Vertebral fracture severity assessment on anteroposterior radiographs with a new semi-quantitative technique.

We developed a new tool to assess the severity of osteoporotic vertebral fracture using radiographs of the spine. Our technique can be used in patient care by helping to stratify patients with osteoporotic vertebral fractures into appropriate treatment pathways. It can also be used for research purposes. PURPOSE: The aim of our study was to propose a semi-quantitative (SQ) grading scheme for osteoporotic vertebral fracture (OVF) on anteroposterior (AP) radiographs. METHODS: On AP radiographs, the vertebrae are divided into right and left halves, which are graded (A) vertical rectangle, (B) square, (C) traverse rectangle, and (D) trapezoid; whole vertebrae are graded (E) transverse band or (F) bow-tie. Type A and B were compared with normal and Genant SQ grade 1 OVF, Type C and D with grade 2 OVF, and Type E and F with grade 3 OVF. Spine AP radiographs and lateral radiographs of 50 females were assessed by AP radiographs SQ grading. After training, an experienced board-certified radiologist and a radiology trainee assessed the 50 AP radiographs. RESULTS: The height-to-width ratio of the half vertebrae varied 1.32-1.48. On lateral radiographs, 84 vertebrae of the 50 patients had OVFs (38 grade 1, 24 grade 2, and 22 grade 3). On AP radiographs, the radiologist correctly assigned 84.2%, 91.7%, and 77.2% and the trainee correctly assigned 68.4%, 79.2%, and 81.8% of grade 1, 2, and 3 OVFs, respectively. Compared with lateral radiographs, the radiologist had a weighted Kappa of 0.944 including normal vertebrae and 0.883 not including normal vertebrae, while the corresponding Kappa values for the trainee were 0.891 and 0.830, respectively. CONCLUSION: We propose a new semi-quantitative grading system for vertebral fracture severity assessment on AP spine radiographs.

Association of cord plasma metabolites with birth weight: results from metabolomic and lipidomic studies of discovery and validation cohorts.

OBJECTIVE: Birth weight is a good predictor of fetal intrauterine growth and long-term health, and several studies have evaluated the relationship between metabolites and birth weight. The aim of this study was to investigate the association of cord blood metabolomics and lipidomics with birth weight, using a two-stage discovery and validation approach. METHODS: Firstly, a pseudotargeted metabolomics approach was applied to detect metabolites in 504 cord blood samples in the discovery set enrolled from the Wuhan Healthy Baby Cohort, China. Metabolome-wide association scan analysis and pathway enrichment were applied to identify metabolites and metabolic pathways that were significantly associated with birth weight adjusted for gestational age Z-score (BW Z-score). Logistic regression models were used to analyze the association of metabolites in the most significantly associated pathways with small-for-gestational age (SGA) at delivery and low birth weight (LBW). Subsequently, 350 cord blood samples in a validation cohort were subjected to targeted analysis to validate the metabolites identified by screening in the discovery cohort. RESULTS: In the discovery set, of 2566 metabolites detected, 2418 metabolites were retained for subsequent analysis after data preprocessing. Of these, 513 metabolites were significantly associated with BW Z-score (P-value adjusted for false discovery rate (PFDR) < 0.05), of which 298 Kyoto Encyclopedia of Genes and Genomes (KEGG)-annotated metabolites were included in the pathway analysis. The primary bile acid biosynthesis pathway was the most relevant metabolic pathway associated with BW Z-score. Elevated cord plasma primary bile acids were associated with lower BW Z-score and higher risk of SGA or LBW in the discovery and validation cohorts. In the validation set, a 2-fold increase in taurochenodeoxycholic acid (TCDCA) and in taurocholic acid (TCA) was associated with a decrease in BW Z-score (estimated ß coefficient, -0.10 (95% CI, -0.20 to 0.00) and -0.18 (95% CI, -0.31 to -0.04), respectively), after adjusting for covariates. In addition, a 2-fold increase in cord plasma TCDCA and of cord plasma TCA was associated with an increased risk of SGA (adjusted odds ratio (OR), 1.52 (95% CI, 1.00-2.30) and 1.77 (95% CI, 1.05-2.98), respectively). The adjusted OR for LBW, for a 2-fold increase in TCDCA and TCA concentration, were 2.39 (95% CI, 1.00-5.71) and 3.21 (95% CI, 0.96-10.74), respectively. CONCLUSIONS: These results indicate a significant association of elevated primary bile acids, particularly TCDCA and TCA, in cord blood with lower BW Z-score, as well as increased risk of SGA and LBW. Abnormalities of primary bile acid metabolism may play an important role in restricted fetal development. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Genotype-phenotype relationship and comparison between eastern and western patients with osteogenesis imperfecta.

