Abstract　　The minimal residual disease (MRD) is the origin element that caused the relapse and drug resistance of hematological malignancies, the immune cells play a great role to clear MRD. A variety of immune cells have anti-tumor effects. However, tumor cells antagonize anti-tumor effects by reprogramming of constituents associated with tumor environment. Many different cell types, including immune cells, mesenchymal cells and tumor cells in tumor microenvironment release exosomes. The latest researches indicate that "cargo" and surface ligands carried by exosomes secreted by hematological malignant cells not only can affect the function of natural killer cell (migration, activation, proliferation, secretion and NKG2D expression), macrophage (migration and secretion) and dendritic cell (maturation and presentation), but also regulate the expression of PD-L1 and CCR2, CCL2 secretion and transformation of monocytes. The altered function of immune cells will eventually have effect on the progression of hematological malignancies.

Objective: To analyze the Oxford classification (MESTC) and the International Study of Kidney Disease in Children (ISKDC) classification for evaluating the clinical manifestations, histological lesion and short-term prognosis of children with Henoch-Schönlein purpura nephritis (HSPN). Methods: According to the Oxford classification and ISKDC classification, the histological lesions of children with HSPN diagnosed by renal biopsy from Beijing Children's Hospital affiliated to Capital Medical University from January 2018 to December 2018 were re-evaluated. The renal biopsy specimens of the selected subjects were scored according to the Oxford classification and the ISKDC classification. According to whether the first symptom was combined with renal performance, MESTC score and ISKDC classification, children were grouped. The differences in clinicopathological manifestations between the groups were compared. Correlation between MESTC and ISKDC grades was analyzed by nonparametric test rank correlation. Kaplan-Meier survival curve and Log-rank test were used to compare the difference of proteinuria remission rate between the two groups. Univariate and multivariate Cox regression equations were used to analyze the influencing factors of the proteinuria remission rate. Results: A total of 78 children with HSPN were enrolled. There were 37 male patients (47.4%) with age of (10.4±2.9) years. When the patients were divided according to MESTC scores and ISKDC classification, the results showed that the proportion of children with nephrotic-range proteinuria in the group of endocapillary hypercellularity (E1, P=0.008), segmental glomerulosclerosis (S1, P=0.015) and ISKDCⅢ(P=0.041) was higher than that of E0, S0 and ISKDCⅡ groups. The proportion of children with E1 (P=0.015), crescents (C1&C2, P=0.025) or ISKDCⅢ(P=0.017) that had been treated with high-dose methylprednisolone was higher. The result of Kaplan-Meier survival curve showed more difficult for proteinuria remission in children with C2 are than C0&C1 group (P=0.026), while no difference were found when children were grouped by M, E, S, T and ISKDC. Multivariate Cox regression analysis showed that the C2 (HR=0.143, 95%CI 0.020-1.046, P=0.055) might be a risk factor for proteinuria remission, while the P value was close to 0.05. Conclusions Children with HSPN scored as ISKDCⅢ, E1 and S1 are more likely to show nephrotic-range proteinuria. C2 may indicate that patients are more difficult to achieve proteinuria remission.

