ObjectiveTo explore the effect of different drying conditions on the appearance and intrinsic quality indicators of Pinelliae Rhizoma for screening suitable drying conditions， so as to provide reference for its standardized production and quality evaluation. MethodsDifferent dried samples of Pinelliae Rhizoma were prepared by lime-assisted sweating method and intermittent drying method. Visual analysis was employed to measure the color brightness values（L^*） of the surface， cross-section and powder of the samples， texture analyzer was used to determine the hardness of the samples under different drying conditions. The total starch content was calculated by measuring the contents of amylose and amylopectin in the samples with ultraviolet-visible spectroscopy. High performance liquid chromatography（HPLC） was used to determine the contents of seven nucleoside components（uracil， hypoxanthine， uridine， inosine， guanosine， β-thymidine and adenosine） in the samples. Pearson correlation analysis was conducted to explore the correlation between the external characteristics and intrinsic indicators of the different dried samples. Principal component analysis（PCA） was used to comprehensively rank the data of various indicators， and partial least squares-discriminant analysis（PLS-DA） was used to screen differential components with variable importance in the projection（VIP） value>1. Furthermore， the difference between the optimal drying condition for Pinelliae Rhizoma and the traditional sun-drying method was explored by independent samples t-test. ResultsWith the increase of temperature， the color of the intermittently dried samples gradually deepened， while their hardness gradually decreased. Concurrently， the contents of extract， total starch， uridine and adenosine exhibited an upward trend， whereas the contents of uracil， hypoxanthine and inosine displayed a downward trajectory. Compared with the intermittent drying group， the content of extract in the samples subjected to lime-assisted sweating increased. With the increase of lime dose， the hardness and the total content of nucleoside components in the samples showed a downward trend， while the total starch content showed an upward trend. Correlation analysis showed that the comprehensive score of L^* was negatively correlated with the contents of uracil， hypoxanthine and inosine， and positively correlated with the contents of uridine， guanosine and adenosine. Hardness was negatively correlated with adenosine content， and positively correlated with the contents of inosine， uracil and hypoxanthine. Through comprehensive consideration and comprehensive score of principal components， the method of 5% lime-mixed sweating for 6 days emerged as the top-ranking approach. Except for the extract， the results of independent samples t-test showed that there was no significant difference between the 5% lime-mixed sweating for 6 days and the traditional sun-drying in terms of other content indicators. ConclusionThe whiteness and firmness of Pinelliae Rhizoma exhibit significant correlations with its chemical composition， while uridine， uracil， guanosine， adenosine and inosine are the key constituents responsible for the quality difference of Pinelliae Rhizoma under different drying conditions. The lime-assisted sweating method optimized in this study can be proposed as a viable alternative to the traditional sun-drying method. This method not only ensures the quality of the medicinal material but also effectively reduces the drying time and prevents mold contamination， which provides a valuable reference for the standardization of drying conditions and the establishment of quality evaluation criteria for Pinelliae Rhizoma.

Alfalfa(Medicago sativa L.)is the most important legume forage crop worldwide with high nutritional value and yield.For a long time,the breeding of alfalfa was hampered by lacking reliable information on the autotetraploid genome and molecular markers linked to important agro-nomic traits.We herein reported the de novo assembly of the allele-aware chromosome-level genome of Zhongmu-4,a cultivar widely cultivated in China,and a comprehensive database of genomic variations based on resequencing of 220 germplasms.Approximate 2.74 Gb contigs(N50 of 2.06 Mb),accounting for 88.39％of the estimated genome,were assembled,and 2.56 Gb contigs were anchored to 32 pseudo-chromosomes.A total of 34,922 allelic genes were identified from the allele-aware genome.We observed the expansion of gene families,especially those related to the nitrogen metabolism,and the increase of repetitive elements including transposable elements,which probably resulted in the increase of Zhongmu-4 genome compared with Medicago truncatula.Population structure analysis revealed that the accessions from Asia and South America had rela-tively lower genetic diversity than those from Europe,suggesting that geography may influence alfalfa genetic divergence during local adaption.Genome-wide association studies identified 101 sin-gle nucleotide polymorphisms(SNPs)associated with 27 agronomic traits.Two candidate genes were predicted to be correlated with fall dormancy and salt response.We believe that the allele-aware chromosome-level genome sequence of Zhongmu-4 combined with the resequencing data of the diverse alfalfa germplasms will facilitate genetic research and genomics-assisted breeding in variety improvement of alfalfa.

