Objective: To investigate the distribution frequency and molecular mechanism of the rare blood type Lu(a-b-) in Shenzhen, and to compare the polymorphisms of the Lutheran blood group system encoding gene LU and the In (Lu) phenotype-related gene KLF1 among Han Chinese, Indian, and Uyghur populations in Xinjiang. Methods: Serological methods were used to screen the Lu(a-b-) phenotype of blood donors in Shenzhen. Third-generation sequencing was employed to sequence the full-length of the LU and KLF1 genes in Lu (a-b-) phenotype samples as well as the samples from the Han Chinese, Indians, and Uyghur population, followed by analysis of gene haplotypes frequencies. Results: Ten individuals with the Lu(a-b-) phenotype were screened out of 14 367 blood donors in Shenzhen, yielding a frequency of approximately 0.07%. Only 2 cases showed mutations in the coding region of the LU gene, while all individuals showed heterozygous mutations in the coding region of the KLF1 gene. The highest mutation frequencies of the LU and KLF1 genes were observed in the Uyghur population in Xinjiang and the Han Chinese in Shenzhen, respectively. Conclusion: All Lu(a-b-) phenotypes are of the In (Lu) type, and their formation mechanism is mainly related to KLF1 gene mutations. Both the LU and KLF1 genes exhibit significant polymorphism in the Han Chinese, Indians, and Uyghur populations.

This study investigates the pharmacokinetics and metabolic characteristics of three marine-derived piericidins as potential drug leads for kidney disease: piericidin A (PA) and its two glycosides (GPAs), glucopiericidin A (GPA) and 13-hydroxyglucopiericidin A (13-OH-GPA). The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate. Rapid absorption of PA and GPAs in mice was observed, characterized by short half-lives and low bioavailability. Glycosides and hydroxyl groups significantly enhanced the absorption rate (13-OH-GPA > GPA > PA). PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes (CYPs) and uridine diphosphoglucuronosyl transferases (UGTs). Glucuronidation emerged as the primary metabolic pathway, with UGT1A7, UGT1A8, UGT1A9, and UGT1A10 demonstrating high elimination rates (30%-70%) for PA and GPAs. This rapid glucuronidation may contribute to the low bioavailability of GPAs. Despite its low bioavailability (2.69%), 13-OH-GPA showed higher kidney distribution (19.8%) compared to PA (10.0%) and GPA (7.3%), suggesting enhanced biological efficacy in kidney diseases. Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability. In conclusion, this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.
Animals ; Male ; Mice ; Aquatic Organisms/chemistry* ; Biological Availability ; Cytochrome P-450 Enzyme System/metabolism* ; Glucuronosyltransferase/metabolism* ; Microsomes, Liver/metabolism* ; Molecular Structure ; Biological Products/pharmacokinetics* ; Pyridines/pharmacokinetics*

This review systematically summarizes the unique metabolic mechanisms of breast cancer,their interac-tions with the tumor microenvironment(TME),and the latest advances in targeted therapies.The interplay between metabolic reprogramming and the TME underpins malignant progression and therapeutic resistance.Breast cancer cells reshape energy supply through the Warburg effect,aberrant fatty acid synthesis,and amino acid metabolism,while immune cells,fibroblasts,and the acidic milieu within the TME promote immune evasion and drug resistance via metabolic coupling.Although traditional strategies targeting key metabolic enzymes remain valuable,they are often insufficient to overcome metabolic adaptability.In recent years,combined metabolic and immunotherapeutic approaches have emerged as promising strategies:by reducing lactate accumulation,restoring T-cell function,and reprogramming tumor-associated macrophages and cancer-associated fibroblasts,these therapies can remodel the immunosuppressive microenvironment and enhance immunotherapy efficacy.The application of metabolomics and single-cell sequencing further elucidates breast cancer heterogeneity,providing a basis for individualized precision treatment.Future challenges include deciphering resistance mechanisms,developing highly selective metabolic in-hibitors,and designing integrated multi-omics-based therapeutic regimens.