Objective To compare target dosimetric distribution and normal tissue radiation between different static intensity-modulated radiation therapy (IMRT)plans and volumetric modulated arc therapy (VMAT),and to identify the best IMRT plan for lymphoma patients needed mediastinal radiation. Methods A total of 11 patients with lymphoma who received first course radiotherapy in the mediastinal region after che-motherapy in Cancer Hospital & Shenzhen Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College from March 2017 to January 2019 were included in the study. There were 8 males and 3 fe-males,2 patients were in Ann Arbor stage Ⅰ-Ⅱ,and 9 cases in Ⅲ-Ⅳ stage. There were 6 patients with Hodgkin lymphoma (HL)and 5 patients with non-Hodgkin lymphoma (NHL). Patients with HL and NHL were given prescript doses of 36 Gy and 50 Gy,respectively. Three plans were designed for each patient:static 5F-IMRT,7F-IMRT and VMAT plan. The target dosimetric distribution,normal tissue radiation dose,and effi-ciency of each plan were evaluated. Results The mean conformity index (CI)and homogeneity index (HI) values of plan target volume (PTV)in 5F-IMRT,7F-IMRT,VMAT plan were 0. 64 ± 0. 06,0. 67 ± 0. 05, 0. 76 ± 0. 04 (F = 17. 045,P < 0. 001)and 1. 07 ± 0. 01,1. 07 ± 0. 01,1. 09 ± 0. 01 (F = 9. 258,P =0. 001),respectively. VMAT showed significantly better CI than two static IMRT plans (both P < 0. 001),but worse HI (both P < 0. 001). The lungs low dose irradiation volume (V (V 5 )and high dose irradiation volume 30 )in 5F-IMRT,7F-IMRT,VMAT plan were (43. 98 ± 7. 77)％,(42. 71 ± 4. 98)％,(55. 92 ± 8. 16)％(F = 8. 281,P = 0. 001)and (8. 19 ± 2. 97)％,(8. 25 ± 2. 87)％,(7. 53 ± 3. 16)％ (F = 0. 140,P =0. 870),respectively. The volume of low dose irradiation in lungs of VMAT plan was significantly higher than 5F-IMRT and 7F-IMRT plans (both P < 0. 001),while high dose volume was no significant difference. The left and right breast low dose irradiation volume (V 4 )in 5F-IMRT,7F-IMRT and VMAT plan were (24. 29 ± 8. 14)％,(23. 87 ± 7. 70)％,(80. 17 ± 22. 92)％ (F = 14. 505,P = 0. 005)and (22. 12 ± 13. 28)％, (21. 13 ± 13. 01)％,(81. 77 ± 20. 76)％ (F = 13. 938,P = 0. 006),respectively. VMAT showed signifi-cantly higher breast low dose irradiation volume than static IMRT plan (both P < 0. 05). The number of monitor units and treatment time in 5F-IMRT,7F-IMRT,VMAT plan were (1622 ± 281)MU,(1729 ± 286)MU, (411 ± 75)MU (F = 105. 277,P < 0. 001)and (6. 79 ± 0. 93)min,(7. 42 ± 0. 95)min,(4. 98 ± 0. 00)min (F = 29. 545,P < 0. 001),respectively. VMAT showed significantly less monitor units than static IMRT (both P < 0. 001)and shorter treatment time (both P < 0. 001). Conclusion For lymphoma patients who have the indication of mediastinal radiotherapy,VMAT is highly efficient and has no definite dose advan-tage,the static 5F-IMRT or 7F-IMRT plan has good conformal and uniform target area,and some organs at risk exposure is even lower.

OBJECTIVE: To investigate whether Ershen Pill (ESP, ) could alleviate the symptom of Pi (Spleen)-Shen (Kidney) yang deficiency (PSYD)-induced diarrhea in rat model and explore its anti-diarrhea mechanism. METHODS: Seventy-five Sprague-Dawley rats were divided into 5 groups by a random number table, including control, positive, model, low-dose (LD) and high-dose (HD) ESP groups, 15 rats in each group. All the rats, except those in the control group, were developed PSYD induced-diarrhea based on its pathology and etiology. The rats in positive, LD and HD ESP groups were treated with Shenling Baizhu Pill (), LD (1.05 g/kg) or HD (3.50 g/kg) ESP petroleum ether extract once a day for 2 weeks, respectively. Body weight change and diarrhea index were measured. The histology scores of the kidney were evaluated via hematoxylin and eosin (HE) staining. Aquaporin-3 (AQP3) expression in the colon was analyzed by immunofluorescence, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot, respectively. RESULTS: Compared with the model group, oral administration of LD and HD ESP prevented body weight loss and inhibited diarrhea after 2-week treatment (P<0.05). Kidney deterioration was impeded, and the histology score in LD and HD ESP groups were 8.2 and 10.5, respectively, which were both higher than those in the model group (P<0.05). In addition, ESP treatment alleviated rat colitis, and HD ESP significantly improved the AQP3 positive staining intensity in the colon tissue compared with the model group. The result from Western blot revealed that AQP3 protein synthesis in colon tissue of LD and HD ESP groups increased by 2.1- and 5.9-fold compared with the model group (P<0.05). qRT-PCR result showed that AQP3 gene expression in the HD ESP group was also up-regulated by 2.5-fold normalized to the model group (P<0.05). CONCLUSION ESP extract effectively alleviates the symptoms of PSYD and relieves PSYD-induced diarrhea by improving AQP3 synthesis in the colon.

