Background and purpose:Cancer of unknown primary (CUP) represents approximately 5%~10%of malignant neoplasms. For CUP patients, identiifcation of tumor origin allows for more speciifc therapeutic regimens and improves outcomes.Methods:By retrieving the gene expression data from ArrayExpress and Gene Expression Omnibus data repositories, we established a comprehensive gene expression database of 5 800 tumor samples encom-passing 22 main tumor types. The support vector machine-recursive feature elimination algorithm was used for feature selection and classiifcation modelling. We further optimized the RNA isolation and real-time quantitative polymerase chain reaction (RTQ-PCR) methods for candidate gene expression proifling and applied the RTQ-PCR assays to a set of formalin-fixed, paraffin-embedded tumor samples.Results:Based on the pan-cancer transcriptome database, we identiifed a list of 96-tumor speciifc genes, including common tumor markers, such as cadherin 1 (CDH1), kallikrein-re-lated peptidase 3 (KLK3), and epidermal growth factor receptor (EGFR). Furthermore, we successfully translated the microarray-based gene expression signature to the RTQ-PCR assays, which allowed an overall success rate of 88.4% (95%CI: 83.2%-92.4%) in classifying 22 different tumor types of 206 formalin-fixed, paraffin-embedded samples. Conclusion:The 96-gene RTQ-PCR assay represents a useful tool for accurately identifying tumor origins. The assay uses RTQ-PCR and routine formalin-ifxed, paraffn-embedded samples, making it suitable for rapid clinical adoption.

Objective To evaluate the health-related quality of life ( HRQL) of patients with adolescent idiopathic scoliosis ( AIS) before treatment. Methods Sixty-two female patients with AIS were evaluated using the Chinese version of Scoliosis Research Society's outcomes instrument 22 ( SRS-22) HRQL questionnaire before treatment. The patients were categorized into thFee groups: a mild deformity group with a major curve Cobb angle less than 30° ( n =14),a moderate deformity group with Cobb angles of 30° to 50° ( n =42), and a severe deformity group with Cobb angles more than 50° ( n =6). Results The severe deformity group scored lowest in the self-image domain.There was,however,no significant difference in the functional activity,pain or mental health domain scores between the three groups. Conclusions The Chinese version of the SRS-22 HRQL questionnaire can be used to assess the HRQL of Chinese AIS patients.AIS patients with a major curve Cobb angle more than 50° have relatively low self-image scores.

Ziziphi Spinosae Semen (ZSS), a traditional Chinese medicine, is used in clinics for the treatment ofinsomnia in China and other Asian countries. Herein, we described for the first time a comparative pharmacokinetics study of the six major compounds of ZSS in normal control (NC) and para-chlor-ophenylalanine (PCPA)-induced insomnia model (IM) rats that were orally administered the aqueous extract of ZSS. An ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass (UHPLC-Q-Orbitrap-MS) method was developed and validated for the simultaneous determination of coclaurine, magnoflorine, spinosin, 6'''-feruloylspinosin, jujuboside A (JuA), and jujuboside B (JuB) in ZSS in rat plasma. The established approach was successfully applied to a comparative pharmacokinetic study. The systemic exposures of spinosin and 6'''-feruloylspinosin were decreased in the IM group compared to the NC group, while plasma clearance (CL) was significantly increased. The Tmax values of JuA and JuB in IM rats were significantly lower than those in NC rats. The T1/2 of JuA in the IM group was significantly accelerated. The pharmacokinetic parameters of coclaurine and magnoflorine were not evidently affected between the two groups. These results indicate that the pathological state of insomnia altered the plasma pharmacokinetics of spinosin, 6'''-feruloylspinosin, JuA, and JuB in the ZSS aqueous extract, providing an experimental basis for the role of ZSS in insomnia treatment. The comparative pharmacokinetics-based UHPLC-Q-Orbitrap-MS using full-scan mode can therefore provide a reliable and suitable means for the screening of potentially effective substances applied as quality markers of ZSS.

OBJECTIVETo explore the feasibility and safety of conditioning regimen containing fludarabine (Flud) for haploidentical hematopoietic stem cell transplantation (HSCT).

METHODSPreparative regimen containing Flud 40 mgxm(-2)xd(-1) on day -7 to -3 in place of cyclophosphamide (CTX) for haploidentical HSCT was given to 35 patients with hematologic malignancies (4 standard risk, 16 high risk, 15 relapse with no remission). All donors received rhG-CSF followed by HSC harvest. One patient received peripheral blood HSCT (PBSCT), one bone marrow transplantation (BMT), and the others BM combination with PBSCT. The regimen-associated side effect, engraftment, incidence of graft-versus-host disease (GVHD) and disease-free survival (DFS) probabilities were observed.