PURPOSE: To evaluate the genotypic and phenotypic relationship in a large cohort of OI patients and to compare the differences between eastern and western OI cohorts. METHODS: A total of 671 OI patients were included. Pathogenic mutations were identified, phenotypic information was collected, and relationships between genotypes and phenotypes were analyzed. Literature about western OI cohorts was searched, and differences were compared between eastern and western OI cohorts. RESULTS: A total of 560 OI patients were identified as carrying OI pathogenic mutations, and the positive detection rate of disease-causing gene mutations was 83.5%. Mutations in 15 OI candidate genes were identified, with COL1A1 (n = 308, 55%) and COL1A2 (n = 164, 29%) being the most common mutations, and SERPINF1 and WNT1 being the most common biallelic variants. Of the 414 probands, 48.8, 16.9, 29.2 and 5.1% had OI types I, III, IV and V, respectively. Peripheral fracture was the most common phenotype (96.6%), and femurs (34.7%) were most commonly affected. Vertebral compression fracture was observed in 43.5% of OI patients. Biallelic or COL1A2 mutation led to more bone deformities and poorer mobility than COL1A1 mutation (all P < 0.05). Glycine substitution of COL1A1 or COL1A2 or biallelic variants led to more severe phenotypes than haploinsufficiency of collagen type I α chains, which induced the mildest phenotypes. Although the gene mutation spectrum varied among countries, the fracture incidence was similar between eastern and western OI cohorts. CONCLUSION: The findings are valuable for accurate diagnosis and treatment of OI, mechanism exploration and prognosis judgment. Genetic profiles of OI may vary among races, but the mechanism needs to be explored.

Deteriorated bone microarchitecture caused by sympathetic overstimulation in pheochromocytoma and paraganglioma.

PURPOSE: Despite the potentially destructive effect of sympathetic activity on bone metabolism, its impact on bone microarchitecture, a key determinant of bone quality, has not been thoroughly investigated. This study aims to evaluate the impact of sympathetic activity on bone microarchitecture and bone strength in patients with pheochromocytoma and paraganglioma (PPGL). METHODS: A cross-sectional study was conducted in 38 PPGL patients (15 males and 23 females). Bone turnover markers serum procollagen type 1 N-terminal propeptide (P1NP) and ß-carboxy-terminal crosslinked telopeptide of type 1 collagen (ß-CTX) were measured. 24-h urinary adrenaline (24hUE) and 24-h urinary norepinephrine levels (24hUNE) were measured to indicate sympathetic activity. High-resolution peripheral quantitative computed tomography (HR-pQCT) was conducted to evaluate bone microarchitecture in PPGL patients and 76 age-, sex-matched healthy controls (30 males and 46 females). Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry (DXA) simultaneously. RESULTS: PPGL patients had a higher level of ß-CTX. HR-pQCT assessment revealed that PPGL patients had notably thinner and more sparse trabecular bone (decreased trabecular number and thickness with increased trabecular separation), significantly decreased volume BMD (vBMD), and bone strength at both the radius and tibia compared with healthy controls. The deterioration of Tt.vBMD, Tb.Sp, and Tb.1/N.SD was more pronounced in postmenopausal patients compared with the premenopausal subjects. Moreover, subjects in the highest 24hUNE quartile (Q4) showed markedly lower Tb.N and higher Tb.Sp and Tb.1/N.SD at the tibia than those in the lowest quartile (Q1). Age-related bone loss was also exacerbated in PPGL patients to a certain extent. CONCLUSIONS: PPGL patients had significantly deteriorated bone microarchitecture and strength, especially in the trabecular bone, with an increased bone resorption rate. Our findings provide clinical evidence that sympathetic overstimulation may serve as a secondary cause of osteoporosis, especially in subjects with increased sympathetic activity.

Correlation of lipocalin 2 and glycolipid metabolism and body composition in a large cohort of children with osteogenesis imperfecta.

PURPOSE: Lipocalin 2 (LCN2) is a newly recognized bone-derived factor that is important in regulation of energy metabolism. We investigated the correlation of serum LCN2 levels and glycolipid metabolism, and body composition in a large cohort of patients with osteogenesis imperfecta (OI). METHODS: A total of 204 children with OI and 66 age- and gender-matched healthy children were included. Circulating levels of LCN2 and osteocalcin were measured by enzyme-linked immunosorbent assay. Serum levels of fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and low- and high-density lipoprotein cholesterol (LDL-C, HDL-C) were measured by automated chemical analyzers. The body composition was measured by dual-energy X-ray absorptiometry. Grip strength and timed-up-and-go (TUG) were tested to evaluate the muscle function. RESULTS: Serum LCN2 levels were 37.65 ± 23.48 ng/ml in OI children, which was significantly lower than those in healthy control (69.18 ± 35.43 ng/ml, P < 0.001). Body mass index (BMI) and serum FBG level were significantly higher and HDL-C levels were lower in OI children than healthy control (all P < 0.01). Grip strength was significantly lower (P < 0.05), and the TUG was significantly longer in OI patients than healthy control (P < 0.05). Serum LCN2 level was negatively correlated to BMI, FBG, HOMA-IR, HOMA-ß, total body, and trunk fat mass percentage, and positively correlated to total body and appendicular lean mass percentage (all P < 0.05). CONCLUSIONS: Insulin resistance, hyperglycemia, obesity, and muscle dysfunction are common in OI patients. As a novel osteogenic cytokine, LCN2 deficiency may be relevant to disorders of glucose and lipid metabolism, and dysfunction of muscle in OI patients.