China is rich in the diversified Chinese medicine resources and is notable for the wide and long-term applications of Chinese medicine. However,the lack of genomic information on medicinal taxa leads to problems in relation to resource conservation and the downstream application of traditional Chinese medicine resources,which restricts the modernization process of traditional Chinese medicine. Molecular phylogenetics is an important tool to understand the origin and evolution of the earth's biodiversity and promote the conservation and use of medicinal taxa. With the development of sequencing technology,the combination of genomic data extends the traditional molecular phylogenetics to the research level of phylogenomics,making it more powerfully applied to all aspects of biological research. Undoubtedly,carrying out phylogenomic research on Chinese medicine species will greatly promote their resources conservation,molecular evaluation and identification,and the exploration and utilization of natural pharmacodynamic components,promoting the modernization of traditional Chinese medicine. This article starts with a brief introduction of the developing history and basic research methods of phylogenomics,and then reviews the current research progress in phylogenomics related to traditional Chinese medicine resources. Finally,it discusses the problems existing in the current research and the next direction of phylogenomics research in medicinal taxa. The article will hopefully provide a reference for relevant researches in future.
China ; Conservation of Natural Resources ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Phylogeny ; Plants, Medicinal ; genetics

DNA metabarcoding,one rapid and robust method using specific standard DNA fragments,has been widely used for rapid species identification of a bulk sample through high-throughput sequencing technologies.While it has been widely used in the studies of metagenomics,animal and plant biodiversity,it has gradually come to be used as a profitable method in species identification of mixed Chinese herbal medicines.In this paper,we mainly summarize the current studies of the application of DNA metabarcoding in species identification of mixed Chinese herbal medicines.Moreover,high-throughput sequencing technologies adopted in those studies,such as Sanger,the next-generation,and third-generation sequencing technologies,are discussed.It is conducted to provide a theoretical guidance for the application of DNA metabarcoding in species identification of mixed Chinese herbal medicines and in more other biodiversity studies.
Biodiversity ; DNA Barcoding, Taxonomic ; DNA, Plant ; genetics ; Drugs, Chinese Herbal ; analysis ; High-Throughput Nucleotide Sequencing ; Plants, Medicinal ; classification

A UPLC method has been developed for simultaneous determination of nine furanocoumarins of Angelica dahurics,and was used for quality evaluation of A. dahurica from different habitats. ACQUITY UPLC BEH C18 chromatographic column was employed,the separation was performed with the mobile phase consisting of acetonitrile and water,and the detection wavelength was set at254 nm. This method was used to simultaneously determine the content of xanthotoxol,oxypeucedaninhydrate,byak-angelicin,psoralen,xanthotoxin,bergapten,oxypeucedanin,imperatorin and isoimperatorin in A. dahurica from different habitats. Then,the further quality assessment of the drug was carried out by similarity evaluation,cluster analysis( CA),principal component analysis( PCA),and orthogonal partial least squares discriminant analysis( OPLS-DA). The content order of measured furanocoumarins from high to low was: oxypeucedanin>imperatorin>isoimperatorin>oxypeucedaninhydrate>bergapten>byak-angelicin>xanthotoxin>xanthotoxol>psoralen,with the mean content 2. 844,1. 277,0. 649 2,0. 216 2,0. 129 8,0. 062 68,0. 052 68,0. 019 30,0. 018 19 mg·g-1,respectively. There were difference between the batches of the drug,and the quality was influenced by smouldering sulphur based on the results of chemical pattern recognition and content determination. Finally,six active ingredients were recognized as the quality makers using OPLS-DA method. The validated UPLC fingerprint combined with chemical pattern recognition method can be used in the quality control and evaluation of A. dahurica.
Angelica ; chemistry ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; standards ; Ecosystem ; Furocoumarins ; analysis ; Quality Control

