Objective To precisely identify the para-Bombay blood types in cancer patients at our hospital, establish a robust system for the identification of challenging blood types in our laboratory, and provide a foundation for precise transfusion practices. Methods We retrospectively analyzed the blood type results of 91 874 cancer patients from January 1, 2019, to December 31, 2023. Conventional serological methods were used to screen for blood types, and suspected para-Bombay blood types were identified. Further analysis was performed using Pacific Biosciences (PacBio) single-molecule real-time sequencing and Sanger sequencing was used to determine the genotypes of the ABO, FUT1, and FUT2 genes. Results Eight cases of para-Bombay blood type were confirmed through serological and molecular biological methods. The FUT1 genotypes identified were: 5 cases of h1h1 (homozygous mutation 551_552delAG) and 3 cases of h1h2 (compound heterozygous mutations of 551_552delAG and 880_882delTT). The FUT2 genotypes identified were: 2 cases of Se³⁵⁷/Se^{357, 716} and 4 cases of Se³⁵⁷/Se³⁵⁷. Additionally, one sample revealed a novel heterozygous mutation, 818C>T, in exon 7 of the ABO gene, which was confirmed by PacBio sequencing to be located on the O haplotype. Conclusion PacBio sequencing technology demonstrates significant advantages in analyzing the haplotypes of para-Bombay blood type genes. This approach supports the establishment of a robust system for the identification of challenging blood types and provides novel evidence for precise transfusion practices in cancer patients.
Humans ; Neoplasms/genetics* ; Fucosyltransferases/genetics* ; ABO Blood-Group System/genetics* ; Male ; High-Throughput Nucleotide Sequencing/methods* ; Galactoside 2-alpha-L-fucosyltransferase ; Female ; Retrospective Studies ; Genotype ; Middle Aged ; Blood Grouping and Crossmatching/methods* ; Adult ; Mutation ; Aged

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Objective To investigate the radioprotection and management of yttrium-90 resin microsphere therapy based on the survey and monitoring of treatment institutions in Guangdong Province, China, and to provide technical reference and basis for the subsequent radiation management of this therapy. Methods Based on the technical data on yttrium-90 resin microsphere therapy collected from both domestic and international sources, an investigation was conducted on some yttrium-90 resin microsphere treatment institutions in Guangdong Province. Radiation level monitoring was carried out in the radioactive workplaces of three hospitals that had conducted yttrium-90 resin microspheres therapy. Environmental X-γ dose rate meters were used for detecting radiation dose equivalent rates, while α and β surface contamination monitors were used for detecting radioactive surface contamination. Additionally, urine samples from two patients were collected within 24 hours post-operation, and total radioactivity was analyzed using low-background α and β counters. Results During the yttrium-90 resin microsphere therapy, the radiation dose equivalent rates around the digital subtraction angiography rooms in the three hospitals ranged from 0.15 to 0.26 μSv/h, and the radiation dose equivalent rates around the observation wards ranged from 0.17 to 0.69 μSv/h. The β radioactive surface contamination values in the workplace control zones ranged from ＜0.07 to 18.7 Bq/cm², while the values in the supervised zones were all less than 0.07 Bq/cm². The total β radioactivity in the urine of the two patients within 24 hours post-operation accounted for approximately 0.0010% to 0.0013% of the yttrium-90 infusion dose. Conclusion The radiation levels at the monitoring sites in the workplaces of the three hospitals are below the national standard limits. The radioprotection and management of yttrium-90 resin microsphere therapy in the three hospitals in Guangdong Province are satisfactory.

