Natural human leukocyte antigen (HLA) antibodies refer to preformed antibodies present in the body that are not induced by prior exposure to allogeneic HLA antigens. In healthy individuals without a sensitization history, the detection rate of natural HLA antibodies is approximately 20%-29% when using screening assays with low sensitivity, and can reach up to 63% when more sensitive HLA-specific detection methods are employed. It is therefore inferred that natural HLA antibodies may also be present in transplant candidates with a similar prevalence. This review comprehensively discusses the potential mechanisms of natural HLA antibody generation, the characteristics of the recognized epitopes, detection techniques, clinical relevance in transplantation, their potential to confound therapeutic decisions, and approaches to distinguish and mitigate their impact. The goal is to raise clinician awareness of the objective existence of natural HLA antibodies, provide guidance on evaluating their association with allograft rejection, and inform appropriate clinical management strategies when encountering natural HLA antibody-positive transplant candidates.

Natural human leukocyte antigen (HLA) antibodies refer to preformed antibodies present in the body that are not induced by prior exposure to allogeneic HLA antigens. In healthy individuals without a sensitization history, the detection rate of natural HLA antibodies is approximately 20%-29% when using screening assays with low sensitivity, and can reach up to 63% when more sensitive HLA-specific detection methods are employed. It is therefore inferred that natural HLA antibodies may also be present in transplant candidates with a similar prevalence. This review comprehensively discusses the potential mechanisms of natural HLA antibody generation, the characteristics of the recognized epitopes, detection techniques, clinical relevance in transplantation, their potential to confound therapeutic decisions, and approaches to distinguish and mitigate their impact. The goal is to raise clinician awareness of the objective existence of natural HLA antibodies, provide guidance on evaluating their association with allograft rejection, and inform appropriate clinical management strategies when encountering natural HLA antibody-positive transplant candidates.

Objective This study aims to evaluate the application of BOPPPS teaching model combined with case and problem-based learning(CPBL)and the scenario simulation in cardiovascular internal medicine education.Methods The study included cardiovascular internal medicine graduates from the 2022 and 2023 cohorts.The 2022 cohort(n=12)served as the control receiving traditional teaching methods,while the 2023 cohort(n=16)was the experimental group,which utilized the BOPPPS model combined with CPBL and scenario simulation.The students theoretical examination scores were assessed and a questionnaire survey was conducted to evaluate self-assessment of abilities and teaching satisfaction among the students in the experimental group.Results The examination scores of experimental group were significantly higher(97.94±3.46)as compared to that of control group(69.13±12.88)(P＜0.05).Over 93.75%of the students in the experimental group strongly or somewhat agreed that the combined teaching model stimulated their learning interest,improved learning efficiency,facilitated their capacity building of autonomous learning,theoretical knowledge,helped establish clinical reasoning,and improved their teamwork skills.Additionally,over 93.75%of the students were highly satisfied with the course design,emphasizing key content,pro-moting teacher-student interaction,and expressed willingness to continue with this teaching method in the future.Conclusions The application of the BOPPPS teaching model combined with CPBL and scenario simulation in cardio-vascular internal medicine education achieved excellent teaching outcomes.It effectively stimulated students interest in learning,enhanced autonomous learning abilities,and received high satisfaction ratings from students.

