Objective To explore the potential clinical value of the ratio of glycated albumin to albumin(GA/ALB)in the occurrence of heart failure(HF)among patients with coronary atherosclerotic heart disease(CHD).Methods A total of 337 CHD patients admitted to the Department of Cardiology in Shanxi Provincial People's Hospital from July 2023 to June 2024 were selected in this study.CHD patients were divided into HF group and non-HF group based on whether they progressed to HF.The clinical data and laboratory parame-ters of the two groups were compared.Restricted cubic spline curve was used to analyze the relationship be-tween GA/ALB levels and the risk of HF in CHD patients.Receiver operating characteristic curve was applied to evaluate the diagnostic efficacy of GA/ALB,GA,platelet to lymphocyte ratio(PLR),and monocyte to lym-phocyte ratio(MLR)in CHD patients with the occurrence of HF.Logistic regression was used to explore the relationship between serum GA/ALB levels and the risk of CHD patients occurrence of HF,and to analyze the degree of influence and stability of subgroup variables on results.Results There were statistically significant differences in GA/ALB,GA,PLR,MLR,and other indicators between the HF group and the non-HF group in CHD patients(P＜0.05).A non-linear relationship was observed between GA/ALB levels and the risk of HF in CHD patients.When the value of GA/ALB multiplied by 10 was less than 5.751,the risk of HF in CHD pa-tients increased with the increase of GA/ALB levels(P＜0.001).GA/ALB was an effective predictor for HF occurrence in CHD patients.Multivariable Logistic regression model showed that GA/ALB was an independ-ent risk factor for CHD patients with occurrence of HF.Subgroup analysis also confirmed the stability of GA/ALB in predicting the occurrence of HF in CHD patients.Conclusion GA/ALB is an independent risk factor for the occurrence of HF in CHD patients,and monitoring GA/ALB levels provides predictive value for the oc-currence of HF in these patients.

Objectives:To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and analyze the effects of treatment-related and socioeconomic factors on physical growth.Methods:Based on the specialized thalassemia database from gene therapy clinical research at the Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, we collected data on height and weight development, family economic status, and medical records of 338 pediatric patients with TDT from October 2023 to May 2024. The length/height-for-age and body mass index (BMI) -for-age were classified based on the Growth Standard for Children under 7 Years of Age, Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years, and Dietary Guidelines for Chinese Residents. Logistic regression analysis was conducted to assess the effects of family economic status and disease-related treatment on length/height-for-age and BMI-for-age.Results:Among the 338 patients, 118 were children and 220 were adolescents (192 males and 146 females), with a median age of 12 years (range: 0.8-18) and a median diagnosis duration of 10.3 years (range: 0.5-17.9). Subtypes included α-thalassemia [21 cases (6.2%) ], β-thalassemia [288 cases (85.2%) ], and combined αβ-thalassemia[29 cases (8.6%) ]. The monthly household income of patients was concentrated in 3 000-5 000 yuan (39.9%) and 5 001-10 000 yuan (34.9%), whereas 67.2% of the families had monthly medical expenses of <3 000 yuan. Of the patients, 75.5% received their first transfusion before 1 year of age. The proportions of children and adolescents with pretransfusion hemoglobin (HGB) of ≤70 g/L were 4.2% and 6.4%, respectively. Adolescents demonstrated significantly higher rates of transfusion frequency of <4 weeks/session, monthly red blood cell infusion of >2 U, serum ferritin (SF) of ≥5 000 μg/L, iron chelation therapy, and splenectomy compared with children (all P<0.05). Of the 338 patients, 26.0%, 22.8%, and 8.9% demonstrated stunted growth, underweight, and concurrent stunted growth with underweight, respectively. No significant difference was observed in the stunted growth rates between children (22.9%) and adolescents (27.7%) ( P=0.402). However, the underweight rate in adolescents (26.8%) was significantly higher than that in children (15.3%) ( P=0.023). The multivariate analysis determined the following risk factors for stunted growth: monthly household income of <10 000 yuan (5 001-10 000 yuan: OR=5.49, 95% CI: 1.48-35.76; 3 000-5 000 yuan: OR=6.87, 95% CI: 1.88-44.60; <3 000 yuan: OR=9.29, 95% CI: 2.20-64.77), pretransfusion HGB of ≤70 g/L ( OR=3.25, 95% CI: 1.07-10.18), and SF of ≥5 000 μg/L ( OR = 3.04, 95% CI: 1.20-7.70). Longer diagnostic duration was associated with underweight ( OR=1.10, 95% CI: 1.01-1.20) . Conclusions:Children and adolescents with TDT with pretransfusion SF of ≥5 000 μg/L, HGB of ≤70 g/L, low monthly household income, or longer diagnosis duration were significantly more likely to experience delayed physical growth.

