OBJECTIVE To establish a method for simultaneous determination of 7 anti-tumor drugs （irinotecan， capecitabine， paclitaxel， docetaxel， tamoxifen， letrozole and methotrexate） in human plasma and apply it to the clinic. METHODS After precipitating with a methanol-acetonitrile mixture （1∶ 1， V/V） containing 0.1% formic acid， liquid chromatography-tandem mass spectrometry （LC-MS/MS） was used to determine the plasma concentration， using deuterium isotopes of each analyte as internal standards. The chromatography was performed on the Agilent Eclipse Plus C18 column with a gradient elution of water （containing 0.1% formic acid+0.04% 5 mmol/L ammonium formate） as mobile phase A and acetonitrile （containing 0.1% formic acid） as mobile phase B. The flow rate was 0.6 mL/min， and the column temperature was set at 40 ℃ . The sample size was 10 μL， and the analysis lasted for 5.5 min. Electrospray ionization was used in positive and negative ion mode， and multiple reaction monitoring mode was used. The ion pairs used for quantitative analysis were m/z 587.1→167.1 （irinotecan）， m/z 360.1→244.1 （capecitabine）， m/z 876.4→308.0 （paclitaxel）， m/z 830.3→304.2 （docetaxel）， m/z 372.1→129.1 （tamoxifen）， m/z 284.1→242.1 （letrozole）， and m/z 455.0→ 308.0 （methotrexate）. A total of 97 patients with malignant tumors in our hospital were selected to measure the plasma concentrations of 7 anti-tumor drugs using the above method. RESULTS The linear ranges of irinotecan， capecitabine， paclitaxel， docetaxel， tamoxifen， letrozole and methotrexate were 2-1 000 ng/mL （r＝0.994 3）， 20-10 000 ng/mL （r＝0.997 5）， 2-1 000 ng/mL （r＝0.997 9）， 1-500 ng/mL （r＝0.995 8）， 1-500 ng/mL （r＝0.995 2）， 1-500 ng/mL （r＝0.996 4）， 10-5 000 （r＝0.997 7）， respectively. The quantitative lower limits were 2， 20， 2， 1， 1， 1 and 10 ng/mL； RSDs of intra-assay precision were 0.08%-14.86% （n＝6）. RSDs of inter-batch precision were 1.51%-11.55% （n＝3）， and the accuracies were 89.17%-114.93% （n＝6）. The matrix effects ranged from 89.89%-119.74% （n＝6）. RSDs of the stability tests were 1.98%-14.88% （n＝6）. The results of E-mail：hangpengzhou@163.com clinical application showed， the average plasma concentrations of irinotecan， capecitabine， paclitaxel and docetaxel were 704.09， 909.40， 36.45， 150.43 ng/mL， respectively. The values of the coefficient of variation were 25.24%， 62.65%， 122.69%， and 92.27%. CONCLUSIONS The established LC-MS/MS method is simple and rapid， and can be used for the simultaneous determination of 7 commonly used anti-tumor drugs in the plasma of patients with malignancy.

Objective To explore the effects of Shaoyao Gancao granule on hair growth,behavior,and the hypothalamic pituitary adrenal(HPA)axis in mice with alopecia areata(AA).Methods Forty-two C3H/HeJ mice were randomly divided into control,model,Shaoyao Gancao granule high-,middle-,low-dose,corticotropin-releasing hormone receptor 1(CRHR1)antagonist,and compound glycyrrhizin tablet(CGT)groups.Photography,dermoscopy,weight analysis,and behavioral measurement were performed.Corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),cortisol,glucocorticoid receptor(GR),and brain-derived neurotrophic factor(BDNF)were also assessed.Results Compared with the model group,high-dose Shaoyao Gancao granules improve hair regeneration and weight gain(P＜0.05),increased the percentage of total exercise distance and central area exercise distance in an open field test(P＜0.05),reduced the immobility time in the forced swimming and tail suspension experiments(P＜0.05),reduced peripheral blood levels of CRH,ACTH,and cortisol(P＜0.05),and increased expression of GR and BDNF in the hippocampus(P＜0.05).Conclusions Shaoyao Gancao granule promotes hair growth and improves behavioral performance in mice with AA.These effects may be related to downregulating CRH,ACTH,and cortisol expression,upregulating GR and BDNF expression,and inhibiting excessive activation of the HPA axis.

The difference in the crystal form of the drug leads to different solubility and stability,affecting drug's the clinical efficacy and bioavailability.Therefore,in recent years,drug crystal forms have received more and more attention from researchers.By reviewing and sorting out relevant literature,this paper summarizes the research progress of drug crystallization theory in recent years from the aspects of influencing factors of drug crystal form,identification and control of drug crystal form,drug crystal form evaluation methods,and applications,aiming to provide a reference for drug crystal form control and process screening.

