Objective To explore the current application of high-throughput drug sensitivity(HDS)testing in children with relapsed and refractory acute leukemia(RR-AL)and analyze the feasibility of salvage treatment plans.Methods A retrospective collection of clinical data from children with RR-AL who underwent HDS testing at the Department of Children's Hematology and Oncology of the First Affiliated Hospital of Zhengzhou University from November 2021 to October 2023 was conducted,followed by an analysis of drug sensitivity results and treatment outcomes.Results A total of 17 children with RR-AL underwent HDS testing,including 7 cases of relapsed refractory acute myeloid leukemia and 10 cases of relapsed refractory acute lymphoblastic leukemia.The detection rate of highly sensitive chemotherapy drugs/regimens was 53%(9/17),while the detection rate of moderately sensitive chemotherapy drugs/regimens was 100%(17/17).Among the 17 RR-AL patients with highly and moderately sensitive chemotherapy drugs and regimens,the MOACD regimen(mitoxantrone+vincristine+cytarabine+cyclophosphamide+dexamethasone)accounted for 100%,with the highest inhibition rate for single-agent mitoxantrone(94%,16/17),and the highest inhibition rate for targeted therapy being bortezomib(94%,16/17).Nine patients adjusted their chemotherapy based on HDS testing results,with 4 undergoing hematopoietic stem cell transplantation.Four patients achieved disease-free survival,while 5 died.Eight patients received empirical chemotherapy,with 2 undergoing hematopoietic stem cell transplantation;4 achieved disease-free survival,while 4 died.Conclusions HDS testing can identify highly sensitive drugs/regimens for children with RR-AL,improving the rate of re-remission and creating conditions for subsequent hematopoietic stem cell transplantation.

Eleutherococcus senticosus is one of the Dao-di herbs in northeast China. In this study, the chloroplast genomes of three E. senticosus samples from different genuine producing areas were sequenced and then used for the screening of specific DNA barcodes. The germplasm resources and genetic diversity of E. senticosus were analyzed basing on the specific DNA barcodes. The chloroplast genomes of E. senticosus from different genuine producing areas showed the total length of 156 779-156 781 bp and a typical tetrad structure. Each of the chloroplast genomes carried 132 genes, including 87 protein-coding genes, 37 tRNAs, and 8 rRNAs. The chloroplast genomes were relatively conserved. Sequence analysis of the three chloroplast genomes indicated that atpI, ndhA, ycf1, atpB-rbcL, ndhF-rpl32, petA-psbJ, psbM-psbD, and rps16-psbK can be used as specific DNA barcodes of E. senticosus. In this study, we selected atpI and atpB-rbcL which were 700-800 bp and easy to be amplified for the identification of 184 E. senticosus samples from 13 genuine producing areas. The results demonstrated that 9 and 10 genotypes were identified based on atpI and atpB-rbcL sequences, respectively. Furthermore, the two barcodes identified 23 genotypes which were named H1-H23. The haplotype with the highest proportion and widest distribution was H10, followed by H2. The haplotype diversity and nucleotide diversity were 0.94 and 1.82×10~(-3), respectively, suggesting the high genetic diversity of E. senticosus. The results of the median-joining network analysis showed that the 23 genotypes could be classified into 4 categories. H2 was the oldest haplotype, and it served as the center of the network characterized by starlike radiation, which suggested that population expansion of E. senticosus occurred in the genuine producing areas. This study lays a foundation for the research on the genetic quality and chloroplast genetic engineering of E. senticosus and further research on the genetic mechanism of its population, providing new ideas for studying the genetic evolution of E. senticosus.
DNA Barcoding, Taxonomic ; Eleutherococcus/genetics* ; Base Sequence ; Chloroplasts/genetics* ; Genetic Variation ; Phylogeny

italic>Atractylodes chinensis has important medicinal and economic values. In this study, the chloroplast genome sequences of four A. chinensis samples from different producing areas were sequenced using the Illumina platform. The specific DNA barcodes were screened and the germplasm resources of A. chinensis samples from different producing areas and the genetic diversity of the population were analyzed basing on the specific barcodes. The whole chloroplast genomes of the four A. chinensis samples had a typical cyclic tetrad structure, with 112 genes annotated. The comparative genomics results indicated that ccsA and trnC-GCA_petN were potential specific DNA barcodes for intraspecific identification of A. chinensis. Polymerase chain reaction (PCR) analysis of ccsA and trnC-GCA_petN was performed on 256 samples from 14 areas in 9 provinces, and the amplification efficiency was 100%. Sequence analysis showed that ccsA and trnC-GCA_petN had 11 and 22 variant positions, which could identify 16 and 22 haplotypes, respectively. The combined sequence analysis identified 39 haplotypes, named Hap1-Hap39, of which the most abundant and widely distributed genotype was Hap9. Haplotype diversity (H_d) = 0.896 and nucleotide diversity (Pi) = 0.002 22 indicated high genetic diversity at the species level in A. chinensis. The genetic distances of the haplotypes were 0.000 00-0.004 88, indicating that there were small genetic differences among the haplotypes. The results of phylogenetic tree analysis showed that 39 haplotypes had very close genetic relationship, and formed two obvious branches with other groups of the same genus except Atractylodes macrocephala. This study plays an important role in the identification of the origin of A. chinensis and the protection and breeding of germplasm resources.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