Objective:To expand the mutation spectrum of familial benign chronic pemphigus (HHD), and to deeply explore the relationship between clinical phenotypes and genotypes.Methods:HHD patients were retrospectively collected from the Department of Dermatology, Hospital for Skin Diseases, Shandong First Medical University from January 2018 to October 2023, and their clinical data and blood samples were also collected. Sanger sequencing and Whole-exome sequencing were performed on 34 HHD patients. Mutations in the ATP2C1 gene were classified into loss-of-function mutations (including frameshift mutations, nonsense mutations, and splicing mutations) and missense mutations. The relationship between clinical phenotypes and genetic mutation types was analyzed using Fisher's exact test or two-independent-sample t test, and further verified by meta-analysis. Results:The 34 HHD patients were all of Chinese Han nationality, including 20 males and 14 females, and their ages ranged from 35 to 77 years. Pathogenic mutations in the ATP2C1 gene were successfully identified in all the 34 patients, including 29 independent mutations, among which there were 9 frameshift mutations, 8 splicing mutations, 6 missense mutations, and 6 nonsense mutations. The age at onset was significantly earlier in the loss-of-function mutation group (37.62 ± 10.10 years) than in the missense mutation group (49.63 ± 14.90 years; t = 2.62, P = 0.013). However, there were no significant differences in gender, family history, disease seasonality, disease severity, or disease progression among patients with different mutation types (all P > 0.05). Meta-analysis showed that the age at onset was significantly earlier in Chinese Han patients with HHD carrying loss-of-function mutations than in those carrying missense mutations (mean difference: -4.61 years, 95% CI: -8.68 - -0.53 years, P = 0.030) . Conclusion:Chinese Han patients with HHD carrying loss-of-function mutations in the ATP2C1 gene showed significantly earlier ages at onset compared with those carrying missense mutations.

Objective To study the plasma metabolomics of mice poisoned by different dosage of the combination of diazepam and ethanol,and to reveal the toxicological mechanisms of combined poisoning of diazepam and ethanol.Methods Female Kunming mice were randomly divided into blank group,single and combined poisoning group(n=6),Based on the LD50 of diazepam co-administered with graded ethanol doses,mice in the single-drug and combined groups received oral gavage at 1/2,1,and 2 × LD50.Retro-orbital blood samples(～500 μL)were collected within 24 hours post-administration and analyzed by UPLC-QE-MS technology.Principal component analysis and orthogonal partial least squares discriminant analysis were used to identify differential metabolites and associated metabolic pathways.Results A total of 387 differential metabolites were identified in the combined poisoning group of diazepam and ethanol implicating the key pathways including tryptophan metabolism,phenylalanine metabolism,arginine and proline metabolism,Glycerophospholipid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion Combined diazepam and ethanol poisoning exerts significant systemic effects by disrupting neurotransmitters conduction,exacerbating oxidative stress response and dysregulating energy metabolism.