Correlation of serum DKK1 level with skeletal phenotype in children with osteogenesis imperfecta.

PURPOSE: We aim to detect serum DKK1 level of pediatric patients with OI and to analyze its relationship with the genotype and phenotype of OI patients. METHODS: A cohort of pediatric OI patients and age-matched healthy children were enrolled. Serum levels of DKK1 and bone turnover biomarkers were measured by enzyme-linked immunosorbent assay. Bone mineral density (BMD) was measured by Dual-energy X-ray absorptiometry. Pathogenic mutations of OI were detected by next-generation sequencing and confirmed by Sanger sequencing. RESULTS: A total of 62 OI children with mean age of 9.50 (4.86, 12.00) years and 29 healthy children were included in this study. The serum DKK1 concentration in OI children was significantly higher than that in healthy children [5.20 (4.54, 6.32) and 4.08 (3.59, 4.92) ng/mL, P < 0.001]. The serum DKK1 concentration in OI children was negatively correlated with height (r = - 0.282), height Z score (r = - 0.292), ALP concentration (r = - 0.304), lumbar BMD (r = - 0.276), BMD Z score of the lumbar spine and femoral neck (r = - 0.32; r = - 0.27) (all P < 0.05). No significant difference in serum DKK1 concentration was found between OI patients with and without vertebral compression fractures. In patients with spinal deformity (22/62), serum DKK1 concentration was positively correlated with SDI (r = 0.480, P < 0.05). No significant correlation was observed between serum DKK1 concentration and the annual incidence of peripheral fractures, genotype and types of collagen changes in OI children. CONCLUSION: The serum DKK1 level was not only significantly elevated in OI children, but also closely correlated to their skeletal phenotype, suggesting that DKK1 may become a new biomarker and a potential therapeutic target of OI.

Secondary infections of COVID-19 in schools and the effectiveness of school-based interventions: a systematic review and meta-analysis.

OBJECTIVES: This meta-analysis explored secondary infections of SARS-CoV-2 and the effectiveness of non-pharmaceutical interventions (NPIs) in school settings, with the aim of providing a reference to formulate scientific prevention and response strategies for similar major public health emergencies in specific settings. STUDY DESIGN: This was a systematic review and meta-analysis. METHODS: Systematic searches were conducted in PubMed, Web of Science and the Cochrane Library through to 1 August 2022 using the following key search terms: COVID-19, SARS-CoV-2, secondary attack rate, school, transmission, etc. The IVhet model was used for the meta-analysis, and the I2 index and Cochran's Q-test were used to assess heterogeneity. Publication bias was examined using Doi plot, Galbraith plots and Luis Furuya-Kanamori index. Prevalence Critical Appraisal Tool was used to assess the quality of the included articles, while Grading of Recommendations Assessment, Development, and Evaluation was used to rate the quality of the evidence. Subgroup analyses were conducted to explore the potential source of heterogeneity. RESULTS: Thirty-four studies involving 226,727 school contacts and 2216 secondary cases were included in this study. The pooled secondary attack rates (SARs) of close contacts, staff contacts and student contacts were 0.67% (95% confidence interval [CI]: 0.11, 1.56), 0.79% (95% CI: 0.00, 6.72) and 0.50% (95% CI: 0.00, 4.48), respectively. Subgroup analysis suggested that multiple or specific combinations (e.g. the combination of contact restriction and hygiene action) of NPIs appeared to be associated with lower SARs. CONCLUSIONS: The SAR of SARS-CoV-2 was low in schools. Multiple or specific combinations of prevention strategies appear to mitigate SARS-CoV-2 transmission in school settings. These findings provide a basis for continuous improvement of response strategies to major public health emergencies in the school environment.

Parent-child interaction, appetite self-regulation, and BMIz in Chinese preschoolers: a mediation analysis.