Objective To assess the efficacy and side effects of intravesical instillation of BCG after transurethral resection of the bladder tumor (TURBT) in non-muscle invasive bladder cancer (NMIBC) patients.Methods The clinical data of patients treated with BCG 120 mg per course induced perfusion or more after TURBT from December 2013 to October 2016 in 18 hospitals of northeast China region,were analyzed retrospectively.The first part,data of 106 patients with moderate,high-risk NMIBC were collected.A total of 83 patients were male,while the other 23 patients were female.The average age was 66.7 years old.The clinical staging were T1 in 86(81.1％) cases,Ta in 20(18.9％) cases and carcinoma in situ in 6 (5.7％) patients.Intravesical instillation of BCG was executed after transurethral resection of the bladder tumor.The incidence rate of recurrence and progression during more than 6 months' follow-up time were observed.Multivariate analyses were done by using logistic analysis and Cox proportional hazards regression model with Kaplan-Meier method.The second part,treatment compliance of 276 patients with bladder cancer,including moderate/high-risk NMIBC in 263 cases,moderate/high-risk NMIBC followed with renal pelvis/ureteral carcinoma in 8 cases were and moderate/high-risk NMIBC with renal pelvis/ureteral carcinoma in 5 cases who treated with BCG after the surgeries,were observed.Patients consisted of 211 males and 65 females with average age of 68.3 years.Results With a median follow-up of 12 months,9 (8.5％) patients experienced tumor recurrence and 2 (1.9％) patients were found progression in the first part.The one-year cancer free recurrence rate of the patients was 91.5％.Statistically significant prognostic factors for recurrence identified by multivariable analyses were prior recurrence of the tumors (OR =3.214,95％CI0.804-12.845,P =0.099).In the second port,an incidence rate of adverse effects was 64.1％ (177/276).The Ⅲ/Ⅳ degree complications were occurred in 11 patients and satisfactory outcomes achieved with active treatment.A total of 36 patients withdrawal with the major causes were recurrence and progression of bladder tumor in 12 cases (4.4 ％),9 cases (3.3 ％) with economic reasons and 11 cases (4.0％) with serious complications.Conclusions NMIBC patients treated with intravesical BCG therapy have approving cancer free recurrence rates and acceptable adverse effects.Prior recurrence may be prognostic factor of recurrence after intravesical BCG therapy.

OBJECTIVE: To analyze the hotspots and related situations of pneumoconiosis research in China from 2001 to2017. METHODS: China National Knowledge Infrastructure and Wanfang Data were used to retrieve relevant literature on China's pneumoconiosis research from 2001 to 2017. Bibliometrics was used to analyze the distribution of publication time,regions,hotspots,authors and their institutions,carrier journals,keywords,etc. RESULTS: A total of 10 208 literature articles on pneumoconiosis research were screened. The number of published literature in 2001-2017 showed an upward trend year by year( P < 0. 01). Provinces in the Eastern area have the largest number of publications. The areas that have the largest number of publications were in Shandong Province,Beijing City and Hebei Province,followed by Anhui Province,Guangdong Province,Jiangsu Province,Liaoning Province,Shanxi Province and Henan Province. Beijing City,Hebei Province,Tianjin City,Liaoning Province,Anhui Province,Jiangsu Province,Hubei Province and Shanghai City are the hotspots for research on pneumoconiosis. The publications were seen in 1 173 journals. Five occupational medical professional periodicals such as Occupation and Health,Chinese Journal of Industrial Hygiene and Occupational Diseases,China Occupational Medicine,Chinese Journal of Industrial Medicine and Industrial Health and Occupational Diseases publish' the most literature on pneumoconiosis research,accounting for 26. 99% of the effective literature.Occupational disease prevention institutions and hospitals are the main organizations for publishing literatures. The focuses of pneumoconiosis research are silicosis and coal worker's pneumoconiosis,etc. CONCLUSION: Generally,the literature on the research of pneumoconiosis in China from 2001 to 2017 is increasing and is focus on some specific hotspots.Pneumoconiosis research has been specialized. An important carrier for publishing research results has been formed.

