Objective To determine the relationship between methylenetetrahydrofolate reductase(MTHFR)C677T,A1298C and multidrug resistance 1(ABCB1)C3435T gene polymorphisms and the adverse reactions of high-dose methotrexate(HD-MTX)in children with acute lymphoblastic leukemia(ALL).Methods Blood samples of ALL children treated with HD-MTX chemotherapy were collected,and the polymorphic polymorphism of MTHFR C677T,A1298C and ABCB1 C3435T genes were detected by sequencing method.The adverse drug reactions after MTX chemotherapy were evaluated according to the common adverse drug reaction grading criteria.The relationship between MTHFR C677T,A1298C and ABCB1 C3435T gene polymorphisms and HD-MTX adverse drug reactions was analyzed.Results The risk of MTHFR A1298C AC+CC type hepatic injury(grade 2)was higher than AA type[odds ratio(OR)2.350,95％confidence interval(CI)=1.038-5.320,P＜0.05],no correlations were found between MTHFR A1298C and myelosuppression,mucositis,gastrointestinal reaction and acute renal impair(all P＞0.05).ABCB1 C3435T CT type hepatic injury(grade 2)was higher than TT type(OR 5.161,95％CI 1.371-19.424,P＜0.05),ABCB1 C3435T CC+CT type hepatic injury(grade 2)was higher than TT type(OR 4.231,95％CI 1.165-15.362,P＜0.05);no correlations were found between ABCB1 C3435T and myelosuppression,mucositis,gastrointestinal reaction and acute renal impair(all P＞0.05).No correlations wre found between MTHFR C677T and HD-MTX adverse drug reactions(all P＞0.05).Conclusion When treating ALL with HD-MTX,adverse drug reactions can be predicted by detecting MTHFR A1298C and ABCB1 C3435T genotypes,so as to implement more scientific individualized medication.

ObjectiveTriple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis, and lacks effective therapeutic targets. Colony stimulating factors (CSFs) are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells, playing an important role in the malignant progression of TNBC. This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes (CRGs), and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy. MethodsWe downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database. Through LASSO Cox regression analysis, we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score (CRRS). We further analyzed the correlation between CRRS and patient prognosis, clinical features, tumor microenvironment (TME) in both high-risk and low-risk groups, and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy. ResultsWe identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model. Kaplan-Meier survival curves, time-dependent receiver operating characteristic curves, and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival, and the predictive ability of CRRS prognostic model was further validated using the GEO dataset. Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients. Moreover, patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil, ipatasertib, and paclitaxel. ConclusionWe have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs, which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment. Moreover, the key genes within this model may represent potential molecular targets for future therapies of TNBC.

Objective To investigate the effect and mechanism of transplantation of neuregulin1(NRG1)gene-modified bone marrow mesenchymal stem cells(BMSCs)on the repair of hemi-transected spinal cord injury(SCI)in rats.Methods Isolated and cultured rat BMSCs,followed by transfection with the NRG1 gene.The levels of NRG1 in BMSCs lysate and culture supernatant was deected by ELISA method,and the proliferation activity of the BMSCs was detected by cell counting method.Forty-three healthy 8-week-old SD rats were randomly divided into control group(n=10),SCI model group(n=10),BMSCs group(n=10),and NRG1-BMSCs group(n=13).After establishing the spinal cord hemisection model,animals received in-situ transplantation of BMSCs or NRG1-BMSCs.On the 1,7,14,21,and 28 days after transplantation,the hind limb motor function was evaluated using BBB score and inclined plate test;on the 7th day after transplantation,the migration and distribution of transplanted cells was monitored using a fluorescence microscope;on the 28th day after transplantation,the pathological changes of rat spinal cord tissues was examined using HE staining and Nissl staining;cell apoptosis using TUNEL staining,and levels of endoplasmic reticulum stress-related proteins[X-box binding protein 1(XBP1),C/EBP homologous protein(CHOP),activating transcription factor 4(ATF4),ATF6,glucose-regulated protein 78(GRP78)]and apoptosis-related proteins[B-cell lymphoma-2(Bcl-2)and Bcl-2-associated protein X(Bax)]in rat spinal cord tissues using Western blotting.Results BMSCs were successfully isolated,cultured,and transfected with the NRG1 gene.ELISA method results showed that the NRG1 contents in the NRG1-BMSCs lysate and culture supernatant were significantly higher than that of BMSCs in a time-dependent manner(P<0.05).The proliferation activity of NRG1-BMSCs was significantly higher than that of BMSCs(P<0.05).On the 21 and 28 days after transplantation,the BBB score and the slope angle of the inclined plate in NRG1-BMSCs group were higher than those in SCI model group or BMSCs group(P<0.05).However,it did not reverse to the level in control group(P<0.05).On the 28th day after transplantation,compared with the SCI model group and BMSCs group,neuronal pyknosis reduced,the Nissl body density increased,the expression levels of XBP1,CHOP,ATF4,ATF6,GRP78,and Bax,and the rate of TUNEL-positive cells significantly reduced in NRG1-BMSCs group(P<0.05),and the expression level of Bcl-2 significantly increased(P<0.05).Conclusion Transplantation of NRG1 gene-modified BMSCs can alleviate SCI and improve the recovery of motor function in rats.The mechanism may be related to promoting the proliferation activity of BMSCs,inhibiting cell apoptosis,and mitigating endoplasmic reticulum stress.