OBJECTIVE: To explore the serological characteristics and bioinformatics analysis results of 4 blood donors with RHCE*cE(281C, 282T) variant allele. METHODS: A total of 4 non-related blood donors with RHCE*cE (281C, 282T) variant allele (donors 1-4) were selected as the study objects. They donated blood at Shenzhen Blood Center from January 2022 to June 2023. The 4 blood donors were all Han. And 5 mL elbow venous blood was collected from these 4 blood donors. Regular serological assaying with 4 kinds of monoclonal antibody reagents was used for determination of the RhCcEe type. The nucleotide sequences of all 10 exons and adjacent flanking intron regions of RHCE gene in these 4 donors were analyzed by Sanger sequencing, and the full-length haplotype analysis of RHCE gene was performed by using the single-molecule real-time sequencing (SMRT) third-generation technology. DeepTMHMM software was used to analyze the structure of protein transmembrane region of wild type and variant RhCcEe protein and predict the location of amino acid substitution. The effects of mutations on RhCcEe protein function were analyzed using PolyPhen-2, SIFT and Mutation Taster bioinformatics software. Robetta and Swiss-PdbViewer v4.1.0 were used for modeling the tertiary structures of RhCcEe to analyze the difference between wild type and variant RhCcEe protein. The mutation was rated according to the standards and guidelines for the classification of genetic variants of the American College of Medical Genetics and Genomics (ACMG). This study has been approved by the Medical Ethics Committee of Shenzhen Blood Center (Approval No. SZBCMEC-2022-024). RESULTS: The RhCcEe phenotypes of the 4 blood donors were CCEweake by serological assaying. The RhE antigen were weakly expressed form 0 to 3+. The analysis of RHCE gene sequence indicated that all the 4 donors with RHCE*cE (281C, 282T) allele. The mutation caused the substitution of a single amino acid in the RhCcEe protein (p.Leu94 Pro) and the amino acid substitution was located in the transmembrane α3 chain resulted in significant changes in the 3D structure of the extracellular region of RhCcEe protein. The substitution was predicted to be "Probably damaging", "Damaging" and "Polymorphism" by PolyPhen-2, SIFT and Mutation Taster bioinformatics software. According to the guidelines of ACMG, the variant was rated to be likely pathogenic. CONCLUSION The RHCE*cE (281C, 282T) variant allele was first found in the Han Chinese population. The serological data of this allele were enriched. It provides an important guarantee for the safety of blood transfusion. Bioinformatics analysis provided evidences for further study of the structure and functions of RhCcEe protein.
Humans ; Blood Donors ; Computational Biology/methods* ; Alleles ; Rh-Hr Blood-Group System/genetics* ; Male ; Female ; Adult ; Exons

Objective To analyze the correlation between the expression of soluble glycoprotein A(GPA)in plasma of healthy blood donors and anti-M and anti-"Mia"antibodies.Methods Plasma from healthy donors from February 9,2022 to February 15,2023 was collected:irregular antibody-negative NN type(group Ⅰ,n=118)and MM type(group Ⅱ,n=51),anti-M antibody positive NN type(group Ⅲ,n=145)and anti-"Mia"antibody positive companion type(group Ⅳ,n= 87),the GPA content in plasma of different individuals in 4 groups was detected,and the difference in GPA expression was analyzed by t-test.Results The average plasma GPA contents in groupsⅠ,Ⅱ,Ⅲ and Ⅳ were 9.941±0.252,10.97±0.256,5.139±0.129 and 4.28±0.139ng/ml,respectively.The average GPA content of groups Ⅰ and Ⅱ was higher,and the average GPA content of groups Ⅲ and Ⅳ was lower,and the differences were statistically significant(all P＜0.01).Conclusion The GPA content in plasma of healthy donors with anti-M and anti-"Mia"antibodies was significantly lower than that of the antibody-negative group.The results of this study lay a foundation for further investigation of whether GPA in plasma has the ability to neutralize anti-M and anti-"Mia"antibodies,improve disease diagnosis and safe blood transfusion.