Objective To investigate the radioprotection and management of yttrium-90 resin microsphere therapy based on the survey and monitoring of treatment institutions in Guangdong Province, China, and to provide technical reference and basis for the subsequent radiation management of this therapy. Methods Based on the technical data on yttrium-90 resin microsphere therapy collected from both domestic and international sources, an investigation was conducted on some yttrium-90 resin microsphere treatment institutions in Guangdong Province. Radiation level monitoring was carried out in the radioactive workplaces of three hospitals that had conducted yttrium-90 resin microspheres therapy. Environmental X-γ dose rate meters were used for detecting radiation dose equivalent rates, while α and β surface contamination monitors were used for detecting radioactive surface contamination. Additionally, urine samples from two patients were collected within 24 hours post-operation, and total radioactivity was analyzed using low-background α and β counters. Results During the yttrium-90 resin microsphere therapy, the radiation dose equivalent rates around the digital subtraction angiography rooms in the three hospitals ranged from 0.15 to 0.26 μSv/h, and the radiation dose equivalent rates around the observation wards ranged from 0.17 to 0.69 μSv/h. The β radioactive surface contamination values in the workplace control zones ranged from ＜0.07 to 18.7 Bq/cm², while the values in the supervised zones were all less than 0.07 Bq/cm². The total β radioactivity in the urine of the two patients within 24 hours post-operation accounted for approximately 0.0010% to 0.0013% of the yttrium-90 infusion dose. Conclusion The radiation levels at the monitoring sites in the workplaces of the three hospitals are below the national standard limits. The radioprotection and management of yttrium-90 resin microsphere therapy in the three hospitals in Guangdong Province are satisfactory.

Objective To analyze the expression levels of serum microRNA(miR)-211 and miR-202 in patients with Alzheimer's disease and their correlation with cognitive function,anxiety and depression.Methods A total of 90 patients with Alzheimer's disease admitted to Hebei Yanda Hospital from March 2019 to March 2022 were selected as the research group.According to the Clinical Dementia Rating(CDR)score,the patients were grouped into mild group(n=24),moderate group(n=48)and severe group(n=18).Another 90 healthy individuals who underwent physical examination were collected as the control group.The expression levels of miR-211 and miR-202 in serum were compared.Pearson method and Spearman method were used to analyze serum miR-211 and miR-202 and their correlation with cognitive function,anxiety and depression.Logistic regression analysis was used to analyze the influencing factors of Alzheimer's disease.Results The expression levels of serum miR-211(0.59±0.16,1.01±0.31)and miR-202(0.35±0.10,1.00±0.32)were significantly reduced in the research group and control group,with significant differences(t=11.422,18.393,all P<0.05).Serum miR-211(0.73±0.21,0.62±0.17,0.32±0.08)expression levels,miR-202(0.51±0.15,0.33±0.10,0.19±0.04)expression levels,mini-mental state examination(MMSE)score(22.54±1.41 score,19.35±1.01 score,16.23±1.00 score)and Montreal cognitive assessment(MoCA)score(25.35±2.60 score,18.59±1.32 score,16.59±1.24 score)in the mild,moderate and severe groups gradually decreased,and the differences were statistically significant(F=32.006,46.917,163.048,163.703,all P<0.05).Compared with mild group,the serum miR-211,miR-202,MMSE and MoCA scores of severe group and moderate group were reduced,and the differences were statistically significant(t=3.685～25.375,all P<0.05).The mild,moderate and severe groups had a gradual increase in Hamilton anxiety scale(HAMA)score(12.34±1.27 score,20.59±2.09 score and 31.29±2.19 score)and Hamilton depression scale(HAMD)score(14.35±2.13 score,23.89±2.20 score and 35.35±1.21 score),and the differences were statistically significant(F=496.059,553.939,all P<0.05).According to Pearson correlation analysis,miR-211 was positively correlated with miR-202(r=0.651,P<0.05).According to Spearman correlation analysis,miR-211 and miR-202 were positively correlated with MMSE and MoCA(r=0.539～0.585,all P<0.05)and negatively correlated with HAMA and HAMD(r=-0.651～-0.539,all P<0.05).Logistic regression analysis showed that the low expression of miR-211[OR(95%CI):5.321(1.648～17.180)]and miR-202[OR(95%CI):3.158(1.989～5.012)]were risk factors for Alzheimer's disease(P<0.05).Conclusion The serum expression levels of miR-211 and miR-202 in patients with Alzheimer's disease were reduced,indicating miR-211 and miR-202 were closely related to cognitive function,anxiety and depression.