Objective:To expand the mutation spectrum of familial benign chronic pemphigus (HHD), and to deeply explore the relationship between clinical phenotypes and genotypes.Methods:HHD patients were retrospectively collected from the Department of Dermatology, Hospital for Skin Diseases, Shandong First Medical University from January 2018 to October 2023, and their clinical data and blood samples were also collected. Sanger sequencing and Whole-exome sequencing were performed on 34 HHD patients. Mutations in the ATP2C1 gene were classified into loss-of-function mutations (including frameshift mutations, nonsense mutations, and splicing mutations) and missense mutations. The relationship between clinical phenotypes and genetic mutation types was analyzed using Fisher's exact test or two-independent-sample t test, and further verified by meta-analysis. Results:The 34 HHD patients were all of Chinese Han nationality, including 20 males and 14 females, and their ages ranged from 35 to 77 years. Pathogenic mutations in the ATP2C1 gene were successfully identified in all the 34 patients, including 29 independent mutations, among which there were 9 frameshift mutations, 8 splicing mutations, 6 missense mutations, and 6 nonsense mutations. The age at onset was significantly earlier in the loss-of-function mutation group (37.62 ± 10.10 years) than in the missense mutation group (49.63 ± 14.90 years; t = 2.62, P = 0.013). However, there were no significant differences in gender, family history, disease seasonality, disease severity, or disease progression among patients with different mutation types (all P > 0.05). Meta-analysis showed that the age at onset was significantly earlier in Chinese Han patients with HHD carrying loss-of-function mutations than in those carrying missense mutations (mean difference: -4.61 years, 95% CI: -8.68 - -0.53 years, P = 0.030) . Conclusion:Chinese Han patients with HHD carrying loss-of-function mutations in the ATP2C1 gene showed significantly earlier ages at onset compared with those carrying missense mutations.

Objective To study the plasma metabolomics of mice poisoned by different dosage of the combination of diazepam and ethanol,and to reveal the toxicological mechanisms of combined poisoning of diazepam and ethanol.Methods Female Kunming mice were randomly divided into blank group,single and combined poisoning group(n=6),Based on the LD50 of diazepam co-administered with graded ethanol doses,mice in the single-drug and combined groups received oral gavage at 1/2,1,and 2 × LD50.Retro-orbital blood samples(～500 μL)were collected within 24 hours post-administration and analyzed by UPLC-QE-MS technology.Principal component analysis and orthogonal partial least squares discriminant analysis were used to identify differential metabolites and associated metabolic pathways.Results A total of 387 differential metabolites were identified in the combined poisoning group of diazepam and ethanol implicating the key pathways including tryptophan metabolism,phenylalanine metabolism,arginine and proline metabolism,Glycerophospholipid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion Combined diazepam and ethanol poisoning exerts significant systemic effects by disrupting neurotransmitters conduction,exacerbating oxidative stress response and dysregulating energy metabolism.

Objective To investigate the safety and efficacy of super-selective arterial embolization in the treatment of abdominal wall hematoma.Methods The clinical data of 11 patients with abdominal wall hematoma,who were admitted to the Northern Jiangsu People's Hospital of China from January 2018 to December 2023,were retrospectively analyzed.All patients received angiography together with super-selective arterial embolization.The effectiveness of embolization treatment was evaluated by the technical success rate and therapeutic effect,and the safety was evaluated by the incidence of complication.Results The median age of the 11 patients was 70 years,91％were female,with a body mass index(BMI)of 25.1 kg/m2,subcutaneous fat thickness of 2.8 cm,and international normalized ratio(INR)of 1.12.DSA showed that 8 patients(72％)had active bleeding signs,3 patients(28％)had no active bleeding signs.Under DSA,a total of 18 responsible vessels,including 6 lumbar arteries(33.3％),5 deep circumflex iliac arteries(27.7％),5 inferior epigastric arteries(27.7％)and 2 iliolumbar arteries(11.3％),were identified and were treated with embolization.The median time spent for operation was 80 minutes.The technical success rate was 100％and the clinical effective rate was 91％.No operation-related major complications occurred,and the median hospital stay was 6 days.Conclusion For the abdominal wall hematoma in aged,obesity patients with underlying diseases,super-selective arterial embolization is a therapeutic method with high technical success rate,high clinical effective rate and satisfactory clinical safety.