Objective To investigate the effect of combination of rope-assisted proprioceptive neuromuscular facilitation(PNF)training and rope-assisted brain-computer interface(BCI)training on upper limb function in stroke patients with hemiplegia. Methods From March,2022 to February,2023,96 inpatients with stroke hemiplegia from the Second Affiliated Hospital of Guangxi Medical University were randomly divided into conventional group(n=32),PNF group(n=32)and combined group(n=32).All the groups received routine rehabilitation treatment.The conventional group re-ceived upper limb PNF training,the PNF group received upper limb rope-assisted PNF training,and the com-bined group received both upper limb rope-assisted PNF training and upper limb rope-assisted BCI training,for four weeks.They were assessed with Functiongal Test for the Hemiplegic Upper Extremity-Hong Kong version(FTHUE-HK),Fugl-Meyer Assessment-Upper Extremities(FMA-UE)and modified Barthel Index(MBI)before and after treatment. Results The intra-group effect(F>341.219,P<0.001),inter-group effect(F>21.705,P<0.001)and interaction effect(F>3.171,P<0.05)were significant in the scores of FTHUE-HK and MBI.The intra-group effect(F=520.472,P<0.001)and inter-group effect(F=41.939,P<0.001)were significant in the scores of FMA-UE,and the interaction effect was not(P>0.05).After treatment,the FTHUE-HK,FMA-UE and MBI scores were the best in the combined group(P<0.05). Conclusion The combination of rope-assisted PNF training with rope-assisted BCI device training could further improve the motor function of the upper limbs in stroke patients with hemiplegia,and enhance their activities of daily liv-ing.

Objective To establish an HPLC fingerprint of Dingdang Qigui Decoction and analyze and evaluate it using chemical pattern recognition technology;To determine the contents of 5 effective chemical components in Dingdang Qigui Decoction;To provide a basis for its quality control.Methods The analysis was performed on Agilent 5 TC-C18(2)column(250 mm×4.6 mm).The mobile phase comprised of acetonitrile-0.1%phosphoric acid aqueous solution with the gradient elution at a flow rate of 1.0 mL/min.The detection wavelength was set at 260 nm.The column temperature was maintained at 30℃and the injection volume was 10 μL.SPSS 26.0 and SIMCA 14.1 were used to perform clustering analysis and principal component analysis on the 10 batches of Didang Qigui Decoction.The landmark components for inter batch differences were selected through orthogonal partial least squares discriminant analysis(OPLS-DA).Results The HPLC fingerprint with eighteen common peaks of Didang Qigui Decoction in 10 batches of sample was established,and the similarities of samples were between 0.828 and 0.989.Five indicative components were identified and quantitatively analyzed by comparing with the reference substances,which were paeoniflorin,mauroisoflavone glucoside,hesperidin,cinnamaldehyde and aloe rhodopsin.The linear ranges was 10.000 0-320.000 0 μg/mL,2.500 0-80.000 0 μg/mL,10.000 0-320.000 0 μg/mL,10.000 0-320.000 0 μg/mL,0.078 1-5.000 0 μg/mL,respectively,and their mean recovery ranged from 100.30%to 104.09%.Clustering analysis and principal component analysis divided 10 batches of samples from Didang Qigui Decoction into 2 categories.Through OPLS-DA screening,hairy pistil isoflavone glycosides,paeoniflorin,and hesperidin were selected as landmark components for quality differences.Conclusion The quality evaluation method for Didang Qigui Decoction established in this study is simple,sensitive,accurate,and reproducible,which can provide a basis for the quality evaluation of Didang Qigui Decoction.

ObjectiveTo investigate the effect of combination of proprioceptive neuromuscular facilitation (PNF) rope training and repetitive transcranial magnetic stimulation (rTMS) on upper limb motor function of stroke patients with hemiplegia. MethodsFrom March, 2021 to February, 2022, 90 stroke inpatients with hemiplegia in the Department of Rehabilitation Medicine, the Second Affiliated Hospital of Guangxi Medical University were divided into control group (n = 30), rope group (n = 30) and combination group (n = 30) randomly. All the groups received routine rehabilitation, while the control group received routine PNF training, the rope group received PNF rope training, and the combination group received PNF rope training and rTMS, for four weeks. They were assessed with Functional Test for the Hemiplegic Upper Extremity-Hong Kong version (FTHUE-HK), Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and modified Barthel Index (MBI) before and after treatment. ResultsThe scores of FTHUE-HK, FMA-UE and MBI increased in all the three groups after treatment (t > 2.167, P < 0.05), and they were more in the combination group than in the rope group (P < 0.05), and in the rope group than in the control group (P < 0.05). ConclusionThe combination of PNF rope training and rTMS is more effective on motor function of upper limbs of stroke patients with hemiplegia than PNF training alone.

