Objective: To develop a RHCE genotyping assay based on kompetitive allele-specific PCR (KASP) and assess its clinical accuracy for RhCE blood group determination. Methods: KASP primers were designed to interrogate three RHCE loci: the 109 bp insertion/deletion in intron 2, c. 307T>C, and c. 676C>G. A total of 1 194 RhD-positive inpatients from Chengdu were typed by both KASP genotyping and manual tube serology. Discordant samples (n=10) were retested by both methods and further resolved by Sanger sequencing. An additional 377 cases were tested for the c. 48C>G locus to evaluate the predictive accuracy of individual loci and combined locus testing for RhC antigen. Results: Genotyping concordance with serology was 100.0% for both the c. 676C>G locus (RhE/Rhe) and the c. 307T>C locus (Rhc). For RhC prediction using the 109 bp insertion, overall accuracy was 99.7% (1 191/1 194); the 3 discordant cases were confirmed by Sanger sequencing to be false negatives attributable to 109 bp deletion in intron 2. Testing the c. 48C>G allele for RhC prediction yielded 7 false positives, with an accuracy of 98.1% (370/377). RhC antigen status was determined by combining the 109 bp insertion and the c. 48C allele. After excluding 10 samples with inconsistent results between the two loci, the accuracy reached 100% in the remaining 367 samples. When both loci were applied in combination, accuracy reached 100% in the 367 cases with concordant results. Among the 1 194 patients, CCee (45.8%) and CcEe (31.7%) were the most common RhCE phenotypes. The e antigen had the highest positivity rate (92.2%), and the Ce haplotype was the most frequent (66.9%). Conclusion: The KASP-based RHCE genotyping method achieves high accuracy for clinical RhCE typing. Combining the 109 bp insertion/deletion with the c. 48C allele significantly improves RhC antigen prediction compared with either locus alone. This method was applied to RhCE genotyping of 1 194 RhD-positive inpatients in Chengdu, providing local RhCE phenotype and haplotype distribution data to support RhCE-matched transfusion practice.

Purpose: Dual anti–human epidermal growth factor receptor 2 (HER2) drugs have become the standard regimen for neoadjuvant systemic treatment (NST) to HER2-positive breast cancer patients. However, the efficacy varies greatly among patients with different HER2 protein expression levels. Materials and Methods: A total of 575 HER2-positive breast cancer patients from multiple centers throughout China from 2013 to 2022 were retrospectively analyzed. We compared clinicopathological features in different HER2 immunohistochemistry classes (HER2 2+/in situ hybridization [ISH] + or HER2 3+), and their difference in response to NST and survival with single or dual anti-HER2 drugs. Drug sensitivity assays were used to evaluate different efficacy of anti-HER2 drugs in vitro. Results: Compared to HER2 3+ subgroup, the HER2 2+/ISH+ group had a higher proportion of hormone receptor–positive status (48.7% vs. 76.1%, p < 0.001), more HER2 protein loss after NST, lower pathological complete response (pCR) rate (46.07% vs. 16.24%, p < 0.001), and tended to have worse disease-free survival (DFS). In HER2 2+/ISH+ patients, treated with pertuzumab and trastuzumab in combination had no significant improvement in pCR (19.12% vs. 12.24%, p=0.287) and DFS (p=0.908) than using alone. Drug sensitivity assay showed poor efficacy with dual anti-HER2 drugs in HER2 2+/ISH+ cell lines; however, fam-trastuzumab deruxtecan drugs had a satisfactory effect. Conclusion Owing to the differences in clinicopathological features and treatment efficacy, we considered the HER2 2+/ISH+ group to be a distinct subtype and defined it as the HER2-moderate–positive subgroup. In this subgroup, dual anti-HER2 drugs did not exert significant improvement in pCR and DFS. Therefore, treatment optimization is warranted, with antibody-drug conjugate drugs as potential options.