Traditional Chinese medicine monomer has certain curative effects in tumor treatment,but its low targeting and difficulty in gathering at the tumor site limit its application.As a new type of drug delivery method,environmentally responsive nano drug delivery system has the advantages of targeted drug delivery,reducing drug side effects,and environmentally responsive release,and has been widely used in tumor treatment.In this paper,by consulting and sorting out the relevant literature,the general situation of traditional Chinese medicine monomers in the treatment of tumors,the classification of environment-responsive traditional Chinese medicine monomer nano drug delivery system,and its application in tumor treatment are summarized in three aspects,to provide ideas for solving the limitations of traditional Chinese medicine monomer in the treatment of tumor.

Objective:To explore the clinical efficacy and risk factors of umbilical cord mesenchymal stem cells (UCMSCs) infusion at an early stage (i.e.gross hematuria) for hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The relevant clinical data were retrospectively reviewed for 300 patients undergoing allo-HSCT from January 2016 to July 2021.According to the presence or absence of HC, they were assigned into two groups of HC (n=89) and non-HC (control, n=211). According to whether or not receiving an infusion of UCMSCs, 51 patients of HC degree Ⅱ-Ⅳ were divided into two groups of UCMSC infusion and non-infusion.The risk factors of HC after allo-HSCT were analyzed by χ2 test.Logistic regression was employed for multivariate analysis of P<0.05.Mann-Whitney U test was utilized for statistically analyzing the duration of gross hematuria and urinary tract irritation symptoms and evaluating the clinical efficacy of UCMSCs infusion for HC. Results:Among them, 89 (29.67%) developed HC post-allo-HSCT.Clinical grades were Ⅰ (n=38, 42.70%), Ⅱ (n=36, 40.45%), Ⅲ (n=13, 14.61%) and Ⅳ (n=2, 2.25%). The median occurrence time was 29 (21.5-35.0) days post-allo-HSCT.In univariate analysis, age ≤30 years, haploid transplantation, antithymocyte globulin (ATG), acute graft-versus-host disease (aGVHD), CMV-DNA positive pretreatment significantly boosted the risk of HC ( P<0.05). In multivariate analysis, aGVHD was an independent risk factor for HC ( OR=10.281, 95% CI: 1.606-65.813, P=0.014). Among 89 HC patients, 38 grade Ⅰ patients were complete remission(CR). Among 51 patients of grade Ⅱ-Ⅳ HC, the outcomes were CR (n=48) and non-remission(NR)(n=3). And 24/51 of them received UCMSCs plus conventional treatment.The duration of gross hematuria was shorter in UCMSCs infusion group than that in UCMSCs non-infusion group [12(9-17) vs 17(12.0-26.5) day] and the difference was statistically significant ( P=0.045). And the duration of urinary tract irritation symptoms was shorter in UCMSCs infusion group than that in UCMSCs non-infusion group [18(11-30) vs 27(18.0-35.5) days] and the difference was statistically significant ( P=0.048). Conclusions:Indicated for post-ALLO-HSCT HC, infusion of UCMSCs may significantly shorten the course of disease.Age ≤30 years, haploid transplantation and preconditioning with positive ATG, aGVHD and CMV-DNA may boost the risks of HC post-allo-HSCT.And aGVHD is an independent risk factor for HC after allo-HSCT.

In this study, the formulation and preparation process of curcumin nanocrystalline injection were optimized to improve curcumin dissolution rate and bioavailability in vivo.Media grinding method was used to prepare curcumin nanocrystals, and the particle size was used as the evaluation index.The Box-Behnken experimental design was used to optimize its formulation and preparation process, and to characterize its physical and chemical properties.In addition, the dissolution of nanocrystal with different particle sizes was investigated by the paddle method, and the pharmacokinetics in rats were studied.The experimental results showed that the optimal formula and process were obtained through Box-Behnken experimental design, and that uniform curcumin nanocrystals with an average particle size of 223.1 nm were obtained.The results of X-ray diffraction and differential scanning calorimetry analysis showed that the crystal form was stable during the preparation of nanocrystals. In vitro dissolution experiments with different particle sizes showed that the dissolution rate and the degree of dissolution would increase if the particle size was smaller.Pharmacokinetic studies in rats showed that cmax and AUC0-∞ of curcumin nanocrystal injection were 4.9 and 4.1 times that of curcumin raw materials, respectively.In summary, the curcumin nanocrystal injection developed in this research have a stable preparation process and can significantly improve the dissolution rate and bioavailability of the drug, which provides some ideas for the research on curcumin preparation.

