes and platinum-based chemotherapy response were measured by odds ratios (OR) and 95% confidence intervals (CI), adjusted for sex, age, smoking, KPS, staging and chemotherapy regiments, by unconditional logistic regression model. The hazard ratios (HR) were estimated by Cox proportional hazards regression model. Results: Among the 903 patients, 462(51.2%) cases received cis-platinum and etoposide treatment while others were treated with carboplatin and etoposide. 656 patients were chemotherapy responders in the study with a response rate of 72.6%. Patients were followed up to get their survival information. The median survival time (MST) of these patients was 25.0 months.We found that rs725521 located in the 3′ near gene region of GSS was significantly associated with chemotherapy response. Compared with the T allele, patients with C allele had a worse chemotherapy response and an increased risk of no-responders (P=0.027). Rs7265992 and rs725521 of GSS were associated with the overall survival (OS) of SCLC patients who received platinum-based chemotherapy (HR=1.16, 95% CI=1.02-1.33, P=0.027; HR=1.17, 95% CI=1.05-1.31, P=0.006, respectively). The patients carrying 1 or 2 risk alleles and the patients carrying 3 or 4 risk alleles had worse MST than the patients without the rs7265992A and rs725521C risk alleles (24.0 and 22.0 versus 30.0 months), with the HR for death being 1.26 (95% CI=1.04-1.54) and with the HR of 1.52 (95%CI=1.18-1.97, P=0.001). Rs2025096 and rs2273684 were not associated with the OS of SCLC patients who received platinum-based chemotherapy. Age ≤ 56, KPS> 80, limited-stage, chemotherapy response and radiation therapy had a remarkably prolonged OS (all P<0.05). Conclusions These results suggest that GSS genetic polymorphism rs725521 plays an important role in the response to platinum-based chemotherapy, while rs7265992 and rs725521 have important effect on the prognosis of SCLC patients, which may be potential genetic biomarkers for personalized treatment of SCLC.

Pulmonary fibrosis (PF) is a pathological change caused by repeated injuries and repair dysfunction of the alveolar epithelium. Our previous study revealed that the residues Asn3 and Asn4 of peptide DR8 (DHNNPQIR-NH₂) could be modified to improve stability and antifibrotic activity, and the unnatural hydrophobic amino acids α-(4-pentenyl)-Ala and d-Ala were considered in this study. DR3penA (DHα-(4-pentenyl)-ANPQIR-NH₂) was verified to have a longer half-life in serum and to significantly inhibit oxidative damage, epithelial-mesenchymal transition (EMT) and fibrogenesis in vitro and in vivo. Moreover, DR3penA has a dosage advantage over pirfenidone through the conversion of drug bioavailability under different routes of administration. A mechanistic study revealed that DR3penA increased the expression of aquaporin 5 (AQP5) by inhibiting the upregulation of miR-23b-5p and the mitogen-activated protein kinase (MAPK) pathway, indicating that DR3penA may alleviate PF by regulating MAPK/miR-23b-5p/AQP5. Safety evaluation showed that DR3penA is a peptide drug without obvious toxicity or acute side effects and has significantly improved safety compared to DR8. Thus, our findings suggest that DR3penA, as a novel and low-toxic peptide, has the potential to be a leading compound for PF therapy, which provides a foundation for the development of peptide drugs for fibrosis-related diseases.

The antimicrobial peptide APKGVQGPNG (named YD), a natural peptide originating from Bacillus amyloliquefaciens CBSYD1, exhibited excellent antibacterial and antioxidant properties in vitro. These characteristics are closely related to inflammatory responses which is the central trigger for liver fibrosis. However, the therapeutic effects of YD against hepatic fibrosis and the underlying mechanisms are rarely studied. In this study, we show that YD improved liver function and inhibited the progression of liver fibrosis by measuring the serum transaminase activity and the expression of α-smooth muscle actin and collagen I in carbon tetrachloride-induced mice. Then we found that YD inhibited the level of miR-155, which plays an important role in inflammation and liver fibrosis. Bioinformatics analysis and luciferase reporter assay indicate that Casp12 is a new target of miR-155. We demonstrate that YD significantly decreases the contents of inflammatory cytokines and suppresses the NF-κB signaling pathway. Further studies show that transfection of the miR-155 mimic in RAW264.7 cells partially reversed the YD-mediated CASP12 upregulation, the downregulated levels of inflammatory cytokines, and the inactivation of the NF-κB pathways. Collectively, our study indicates that YD reduces inflammation through the miR-155–Casp12–NF-κB axis during liver fibrosis and provides a promising therapeutic candidate for hepatic fibrosis.