OBJECTIVES: Research on parent-child interaction (PCI) and its impact on children's weight status is a thriving study area. However, their potential pathways have not been established. This study investigated the association between PCI and children's body-mass index z score (BMIz) examining the role of appetite self-regulation (ASR) as a mediator. STUDY DESIGN: Mediation analysis. METHODS: We included children from 33 kindergartens in Wuhan with parents' consent, measuring children's height and weight, and calculating BMIz. To assess the PCI quality, we utilized the Brigance Parent-Child Interactions Scale. Additionally, children's ASR was tested by satiety responsiveness (SR) and food responsiveness (FR) using the Children's Eating Behavior Questionnaire. Quantile regression was employed to examine the PCI-BMIz association, while mediation analysis was conducted to explore ASR's mediating effect on the relationship between PCI and BMIz. RESULTS: Of 3973 children (53.88% boys) included in the analysis, the mean BMIz was 0.24 ± 1.13. The results revealed that children with poorer PCI quality have higher BMIz across all selected BMIz percentiles, except for the 5th percentile. Furthermore, these associations were significant across most percentiles, whether for boys or girls. Mediation analysis suggested that these associations were partially mediated by children's ASR (indFR = -0.026, PFR < 0.001; indSR = -0.058, PSR < 0.001), with stronger effects observed among boys. CONCLUSION: The variation in how strongly BMIz was linked to PCI across different percentiles suggests that children with poorer PCI have higher BMIz. The link is partially mediated through children's ASR. It's important to pay attention to the PCI quality in children with higher BMIz levels, especially in boys.

Associations of ambient temperature and total cloud cover during pregnancy with newborn vitamin D status.

OBJECTIVES: We aimed to estimate the effects of temperature and total cloud cover before birth on newborn vitamin D status. STUDY DESIGN: Prospective birth cohort. METHODS: This study included 2055 mother-newborn pairs in Wuhan, Hubei province, China. The data of temperature and total cloud cover from 30 days before birth were collected, and cord blood 25-hydroxyvitamin D [25(OH)D] were determined. Restricted cubic spline regression models, multiple linear regression models, and logistic regression models were applied to estimate the associations. RESULTS: A "J" shaped curve was observed between temperature and vitamin D status, and an inverse "J" shaped curve was observed between total cloud cover and vitamin D status. Compared to the fourth quartile (75-100th percentile, Q4) of average temperature (30 days before birth), the odds ratio (OR) for Q1 (0-25th percentile) associated with the vitamin D deficiency occurrence (<20 ng/mL) was 3.63 (95% CI, 1.54, 8.65). Compared to Q1 of the average total cloud cover (30 days before birth), the OR associated with the occurrence of vitamin D deficiency was 2.38 (95% CI, 1.63, 3.50) for the Q4. CONCLUSIONS: Low temperature and high cloud cover before delivery were significantly associated with an increased probability of vitamin D deficiency in newborns. The findings suggested that pregnancy women lacking sufficient sunlight exposure still need vitamin D supplement to overcome the potential vitamin D deficiency status.

[Design of an improved percutaneous transhepatic cholangio drainage tube based on MRCP imaging data].

Objective: Quantified MRCP imaging data was used as a reference for design and preparation of a modified percutaneous transhepatic cholangio drainage (PTCD) tube. Methods: 3.0 T upper abdominal MR and MRCP imaging data of 2 300 patients treated from July 2015 to July 2020 at the Department of Radiology of the Affiliated Cancer Hospital of Zhengzhou University were screened and a total of 381 patients diagnosed with biliary duct structures were identified. Causative etiologies among these patients included pancreatic adenocarcinoma (pancreatic head), cholangiocarcinoma, ampullary carcinoma, as well as intrahepatic and/or extrahepatic bile duct dilation. An improved PTCD tube was designed based on MRCP quantification of left and right hepatic and common hepatic duct length. Results: In the setting of biliary obstruction caused by malignancy, the distance of the left hepatic duct from its origin to the point of left and right hepatic duct confluence was 15.9±3.8 mm, while the distance of the right hepatic duct from its origin to the point of left and right hepatic duct confluence was 12.4±3.2 mm; the length of the bile duct from its origin to the point of left and right hepatic duct confluence was 34.0±8.1 mm. The improved PTCD tube design incorporated an altered length of the drainage orifice. Conclusion: MRCP imaging of the biliary tract is effective for measuring biliary tract length in the setting of pathological dilation. Based on our biliary tract measurements, a modified PTCD tube was designed to more effectively meet drainage requirements and manage biliary obstruction caused by Bismuth-Corlette type Ⅱ and Ⅲ malignancies.

[Pathogenetic analysis of transfusion-related acute lung injury caused by human leukocytes antigen antibody against human leukocyte antigen].