OBJECTIVE: To investigate the differentially expressed microRNAs(miRNAs) in human embryonic lung fibroblast MRC-5 cells stimulated by transforming growth factor-β1(TGF-β1) using microarray chip, and screen for key genes and signaling pathways of fibroblast trans-differentiation. METHODS: The miRNA expression gene chip dataset GSE43992 on TGF-β1 stimulated MRC-5 cells were downloaded from high-throughput Gene Expression Omnibus(GEO) database of National Center for Biotechnology Information of the United States. The R language Limma package was used to screen the differentially expressed miRNAs. Corresponding target genes were predicted by miRWalk database performed by Gene Ontology(GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway enrichment analysis. The protein-protein interaction(PPI) network was constructed by the search tool for the Retrieval of Interacting Genes database. RESULTS: A total of five differentially expressed miRNAs were identified, including four up-regulated miRNAs and one down-regulated miRNA; and 42 corresponding differentially expressed target genes were predicted. GO analysis indicated that the target genes were significantly enriched in collagen catabolic process, extracellular matrix organization, membrane organization, collagen fibril organization, and cellular response to amino acid stimulus. The results of KEGG pathway analysis showed that the signaling pathways corresponding to miRNAs and target genes were mainly concentrated in 18 signaling pathways, that were mainly related to the age-ethnic signaling pathways and protein digestion and absorption miRNAs in tumors and diabetic complications. The core genes transfected into the myofibroblasts by the three fibroblasts screened by the PPI network were threonine kinase 1, estrogen receptor 1 and β-catenin. CONCLUSION: Five differentially expressed miRNAs, 42 target genes, 18 signaling pathways, and 3 core genes related to TGF-β1-induced MRC-5 cell trans-differentiation were screened. It can provide new reference for the treatment and research of many diseases including pneumoconiosis and pulmonary fibrosis.

OBJECTIVE: To analyze transforming growth factor-β1( TGF-β1)-induced differentially expressed genes( DEGs) in human embryonic lung fibroblast( IMR-90) using microarray,and to screen the key genes and signaling pathways related to trans-differentiation of fibroblast.METHODS: The gene chip GSE17518,attained from TGF-β1 stimulated IMR-90 cells,was downloaded from the Gene Expression Omnibus database.The DEGs were screened by GENE-E software.Then,the DEGs were imported into the DAVID online database for Gene Ontology( GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment analysis.The proteinprotein interaction( PPI) network was constructed and the hub genes were screened using STRING database and Cytoscape software.RESULTS: A total of 394 DEGs related to TGF-β1 stimulation were identified,including 171 down-regulated genes and 223 up-regulated genes.The results of GO analysis showed that the DEGs were widely distributed in cytoplasm,cell membrane,extracellular matrix( ECM) and exosomes,regulating biological functions such as ECM organization,cell migration and adhesion,cell proliferation and apoptosis.The results of the KEGG pathway analysis indicated that most of DEGs were enriched in cell focal adhesion,ECM-receptor interaction and phosphoinositide 3 kinase-Protein kinase B( PI3K-Akt) signaling pathways.The PPI network screened 10 core genes,included nucleolar protein 2( NOP2),succinate dehydrogenase B,glutamyl-prolyl-tRNA synthetase( EPRS),FtsJ homolog 3( FTSJ3),prefoldin subunit 4,Ras-related C3 botulinum toxin substrate 2,signal recognition particle receptor subunit beta,succinate-Co A ligase GDPforming beta subunit,pumilio RNA binding family member 3( KIAA0020),and general vesicular transport factor p115.NOP2,EPRS,FTSJ3,KIAA0020 were mainly distributed in M1 module.The NOP2 is the core gene with the highest number of nodes in M1 module.CONCLUSION: A total of 10 core differential genes and 7 signaling pathways related to TGF-β1 stimulation were screened.Among them,focal adhesion,ECM-receptor interaction,PI3K-Akt and NOP2,EPRS,FTSJ3,KIAA0020 may provide new direction for research of mechanisms of abnormal activation of fibrotic diseases including silicosis in incidence and development of multiple lung fibrotic diseases.