OBJECTIVE: To explore the clinical phenotypes and genetic variant in a neonatal case of Mitochondrial DNA depletion syndrome type 13 (MTDPS13). METHODS: Clinical data and results of genetic testing of a neonate admitted to the Children's Hospital of Zhejiang University School of Medicine in January 2023 was retrospectively analyzed. The study was approved by the Medical Ethics Committee of the Children's Hospital of Zhejiang University. RESULTS: The male infant was admitted to the NICU due to tachypnea and persistent lactic acidosis 6 hours after birth. At admission, distinctive facial features were noted. Laboratory tests showed elevated lactic acid (< 30 mmol/L). Whole-exome sequencing revealed that he has harbored homozygous c.141del frameshift mutation of FBXL4 gene, which was unreported previously. The mutation was inherited from both of his parents and classified as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION The clinical phenotypes of this case of MTDPS13 is characterized by lactic acidosis, distinctive facial features, growth retardation and developmental delay, for which the homozygous c.141del variant of the FBXL4 gene may be accountable.
Humans ; Male ; F-Box Proteins/genetics* ; Infant, Newborn ; Ubiquitin-Protein Ligases/genetics* ; DNA, Mitochondrial/genetics* ; Mitochondrial Diseases/genetics* ; Acidosis, Lactic/genetics* ; Mutation ; Phenotype ; Frameshift Mutation ; Exome Sequencing

Objective:To explore the clinical phenotypes and genetic variant in a neonatal case of Mitochondrial DNA depletion syndrome type 13 (MTDPS13).Methods:Clinical data and results of genetic testing of a neonate admitted to the Children′s Hospital of Zhejiang University School of Medicine in January 2023 was retrospectively analyzed. The study was approved by the Medical Ethics Committee of the Children′s Hospital of Zhejiang University(Ethic No.2023-IRB-0093-P-01).Results:The male infant was admitted to the NICU due to tachypnea and persistent lactic acidosis 6 hours after birth. At admission, distinctive facial features were noted. Laboratory tests showed elevated lactic acid (> 30 mmol/L). Whole-exome sequencing revealed that he has harbored homozygous c. 141del frameshift mutation of FBXL4 gene, which was unreported previously. The mutation was inherited from both of his parents and classified as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion:The clinical phenotypes of this case of MTDPS13 is characterized by lactic acidosis, distinctive facial features, growth retardation and developmental delay, for which the homozygous c. 141del variant of the FBXL4 gene may be accountable.

Objective:To explore the clinical phenotypes and genetic variant in a neonatal case of Mitochondrial DNA depletion syndrome type 13 (MTDPS13).Methods:Clinical data and results of genetic testing of a neonate admitted to the Children′s Hospital of Zhejiang University School of Medicine in January 2023 was retrospectively analyzed. The study was approved by the Medical Ethics Committee of the Children′s Hospital of Zhejiang University(Ethic No.2023-IRB-0093-P-01).Results:The male infant was admitted to the NICU due to tachypnea and persistent lactic acidosis 6 hours after birth. At admission, distinctive facial features were noted. Laboratory tests showed elevated lactic acid (> 30 mmol/L). Whole-exome sequencing revealed that he has harbored homozygous c. 141del frameshift mutation of FBXL4 gene, which was unreported previously. The mutation was inherited from both of his parents and classified as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion:The clinical phenotypes of this case of MTDPS13 is characterized by lactic acidosis, distinctive facial features, growth retardation and developmental delay, for which the homozygous c. 141del variant of the FBXL4 gene may be accountable.