From September 2019 to October 2020, pathogenetic analysis of three patients clinically diagnosed as transfusion-related acute lung injury (TRALI) caused by human leukocyte antibodies was conducted by Guangzhou Blood Centre, including 2 males and 1 female, aged 56, 50 and 20 years old, respectively. Solid phase agglutination, anti-human globulin test and flow cytometry method were used to detect the presence of antibodies against patients. Sequencing-based human leukocyte antigen (HLA-SBT) typing technique was used to detect the human leukocyte antigen (HLA) genotypes of patients. Lifecodes single antigen class Ⅰ/Ⅱ kit (LSA-Ⅰ/Ⅱ) were used to detect the specificity of HLA-class Ⅰ and class Ⅱ antibodies in donor blood by Luminex 200 liquid suspension chip system. The HLA specific antibodies and corresponding epitopes in donors were also analyzed. The results showed that　HLA class Ⅰ or class Ⅱ specific antibodies against TRALI patients were detected in the blood donors. The plasma of donor 3 received by patient 1 contained antibodies against the patient's HLA-DRB1*09∶01 antigen, and the epitopes mediating the antibody reaction of the donor and recipient were 70R, 31I, 70QA. There were antibodies against the HLA-A*11∶02, HLA-A*11∶01, DRB1*12∶02, and DRB1*09∶01 antigens of patient 2 in the plasma of donor 4, and the associated antigenic epitopes were 151AHA, 57V, and 16Y. Antibodies against the HLA-DRB1*14∶04, DRB1*11∶01, and DPB1*05∶01 antigens of patient 3 were present in the plasma of donor 6 and donor 7, and the associated epitopes were 96HK, 140TV, 13SE, and 111K.　Three cases of TRALI were confirmed to be caused by HLA antibodies through laboratory analysis, and human leukocyte antibody detection should be paid attention in clinically suspected cases of TRALI, and targeted diagnosis and treatment should be given.

[Advances in electrowetting-on-dielectric digital microfluidics technology for disease diagnosis and prevention applications].

Rapid and accurate diagnostic technologies are crucial for early detection and diagnosis of diseases. Electrowetting-on-dielectric digital microfluidics, with its high-precision detection and high-throughput screening capabilities, significantly enhances the accuracy and efficiency in early disease diagnosis and personalized treatment, enabling swift disease detection and widespread screening. This article provides a comprehensive review of the working principles and fabrication processes of digital microfluidic chips based on electrowetting on dielectric method. It details the latest research progress in the areas of nucleic acids, proteins, and cells, organizes the commercialization of digital microfluidics technology, and finally discusses the current challenges and future directions of digital microfluidic chips.

[A prospective birth cohort study on the association between gestational blood pressure and neurodevelopment in 2-year-old children].

Objective: To investigate the association between gestational blood pressure and neurodevelopment in 2-year-old children. Methods: Based on the"Wuhan Healthy Baby Birth Cohort", 3 754 mother-infant pairs were enrolled in this study. Based on multiple blood pressure measurements during pregnancy, the mean, cumulative, and variability of blood pressure throughout the entire pregnancy and each trimester were calculated. Blood pressure variability was evaluated using standard deviation (SD), coefficient of variability (CV), and variability independent of mean (VIM). Follow-up testing of neurodevelopment in infants and young children at the age of two was conducted to obtain the Mental Development Index (MDI) and the Psychomotor Development Index (PDI). The multivariate linear regression and generalized estimation equation were used to analyze the association between gestational blood pressure data and neurodevelopmental index. Results: The age of 3 754 pregnant women was (29.1±3.6) years, with a pre-pregnancy BMI of (20.9±2.7) kg/m² and a gestational age of (39.3±1.2) weeks. The birth weight of 3 754 children was (3 330.9±397.7) grams, and the birth length was (50.3±1.6) centimeters. The results of the multivariate linear regression analysis showed that after adjusting for relevant confounding factors, the mean blood pressure, cumulative blood pressure, standard deviation of blood pressure, coefficient of variation of blood pressure, independent blood pressure variability of systolic blood pressure, diastolic blood pressure, and pulse pressure throughout pregnancy were negatively associated with the MDI and PDI scores of 2-year-old children. The analysis results of the generalized estimation equation showed that after adjusting for relevant confounding factors, the average systolic blood pressure in the first, second, and third trimesters was negatively associated with MDI/PDI. The negative association between cumulative blood pressure and MDI/PDI was only found in the first trimester. The negative association between blood pressure variation during pregnancy and MDI/PDI was mainly concentrated in the second and third trimesters. Conclusion: There is a negative association between gestational blood pressure and the neurodevelopmental index of 2-year-old children.

[Application of serum tumor specific protein 70 for prognostic stratification in acute myeloid leukemia].