Objectives:To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and analyze the effects of treatment-related and socioeconomic factors on physical growth.Methods:Based on the specialized thalassemia database from gene therapy clinical research at the Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, we collected data on height and weight development, family economic status, and medical records of 338 pediatric patients with TDT from October 2023 to May 2024. The length/height-for-age and body mass index (BMI) -for-age were classified based on the Growth Standard for Children under 7 Years of Age, Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years, and Dietary Guidelines for Chinese Residents. Logistic regression analysis was conducted to assess the effects of family economic status and disease-related treatment on length/height-for-age and BMI-for-age.Results:Among the 338 patients, 118 were children and 220 were adolescents (192 males and 146 females), with a median age of 12 years (range: 0.8-18) and a median diagnosis duration of 10.3 years (range: 0.5-17.9). Subtypes included α-thalassemia [21 cases (6.2%) ], β-thalassemia [288 cases (85.2%) ], and combined αβ-thalassemia[29 cases (8.6%) ]. The monthly household income of patients was concentrated in 3 000-5 000 yuan (39.9%) and 5 001-10 000 yuan (34.9%), whereas 67.2% of the families had monthly medical expenses of <3 000 yuan. Of the patients, 75.5% received their first transfusion before 1 year of age. The proportions of children and adolescents with pretransfusion hemoglobin (HGB) of ≤70 g/L were 4.2% and 6.4%, respectively. Adolescents demonstrated significantly higher rates of transfusion frequency of <4 weeks/session, monthly red blood cell infusion of >2 U, serum ferritin (SF) of ≥5 000 μg/L, iron chelation therapy, and splenectomy compared with children (all P<0.05). Of the 338 patients, 26.0%, 22.8%, and 8.9% demonstrated stunted growth, underweight, and concurrent stunted growth with underweight, respectively. No significant difference was observed in the stunted growth rates between children (22.9%) and adolescents (27.7%) ( P=0.402). However, the underweight rate in adolescents (26.8%) was significantly higher than that in children (15.3%) ( P=0.023). The multivariate analysis determined the following risk factors for stunted growth: monthly household income of <10 000 yuan (5 001-10 000 yuan: OR=5.49, 95% CI: 1.48-35.76; 3 000-5 000 yuan: OR=6.87, 95% CI: 1.88-44.60; <3 000 yuan: OR=9.29, 95% CI: 2.20-64.77), pretransfusion HGB of ≤70 g/L ( OR=3.25, 95% CI: 1.07-10.18), and SF of ≥5 000 μg/L ( OR = 3.04, 95% CI: 1.20-7.70). Longer diagnostic duration was associated with underweight ( OR=1.10, 95% CI: 1.01-1.20) . Conclusions:Children and adolescents with TDT with pretransfusion SF of ≥5 000 μg/L, HGB of ≤70 g/L, low monthly household income, or longer diagnosis duration were significantly more likely to experience delayed physical growth.

Objective:To establish a rapid quantitative PCR (qPCR) technique for Mycobacterium marinum skin infections, and to analyze its clinical diagnostic efficiency. Methods:DNA was extracted from Mycobacterium marinum colonies and serially diluted (10 -1 to 10 -8). Twelve pairs of previously reported primers and probes, as well as 6 pairs of newly designed primers and probes in this study, were used for qPCR amplification to identify the most sensitive primers and probes for the detection of Mycobacterium marinum. Skin lesion tissues were collected from 72 patients with confirmed Mycobacterium marinum infections (experimental group) and 68 with other mycobacterial infections (control group) at Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences in 2021. These skin tissues were subjected to qPCR amplification, interferon-gamma release assay (IGRA), acid-fast staining, and tissue culture to evaluate the diagnostic efficacy. Results:The newly designed primers and probes targeting the mycobacterial enhanced infection locus 2 (Mel2) demonstrated the highest sensitivity, with a detection limit of 0.86 copies/μl (cycle threshold value = 37) ; the qPCR amplification with the Mel2 primers/probes did not yield positive results when used for the detection of other mycobacteria (including Mycobacterium leprae and Staphylococcus spp) . Among the 72 patients in the experimental group, 44 were positive for qPCR with a sensitivity of 61.1% (95% CI: 49.6% - 71.5%), and 47 were positive for culture with a sensitivity of 65.2% (95% CI: 53.8% - 75.3%) ; all the 68 controls were negative for both qPCR and culture, with their specificities both being 100%. Among 65 patients subjected to IGRA, 31 were positive with a sensitivity of 47.7% (95% CI: 36.0% - 59.6%), while 16 out of 25 controls were negative for IGRA with a specificity of 64.0% (95% CI: 44.5% - 79.8%). Among 58 patients subjected to acid-fast staining, 37 were positive with a sensitivity of 63.8% (95% CI: 50.9% - 74.9%), and 52 out of 66 controls were negative for acid-fast staining with a specificity of 78.8% (95% CI: 67.5% - 86.9%). The combination of qPCR and culture resulted in a sensitivity of 93% and a specificity of 100% for the detection of Mycobacterium marinum. Conclusion:In this study, a highly sensitive qPCR assay was developed for the detection of Mycobacterium marinum, and its combination with culture could further improve the detection sensitivity.