Objective:To investigate the effect of astragaloside IV (AS-IV) on the secretion of stromal cell-derived factor-1α (SDF-1α) and CXC chemokine receptor 4 (CXCR4) by high glucose injured human umbilical vein endothelial cells (HUVECs), so as to lay a foundation for further study on AS-IV improving angiogenesis by regulating SDF-1 α/CXCR4 axis of endothelial cells.Methods:HUVECs were isolated and cultured from the umbilical vein of full-term healthy newborns and identified by von Willebrand factor (vWF) combined with 4-diamino-2-phenylindole (DAPI) nuclear staining. The obtained HUVECs was cultured in EGM-2 medium with 30 mmol/L glucose for 120 h to obtain high glucose damaged HUVECs. After intervention with different concentration gradients (25 mg/L, 50 mg/L, 100 mg/L, 200 mg/L, 400 mg/L) AS-IV for 72 hours, the contents of SDF-1α and CXCR4 were detected by enzyme linked immunosorbent assay (ELISA) method to determine the best concentration of AS-IV. The supernatant of damaged HUVECs were collected at 6, 12, 24, 48 and 72 hours after intervention with the best concentration of AS-IV, and the contents of SDF-1α and CXCR4 were detected by ELISA method to determine the best action time of AS-IV. The damaged HUVECs was randomly divided into experimental group and control group, and the blank group was set up at the same time. The experimental group was treated with the best concentration of AS-IV and the best time, the control group and the blank group were treated with the same volume of phosphate buffered saline (PBS) solution, and the contents of SDF-1α and CXCR4 in each group were detected by ELISA method.Results:The vWF factor on the cell membrane was green fluorescence, and the nucleus was blue after DAPI staining. When the fusion image showed green fluorescence, HUVECs were identified by blue fluorescence. The expression of SDF-1α in damaged HUVECs was the best when treated with AS-IV of 100 mg/L for 24 hours (1 642.87 pg/ml), and the expression of CXCR4 in damaged HUVECs was the best when treated with AS-IV of 50 mg/L for 48 hours (8.44 ng/ml). Compared with the control group, the contents of SDF-1α and CXCR4 in the experimental group were significantly increased, and the difference was statistically significant ( P<0.05). While the contents of SDF-1α and CXCR4 in the experiment group were slightly less than those in the blank group and there was no statistically significant difference ( P>0.05). Conclusions:AS-IV can promote the expression of SDF-1α and CXCR4 in HUVECs damaged by high glucose to return to normal physiological level, so as to play the role of vascular repair and neovascularization.

Objective:To investigate the effects of Astragaloside Ⅳ on the secretion of exosomes in human endothelial progenitor cells (EPCs) and the expression of microRNA (miRNA)-126 in exosomes.Methods:The umbilical cord blood from one healthy full-term newborn from the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine in 2019 was harvested for isolating mononuclear cells by density gradient centrifugation and cultured for 7 days. Morphological observation was performed during this period. Cells of the third passage were collected for identification by CD31 immunomagnetic bead sorting and double fluorescence staining. According to the random number table, the identified EPCs were divided into Astragaloside Ⅳ group and phosphate buffer solution (PBS) group. The cells in Astragaloside Ⅳ group were cultured with Astragaloside Ⅳ in final mass concentration of 100 mg/L for 24 hours, and the cells in PBS group were cultured with the same volume of PBS for 24 hours. After culture, the exosomes from the cell culture supernatant of the two groups were collected, and the expressions of characteristic markers of exosomes CD9, CD63, and CD81 were detected by Western blotting, the morphology of EPC exosomes (EPC-Exos) was observed under transmission electron microscope, and the particle size of EPC-Exos was detected by nanoparticle tracking analysis technique. The concentration of EPC-Exos was determined by dioctyl butyric acid method (the sample number was 3), and the expressions of miRNA-126-3p and miRNA-126-5p related to angiogenesis in EPC-Exos were determined by reverse transcription polymerase chain reaction (the sample number was 3). Data were statistically analyzed with independent sample t test. Results:(1) On the 4th day of culture, the cells began to adhere to the wall, and the multi-forms such as circle, fusiform, and strip appeared at the same time. On the 7th day of culture, the edge of the cells was clear and arranged like a paving stone, the central cells were round, and the surrounding cells were fusiform. (2) CD31 immunomagnetic beads sorting method identification showed that the membrane was stained with green fluorescence and the nucleus was stained with blue fluorescence. Double fluorescence staining method showed that the cells were orange-yellow. The cells were identified as EPCs. (3) After 24 hours of culture, the expressions of CD9, CD63, and CD81 in EPC-Exos were all positive, confirming that EPC-Exos were extracted successfully in this experiment. (4) After 24 hours of culture, the EPC-Exos of the two groups showed round membrane vesicles, and there was no significant difference in morphology. (5) After 24 hours of culture, the particle size of 98.7% EPC-Exos in Astragaloside Ⅳ group was 84.7 to 143.1 nm, and that of 98.0% EPC-Exos in PBS group was 88.7 to 123.5 nm. (6) After 24 hours of culture, the mass concentration of EPC-Exos in Astragaloside Ⅳ group was (310±5) μg/mL, which was significantly higher than (257±5) μg/mL in PBS group, t=13.369, P<0.01. (7) After 24 hours of culture, there were more miRNA-126-3p ( t=16.062, P<0.01) and miRNA-126-5p ( t=3.252, P<0.05) in EPC-Exos of Astragaloside Ⅳ group than in PBS group. Conclusions:Astragaloside Ⅳ can improve the function of human EPC secretory exosomes, and the secreted exosomes are loaded with miRNA-126.