Objective: To assess the value of serum tumor specific protein 70 (SP70) for prognostic stratification in acute myeloid leukemia (AML). Methods: A cohort study design was adopted. 129 newly diagnosed AML patients from September 2022 to January 2024 at the Hematology Department of the First Affiliated Hospital of Nanjing Medical University were included, as well as a control group consisted of 120 healthy individuals and 7 cases with benign hematologic diseases during the same period (total 127 cases). Clinical data were collected from Electronic Medical Records. According to the 2023 edition of the Chinese Leukemia Diagnosis and Treatment Guidelines, AML patients with good or moderate prognosis were categorized as low-to-intermediate risk, while those with poor prognosis were high-risk group. Univariate and multivariate logistic regression analyses were used to identify variables significantly associated with AML prognostic risk. ROC analysis was used to evaluate diagnostic performance. A nomogram for predicting patient prognostic risk was constructed by R 4.0.2 software, and the internal validation was performed using bootstrapping. Results: Among 129 AML patients, there were 71 males (55.0%) and 58 females (45.0%), with 42 (32.6%) classified as high-risk and 87 (67.4%) as low-intermediate risk. The high-risk group had a significantly higher median age [62 (48, 67) years] compared to the low-intermediate risk group [50 (35, 63) years, Z=-2.381, P=0.017], and a significantly higher proportion of males (30 patients, 71.4%) compared to the low-intermediate risk group (41 patients, 47.1%, χ2=6.760, P=0.009). Multivariate logistic regression analysis indicated that serum SP70 (OR=2.54, 95%CI: 1.68-3.84, P<0.001), hemoglobin (HB) (OR=0.96, 95%CI: 0.93-0.99, P<0.05), and bone marrow blast (BM blast) (OR=1.07, 95%CI: 1.02-1.13, P<0.05) were independent risk factors for high-risk prognosis in AML patients. ROC analysis showed that the area under the curve (AUC) for SP70 predicting high-risk patients was 0.908 (cut-off value of 5.74 ng/ml, 95%CI: 0.845-0.952, sensitivity 90.5%, specificity 82.8%). The combined model of serum SP70, HB, and BM blasts had an AUC of 0.931 (95%CI: 0.890-0.973); C-index=0.925 (95%CI: 0.876-0.963),with no statistically significant difference compared to serum SP70 alone (Z=1.693,P>0.05). Conclusion: Serum SP70 may be a promising non-invasive molecular biomarker for prognostic stratification in AML.

[Study on the risk factors of coal workers' pneumoconiosis and the mechanism of pyroptosis in peripheral blood].

Objective: To explore the risk factors of coal workers' pneumoconiosis, reveal the molecular mechanism of pyroptosis in peripheral blood of coal workers' pneumoconiosis patients, and provide new strategies and potential diagnostic biomarkers for the treatment of the disease. Methods: From January 1, 2020 to December 31, 2022, workers with suspected occupational diseases who were diagnosed with coal workers' pneumoconiosis in the Third People's Hospital of Xinjiang Uygur Autonomous Region were included in the study, including 77 patients with coal workers' pneumoconiosis stage Ⅰ, 10 patients with stage Ⅱ, 6 patients with stage Ⅲ, and 49 workers with dust-free lung disease as the control group. General information of the subjects was collected, blood samples were collected for routine blood and blood biochemical results, and plasma levels of interleukin (IL) -1ß and IL-18 were measured. Combined with the results of clinical examination, multi-factor ordered logistic regression analysis was carried out to evaluate the influencing factors of coal workers' pneumoconiosis. At the same time, the expression of pyroptosis related proteins in blood cells was detected to reveal the molecular mechanism of coal workers' pneumoconiosis. Results: All 142 subjects were male, with an average age of (51.65±6.31) years old and an average working age of (15.94±9.38) years. There were significant differences in smoking age (F=4.95, P=0.003) and lunch break distribution (H=8.84, P=0.031) among all groups. The hemoglobin content of stage Ⅰ patients was higher than that of stage Ⅱ patients, and the neutrophil percentage of stage Ⅲ patients was higher than that of the other 3 groups (P<0.05). The levels of total bilirubin and indirect bilirubin in stage Ⅰ patients were higher than those in control group, while the erythrocyte sedimentation rate in stage Ⅱ patients was higher than that in the other 3 groups (P<0.05). The levels of IL-18 and IL-1ß in stage Ⅲ of coal workers' pneumoconiosis were higher than those in the other 3 groups (P<0.05). Multiple logistic regression analysis showed that smoking age (OR=1.03, 95%CI: 1.00-1.06) and IL-1ß level (OR=4.61, 95%CI: 1.59-13.32) were independent risk factors for coal workers' pneumoconiosis (P<0.05). Compared with the control group, the expression levels of nucleotide-binding of oligomeric domain-like receptor protein 3 (NLRP3), Caspase-1, GSDMD, Caspase-4 and other proteins in stage Ⅲ of coal workers' pneumoconiosis were significantly increased (P<0.05) . Conclusion: Smoking age is a risk factor for coal workers' pneumoconiosis, IL-1ß may be a potential biomarker for the diagnosis of coal workers' pneumoconiosis, and pyroptosis may play a role in the development of peripheral inflammation of coal workers' pneumoconiosis.

IL-37 alleviates intervertebral disc degeneration via the IL-1R8/NF-κB pathway.