Objective To discuss the clinical significance of peripheral neutrophil-to-lymphocyte ratio (NLR) changes in patients with castration-resistant prostate cancer (CRPC) after receiving argon-helium cryoablation.Methods A total of 33 CRPC patients,who were treated with argon-helium cryoablation at Tianjin Medical University Cancer Hospital,were included in this study.The clinical and pathological data were collected and analyzed.The following factors that might affect the postoperative overall survival (OS) of patients were analyzed with univariate and multivariate analysis:age,baseline PSA level,hemoglobin,white blood cell count,platelet count,albumin,alkaline phosphatase,NLR,platelet-to-lymphocyte ratio (PLR),hormone sensitive time,chemotherapy,bone metastasis,Gleason score,ECOG score,PSA effective rate.Results A total of 33 patients were enrolled in this study,the average age was 69 years (50-82 years) and the median survival time was 28 months (6-55 months).Univariate analysis showed that the baseline PSA level,alkaline phosphatase,NLR,hormone sensitive time,chemotherapy,bone metastases,Gleason score and PSA effective rate were significantly correlated with OS of CRPC patients after receiving cryoablation (P＜0.05).Multivariate analysis showed that the baseline PSA level (P=0.003),NLR (P=0.009),Gleason score (P＜0.001) were independent predictive factors for OS of CRPC patients after cryoablation therapy.Conclusion NLR can be used as a prognostic predictor for CRPC patients undergoing argon-helium cryoablation,and the increased NLR indicates a poor prognosis.(J Intervent Radiol,2017,26:237-242)

BACKGROUND:On CT reconstruction of three-dimensional (3D) model, fracture virtual reduction and internal fixation cannot be achieved, and reasonable operation scheme cannot be formulated. Digital design can fuly meet the needs of clinical orthopedics physicians. Standard parts database can provide the possibility to choose the ideal internal fixation. 3D printing makes the reasonable operation scheme accurate in clinical implementation. OBJECTIVE:To discuss the feasibility, accuracy and minimal invasion of internal fixation in treatment of the distal femoral fracture with digital design of standard parts database by 3D printing. METHODS: (1) Nine adult lower extremity specimens were selected to take continuously thin-layer CT scanning. After Dicom images were imported into the mimics software, the model was established. According to the AO classification, they were classified into A1-3, B1-3 and C1-3 types of distal femoral fracture by virtual design. Internal fixation with plate and screw formed standard parts database virtualy. It was printed out the pilot hole of the navigation module design by three-dimensional printing forming technique. Plate and screw were inserted assisted by the module. X-ray and CT scan were taken postoperatively to access the position. (2) 30 patients with distal femoral fracture were subjected to above fixation. The operation time, intraoperative blood loss and postoperative drainage were recorded. Imaging and curative effects were evaluated during folow-up. RESULTS AND CONCLUSION: (1) Nine samples underwent X-ray and CT scan. 3D reconstruction results revealed plate position, screw entry point, nail direction, length and diameter were consistent with presetting data in Mimics software. The navigation models were designed to fit the lateral bony structure of distal femur. There were good fitting degree, good card position and good stability when the navigation was applied. It could guide plant and screw implantation. (2) In 30 cases, the operation time was (104.63±26.12) minutes, intraoperative blood loss was (121.74±11.49) mL, and postoperative drainage volume was (30.29±6.38) mL. Al patients were folowed up. According to Schagzker criterion, the efficiency of 22 cases was excelent, 6 cases good and 2 cases average, and the excelent and good rate was 93%. The parameters of length, diameter, orientation and angle were consistent with that preoperatively. (3) Internal fixation formed by standard parts database assisted by 3D printing navigation model has advantages of high accuracy, short process, lessened blood loss, high safety, less complications, and precise fixation. Digital design of standard parts database via3D printing navigation module is expected to achieve implant navigation and application.