Objective To investigate the mechanism of the preventive effect of alum-borneol nanoemulsion on hypertrophic scars by observing its effect on cAMP-response element-binding protein 3-like 1(CREB3L1)and inflammatory damage in hypertrophic scar tissues of rabbit ear.Methods Thirty New Zealand big-eared white rabbits were randomly divided into blank group,model group,alum-borneol nanoemulsion low-,medium-,and high-dose groups(8.15,16.3,and 32.6 mg·mL-1),and asiaticoside group.The animal model was established by thermal injury.Topical application of appropriate drugs was given on the 14th day after successful modeling of deep Ⅱ-degree burns.Equal amounts of saline were applied externally to the blank and model groups twice daily and administered continuously until the 35th day.Histopathological changes in rabbit ear scar tissue were observed by hematoxylin-eosin(HE)staining.Masson staining was used for collagen deposition in scar tissue.Coexpression of CREB3L1/alpha-smooth muscle actin(α-SMA)in rabbit ear scar tissue was detected by immunofluorescence double-labeling assay.Enzyme-linked immunosorbent assay(ELISA)was applied for the detection of interleukin-6(IL-6)and interleukin-10(IL-10)in scar tissue.Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)was applied for the detection of CREB3L1,Collagen Type I(COL-Ⅰ),Collagen Type Ⅲ(COL-Ⅲ),and α-SMA mRNA expression.Protein expression of CREB3L1,COL-Ⅰ,COL-Ⅲ,and α-SMA was detected by protein immunoblotting analysis(Western Bolt).Results Compared with the blank group,the scar proliferation index of the model group was significantly increased(P<0.01).Pathologic changes including the thickening of the dermis,the formation of dense reticular fibers,and accompaniment of inflammatory cell infiltration were observed.Masson staining reveals thickening of the dermis,disordered arrangement and large deposits of blue-stained collagen fibers.Double-labeling immunofluorescence results showed that positive expression of CREB3L1 and α-SMA in scar tissue increased.IL-6 levels were significantly increased(P<0.01),while IL-10 levels were significantly decreased(P<0.01).The relative mRNA expression of CREB3L1,COL-Ⅰ,COL-Ⅲ,and α-SMA in the scar tissue of rabbit ear was significantly increased(P<0.01).The protein expression of CREB3L1,COL-Ⅰ,COL-Ⅲ,and α-SMA was significantly increased(P<0.01).Compared with the model group,the scar proliferation index was significantly decreased after the treatment of medium-,high-dose of alum-borneol nanoemulsion and asiaticoside(P<0.01,P<0.05,P<0.01).Pathologic changes including the thinning of the dermis,as well as varying degrees of reduction of inflammatory cells and blue-stained collagen fibers were found.Double-labeling immunofluorescence showed positive expression of CREB3L1 and α-SMA in scar tissue decreased.IL-6 levels significantly reduced(P<0.01),while IL-10 levels significantly raised(P<0.01).The alum-borneol nanoemulsion medium-,high-dose and asiaticoside groups could significantly down-regulate the mRNA expression of CREB3L1,COL-Ⅰ,COL-Ⅲ,and α-SMA(all P<0.01),and reduce the protein expression of CREB3L1,COL-Ⅰ,COL-Ⅲ,and α-SMA(P<0.05,P<0.01).Conclusion Alum-borneol nanoemulsion may prevent hyperplastic scar formation by regulating the expression of CREB3L1 and related fibrotic proteins and reducing inflammatory level,which enriches the scientific connotation of"prevention of disease from exacerbating"and"treatment of the disease before its onset"in Chinese medicine.