OBJECTIVE: To explore the clinical and genetic characteristics of a child with MEGDEL syndrome. METHODS: Clinical data of the child was reviewed. Peripheral blood samples of the child and his parents were collected. Mitochondrial genome and the whole exome of the child were analyzed by next-generation sequencing. Candidate variants and its origin were verified by Sanger sequencing and fluorescence quantitative PCR. RESULTS: The patient, a 2-year-and-6-month-old male, has featured hypoglycemia, mental and motor retardation with regression. Cranial MRI showed bilateral putamen damage suggestive of Leigh syndrome. Testing of urine organic acid indicated that the level of 3-methylpentenoic acid was slightly increased. Whole exome sequencing revealed that the child has harbored heterozygous deletion of exons 6 to 17 and c.307A>T nonsense variant of the SERAC1 gene, which were respectively inherited from his parents who were asymptomatic. Treatment with Levocarnitine, vitamin B1, vitamin B2, coenzyme Q10, baclofen and glucuronolactone resulted in improvement of sleep and mental state. CONCLUSION A case of MEGDEL syndrome without deafness was diagnosed. Discovery of the nonsense mutation and large fragment deletion have enriched the spectrum of SERAC1 gene variants.
Child, Preschool ; Hearing Loss, Sensorineural/genetics* ; Humans ; Leigh Disease ; Male ; Metabolism, Inborn Errors/genetics* ; Molecular Biology ; Mutation

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

Objective To analyze the characteristics of papers published in Organ Transplantation in the past ten years. Methods The academic papers published in Organ Transplantation from January 2010 to December 2019 were retrieved from China National Knowledge Infrastructure (CNKI). The publication volume, the funded paper ratio, authors, research institutions and keywords were analyzed by information visualization software CiteSpace 5.3 and VOSviewer 1.6. Results From 2010 to 2019, a total of 919 academic papers were published in Organ Transplantation, with an average annual publication volume of 92, showing an overall stable trend. The funded paper ratio and the ratio of papers with funding support at the provincial level or above increased year by year, reaching 100% in 2019. High-yield authors mainly formed two research teams led by Shi Bingyi and Chen Guihua respectively. The first authors were distributed across China. In recent years, as many as 58 programmatic papers were published by national academic institutions, especially signed by Branch of Organ Transplantation of Chinese Medical Association. The average number of authors per paper was 4.94 in Organ Transplantation, and the proportion of papers contributed by two or more authors remained above 90% in recent years. According to the analysis of research institutions, the average number of institutions per paper was 1.60 in Organ Transplantation. Keyword co-occurrence network analysis demonstrated that liver transplantation, renal transplantation and organ transplantation were the research hotspots in the field of organ transplantation. Keyword cluster analysis showed that research mainly focused on 9 fields, such as liver transplantation, renal transplantation, organ transplantation, organ donation, posttransplantation complications, transplantation immunity, end-stage liver disease, xenotransplantation and stem cell transplantation. Keyword burst analysis showed that xenotransplantation, α-1, 3-galactose, transplantation immunity, apoptosis, donor specific antibody (DSA), antibody-mediated rejection (AMR) and flow cytometry were the research hotspots. Conclusions The authors that publish academic papers in Organ Transplantation come from major transplantation centers all over the country. The papers of Organ Transplantation cover the research hotspots of each branch in the field of organ transplantation, and include a large quantity of programmatic papers signed and published by national academic institutions, which show the frontier hotspots and the highest level of research in the field of organ transplantation in China, making Organ Transplantation an excellent academic journal.

Objective:To explore the effects of nurse as standardized patient (NSP) in clinical apprenticeship and objective structured clinical examination (OSCE) of psychiatric nursing.Methods:Totally 260 undergraduate nursing students admitted to the School of Nursing of a medical university in 2017 were selected into experimental group, who were taught in combination of real patients and NSP, and received assessment of clinical apprenticeship skills through OSCE involving NSP. Totally 286 undergraduate nursing students admitted in 2016 were selected into control group, who received conventional clinical apprenticeship teaching and assessment. The discrimination and difficulty of the assessment of the experimental group was considered, and the test scores, the degree of recognition of the assessment form by the nursing students, and the ability of critical thinking were compared between the two groups.Results:Totally 247 nursing students in the experimental group and 280 in the control group completed the study. The degree of difficulty and discrimination met the assessment requirements. There was a statistically significant difference in apprenticeship performance between the two groups ( P<0.01) . After OSCE, the recognition scores of the two groups for OSCE were (3.22±0.64) and (4.17±0.58) , respectively, and the difference was statistically significant ( P<0.01) . The total scores of Critical Thinking Disposition Inventory-Chinese Version (CTDI-CV) of the two groups were (278.29±25.66) and (289.53±35.43) , respectively, and the difference was statistically significant ( P<0.01) . There were statistically significant differences in the scores of CTDI-CV in 4 dimensions between the two groups, they are open-mindedness, analytical ability, systematic ability and self-confidence ( P<0.05) . Conclusions:The NSP-based clinical apprenticeship and OSCE for psychiatric nursing is feasible and practical, which can improve students' critical thinking ability, and is worth referencing and promoting.