By searching the papers about medical ethics education in Chinese database CNKI and foreign database Web of Science Core Collection, and using the bibliometrics software CiteSpace to draw the knowledge map of medical ethics education at home and abroad, this paper conducted a quantitative and qualitative analysis of the evolution of hot spots and the development trend of medical ethics education research, and found that the development level of medical ethics education in the world varies greatly. China has experienced the development and evolution from medical ethics education to medical humanities, and its research hotspots mainly focus on the topics of "medical ethics" "medical education" "practice teaching" "medical humanities" "teaching reform" and so on. While foreign countries focus on "medical education" "clinical ethics" "hospice care" "health care" "global public health" "science and technology ethics" "organ transplantation" "curriculum construction" "health policy" and other topics. Through the comparative analysis of the development trend and the evolution of hot spots of education, this paper put forward theoretical reference direction for improving the medical ethics education system in China and further perfecting the discipline construction of medical ethics in China.

OBJECTIVES: Patients from different social environments and cultural backgrounds have different nursing needs. If nurses ignore the cultural differences of patients, it is easy to lead to the strained nurse-patient relationship, affect the nursing effect and cause harm to patients. Critical cultural competence (CCC) can help nurses to meet the nursing needs of patients from different cultural backgrounds, which is beneficial to building a harmonious nurse-patient relationship and improving the quality of nursing. Almutairi, et al designed the Critical Cultural Competence Scale (CCCS) which can be used to evaluate accurately nurses' CCC. No studies have reported the development of a critical cultural competence measurement tool for nurses or the introduction of foreign scales in China. This study aims to conduct Chinese and cross-cultural debugging and test the reliability of the English version of the CCCS in order to form CCCS suitable for Chinese cultural background and provide an effective evaluation tool for investigating the current situation of clinical nurses' CCC. METHODS: This study used Brislin's back-translation model to translate and back-translation the English version of CCCS. The Chinese version of CCCS was then created through cross-cultural debugging by expert consultation and a pre-survey with a sample size of 30 clinical nurses. From August to October 2019, 580 clinical nurses were surveyed using a whole group sampling method. The participants were randomly divided into 2 groups with a 7꞉3 ratio. One group (n=406) was used for exploratory factor analysis and reliability analysis, while the other group (n=174) was used for confirmatory factor analysis. Six experts used the scale-level content validity index (S-CVI) and the item-level content validity index (I-CVI) to assess content validity. In the exploratory factor analysis, items were screened using the critical ratio method, and were tested using the KMO (Kalser-Meyer-Olkin) index, Bartlett's sphericity test, and principal component analysis. In the confirmatory factor analysis, average variance extracted (AVE), goodness of fit index (GFI), adjusted goodness of fit index (AGFI), and root mean square error of approximation (RMSEA) were used to assess the degree of fit of the constructed model. For the total scale and the 4 subscales, the Cronbach's α coefficient, split-half reliability, and retest reliability were used to assess the scale's reliability. RESULTS: The S-CVI was 0.930, while the I-CVI ranged from 0.833 to 0.944. For all items, the critical ratio exceeded 3, and the difference between the high and low subgroups was statistically significant (P<0.05). Exploratory factor analysis revealed critical knowledge subscale had a KMO value of 0.676, with the total scale and other 3 subscales all having a KMO value >0.8 and a chi-square value of 814.32 to 12 442.45 for the Bartlett's spherical test, with degree of freedom ranging from 21 to 136 (P<0.001), indicating that all items were suitable for factor analysis. The principal component analysis showed that 17, 12, 7, and 7 items were extracted from the 4 subscales, with 4, 3, 2, and 2 components whose eigenvalues were more than 1, and the cumulative variance contribution was 66.0%, 54.3%, 56.6%, and 70.2%, respectively. The confirmatory factor analysis showed that the AVE of the 4 subscales were 0.637, 0.499, 0.560, and 0.565, GFI was 0.904, AGFI was 0.863, and RMSEA was 0.076. The Cronbach's α coefficient for the total scale and subscales ranged from 0.811 to 0.878, the split-half reliability ranged from 0.707 to 0.842, and the retest reliability was 0.827. CONCLUSIONS The Chinese version of the CCCS has good reliability and validity, and it can be used as a valid assessment tool for clinical nurses' critical cultural competence in China.
Humans ; Cultural Competency ; Reproducibility of Results ; Psychometrics/methods* ; Factor Analysis, Statistical ; China