OBJECTIVE: Intervertebral disc degeneration (IDD) has been reported to be a major cause of low back pain (LBP). Interleukin (IL)-37 is an anti-inflammatory cytokine of the interleukin-1 family, which exerts salutary physiological effects. In this study, we assessed the protective effect of IL-37 on IDD progression and its underlying mechanisms. METHODS: Immunofluorescence (IF) was conducted to measure IL-37 expression in nucleus pulposus tissues. CCK-8 assay and Edu staining were used to examine the vitality of IL-37-treated nucleus pulposus cells (NPCs). Western blot, qPCR, ELISA as well as immunohistochemistry were used to assess senescence associated secreted phenotype (SASP) factors expression; and NF-κB pathway was evaluated by western blot and IF; while IL-1R8 knock-down by siRNAs was performed to ascertain its significance in the senescence phenotype modulated by IL-37. The therapeutic effect of IL-37 on IDD were evaluated in puncture-induced rat model using X-ray, Hematoxylin-Eosin, Safranin O-Fast Green (SO), and alcian blue staining. RESULTS: We found IL-37 expression decreased in the IDD process. In vitro, IL-37 suppressed SASP factors level and senescence phenotype in IL-1ß treated NPCs. In vivo, IL-37 alleviated the IDD progression in the puncture-induced rat model. Mechanistic studies demonstrated that IL-37 inhibited IDD progression by downregulating NF-κB pathway activation in NPCs by activating IL-1R8. CONCLUSION: The present study suggests that IL-37 delays the IDD development through the IL-1R8/NF-κB pathway, which suggests IL-37 as a promising novel target for IDD therapy.

PTH level might be associated with impaired quality of life in patients with nonsurgical hypoparathyroidism.

OBJECTIVE: Nonsurgical hypoparathyroidism (ns-HP) is a rare disease. There are few studies on Quality of Life (QoL) among patients with ns-HP. This study aimed to investigate the QoL among ns-HP patients with regular conventional treatment, and explore the influence factors affecting QoL among these Chinese ns-HP patients. METHODS: This is a cross-sectional study comparing 101 patients identified as ns-HP and 101 healthy controls. The questionnaires of Short Form 36 Health Survey questionnaire version 2(SF-36v2) were used to evaluate QoL. RESULTS: Scores of all eight subdomains of SF-36v2 and physical component scores (PCS), mental component scores (MCS) were significantly lower in the ns-HP group compared with the healthy controls. The indices of all subdomains of SF-36v2 between Q1 (the lowest quartile) and Q4 (the highest quartile) groups were compared, suggesting higher percentages of detectable parathyroid hormone (PTH) before treatment in Q4 group among all QoL indices except two subdomains (physical function and body pain). CONCLUSION: Both mental and physical QoL were impaired in the ns-HP patients even with regular conventional treatment for hypocalcemia, which were more severe in cases with lower baseline PTH levels.

Expression of ICAM-1 and E-selectin in different metabolic obesity phenotypes: discrepancy for endothelial dysfunction.

OBJECTIVES: Endothelial dysfunction, the earliest vascular alteration, is a consequence of metabolic disorders associated with obesity. However, it is still unclear whether a proportion of obese individuals without metabolic alterations associated with obesity, defined as "metabolically healthy obesity (MHO)", exhibit better endothelial function. We therefore aimed to investigate the association of different metabolic obesity phenotypes with endothelial dysfunction. METHODS: The obese participants without clinical cardiovascular disease from the MESA (Multi-Ethnic Study of Atherosclerosis) were allocated to the different metabolic obesity phenotypes based on their metabolic status, including MHO and metabolically unhealthy obesity (MUO). Associations of metabolic obesity phenotypes with the biomarkers of endothelial dysfunction, including soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin), were evaluated using multiple linear regression models. RESULTS: Plasma levels of sICAM-1 and sE-selectin were respectively measured in 2371 and 968 participants. Compared to the non-obese participants, those with MUO were associated with higher concentrations of sICAM-1 (ß 22.04, 95% CI 14.33-29.75, P < 0.001) and sE-selectin (ß 9.87, 95% CI 6.00-13.75, P < 0.001) after adjusting for confounders. However, no differences were found for the concentrations of sICAM-1 (ß 0.70, 95% CI - 8.91 to 10.32, P = 0.886) and sE-selectin (ß 3.69, 95% CI - 1.13 to 8.51, P = 0.133) in the participants with MHO compared to the non-obese participants. CONCLUSIONS: Individuals with MUO were associated with elevated biomarkers of endothelial dysfunction, but the association with endothelial dysfunction was not found in those with MHO, indicating that the individuals with MHO might exhibit better endothelial function.

High prevalence of vertebral deformity in tumor-induced osteomalacia associated with impaired bone microstructure.