BACKGROUND:Internal heat-type acupuncture therapy is a new treatment technique that combines acupuncture therapy with hyperthermia.It has good clinical effects on steroid-induced osteonecrosis of the femoral head,but the mechanism of action is still not fully clear. OBJECTIVE:To explore the possible mechanism of internal heat-type acupuncture therapy in treating steroid-induced osteonecrosis of the femoral head in rabbits. METHODS:Thirty-two New Zealand rabbits were randomly divided into blank group,model group,internal heat-type acupuncture group and shock wave group using a random number table method,with 8 rabbits in each group.The model group,internal heat-type acupuncture group and shock wave group were modeled using methylprednisolone sodium succinate combined with Escherichia coli endotoxin.The internal heat-type acupuncture group received an internal heat-type acupuncture intervention on the buttocks of rabbits,once a week,for 20 minutes each time.The shock wave group received shock wave intervention on the buttocks of rabbits,once a week,with 2 000 beats per session.The blank group and model group were not given any treatment.After 4 weeks of intervention,blood samples and bilateral femoral head samples were collected from experimental rabbits.The levels of tumor necrosis factor-α and interleukin-6 in serum were detected by ELISA;the histomorphology of the femoral head was observed using hematoxylin-eosin staining and the rate of empty lacunae was calculated;the protein expressions of matrix metalloproteinase 2,matrix metalloproteinase 9,matrix metalloproteinase tissue inhibitor 1,and matrix metalloproteinase tissue inhibitor 2 were detected by immunohistochemistry and western blot. RESULTS AND CONCLUSION:Compared with the blank group,the model rabbits showed reduced food intake,mental fatigue,and decreased activity;compared with the model group,the above performance of the experimental rabbits was significantly improved after internal heat-type acupuncture and shock wave treatment.Compared with the blank group,the histomorphology of the femoral head in the model group deteriorated significantly and the rate of empty bone lacuna increased(P<0.001),while the histomorphology of the femoral head in the internal heat-type acupuncture group and shock wave group was significantly improved compared with the model group,and the rate of empty bone lacuna was reduced(P<0.001).The serum levels of tumor necrosis factor-α and interleukin-6 in the model group were significantly higher than those in the blank group(P<0.05),while the serum levels of tumor necrosis factor-α and interleukin-6 in the internal heat-type acupuncture group and the shock wave group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 in the femoral head of the model group were significantly increased,while the expression levels of matrix metalloproteinase tissue inhibitor 1 and matrix metalloproteinase tissue inhibitor 2 were significantly decreased(P<0.001);compared with the model group,the protein expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 were significantly decreased,while the protein expression levels of matrix metalloproteinase tissue inhibitor 1 and matrix metalloproteinase tissue inhibitor 2 were significantly increased in the internal heat-type acupuncture group and the shock wave group(P<0.001).Overall,these findings indicate that internal heat-type acupuncture may promote the repair of the necrotic femoral head by regulating the levels of matrix metalloproteinases/matrix metalloproteinase tissue inhibitors and serum inflammatory factors,thus treating early steroid-induced osteonecrosis of the femoral head.