Objective:To investigate the association between estimated cumulative low-density lipoprotein cholesterol (LDL-C) exposure and the severity of coronary artery disease and long-term adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS).Methods:The subjects were from the PROMISE study. This study was a prospective cohort study led by Fuwai Hospital, Chinese Academy of Medical Sciences, with participation from eight regional tertiary hospitals as sub-centers, and enrolled 18 701 patients with confirmed coronary heart disease between January 2015 and May 2019. Among them, 8 429 patients with ACS were included in this study. The estimated cumulative LDL-C exposure was calculated by multiplying LDL-C by age. Participants were then divided into four groups based on quartiles. Baseline data and coronary angiography data were collected, and participants were followed for 2 years. The primary endpoint was MACCE, which was composed of all-cause death, cardiac death, myocardial infarction, revascularization, and stroke. Spearman correlation analysis was used to estimate the correlation between cumulative LDL-C exposure and the severity of coronary artery disease. The differences in MACCE among the four groups were compared, and multivariate Cox regression was used to divide the estimated cumulative exposure LDL-C into two groups, three groups, and four groups to analyze its relationship with MACCE.Results:The 8 429 ACS patients included in the study had an age of (60.9±11.4) years, with 1 951(23.1%) females. Spearman correlation analysis revealed that estimated cumulative LDL-C exposure was positively associated with the preoperative SYNTAX score, three-vessel lesions disease, left main disease, and the number of target lesions (correlation coefficients r=0.14, 0.10, 0.04 and 0.03, respectively, with all P<0.05). The 2-year follow-up results indicated that the incidence rates of MACCE, all-cause death, cardiac death, myocardial infarction, and stroke in ACS patients grouped by different levels of estimated cumulative LDL-C exposure were statistically significant (all P<0.05). The results of the Cox multivariate regression analysis showed that when the estimated cumulative LDL-C exposure was treated as a continuous variable and analyzed in two, three, and four groups, with the lowest group as the reference, the risk of MACCE occurrence in the high-value group increased by 21% (95% CI 1.08-1.37, P=0.002), 24% (95% CI 1.07-1.43, P=0.004), and 21% (95% CI 1.02-1.43, P=0.025) respectively. Conclusions:A positive correlation was found between estimated cumulative LDL-C exposure and severity of coronary artery disease. High estimated cumulative LDL-C exposure level is a risk factor for MACCE in ACS patients within 2 years.

Objective: To analyze the demographic characteristics of patients with red blood cell transfusion reactions, the usage of red blood cell preparations, and the differences in the composition ratio of adverse reactions based on multi-center data from the Haemovigilance Network, in order to reveal the clinical characteristics of red blood cell transfusion and its underlying issues. Methods: Clinical data of patients who experienced transfusion reactions after red blood cell transfusion in the Haemovigilance Network from 2018 to 2023 were collected. The demographic characteristics of patients who experienced transfusion reactions with different types of red blood cell preparations, the utilization of these preparations, and the differences of the composition ratios of transfusion reactions were analyzed. Count data were expressed as numbers (n) or percentages (%), and comparisons between groups were performed using the Chi-square test. Results: Red blood cell transfusion reactions were more common in females (53.56%), with the majority of patients aged 50-69 years (35.54%). The Han polulation accounted for the vast majority of patients (92.77%), and patients in the hematology and obstetrics/gynecology departments had a relatively high proportion of transfusion reactions (13.26% and 14.26%, respectively). Leukocyte-reduced red blood cells and suspended red blood cells were the most common types of transfusion reactions reported among red blood cell preparations. Allergic reactions and non-hemolytic febrile reactions were the most common transfusion reactions, and there were significant differences in the composition ratios of allergic reactions (χ =869.89, P<0.05) and non-hemolytic febrile reactions (χ =812.75, P<0.05) across various types of red blood cell preparations. Conclusion: There are differences in the demographic characteristics and composition ratio of transfusion reactions among different red blood cell preparations. The management of red blood cell transfusion reactions should be tailored to patient characteristics and conditions, and the selection and use of blood products should be optimized to reduce or avoid the occurrence of transfusion reactions, such as considering the use of washed red blood cells for patients with a history of transfusion allergies or those prone to allergies.

In this study, the pharmacokinetic characteristics and tissue distribution of cannabidiol(CBD)/γ-polyglutamic acid-g-cholesterol(γ-PGA-g-CHOL) nanomicelles [CBD/(γ-PGA-g-CHOL)NMs] were investigated by pharmacokinetic experiments, and the effect of CBD/(γ-PGA-g-CHOL)NMs on the lipopolysaccharide(LPS)-induced inflammatory damage of cells was evaluated by cell experiments. CBD/(γ-PGA-g-CHOL)NMs were prepared by dialysis. The CBD concentrations in the plasma samples of male SD rats treated with CBD and CBD/(γ-PGA-g-CHOL)NMs were investigated, and the pharmacokinetic parameters were calculated and compared. UPLC-MS/MS was employed to determine the concentration of CBD in tissue samples. The heart, liver, spleen, lung, kidney, and muscle samples were collected at different time points to explore the tissue distribution of CBD and CBD/(γ-PGA-g-CHOL)NMs. The Caco-2 cell model of LPS-induced inflammation was established, and the cell viability, transepithelial electrical resistance(TEER), and secretion levels of inflammatory cytokines were determined to compare the anti-inflammatory activity between the two groups. The results showed that CBD/(γ-PGA-g-CHOL)NMs had the average particle size of(163.1±2.3)nm, drug loading of 8.78%±0.28%, and encapsulation rate of 84.46%±0.35%. Compared with CBD, CBD/(γ-PGA-g-CHOL)NMs showed increased peak concentration(C_(max)) and prolonged peak time(t_(max)) and mean residence time(MRT_(0-t)). Within 24 h, the tissue distribution concentration of CBD/(γ-PGA-g-CHOL)NMs was higher than that of CBD. In addition, both CBD and CBD/(γ-PGA-g-CHOL)NMs significantly enhanced Caco-2 cell viability and TEER, lowered the secretion levels of inflammatory cytokines, and alleviated inflammation. Moreover, CBD/(γ-PGA-g-CHOL)NMs demonstrated stronger anti-inflammatory effect. It can be inferred that γ-PGA-g-CHOL blank nanomicelles are good carriers of CBD, being capable of prolonging the circulation time of CBD in the blood, improving the bioavailability and tissue distribution concentration of CBD, and protecting against LPS-induced inflammatory injury. The findings can provide an experimental basis for the development and clinical application of oral CBD preparations.
Animals ; Cannabidiol/administration & dosage* ; Polyglutamic Acid/analogs & derivatives* ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Anti-Inflammatory Agents/administration & dosage* ; Micelles ; Caco-2 Cells ; Cholesterol/pharmacokinetics* ; Tissue Distribution ; Nanoparticles/chemistry*