PURPOSE: Patients with tumor-induced osteomalacia (TIO) often suffer from irreversible height loss due to vertebral deformity. However, the prevalence of vertebral deformity in TIO patients varies among limited studies. In addition, the distribution and type of vertebral deformity, as well as its risk factors, remain unknown. This study aimed to identify the prevalence, distribution, type and risk factors for vertebral deformity in a large cohort of TIO patients. METHODS: A total of 164 TIO patients were enrolled in this retrospective study. Deformity in vertebrae T4-L4 by lateral thoracolumbar spine radiographs was evaluated according to the semiquantitative method of Genant. Bone microstructure was evaluated by trabecular bone score (TBS) and high-resolution peripheral QCT (HR-pQCT). RESULTS: Ninety-nine (99/164, 60.4%) patients had 517 deformed vertebrae with a bimodal pattern of distribution (T7-9 and T11-L1), and biconcave deformity was the most common type (267/517, 51.6%). Compared with patients without vertebral deformity, those with vertebral deformity had a higher male/female ratio, longer disease duration, more height loss, lower serum phosphate, higher bone turnover markers, lower TBS, lower areal bone mineral density (aBMD), lower peripheral volumetric BMD (vBMD) and worse microstructure. Lower trabecular vBMD and worse trabecular microstructure in the peripheral bone and lower spine TBS were associated with an increased risk of vertebral deformity independently of aBMD. After adjusting for the number of deformed vertebrae, we found little difference in clinical indexes among the patients with different types of vertebral deformity. However, we found significant correlations of clinical indexes with the number of deformed vertebrae and the spinal deformity index. CONCLUSION: We reported a high prevalence of vertebral deformity in the largest cohort of TIO patients and described the vertebral deformity in detail for the first time. Risk factors for vertebral deformity included male sex, long disease duration, height loss, abnormal biochemical indexes and bone impairment. Clinical manifestation, biochemical indexes and bone impairment were correlated with the number of deformed vertebrae and degree of deformity, but not the type of deformity.

[Analysis of the relationship between PI-RADS scores and the pathological results of targeted biopsy based on MRI].

Objective: To analyze the relationship between Prostate Imaging Reporting and Data System (PI-RADS) scores and the pathological results of transperineal magnetic resonance-ultrasound fusion guided biopsy. Methods: The clinical data, magnetic resonance imaging (MRI) results and prostate puncture biopsies of 517 patients who were assigned to PI-RADS score of 4 or 5 and underwent transperineal magnetic resonance-ultrasound fusion guided biopsy at The First Affiliated Hospital of Nanjing Medical University from June 2019 to March 2022 were retrospectively analyzed. Patients were divided into the PI-RADS 4 and PI-RADS 5 groups according to their PI-RADS scores and were stratified by their prostate specific antigen (PSA) values (PSA<10 ng/ml vs. PSA 10-20 ng/ml). The pathological negative rates from the biopsy, the distribution of the grade groups according to the grading system by World Health Organization/International Society of Urological Pathology (WHO/ISUP), the detection rates of prostate cancer (PCa) and clinically significant prostate cancer (CsPCa)between the groups were compared. Results: 369 patients with a PI-RADS score of 4 and 148 patients with a PI-RADS score of 5 were included in our research. The overall detection rates of PCa and CsPCa were 77.8% (402/517) and 66.7% (345/517), respectively. In the PI-RADS 4 group, patients with prostate negative biopsies or in WHO/ISUP 1, 2, 3, 4, or 5 grade groups accounted for 28.2%, 12.7%, 20.1%, 17.1%, 18.4% and 3.5%, respectively, whereas in the PI-RADS 5 group the rates were 7.4%, 6.8%, 22.3%, 22.3%, 26.4%, and 14.9%, respectively. The difference was statistically significant (P<0.001). The detection rates of PCa and CsPCa in the PI-RADS 4 group [71.8% (265/369) vs. 59.1% (218/369), P<0.001] were lower than those of the PI-RADS 5 group [92.6% (137/148) vs. 85.8% (127/148), P<0.001]. In the PI-RADS 4 group, the proportion of patients classified into WHO/ISUP 4-5 grade groups was lower than that of patients in the PI-RADS 5 group [22.0% (81/369) vs 41.2% (61/148) (P<0.001)]. The detection rates of PCa and CsPCa in the PSA<10 ng/ml stratification were less than that in the PSA 10-20 ng/ml stratification[74.1% (281/379) vs. 87.7% (121/138), P=0.001], and [60.9% (231/379) vs. 82.6% (114/138), P<0.001]. For patients with PSA<10 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS5 group [70.9% (217/306) vs. 87.7% (64/73), P=0.003], and [56.2% (172/306) vs. 80.8% (59/73), P<0.001]. For those with a PSA value of 10-20 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group [76.2% (48/63) vs. 97.3% (73/75), P<0.001], and [73.0% (46/63) vs. 90.7% (68/75), P=0.006]. There were statistically significant differences in the proportions of patients with prostate negative biopsy and those falling into WHO/ISUP grade groups 1, 2, 3, 4, or 5 (P<0.001) between the PI-RADS 4 group and the PI-RADS 5 group in both stratifications. Conclusions: In this study, the detection rates of CsPCa and PCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group. With the increase of PI-RADS scores, the detection rate of high-grade PCa increased. The same results held for patients with PSA<10 ng/ml or with PSA 10-20 ng/ml.