RESULTSAll patients achieved sustained, full donor-type engraftment. Thirty-four patients obtained primary durable engraftment, and 1 who rejected graft from his mother obtained successful durable engraftment after the second graft from his father. The cumulative incidence of grade III-IV acute GVHD and chronic GVHD was 12.1% and 31.7%, respectively. With a follow-up duration of 8-25 months, 6 patients were dead, in which 3 died of relapse, 2 of acute GVHD, 1 of fungal infection, none died of regimen-associated side effect. The other 29 patients remained alive and DFS probability was 79.7%.

CONCLUSIONFlud based conditioning regimens for haploidentical HSCT is safe and feasible, which reduces regimen-associated side effect, with no increasing the rate of relapse and infection, and decreases the incidence of aGVHD.

Adolescent ; Adult ; Child ; Child, Preschool ; Cyclophosphamide ; Feasibility Studies ; Female ; Graft vs Host Disease ; prevention & control ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Transplantation Conditioning ; adverse effects ; methods ; Transplantation, Homologous ; Vidarabine ; adverse effects ; analogs & derivatives ; therapeutic use ; Young Adult

Background::The goal of the assisted reproductive treatment is to transfer one euploid blastocyst and to help infertile women giving birth one healthy neonate. Some algorithms have been used to assess the ploidy status of embryos derived from couples with normal chromosome, who subjected to preimplantation genetic testing for aneuploidy (PGT-A) treatment. However, it is currently unknown whether artificial intelligence model can be used to assess the euploidy status of blastocyst derived from populations with chromosomal rearrangement.Methods::From February 2020 to May 2021, we collected the whole raw time-lapse videos at multiple focal planes from in vitro cultured embryos, the clinical information of couples, and the comprehensive chromosome screening results of those blastocysts that had received PGT treatment. Initially, we developed a novel deep learning model called the Attentive Multi-Focus Selection Network (AMSNet) to analyze time-lapse videos in real time and predict blastocyst formation. Building upon AMSNet, we integrated additional clinically predictive variables and created a second deep learning model, the Attentive Multi-Focus Video and Clinical Information Fusion Network (AMCFNet), to assess the euploidy status of embryos. The efficacy of the AMCFNet was further tested in embryos with parental chromosomal rearrangements. The receiver operating characteristic curve (ROC) was used to evaluate the superiority of the model. Results::A total of 4112 embryos with complete time-lapse videos were enrolled for the blastocyst formation prediction task, and 1422 qualified blastocysts received PGT-A ( n = 589) or PGT for chromosomal structural rearrangement (PGT-SR, n = 833) were enrolled for the euploidy assessment task in this study. The AMSNet model using seven focal raw time-lapse videos has the best real-time accuracy. The real-time accuracy for AMSNet to predict blastocyst formation reached above 70% on the day 2 of embryo culture, and then increased to 80% on the day 4 of embryo culture. Combing with 4 clinical features of couples, the AUC of AMCFNet with 7 focal points increased to 0.729 in blastocysts derived from couples with chromosomal rearrangement. Conclusion::Integrating seven focal raw time-lapse images of embryos and parental clinical information, AMCFNet model have the capability of assessing euploidy status in blastocysts derived from couples with chromosomal rearrangement.

Objective To establish the distribution zoning of Ziziphus jujuba var.spinosa in Shanxi Province;To help the development of Z.jujuba var.spinosa industry in Shanxi Province.Methods Combined with the information of longitude and latitude of sample points from the forth national survey resources and environment factors data in Grid Database of Spatial Information of TCM Resources,the MaxEnt model and ArcGIS were applied to analyze the main environmental factors affecting the suitability distribution of Z.jujuba var.spinosa.Results Dominant ecological factors for the suitability distribution of Z.Jujuba var.spinosa were vegetation type,lowest temperature of coldest month,monthly precipitation in November,monthly precipitation in October,altitude,and slope.The reclassified suitability grid data of ArcGIS software showed that Z.jujuba var.spinosa suitability distribution area including 0.73×104 km2 of high suitability area,1.41×104 km2 of medium suitability area and 4.33×104 km2 of low suitability area.The potential suitable distribution areas of Z.jujuba var.spinosa were mainly concentrated in the central and southern Shanxi Province.Conclusion This study shows that the most suitable growth area of Z.jujuba var.spinosa is mainly located in central and southern Shanxi Province,which can provide reference for the development,utilization and standardized planting of wild resources of Z.jujuba var.spinosa.

