Objective: To investigate the prevalence and influencing factors of dyslipidemia among residents in Changzhou City, Jiangsu Province, so as to provide insights into improving prevention and control strategies of dyslipidemia. Methods: Permanent residents aged 35 to 75 years were recruited based on the Early Screening and Comprehensive Intervention Project for High-risk Populations of Cardiovascular Disease in Changzhou City from 2016 to 2023. Demographic information, body mass index (BMI), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were investigated through questionnaire surveys, physical examinations and laboratory tests, and the prevalence of dyslipidemia were analyzed. Factors affecting dyslipidemia were identified using a multivariable logistic regression model. Results: A total of 22 447 residents were surveyed, including 9 142 males (40.73%) and 13 305 females (59.27%), and had a median age of 57.00 (interquartile range, 18.00) years. There were 7 535 cases of dyslipidemia, with a prevalence rate of 33.57%. The prevalence rates of low HDL-C, high TG, high TC, and high LDL-C were 22.27%, 15.89%, 4.06% and 2.27%, respectively. Multivariable logistic regression analysis showed that the residents who were male (OR=1.780, 95%CI: 1.645-1.924), had more than 50 000 yuan of annual household income (OR=1.215, 95%CI: 1.142-1.293), had higher educational level (junior high school/senior high school/technical secondary school, OR=1.138, 95%CI: 1.047-1.237; junior college and above, OR=1.232, 95%CI: 1.095-1.386), smoked frequently (OR=1.504, 95%CI: 1.369-1.653), were overweight (OR=1.763, 95%CI: 1.650-1.885) or obese (OR=2.351, 95%CI: 2.149-2.572), had hypertension (OR=1.478, 95%CI: 1.384-1.579) and diabetes (OR=1.706, 95%CI: 1.586-1.835) had a higher risk of dyslipidemia; while the residents who consumed alcohol at 4 times per week and more (OR=0.619, 95%CI: 0.557-0.688) had a lower risk of dyslipidemia. Conclusions The main types of dyslipidemia are low HDL-C and high TG among residents aged 35 years and above in Changzhou City. The prevalence of dyslipidemia is mainly associated with gender, annual household income, educational level, smoking, alcohol consumption, BMI, hypertension and diabetes.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

OBJECTIVES: To investigate the mechanism of DDX17 for regulating proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) during the development of pulmonary hypertension (PH). METHODS: In murine PASMCs cultured under normoxic or hypoxic conditions, the effects of transfection with si-Ddx17 and insulin treatment, alone or in combination, on cell proliferation and migration were evaluated using Ki-67 immunofluorescence staining, scratch assay and Transwell assay. Western Blotting was performed to detect the changes in protein expression levels of DDX17, 4EBP1, S6, p-4EBP1, and p-S6. In a mouse model of PH induced by intraperitoneal injection of monocrotaline (MCT), the changes in pulmonary vasculature were examined using HE staining following tail vein injection of AD-Ddx17i. RESULTS: The PASMCs in hypoxic culture exhibited significantly enhanced cell proliferation and migration and protein expressions of p-4EBP1 and p-S6, and these changes were obviously reversed by transfection with si-Ddx17. Treatment with insulin significantly attenuated the effect of si-Ddx17 against hypoxic exposure-induced changes in PASMCs. In the mouse model of MCT-induced PH, transfection with AD-Ddx17i obviously alleviated pulmonary vascular stenosis and intimal hyperplasia. CONCLUSIONS The expression of DDX17 is elevated in hypoxia-induced PASMCs and PH mice, and silencing DDX17 significantly inhibits PASMC proliferation and migration in vitro and pulmonary vascular remodeling in PH mice by reducing mTORC1 activity.
Animals ; Cell Proliferation ; Cell Movement ; DEAD-box RNA Helicases/metabolism* ; Myocytes, Smooth Muscle/metabolism* ; Mice ; Pulmonary Artery/cytology* ; Hypertension, Pulmonary/metabolism* ; Mechanistic Target of Rapamycin Complex 1 ; Cells, Cultured ; Muscle, Smooth, Vascular/cytology*

Host-derived small RNAs are emerging as critical regulators in the dynamic interactions between host tissues and the microbiome, with implications for microbial pathogenesis and host defense. Among these, transfer RNA-derived small RNAs (tsRNAs) have garnered attention for their roles in modulating microbial behavior. However, the bacterial factors mediating tsRNA interaction and functionality remain poorly understood. In this study, using RNA affinity pull-down assay in combination with mass spectrometry, we identified a putative membrane-bound protein, annotated as P-type ATPase transporter (PtaT) in Fusobacterium nucleatum (Fn), which binds Fn-targeting tsRNAs in a sequence-specific manner. Through targeted mutagenesis and phenotypic characterization, we showed that in both the Fn type strain and a clinical tumor isolate, deletion of ptaT led to reduced tsRNA intake and enhanced resistance to tsRNA-induced growth inhibition. Global RNA sequencing and label-free Raman spectroscopy revealed the phenotypic differences between Fn wild type and PtaT-deficient mutant, highlighting the functional significance of PtaT in purine and pyrimidine metabolism. Furthermore, AlphaFold 3 prediction provides evidence supporting the specific binding between PtaT and Fn-targeting tsRNA. By uncovering the first RNA-binding protein in Fn implicated in growth modulation through interactions with host-derived small RNAs (sRNAs), our study offers new insights into sRNA-mediated host-pathogen interplay within the context of microbiome-host interactions.
Fusobacterium nucleatum/growth & development* ; RNA-Binding Proteins/genetics* ; Bacterial Proteins/genetics* ; RNA, Bacterial/metabolism* ; Humans ; RNA, Transfer/metabolism*