MYB transcription factors, one of the largest transcription factor families in plants, play an important role in signal transduction, plant growth and plant resistance. In this study a full-length cDNA of the PnMYB1R1 gene was cloned from Panax notoginseng. Sequence analysis, prokaryotic expression and purification, subcellular location, transcriptional activity analysis, tissue-specific analysis and expression analysis under different abiotic stresses was performed. The open reading frame (ORF) of PnMYB1R gene was 738 bp, encoding a protein of 245 amino acids with a predicted molecular mass (MW) of 27.0 kD. The sequence analysis and polygenetic analysis indicated that the PnMYB1R1 protein contains a conserved R3 domain, belonging to TRF-like protein in 1R-MYB-type transcription factors. The recombinant PnMYB1R1 protein was expressed in Escherichia coli BL21(DE3) cells using the prokaryotic expression vector pET28a-PnMYB1R1 and was purified. Subcellular localization analysis showed that PnMYB1R1 was localized in the nucleus. Transcriptional activity analysis indicated that the PnMYB1R1 transcription factor has transcriptional activation activity. Expression analysis indicated that PnMYB1R1 was primarily expressed in roots, followed by stems and leaves, and then rootlets. The expression level of PnMYB1R1 in root, stems, leaves and rootlets was influenced by salt, low temperature and drought treatment, while the abundance of PnMYB1R1 was significantly induced by salt stress in these tissues. These results provide valuable insights into the role of 1R-MYB transcription factors in plant defense.

Rhei Rhizoma is commonly used as a traditional Chinese medicine with multiple botanical origins. Different botanical sources may have different pharmacological activities. The germplasm resources of commercial Rhei Rhizoma were determined based on the chloroplast gene matK, and the anthraquinone and free anthraquinone content was determined by UPLC to analyze quality of commercial Rhei Rhizoma. Eighty-nine commercial Rhei Rhizoma samples were collected from 40 cities in 27 provinces. DNA was extracted and the matK gene was amplified by PCR. Results indicated that the collected samples were from the same botanical origin, Rheum palmatum, and 8 genotypes were identified, including Rp1, Rp2, Rp3, Rp4, Rp5, Rp6, Rp10 and Rp12. Rp4 and Rp6, cultivated in Gansu, Sichuan and Yunnan provinces were the main circulating genotypes, representing 40.45% and 37.08% of the total samples, respectively. Phylogenetic tree analysis showed that the eight genotypes were mainly divided into two branches, of which the main genotypes Rp4 and Rp6 were in one branch. Genetic distance analysis indicated that the genetic separation of the eight genotypes was between 0.001 and 0.010. UPLC analysis indicated that 93.26% of the samples met the Pharmacopoeia standards. There were significant differences in the content of total anthraquinone and free anthraquinone among the samples, in which the difference in free anthraquinone was 1.01% and the difference in total anthraquinone content was 3.79%, indicating that the quality of commercial Rhei Rhizoma samples varies considerably. There was no significant difference in the content of total anthraquinone and free anthraquinone in commercial Rhei Rhizoma among different collection provinces and genotypes. This study will help guide the circulation of Rhei Rhizoma in the market and provides valuable insights for molecular identification and quality analysis of other traditional Chinese medicines.

Scutellaria baicalensis is a commonly used Chinese medicinal herb. In this study, we identified the germplasm resources of commercial S. baicalensis samples based on trnH-psbA, petA-psbJ, and ycf4-cemA sequences according to the available chloroplast genome sequencing results, and measured the content of baicalin by HPLC. Through the above means we determined the best DNA barcode that can be used to detect the germplasm resources and evaluate the quality of commercial S. baicalensis samples. A total of 104 samples were collected from 24 provinces, from which DNA was extracted for PCR amplification. The amplification efficiencies of trnH-psbA, petA-psbJ, and ycf4-cemA sequences were 100%, 59.62%, and 25.96%, respectively. The results of sequence analysis showed that 5, 4, and 2 haplotypes were identified based on trnH-psbA, petA-psbJ, and ycf4-cemA sequences, respectively. However, the sequences of haplotypes in commercial samples were different from that of the wild type, and the joint analysis of three fragments of S. baicalensis only identified 6 haplotypes. Furthermore, the phylogenetic analysis and genetic distance analysis indicated that trnH-psbA could be used to identify S. baicalensis from adulterants. The above analysis showed that trnH-psbA was the best fragment for identifying the germplasm resources of commercial S. baicalensis samples. We then analyzed the haplotypes(THap1-THap5) of commercial S. baicalensis samples based on trnH-psbA and found that THap2 was the main circulating haplotype of the commercial samples, accounting for 86.55% of the total samples, which indicated the scarce germplasm resources of commercial S. baicalensis samples. The content of baicalin in all the collected commercial S. baicalensis samples exceeded the standard in Chinese Pharmacopoeia and had significant differences(maximum of 12.21%) among samples, suggesting that the quality of commercial S. baicalensis samples varied considerably. However, there was no significant difference in baicalin content between different provinces or between different haplotypes. This study facilitates the establishment of the standard identification system for S. baicalensis, and can guide the commercial circulation and reasonable medication of S. baicalensis.
Chromatography, High Pressure Liquid ; DNA Barcoding, Taxonomic/methods* ; DNA, Plant/genetics* ; Phylogeny ; Scutellaria baicalensis/genetics*