Objective To explore the role of sulodexide(SDX)in neointimal hyperplasia of arteriovenous fistulas(AVFs)in chronic kidney disease(CKD)rats and its possible mechanism.Methods A total of 18 male rats(weighing 300±50 g)were randomly and equally divided into AVF group,CKD+AVF group(CKD induction followed by AVF surgery and then gavaged with normal saline for 2 months),and CKD+AVF+SDX group[treated as in the CKD+AVF group but with 8 mg/(kg·d)SDX gavage].HE staining was used to observe the degree of neointimal hyperplasia.The expression of Hippo pathway related molecules,Yes-associated protein(YAP),pYAP and connective tissue growth factor(CTGF,YAP downstream target protein,one of mesenchymal marker)was detected by immunofluorescence assay.After human umbilical vein cell fusion EAHy926 cells were treated with 0,2.5,5,10,20 or 40 μg/mL SDX for 24 h,and with 2.5 μg/mL SDXfor24,48 or 72 h,respectively,CCK-8 assay was used to measure cell survival rate.Moreover,the serum sample from CKD rat was used to treat EAHy926 cells,and then the cells were treated with SDX or YAP inhibitor verteporfin.The expression levels of YAP,pYAP,CTGF and endothelial cell marker CD31 were detected by Western blotting.Results HE staining and immunofluorescence assay showed that CKD rats had serious neointimal hyperplasia in AVFs(P＜0.05),and slightly lower expression of pYAP and enhanced expression of CTGF(P＜0.05)when compared with the rats of the AVF group.While,SDX treatment alleviated the neointimal hyperplasia of AVFs,enhanced the expression of pYAP and reduced the expression of CTGF(P＜0.05).CCK-8 assay showed that cell survival rate was decreased significantly in a dose-and time-dependent manner after SDX treatment(P＜0.05).Western blotting revealed that SDX increased the expression of pYAP and CD31 while inhibited the expression of CTGF in EAHy926 cells(P＜0.05),which was consistent with the effect of verteporfin treatment.Conclusion SDX can block YAP activation caused by CKD and attenuate neointimal hyperplasia in AVFs.

In this work,a tetrahedral DNA nanostructure(TDN)functionalized rotational paper-based analytical device(RPAD)was constructed for rapid and highly sensitive detection of aflatoxin B1(AFB1)using exonucleaseⅠ(ExoⅠ)and G-quadruplex(G4)dimer.Herein,a single-stranded DNA,containing both of the G4 dimer sequence and AFB1 recognition sequence,was used as the recognition probe(G4 dimer probe).TDN was used to precisely regulate the orientation and distribution density of G4 dimer probe to improve the recognition efficiency of the system.ExoⅠas a single stranded DNA specific nuclease was introduced for effective amplification of the detection signal.G4 dimer was employed to enhance the fluorescence signal of thioflavin T(ThT).In the absence of AFB1,the G4 dimer structure of G4 dimer probe could specifically bind with ThT to generate dramatic fluorescence enhancement.However,in the presence of AFB1,AFB1 could specifically bind with G4 dimer probe,resulting in the dissociation of G4 dimer probe from TDN and further be digested by ExoⅠ.At the same time,the released AFB1 could bind to G4 dimer probe on the TDN again by this way to generate signal amplification.After this cycle,the amount of aptamer on the TDN was decreased,accompanied by the reduction of G4 dimer on TDN.In this case,the fluorescence intensity of the system was reduced.The designed RPAD showed a good linear response in AFB1 concentration range of 0.0001-500 ng/mL and the limit of detection was 0.1 pg/mL.Moreover,the proposed strategy was successfully applied to detection of AFB1 in peanut and wine.The developed TDN/G4 dimer/ExoⅠstrategy improved the specificity and sensitivity of the system significantly.