Objective:To investigate the application value of the teaching evaluation method guided by cultivating "excellent doctors" in the clinical teaching of dermatology and venereology.Methods:A non-simultaneous control study was conducted, and the medical students who received theoretical learning and clinical internship in Department of Dermatology and Venereology, Affiliated Hospital of North Sichuan Medical College, from March 2020 to February 2022, were enrolled as subjects. According to the order of enrollment, 32 students who were enrolled from March 2020 to February 2021 were set up as control group, and 31 students who were enrolled from March 2021 to February 2022 were set up as experimental group. The students in the control group received lecture-based learning, and those in the experimental group received clinical teaching using a teaching and evaluation method guided by cultivating "excellent doctors". After the course ended, the two groups were compared in terms of the scores of theoretical knowledge and operation skills, clinical thinking ability [Self-Assessment of Clinical Reasoning and Reflection (SACRR)], core competence [Mini-Clinical Evaluation Exercise (Mini CEX)], and degree of satisfaction with teaching. SPSS 25.0 software was used to perform the independent samples t-test, the Mann-Whitney U test, the chi-square test, and the rank sum test. Results:One student in the control group voluntarily withdrew from the study, and one student in the experimental group did not complete the contents of internship. Finally, 31 students in the control group and 30 in the experimental group were included in the study. After 4 weeks of internship, compared with the control group, the experimental group had significantly higher scores of theoretical knowledge (88.00±4.30 vs. 85.71±4.12, t=2.12, P=0.040) and operation skills (91.87±3.99 vs. 88.23±3.84, t=3.63, P<0.05). After 4 weeks of internship, compared with the control group, the experimental group had significantly higher information systematization score (47.23±3.11 vs. 45.16±3.00), analysis problem score (34.87±2.30 vs. 31.29±2.30), truth finding score (16.30±1.49 vs. 14.45±1.52), reflective ability score [3.50 (3.00, 4.00) vs. 3.00 (3.00, 3.00)], and total score of SACRR (101.87±4.47 vs. 93.90±4.47), with significant differences between the two groups ( t/ Z=2.65, 6.17, 4.79, 3.15, and 6.96, all P<0.05). After 4 weeks of internship, the experimental group had a significantly better core competence than the control group ( Z=2.12, P=0.030); compared with the control group, the experimental group had significantly higher classroom teaching score (20.17±1.98 vs. 18.45±2.23, t=3.17, P<0.05), clinical practice score (19.83±2.10 vs. 17.65±2.17, t=4.00, P<0.05), learning plan score (18.63±2.24 vs. 17.03±2.15, t=2.85, P<0.05), teaching resource score (20.07±1.82 vs. 18.58±2.00, t=3.04, P<0.05) and total score (78.70±3.67 vs. 71.71±4.13, t=6.98, P<0.05). Conclusions:The application of the teaching and evaluation method guided by cultivating "excellent doctors" in the clinical teaching of dermatology and venereology can improve clinical theoretical knowledge, practical operation skills, clinical thinking ability, and core ability among interns and thus help to improve teaching quality. Therefore, it holds promise for clinical application.

Objective To investigate the dietary patterns of rural residents in the high-incidence areas of esophageal cancer (EC), and to explore the clustering and influencing factors of risk factors associated with high-incidence characteristics. Methods A special structured questionnaire was applied to conduct a face-to-face survey on the dietary patterns of rural residents in Yanting county of Sichuan Province from July to August 2021. Univariate and multivariate logistic regression models were used to analyze the influencing factors of risk factor clustering for EC. Results There were 838 valid questionnaires in this study. A total of 90.8% of rural residents used clean water such as tap water. In the past one year, the people who ate fruits and vegetables, soybean products, onions and garlic in high frequency accounted for 69.5%, 32.8% and 74.5%, respectively; the people who ate kimchi, pickled vegetables, sauerkraut, barbecue, hot food and mildew food in low frequency accounted for 59.2%, 79.6%, 68.2%, 90.3%, 80.9% and 90.3%, respectively. The clustering of risk factors for EC was found in 73.3% of residents, and the aggregation of two risk factors was the most common mode (28.2%), among which tumor history and preserved food was the main clustering pattern (4.6%). The logistic regression model revealed that the gender, age, marital status and occupation were independent influencing factors for the risk factors clustering of EC (P<0.05). Conclusion A majority of rural residents in high-incidence areas of EC in Yanting county have good eating habits, but the clustering of some risk factors is still at a high level. Gender, age, marital status, and occupation are influencing factors of the risk factors clustering of EC.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition characterized by persistent airflow obstruction caused by long-term airway inflammation or alveolar abnormalities, often manifested as chronic respiratory symptoms and decreased lung function. In recent years, experimental research has shown that mesenchymal stem cells (MSC) have anti-inflammatory, immunomodulatory, and repairing properties of lung epithelial cells, which can be used to treat various diseases including COPD. This article is mainly based on the main findings of in vitro and in vivo animal model experiments and clinical studies of MSC treatment for COPD. It summarizes and discusses the possible mechanisms of action of MSC as a new therapy, and provides new ideas for clinical treatment of COPD.

Background::Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors.Methods::The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020.Results::The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy.Conclusions::We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.