BACKGROUND:Preliminary experiments have performed three-dimensional (3D) reconstruction of proximal tibial fractures, digital steel plate design, the establishmentof the proximal tibia plate standard parts library and the operation simulation of 3D printing. OBJECTIVE:To explore feasibility and accuracy of standard parts library plates and screws in the proximal tibial fracture internal fixation navigation in digital design combined with 3D printing model on the basis of preliminary studies. METHODS:Dicom format images of continuous thin layer CT scanning were colected in 20 cases of proximal tibial fractures, and uploaded in Mimics software for 3D reconstruction and fracture reduction. Plate and screw selected from standard part library wereusedfor virtual fixation. Navigation module with screw channel was designed. 3D printing skeleton, bone plate, and navigation module were used for skeleton model and internal fixation. Screw and plate were placed by navigation. Navigation module card, nail and board position were observed. Postoperative appearance and CT scanning were utilized to assess outcomes. RESULTS AND CONCLUSION:After CT scanning and reconstructionin 20 skeleton models, in combination with appearance, the position of plate, screw insertion point, the direction, length and diameter of the screw were consistent with that in Mimics software. The navigation module and the corresponding proximal end of the tibia were closely bonded with good fitting degree. In the application, card slots and stability were good, and could perfectly guide plate and screw placement. These reuslts suggest that with the aid of navigation module, standard parts library plate internal fixation for proximal tibia fracture has high accuracy. On the basis of digital design and 3D printing, digital internal fixation technology of standard parts library plate is expected to achieve good implant navigation in the department of orthopedics.

BACKGROUND:Odontoid fracture is very common in cervical spine injuries, the special position of odontoid process, which is adjacent to important anatomic structure, makes screw placement difficult, and a slight discrepancy in position and orientation of the inserted screw leads to a decrease in intensity of internal fixation, even invalid internal fixation. Therefore, it is very necessary to develop an individualized treatment protocol by which screws can be precisely and safely placed and which is worthy of clinical popularization. OBJECTIVE:To study the navigation of Mimics software and three dimensional (3D)-printed module in anterior odontoid cannulated screw fixation and to investigate its feasibility and accuracy. METHODS:Sixteen human cadaveric cervical spines were scanned by a continuous thin-slice CT scanner. Original DICOM CT images were three-dimensional y reconstructed using Mimics software. The screw channel and support column were designed for C2 vertebra odontoid cannulated screw fixation for odontoid fracture. Segmentation of bone surface was performed. Navigation modules with screw channel were built using 3D printing technique. Navigation modules were used to aid screw placement. Screw fitting and placement were evaluated using X-ray and CT scan. RESULTS AND CONCLUSION:Total y 16 navigation modules were built and 22 screws were implanted. During and after screw placement, the cortical bone along screw channel and surrounding the vertebral body was not cracked. Postoperative X-ray and CT scans showed that some factors regarding screw placement such as entry point, orientation and depth of placement were consistent with those ideal factors simulated by Mimics software. The navigation modules were closely attached to the corresponding bony structure in front of the vertebral body, with a satisfactory gomphosis. Screw fitting and stability were good during application. These results verify that with the aid of navigation module, anterior odontoid cannulated screw fixation is reliable for treatment of odontoid fracture, which provides insights into the popularization of 3D printing-based digital navigation technique in orthopedic implantation.