Objective:To explore the relationship between psychological resilience,professional identity and employment pressure of nursing students with different educational levels,and analyze its influencing factors.Methods:A total of 208 nursing students with different educational levels were investigated by using the general information questionnaire,the employment pressure questionnaire of nursing students,the psychological resilience scale and the professional identity questionnaire.The correlation among psychological resilience,professional identity and employment stress was analyzed by Pearson correlation analysis.Results:The total score of professional identity,psychological resilience,and employment stress was(54.46±12.34),(57.62±18.66),and(98.30±20.25),respectively.There was no significant difference in professional identity score and psychological resilience score among nursing students with different educational levels(P＞0.05).There was no significant difference in the employment stress scores between nursing students upgrading from a junior college and undergraduate and junior college nursing students(P＞0.05),while the employment stress score of junior college nursing students were significantly higher than that of undergraduate nursing students(P＜0.05).Pearson correlation analysis showed that the total score of employment stress was positively correlated with the total score of psychological resilience(r=0.252),and the total score of professional identity(r=0.312)(P＜0.01).Conclusions:The psychological resilience of nursing students is at the average level,professional identity is low,and the employment pressure of junior college nursing students is higher than that of undergraduates.Targeted interventions should be developed to improve the psychological resilience and professional identity of nursing students,and reduce the employment pressure level of junior college nursing students.

As a large family of transcription factors, the MYB family plays a vital role in regulating flower development. We studied the MYB family members in Lonicera macranthoides for the first time and identified three sequences of 1R-MYB, 47 sequences of R2R3-MYB, two sequences of 3R-MYB, and one sequence of 4R-MYB from the transcriptome data. Further, their physicochemical properties, conserved domains, phylogenetic relationship, protein structure, functional information, and expression were analyzed. The results show that the 53 MYB transcription factors had different conserved motifs, physicochemical properties, structures, and functions in wild type and 'Xianglei' cultivar of L. macranthoides, indicating their conservation and diversity in evolution. The transcript level of LmMYB was significantly different between the wild type and 'Xianglei' cultivar as well as between flowers and leaves, and some genes were specifically expressed. Forty-three out of 53 LmMYB sequences were expressed in both flowers and leaves, and 9 of the LmMYB members showed significantly different transcript levels between the wild type and 'Xianglei' cultivar, which were up-regulated in the wild type. The results provide a theoretical basis for further studying the specific functional mechanism of the MYB family.
Transcription Factors/metabolism* ; Lonicera/metabolism* ; Phylogeny ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant

Arrhythmia, a common and frequently occurring cardiovascular disease, causes a heavy burden on the public health of China. Approximately 20 million patients are suffering from this disease in China and treated by pharmacological and surgical therapies. However, antiarrhythmic drugs can cause arrhythmia and surgical treatment has the risks of failure and recurrence. Therefore, the clinical outcome of arrhythmia remains to be improved. According to the traditional Chinese medicine(TCM) theory, arrhythmia is a disease of palpitation induced by 7 conditions: liver depression and Qi stagnation, accumulation of turbid phlegm, fluid retention attacking the heart, fire-heat disturbing the heart, stasis obstruction of heart vessel, cold congealing in heart vessel, and the deficiency of Qi, blood, Yin, and Yang. Therefore, this study concisely proposed 7 TCM syndromes of arrhythmia, including the palpitation due to depression, phlegm, fluid retention, fire, blood stasis, cold, and deficiency. The corresponding treatment strategies were recommended as follows: Chaihu Longgu Muli Decoction for the palpitation due to depression, Wendan Decoction for the palpitation due to phlegm, Linggui Zhugan Decoction for the palpitation due to fluid retention, Sanhuang Xiexin Decoction for the palpitation due to fire, Xuefu Zhuyu Decoction for the palpitation due to blood stasis, and Mahuang Fuzi Xixin Decoction for the palpitation due to cold, and Guizhi Gancao Decoction, Guizhi Gancao Longgu Muli Decoction, Huanglian Ejiao Decoction, Zhigancao Decoction, and Guipi Decoction for the palpitation due to the deficiency of Qi, blood, Yin, and Yang. Multiple formulas should be combined if the patient presents several TCM syndromes simultaneously. According to the principles of the correspondence between formula and syndrome and the treatment with consideration to both pathogenesis and pathology and both herbal nature and pharmacology, this study proposed an integrated treatment model of "pathogenesis-pathology-nature-pharmacology" to enhance the clinical efficacy of classic herbal formulas in the treatment of arrhythmia.
Humans ; Medicine, Chinese Traditional ; Syndrome ; Drugs, Chinese Herbal/therapeutic use* ; Heart Failure/drug therapy* ; Arrhythmias, Cardiac/drug therapy* ; China