Cancerous fever is one of the common symptoms of advanced malignant tumors,which seriously affects the quality of life and survival of patients. At present,the clinical research on the treatment of cancerous fever by traditional Chinese medicine is limited,and there is a lack of research on the medication rules from multiple dimensions of disease-symptom-syndrome. The treatment of cancerous fever has not made substantial progress. In this study,we collected the literature on treatment of cancerous fever in Chinese medicine,and concluded that common syndrome types include Yin deficiency type,Qi deficiency type,Yang deficiency type,blood stasis type,damp-heat accumulation type,toxic heat flourishing type and liver meridian stagnated heat type. Two hundreds and fifty-seven prescriptions for Chinese medicine and 249 flavors for single medicine were extracted. The analysis of the drug composition of the drug found that the cancerous fever treatment was mainly based on heat-clearing drugs and deficiency-nourishing drugs. Apriori association analysis of the drug found that the second and third related drugs were mainly Rehmanniae Radix,Moutan Cortex,Artemisiae Annuae Herba,Trionycis Carapax and Anemarrhenae Rhizoma. The top five gray correlation degrees were Psoraleae Fructus,Bupleuri Radix,Hordei Fructus Germinatus,Scutellariae Radix and Massa Medicata Fermentata. And seven new prescriptions were evolved. The results showed that the treatment of cancerous fever can be started from the disease-symptom-syndrome,nourishing Yin and clearing heat is an important method for " disease differentiation and treatment". The combination of Bupleuri Radix and Scutellariae Radix is the embodiment of " symptom differentiation and treatment". The new prescriptions conform to the idea of " syndrome differentiation and treatment" of traditional Chinese medicine can provide reference for clinical medication. The grey screening method combined with multivariate analysis method was used to analyze the prescription rules of Chinese medicine in the treatment of cancer fever,which followed the black box structure of traditional Chinese medicine,made the potential rule of prescriptions explicit,broadened its thinking of Chinese medicine treatment,and made up for the deficiency of traditional analysis methods.
Drugs, Chinese Herbal ; therapeutic use ; Fever ; drug therapy ; etiology ; Humans ; Medicine, Chinese Traditional ; Meridians ; Multivariate Analysis ; Neoplasms ; complications ; drug therapy ; Quality of Life

OBJECTIVE: Cancer is a serious threat to human health. Despite extensive research on cancer treatment, there is a growing demand for new therapies. CD147 is widely involved in tumor development, but it is unclear whether cancer cell malignancy is affected by CD147 expression level. The first compound (AC-73) targeting CD147 could only act on advanced tumors and inhibit metastasis. Therefore, new compounds with better anticancer activity should be explored. METHODS: Wst-1 assays were used to confirm the effect of novel compounds on proliferation. Apoptosis tests were used to evaluate their proapoptotic capacity. A nude mouse model was used to demonstrate in vivo anticancer activity and safety of the compounds. Western blots were used to suggest a molecule mechanism. RESULTS: There is a positive correlation between CD147 expression and tumor cell proliferation. A new compound, HA-08, was synthesized and proved to be more active than AC-73. HA-08 could inhibit cancer cell viability and promote cancer cell apoptosis both in vitro and in vivo. HA-08 induces cancer apoptosis, mainly by disrupting the CD147-CD44 interaction and then down-regulating the JAK/STAT3/Bcl-2 signaling pathway. CONCLUSION Our results have clarified the tumor specificity of CD147 and its drug target characteristics. The biological profile of HA-08 suggests that this compound could be developed as a potential anticancer agent.

OBJECTIVE: To investigate the mechanisms underlying ozone-induced inactivation of poliovirus type 1 (PV1). METHODS: We used cell culture, long-overlapping RT-PCR, and spot hybridization assays to verify and accurately locate the sites of action of ozone that cause PV1 inactivation. We also employed recombinant viral genome RNA infection models to confirm our observations. RESULTS: Our results indicated that ozone inactivated PV1 primarily by disrupting the 5'-non-coding region (5'-NCR) of the PV1 genome. Further study revealed that ozone specifically damaged the 80-124 nucleotide (nt) region in the 5'-NCR. Recombinant viral genome RNA infection models confirmed that PV1 lacking this region was non-infectious. CONCLUSION In this study, we not only elucidated the mechanisms by which ozone induces PV1 inactivation but also determined that the 80-124 nt region in the 5'-NCR is targeted by ozone to achieve this inactivation.
5' Untranslated Regions ; Animals ; Cercopithecus aethiops ; Genome, Viral ; drug effects ; Oxidants, Photochemical ; pharmacology ; Ozone ; pharmacology ; Poliovirus ; drug effects ; Vero Cells ; Virus Inactivation