Objective To explore the effect of the cancer pain nursing team in standardized nursing inter-vention of pain in elderly cancer patients.Methods 76 patients in Department of Pain in our hospital were selected in our research.A random number table method was used to divide them into the control group and the observation group,with 38 cases in each group.Conventional treatment and nursing care was given to control group.The observa-tion group received routine treatment and nursing care by cancer pain nursing team,which the content of nursing was same,but the nursing method is different.Before and after the intervention,impact on pain intensity,adverse reactions and satisfaction for medical and nursing were compared between the two groups.Results Before nursing intervention, the pain score between the two groups had no statistically significant difference(P >0.05).After nursing interven-tion,pain score of the observation group was 1.5 (1,2)points,which was lower than 2(1,3)points in the control group,the observation group had better analgesic effect than the control group (Z = -4.385,P =0.000).The incidence rate of adverse reaction of the observation group was 13.16%,which was lower than 47.37% of the control group,the difference between the two groups was statistically significant(χ2 =10.537,P =0.001).The satisfaction for medical nursing process in the observation group was (9.74 ±0.45 )points,which was higher than (9.42 ± 0.76)points of the control group (t =2.213,P =0.030).Conclusion For senile cancer patients,the cancer pain nursing team could implement the standardized nursing intervention to relieve the body pain level,reduce the adverse drug reactions,so as to improve the quality of life.

Objective To investigate the ultrasound characteristics,etiology and prognosis in hydrops fetalis.Methods From September 2002 to May 2010,156 hydrops fetalis presented in Shenzhen Maternity and Child Healthcare Hospital were studied retrospectively,including ultrasound characteristics,etiology,and prognosis.Results All of the 112 typical hydrops fetalis,20 cases with isolated ascites,8 cases with isolated pleural effusion,7 cases with isolated pericardial effusion,5 cases with isolated subcutaneous edema,4 cases with isolated placental thickening were observed by ultrasonography.The major etiology and associated diagnosis consisted of 35.9％ (56/156) of non-immune anemia,9.6％ (15/156) of cardiac abnormalities,7.1％ (11/156) of intrauterine infection,6.4％ (10/156) of twin problems,5.8％ (9/156) of meconium peritonitis,5.1％ (8/156) of thoracic-lung disease,4.5％ (7/156) of chromosomal abnormalities,1.9％ (3/156) of immune anemia.Alpha thalassemia was the most common non-immune anemia (96％,54/56).An etiology and associated diagnosis could be determined in 81.4％ ( 127/156 ) of cases.Follow-up data showed that 7 cases were fetal death,110 women elected to terminate their pregnancies,3 cases lost follow-up,the other 36 cases preserve continuing pregnancy,including 28 liveborn infants and 8 fetal deaths.Etiology of twin-twin transfusion syndrome,meconium peritonitis,congenital chylothorax,intrauterine infection,cardiac abnormalities and so on had survived fetuscases.The survival rate of typical hydrops fetalis in the present series was 3.6％ ( 4/112 ).Conclusions Ascites is the most common characteristics of sonogram in hydrops fetalis.The etiology of hydrops fetalis is extremelycomplex.The prognosis is associated with the etiology and hydrops subtype.