Objective To grasp the main environmental factors affecting the growth of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao;To predict the distribution of suitable areas of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province;To provide references for the rational distribution of the resources in Shanxi Province.Methods This study utilized the sample point longitude and latitude information collected in the"Fourth Survey of Chinese Materia Medica Resources"database in Shanxi Province.The data were supplemented by searching the China Digital Herbarium and retrieving related literature records.347 sample points distribution data and environmental factors were added to the MaxEnt model.The main environmental factors and contribution rates affecting the geographical distribution of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao were screened out.The ArcGIS software was used to divide the ecological suitable area of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province.Results The area under the ROC curve of the established MaxEnt model was 0.909,indicating that the model prediction results were accurate.The model screened 19 environmental factors.Among them,climate factor was the most important environmental factor,followed by biological factor and topographic factor,and soil factor had the least influence.The potential suitable areas of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province were mainly distributed in the northern mountainous areas,presenting a trend of gradually decreasing suitability levels from north to south.Under the current climate conditions,the most suitable area for Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province was 15 424 km2,the suitable area was 19 856 km2,the sub suitable area was 59 436 km2,and the unsuitable area was 61 894 km2.Conclusion Based on MaxEnt model and ArcGIS software,this study predicts the distribution of suitable areas of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province,which has certain reference value for the protection and rational distribution of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao resources in Shanxi Province.

Objective To establish ecological suitability zone of Forsythia suspensa(Thunb.)Vahl in Shanxi Province;To study the quality regionalization of Forsythia suspensa(Thunb.)Vahl from different producing areas in Shanxi Province;To provide reference for reasonable planting and wild tending of Forsythia suspensa(Thunb.)Vahl.Methods Maximum entropy(MaxEnt)model and ArcGIS software were used to study the ecological suitability of Forsythia suspensa(Thunb.)Vahl in Shanxi Province;By screening the main environmental factors and combining them with the content of forsythoside and forsythoside A in Forsythia suspensa(Thunb.)Vahl of different regions,a quality zoning of Forsythia suspensa Thunb.Vahl medicinal materials in Shanxi Province based on forsythoside,forsythoside A and environmental factors was constructed.Results The ecological suitable areas of Forsythia suspensa Thunb.Vahl in Shanxi Province were mainly distributed in the southern part of Shanxi Province,mainly in Linfen,Yuncheng,Changzhi,and Jincheng.The general contents of forsythoside and forsythoside A in the Forsythia suspensa(Thunb.)Vahl medicinal material were gradually reduced from southern part to northern part of Shanxi Province.The comprehensive quality was high in southern part of Shanxi Province,mainly in Linfen,Changzhi,Yuncheng and Jincheng.Conclusion The results of this study are consistent with the actual survey.The southern part of Shanxi province is a suitable planting area for high quality Forsythia suspensa(Thunb.)Vahl,which provides a reference for the standardized planting and wild tending of Forsythia suspensa(Thunb.)Vahl.

ObjectiveTo optimize and establish a multiplex polymerase chain reaction （PCR） system to simultaneously identify Ziziphi Spinosae Semen （ZSS），Hovenia acerba semen （HAS），and Ziziphi Mauritianae Semen （ZMS）， etermine their content to solve the problem of adulteration of ZSS pieces and its preparations. MethodAfter the analysis and comparison of the internal transcribed spacer （ITS） sequence differences of ZSS and its adulterants，specific single nucleotide polymorphism （SNP） sites were found，and specific primers for identification were designed. The samples of ZSS，HAS， and ZMS from different sources were specifically amplified under the conditions of optimized annealing temperature，the number of cycles， and concentration of primers，as well as different polymerases and PCR systems after evaluation. Identification was carried out according to the size of specific amplification bands，and the lower limit of detection （LOD） and adulteration LOD were studied. ResultWhen the annealing temperature was 63 ℃ and the number of cycles was 23，549，169，389 bp specific bands were amplified from ZSS，HAS， and ZMS. The lower LOD of this method was 0.24 ng and 1.2 ng for ZSS and HAS， respectively. The adulteration LOD for ZSS，HAS， and ZMS was 0.5%，2%， and 2% respectively. ConclusionThe established multiplex allele-specific PCR identification method can accurately identify ZSS，HAS， and ZMS at the same time，which can provide a basis for solving the problem of adulteration of ZSS and references for controlling the quality，security， and clinical application of ZSS.