Objective To investigate the alterations of Treg cells , Th17 cells and related cyto-kines in peripheral blood of patients during the early stage of hand-foot-mouth disease ( HFMD) .Methods Flow cytometry was performed to analyze the percentages of Treg cells ( CD4+CD25+Foxp3 T cells) and Th17 cells ( CD3+CD8-IL-17+T cells) in peripheral blood samples collected from 49 patients with severe HFMD , 26 patients with common HFMD and 30 healthy children.The levels of IL-6, IL-10, IL-17, IL-23 and TGF-β1 in serum samples were measured by ELISA .Results The percentages of Treg cells , ratios of Treg/Th17 cells, serum levels of TGF-β1 and IL-10 in patients with HFMD were significantly decreased as compared with those of control group (F=5.580, 6.205, 0.000, 0.014, respectively, P<0.05).Patients with se-vere HFMD showed a significantly increased Th17 cells (F=3.189 P<0.05) and a tendency of enhanced IL-17 expression , but no significant differences with the levels of IL-17 were observed .No significant differ-ences with the expression of IL-23 in the patients among each group were detected (P>0.05).The levels of IL-6 in serum samples from severe disease group were obviously increased as compared with those of common HFMD group and control group (F=7.318, P<0.05).Conclusion The results of this study demonstrated that the levels of Treg , Th17 cells and some related cytokines were varied in peripheral blood of patients dur-ing the early stage of HFMD .Inflammatory responses were enhanced to promote anti-virus activities by sup-pressing Treg cells and stimulating Th17 cells.

OBJECTIVEThe relationship between polymorphisms of ALAD and VDR genes and individual susceptibility of lead poisoning was investigated in children highly-exposed to lead.

METHODFour hundred and sixty-nine children were recruited into this study and the blood lead, ZPP, hemoglobin as well as three physical developmental indexes (head circumference, height and weight) were measured. VDR and ALAD gene polymorphisms were analyzed by the methods of PCR-RFLP.

RESULTSThe subjects with ALAD2 allele had higher ZPP level (10.12 micro mol/L vs 12.87 micro mol/L) (P = 0.017). The subjects with B allele has larger head circumference than only with b allele (51.19 cm vs 50.75 cm) (P = 0.028).

CONCLUSIONSIt was suggested that the ALAD gene polymorphism modified the relationship between blood lead and ZPP and the VDR gene variants influenced the skull development in children living under lead-polluted environment. The polymorphism of ALAD and VDR genes might serve as the molecular inherited factors modifying the susceptibility of lead poisoning.

Alleles ; Body Height ; drug effects ; genetics ; Body Weight ; drug effects ; genetics ; Child ; China ; epidemiology ; Environmental Pollution ; adverse effects ; Female ; Gene Frequency ; Genotype ; Humans ; Lead ; adverse effects ; blood ; Lead Poisoning ; epidemiology ; etiology ; genetics ; Male ; Polymorphism, Genetic ; Porphobilinogen Synthase ; genetics ; Receptors, Calcitriol ; genetics

Objective To preliminarily investigate the anti-tumor effects of phytosphingosine(PHS)and the involvement of inducing apoptosis of leukemia cells.Methods Cellular model of leukemia was established in leukemia cell lines K562 and SUP-B15.CCK-8 assay and EdU assay were used to measure the viability and DNA synthesis of K562 and SUP-B15 cells.RNA-seq was carried out to verify the differentially expressed genes(DEGs)after PHS treatment.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were applied to analyze the involved functions and signaling pathways.Comparative Toxicogenomics Database(CTD)and Discovery Studio software were employed to predict the underlying targets of PHS and molecular docking.Cell apoptosis was detected by flow cytometry,mitochondrial membrane potential was evaluated by JC-1 probe,and protein expression of key molecules was validated by Western blotting.Results PHS inhibited the proliferation of K562 and SUP-B15 cells in a time-and dose-dependent manner.The half-maximal inhibitory concentration(IC50)of K562 cells was 17.67 and 12.52 pmol/L for 24 and 48 h,respectively,and the IC50 value of SUP-B15 cells was 17.58 and 14.86 μmol/L for 24 and 48 h,respectively.PHS treatment at a dose of 20 μmol/L for 48 h resulted in significant inhibition of DNA synthesis.GO enrichment analysis of the K562 cells showed that PHS might be involved in positive regulation of apoptotic process,plasma membrane and its integral components,and protein kinase binding and activity.Reverse predictive analysis showed that BCL-2 protein was the most likely target of PHS.PHS significantly increased the apoptotic rate of leukemia cells(P＜0.05)in a dose-dependent manner,reduced the mitochondrial membrane potential,and down-regulated BCL-2 level(P＜0.05)and up-regulated the levels of Cleaved caspase-3 and Cleaved caspase-9(P＜0.05).Conclusion PHS may inhibit the proliferation of leukemia cells by inducing mitochondria-dependent apoptosis,possibly through PHS and BCL-2 interaction.