The relationship between disease and syndrome is a research focus in integrated traditional Chinese and western medicine. Depending on the focus, the disease-syndrome combination for treatment is manifested as the different treatment methods for the same disease and the same treatment method for different diseases based on the syndrome, and different treatment methods for the same syndrome and the same treatment method for different syndromes based on the disease. The mainstream model is the combination of di-sease identification in modern medicine with syndrome identification and core pathogenesis in traditional Chinese medicine. However, current research on the combination of disease and syndrome and core pathogenesis tends to focus on the heterogeneity between disease and syndrome and the separation of syndrome and treatment. Therefore, the study proposed the research idea and model of core formulas-syndromes(CFS). According to the theory of formula-syndrome correspondence, the research idea of CFS deepens the research on core pathogenesis, which aims to summarize the core formulas and syndromes for diseases. The research fields include diagnostic criteria for the indications of formulas, distribution patterns of formulas and syndromes for diseases, the evolution of medicinal-syndrome based on formulas-syndromes, formula combination law based on formulas-syndromes, and the dynamic evolution of formulas-syndromes. Through the summary of ancient classics, clinical experience, and medical records, and with the methods of expert consultation, factor analysis, and clustering analysis, research on the diagnostic criteria for the indications of formulas aims to explore the diagnosis information such as the diseases, symptoms, signs, and pathophysiology. The research on the distribution patterns of formulas and syndromes for diseases tends to summarize the specific types of formulas and syndromes for the diseases through literature research and clinical cross-sectional studies based on the establishment of diagnostic criteria for the indications of formulas. The research on the evolution of medicinal-syndrome aims to clarify the medicinal-syndrome law through literature and clinical research. The formula combination law refers to the fact that the core prescriptions for a disease often appear in combination with other prescriptions on a regular basis. The dynamic evolution of formulas-syndromes refers to the continuous transformation and change of formulas and syndromes in the process of disease development with changes in time and space. The CFS is conducive to the unification of disease, syndrome and treatment and to the deepening of the research model of disease and syndrome integration.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Syndrome ; Cross-Sectional Studies ; Medicine, Chinese Traditional ; Prescriptions

Hypertension and its target organ damage have become a major public health problem. Sexual dysfunction is a new problem in the treatment of modern hypertension. Modern pathophysiological studies have shown that hypertension can lead to sexual dysfunction. In addition, three major hypotensive drugs represented by diuretics can also lead to sexual dysfunction. In traditional Chinese medicine(TCM), hypertension belongs to "vertigo" "headache" "head wind", etc. In the past, the understanding of the TCM pathogenesis of hypertension was mainly from the perspectives of "liver wind" and "Yang hyperactivity". However, based on the in-depth research on ancient and modern literature and medical records and many years of clinical practice, it has been identified that kidney deficiency was the key pathogenesis. Hypertension complicated with sexual dysfunction belongs to the category of kidney deficiency syndrome in TCM, especially the deficiency of kidney Yin. Previous studies by other research groups showed that Yin-enriching and kidney-tonifying method could effectively reduce blood pressure, improve sexual dysfunction, reverse risk factors, and protect target organs. This article systematically discussed the TCM understanding, modern pathophysiological mechanism, and the clinical treatment strategy of kidney-tonifying drugs(single drugs and compounds) in the treatment of hypertension complicated with sexual dysfunction in order to provide a scientific basis for kidney-tonifying method in the treatment of hypertension complicated with sexual dysfunction.
Humans ; Antihypertensive Agents/therapeutic use* ; Medicine, Chinese Traditional ; Hypertension/drug therapy* ; Blood Pressure ; Risk Factors ; Drugs, Chinese Herbal/therapeutic use*