OBJECTIVES: To explore the effect of polydatin on the proliferation and apoptosis of acute monocytic leukemia cell line THP-1 and the possible mechanism. METHODS: After THP-1 cells were treated with polydatin at gradient concentrations for 24 hours and 48 hours, their proliferation was determined by CCK-8 assay, and half maximal inhibitory concentration (IC50) was calculated. Logarithmically growing THP-1 cells were divided into two groups, a polydatin treatment group (treated with IC50 of polydatin) and a blank control group (treated without polydatin solution), and incubated for 48 hours. Cell apoptosis and cell cycle were measured by flow cytometry. The expression levels of PI3K, AKT, p-AKT, mTOR, p-mTOR, p70 S6K, and p-p70 S6K proteins were measured by Western blotting. RESULTS: After treatment with polydatin, the proliferation of THP-1 cells was strongly inhibited, and the IC50 at 48 hours was 1 800 μmol/L. After treatment with 1 800 μmol/L polydatin solution for 48 hours, the apoptosis rate of THP-1 cells increased significantly compared with the blank control group (P<0.05). The cell cycle was arrested in the G₀/G₁ and S phases, with a significantly increased proportion of cells in the G₀/G₁ phase and a significantly decreased proportion of cells in the S phase, as compared with the blank control group (P<0.05). The expression levels of PI3K, AKT, p-AKT, mTOR, p-mTOR, p70 S6K, and p-p70 S6K proteins decreased significantly compared with the blank control group (P<0.05). CONCLUSIONS Polydatin can effectively inhibit the proliferation, block the cell cycle, and induce the apoptosis of THP-1 cells, which may be related to inhibition of the PI3K/AKT/mTOR signaling pathway.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Glucosides/pharmacology* ; Humans ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Signal Transduction ; Stilbenes/pharmacology* ; THP-1 Cells ; TOR Serine-Threonine Kinases

ObjectiveTo study the possible molecular mechanism of baicalein （BAI）-mediated focal adhesion kinase （FAK） in the regulation of phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to inhibit the proliferation and migration of gastric cancer HGC-27 cells. MethodThe gastric epithelial GES-1 cells and gastric cancer HGC-27 cells were respectively treated with BAI （0， 5， 15， 25， and 50 μmol·L^-1） for 48 h， and then methyl thiazolyl tetrazolium （MTT） assay was adopted to detect effect of BAI on cell proliferation. Western blot （WB） was employed to detect the expression of FAK and the proteins related to epithelial-mesenchymal transition （EMT） and PI3K signaling pathway after intervention with different concentrations of BAI. The HGC-27 cells stably overexpressing FAK were constructed with lentivirus-mediated transfection technique， and the transfection of FAK was detected through WB and green fluorescent protein （GFP）. The cells were divided into empty vector （NC） group， BAI group， FAK overexpression group， and BAI-treated FAK overexpression group， and cell proliferation activity was detected by MTT assay. The colony formation and cell migration were observed via colony formation assay and Transwell migration assay， respectively. The expression of proteins involved in EMT and PI3K signaling pathways were detected by Western blot. ResultCompared with the NC group， BAI （15， 25 and 50 μmol·L^-1） inhibited the proliferation of HGC-27 cells in a dose-dependent manner （P<0.05， P<0.01） while did not affect that of GES-1 cells. BAI （5， 15 and 25 μmol·L^-1） down-regulated the expression level of p-FAK （P<0.05， P<0.01）. Compared with NC group， FAK overexpression group showed up-regulated expression level of FAK in HGC-27 cells. The HGC-27 cells in both NC group and FAK overexpression group had green fluorescence. Compared with NC group， BAI inhibited the growth， colony formation， and migration， while FAK overexpression promoted those of HGC-27 cells. The treatment of FAK overexpression group with BAI inhibited the enhancement of cell proliferation and migration （P<0.05）. WB showed that compared with NC group， BAI （15， 25 μmol·L^-1） significantly up-regulated the expression of E-cadherin protein and down-regulated that of Vimentin， Snail， p-PI3K， and p-Akt protein in HGC-27 cells （P<0.05， P<0.01）. Compared with NC group， FAK overexpression group showed down-regulated expression of E-cadherin， up-regulated expression of p-FAK， Vimentin， and Snail， and increased ratios of p-FAK/FAK， p-PI3K/PI3K and p-Akt/Akt （P<0.05）. This phenomenon would be reversed after BAI treatment. ConclusionBAI can affect the proliferation and migration of gastric cancer HGC-27 cells by mediating FAK to regulate PI3K/Akt signaling pathway.

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.
Adolescent ; Adult ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Middle Aged ; Pandemics ; Pneumonia, Viral ; drug therapy ; Prospective Studies ; Young Adult