In order to standardize the quality control of traditional Chinese medicine（TCM） dispensing granules， the Chinese Pharmacopoeia Commission has promulgated and implemented 200 national drug standards for TCM dispensing granules， but there are still varieties of TCM dispensing granules without unified standards. Many provinces have actively invested in the formulation of provincial standards for TCM dispensing granules to make up for the gaps in standards for varieties of traditional Chinese medicine dispensing granules other than the national standards. By the end of July 2022， 29 provincial-level administrative regions have successively promulgated and implemented a total of 5 602 provincial standards for TCM dispensing granules， involving more than 400 varieties. In order to better understand the formulation and characteristics of provincial standards， this study took 105 provincial standards that have been promulgated and implemented in Henan province as an example， and comprehensively analyzed the formulation and characteristics through quality control indicators such as dry extract rate of raw materials， contents of index components and their transfer rates， specifications and so on. The formulation and characteristics of the same TCM dispensing granules in the provincial standards of different provinces were further analyzed， in order to provide reference for the formulation of provincial standards of TCM dispensing granules and the implementation of national standards.

Objective To evaluate the predictive value of a dose-surface histogram (DSH) for radiation cystitis (RC) in patients with cervical cancer. Methods We retrospectively included 190 patients with cervical cancer who underwent image-guided radiotherapy (IGRT) from the HIS system of The First Affiliated Hospital of Hebei North University from May 2013 to May 2023. The patients were divided into test group (n = 100) and control group (n = 90). The dose distribution in the bladder was evaluated by using a DSH for the test group and using a dose-volume histogram (DVH) for the control group. Receiver operating characteristic curves were used to evaluate the predictive value of DSH for RC in comparison with DVH. Results There were no significant differences in baseline data and RC incidence between the two groups (all P＞0.05). All evaluation indicators were significantly different between DSH and DVH (all P＜0.05). The predictive value of S₄₅ and V₄₅ for the incidence of grade-I, -II, and -III RC was low (all P＜0.05). The predictive value of S₅₀ and V₅₀ for the incidence of grade-I, -II, and -III RC was moderate (all P＜0.05). S₅₅−S₅₇ and V₅₅−V₅₇ showed high value for predicting the incidence of grade-I, -II, and -III RC (all P＜0.05). Conclusion DSH shows basically the same predictive value for the incidence of RC caused by IGRT in cervical cancer as DVH, which is expected to become a new tool for evaluating radiotherapy plans.

OBJECTIVE To predict the in vivo bioequivalence of lenvatinib mesilate capsules and reference preparation by using the parallel artificial membrane permeability analysis. METHODS Based on the biopharmaceutics classification system classification of lenvatinib mesilate and the parallel artificial membrane permeation model, the in vitro dissolution permeation rate test model of lenvatinib mesilate capsules was established, through real-time monitoring of the dissolution and penetration of lenvartinib mesylate capsules and reference preparations in fasting gastric juice, intestinal fluid and postprandial intestinal fluid, the flux and total penetration of drugs through the membrane were calculated. RESULTS In fasting state and fed state, the 90% confidence interval of geometric mean ratio of two key quality parameters (permeation flux and permeation amount) of the preparation A all were in the range of 80.00%−125.00%, the preparation B did not fall into this interval. CONCLUSION This research method can predict the bioequivalence of renvartinib mesylate capsule and reference preparation, and has a certain correlation in vivo and in vitro.

OBJECTIVE： To establish the elimination method of outliers based on Grubbs rule and MATLAB language， and to evaluate the effects of it on drug bitterness evaluation. METHODS： Referring to Grubbs rule， the automatic cyclic outliers elimination method based on MATLAB language was established. Totally 20 volunteers were included in single oral taste test （Tetrapanax papyrifer） and multiple oral taste test （10 kinds of medicinal material as T. papyrifer， Changium smyrnioides， Poria cocos， etc.）. Seven sensors were selected for electronic tongue test （Clematis armandii）. The data of bitterness evaluation in above tests （oral taste test as bitterness value， electronic tongue test as response value of sensors） were used as the data source. Five researchers were selected and adopted table-by-table elimination method based on Grubbs rule （method one）， Excel software elimination method based on Grubbs rule （method two） and automatic cyclic outliers elimination method based on Grubbs rule and MATLAB language （method three） to judge and eliminate the outliers. The effects of above three methods were evaluated with the removal time and error rate of outliers as indexes. RESULTS： There were two outliers in the data of bitterness evaluation in single oral taste test； the elimination time of the three methods were（745.400 0±25.904 4），（288.333 3±31.253 1）and（0.000 3±0.000 0）s， respectively； error rates were 20.0％， 0 and 0， respectively. There were six outliers in the data of bitterness evaluation in multiple oral taste test； the elimination time of three methods were （3 693.107 7±75.023 3）， （1 494.761 4±53.826 9）， （0.005 2±0.000 0）s， respectively； error rates were 10.0％， 4.0％， 0， respectively. There were three outliers in the data of bitterness evaluation in electronic tongue test； the elimination time of three methods were （2 992.673 3±84.117 6）， （1 276.367 1±55.024 5）， （0.002 3±0.000 0）s， respectively； error rates were 5.7％， 2.9％， 0， respectively. The elimination results of the three methods were consistent. The elimination time of method two was significantly shorter than that of method one （P＜0.01）； the elimination time of method three was significantly shorter than those of method one and method two （P＜0.01）. There was no significant difference in error rate of 3 methods （P＞0.05）. CONCLUSIONS： The automatic cyclic elimination method of outliers based on Grubbs rule and MATLAB language can significantly shorten the elimination time of outliers in data of drug bitterness evaluation， improve the efficiency of data processing， and is suitable for drug bitterness evaluation.