Objective:To analyze the predictive effects of the Big Five personality traits and emotions on self-management behaviors in patients with type 2 diabetes mellitus (T2DM).Methods:This study was a cross-sectional research. From 2016 to 2020, community interventions for self-management among patients with chronic diseases were conducted in Hangzhou, targeting patients with type 2 diabetes recruited from 69 community health service centers across the city. The data for this study were derived from the baseline information collected during the community intervention. The Chinese Big Five Personality Inventory (CBF-PI-15), the Type 2 Diabetes Self-Management Scale (2-DSCS), the Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS) were employed for questionnaire assessments. Biochemical indicators, including postprandial 2-hour blood glucose, glycated hemoglobin (HbA 1c), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were measured. Spearman correlation analysis was used to examine the relationship between personality traits, relevant biochemical indicators, and self-management behaviors. Hierarchical regression analysis was employed to assess the predictive effects of the Big Five personality traits and emotions on self-management behaviors after controlling for demographic characteristics and factors related to health status. Results:A total of 839 patients were included in this study, comprising 518 females (61.75%) and 321 males (38.25%), with an average age of (66.92±8.67) years and an average disease duration of (8.87±6.91) years. There were significant differences in self-management behavior scores among patients with varying disease durations, educational levels, treatment methods, and levels of anxiety and depression ( t/F=6.172, 3.340, 4.699, 16.007, 27.127, all P<0.05). Neuroticism showed a negative correlation with various dimensions of self-management behaviors ( r=-0.130--0.073), while conscientiousness and agreeableness were positively correlated with various dimensions of self-management behaviors ( r=0.072-0.215). Dietary control score was negatively correlated with HbA 1c and LDL-C ( r=-0.106, -0.077), and regular exercise score was negatively correlated with postprandial 2-hour blood glucose, HbA 1c, TG, TC, HDL-C, and LDL-C ( r=-0.115--0.071). The total score of the 2-DSCS was negatively correlated with HbA 1c, TG, and TC ( r=-0.104--0.071). Patients with a disease duration exceeding 15 years and those receiving insulin injections or a combination of oral medication and insulin injections had higher total 2-DSCS score ( β=0.085, 0.146, 0.118, all P<0.05). Conversely, patients with higher HbA 1c and SDS standard scores had lower total 2-DSCS score ( β=-0.151, -0.328, both P<0.05), while those with higher agreeableness scores had higher total 2-DSCS score ( β=0.143, P<0.05). Conclusion:The traits of neuroticism, conscientiousness, and agreeableness within the Big Five Personality Traits, as well as anxiety and depressive emotions, are correlated with self-management behaviors. Specifically, agreeableness has a positive predictive effect on self-management behaviors, whereas depressive emotions have a negative predictive effect.

[Objective]To summarize Professor ZHANG Yonghua's clinical experience in treating emotional-type insomnia based on the"wind movement smoothening the Xuanfu(pores)"theory for clinical reference.[Methods]Through learning,case collection,literature review and combining modern medical mechanisms,the article explains Professor ZHANG's understanding of the pathogenesis of emotional-type insomnia,explores the syndrome differentiation methods and treatment approaches based on the"wind movement smoothening the Xuanfu"theory,and provides a clinical case for verification.[Results]The core pathogenesis of insomnia caused by emotional disorders is the blockage of the"Xuanfu".Professor ZHANG points out that patients with emotional disorders suffer from the blockage of the"Xuanfu"due to the disharmony of Qi movement,internal disturbance of depressed fire,deficiency of Qi and blood,and accumulation of phlegm and blood stasis,which lead to prolonged and difficult-to-treat insomnia.His treatment approach often starts from"unblocking the Xuanfu",advocating the basic therapeutic method of"wind movement smoothening Xuanfu",using wind herbs to relieve depression and regulate Qi,disperse fire and clear heat,tonify deficiency and nourish the spirit,remove phlegm and resolve blood stasis to unblock the Xuanfu,and harmonize Yin and Yang to restore balance.The attached medical case was a patient of insomnia due to dissociative conversion disorder,whose main pathogenesis was the blockage of the Shaoyang pivot and the internal hyperactivity of the heart fire of the Shaoyin,presenting the syndrome of depressed gallbladder and phlegm-heat.The treatment approach was to resolve phlegm and clear heat,subdue the floating Yang,further regulate the exterior and interior,harmonize Yin and Yang,and unblock the Xuanfu to relieve depression,so as to enable the patient to sleep peacefully.[Conclusion]Professor ZHANG's treatment of emotional-type insomnia based on the"wind movement smoothening the Xuanfu"theory is highly effective and offers a new approach to treating insomnia with traditional Chinese medicine,which is worth promoting and applying.

[Purpose]To analyze the incidence and mortality of lung cancer in Zhejiang cancer regi-stration areas in 2021 and trends from 2000 to 2021.[Methods]Using data from Zhejiang cancer registration areas from 2000 to 2021,the crude rate,age-standardized rate by Chinese standard population(ASRC)and the world standard population(ASRW),and composition ratio were calcu-lated to describe the incidence and mortality in 2021.Joinpoint regression was employed to ana-lyze temporal trends over the 22 years,calculating the annual percentage change(APC),average annual percentage change(AAPC),and their 95％confidence intervals(CI).[Results]The crude incidence rate of lung cancer in 2021 was 128.58/105,with an ASRC of 68.74/105,ac-counting for 24.22％of all cancers;the crude mortality rate was 51.55/105,with an ASRC of 21.58/105,constituting 27.98％of all cancer deaths.Both crude incidence rate(AAPC=5.73％,P＜0.001)and ASIRC(AAPC=4.14％,P＜0.001)of lung cancer showed significant increasing trends from 2000 to 2021.The crude mortality rate increased slowly(AAPC=1.76％,P＜0.001),while the ASMRC(AAPC=-0.40％,P=0.035)exhibited a modest decline.The increase in incidence was more pronounced in females than males,though no statistically significant difference was observed in mortality trends.The incidence rates in urban and rural areas showed similar growth trends;the crude mortality rate in rural areas was growing significantly faster than that in urban areas,and the decline in the ASRC was only statistically significant in urban areas.The incidence rate was in-creasing in all age groups.The mortality rate was declining among younger people(＜65 years old).The age group of 15～44 years old demonstrated a greater increase in incidence and a sharper decline in mortality than those aged 45 years old and above.[Conclusion]From 2000 to 2021,Zhejiang Province experienced a marked rise in lung cancer incidence with escalating disease burden.Despite severe population aging,ASRC of mortality declined steadily,reflecting effective prevention and control measures.

Objective:To discuss the efficacy of treating allergic rhinoconjunctivitis(ARC)with intranasal acupuncture at Neiyingxiang(EX-HN9)and Biqiu(Extra)points and the effects on inflammatory cells.Methods:A total of 207 ARC patients were recruited and divided into an observation group(104 cases)and a control group(103 cases)using the random number table method.The control group was prescribed desloratadine dispersible tablets and azelastine hydrochloride eye drops for 1 week,and the observation group was given additional acupuncture at bilateral Neiyingxiang(EX-HN9)and Biqiu(Extra)points,once daily consecutively over 1 week.The clinical efficacy was compared between the two groups when the treatment finished.Before and after treatment,both groups were scored using the rhinoconjunctivitis quality of life questionnaire(RQLQ),and the levels of blood eosinophils(EOS)and interleukin(IL)-17 were detected.The cured cases were observed for recurrence rate at the 6-month follow-up.Results:The observation group had more significant clinical efficacy than the control group(P<0.05).After treatment,The RQLQ score declined in both groups(P<0.05)and was lower in the observation group than in the control group(P<0.05).After the intervention,the levels of blood EOS and IL-17 dropped in the two groups and were lower in the observation group than in the control group(P<0.05).At the 6-month follow-up among the cured cases,a lower recurrence rate was found in the observation group compared to the control group(P<0.05).Conclusion:Based on conventional medications,acupuncture at Neiyingxiang(EX-HN9)and Biqiu(Extra)points can notably enhance the clinical efficacy in treating ARC patients,reducing the inflammatory cells and lowering the recurrence rate.