OBJECTIVE: This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity. METHODS: We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set). RESULTS: In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02-1.72; additive model: OR = 1.22, 95% CI: 1.01-1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01-1.69; additive model: OR = 1.21, 95% CI: 1.00-1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01-1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03-1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04-1.66) polymorphisms were significantly associated with NAFLD in children with obesity ( P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional ( P < 0.05), demonstrating a negative interaction between the three genes. CONCLUSION In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.
Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Child ; Male ; Female ; Genetic Predisposition to Disease ; Case-Control Studies ; Exome Sequencing ; Adolescent ; Polymorphism, Single Nucleotide ; Obesity/complications* ; Pediatric Obesity/complications* ; China

Objective To understand the current situation of human brain donation in Hebei Province by analyzing the basic information of Human Brain Bank samples of Hebei Medical University in order to provide basic data support for subsequent scientific research.Methods The samples collected from the Human Brain Bank of Hebei Medical University were analyzed(from December 2019 to February 2024),including gender,age,cause of death,as well as quality control data such as postmortem delay time,pH value of cerebrospinal fluid and and RNA integrity number and result of neuropathological diagnosis.Results Until February 2024,30 human brain samples were collected and stored in the Human Brain Bank of Hebei Medical University,with a male to female ratio of 9∶1.Donors over 70 years old accounted for 53％.Cardiovascular and cerebrovascular diseases(36.67％)and nervous system diseases(23.33％)accounted for a high proportion of the death causes.The location of brain tissue donors in Shijiazhuang accounted for 90％donations,and the others were from outside the city.The postmortem delay time was relatively short,90％within 12 hours and 10％more than 12 hours.69.23％of the brain samples had RNA integrity values greater than 6.Cerebrospinal fluid pH values ranged from 5.8 to 7.5,with an average value of 6.60±0.45.Brain weights ranged from 906-1496 g,with an average value of(1210.78±197.84)g.Three apolipoprotein E(APOE)alleles were detected including five genotypes(ε2/ε3,ε2/ε4,ε3/ε3,ε3/ε4,ε4/ε4).Eleven staining methods related to neuropathological diagnosis had been established and used.A total of 12 cases were diagnosed as neurodegenerative diseases(including Alzheimer's disease,Parkinson's disease,multiple system atrophy,corticobasal degeneration and progressive supranuclear palsy,etc.),accounting for 40％donated brains.The comorbidity rate of samples over 80 years old was 100％.Conclusion The summary and analyses of the data of brain donors in the Human Brain Bank of Hebei Medical University can reflect the current situation of the construction and operation of the brain bank in Hebei Province,and it can also be more targeted to understand and identify potential donors.Our information can provide reference for the construction of brain bank and provides more reliable materials and data support for scientific research.

Periodontitis is a critical risk factor for the occurrence and development of diabetes.Porphyromonas gingivalis may participate in insulin resistance(IR)caused by periodontal inflammation,but the functional role and specific mechanisms of P.gingivalis in IR remain unclear.In the present study,clinical samples were analysed to determine the statistical correlation between P.gingivalis and IR occurrence.Through culturing of hepatocytes,myocytes,and adipocytes,and feeding mice P.gingivalis orally,the functional correlation between P.gingivalis and IR occurrence was further studied both in vitro and in vivo.Clinical data suggested that the amount of P.gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score.In vitro studies suggested that coculture with P.gingivalis decreased glucose uptake and insulin receptor(INSR)protein expression in hepatocytes,myocytes,and adipocytes.Mice fed P.gingivalis tended to undergo IR.P.gingivalis was detectable in the liver,skeletal muscle,and adipose tissue of experimental mice.The distribution sites of gingipain coincided with the downregulation of INSR.Gingipain proteolysed the functional insulin-binding region of INSR.Coculture with P.gingivalis significantly decreased the INSR-insulin binding ability.Knocking out gingipain from P.gingivalis alleviated the negative effects of P.gingivalis on IR in vivo.Taken together,these findings indicate that distantly migrated P.gingivalis may directly proteolytically degrade INSR through gingipain,thereby leading to IR.The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.

Objective:To investigate the predictive value of the quantitative parameters of dual-layer detector spectral CT in arterial and venous phases for the differentiation degree and the E-cadherin protein expression of gastric cancer.Methods:This was a cross-sectional study. The preoperative data from the dual-layer detector spectral CT images among 183 patients with gastric adenocarcinoma confirmed by operation and pathology was retrospectively analyzed from October 2021 to October 2022 in the First Affiliated Hospital of Fujian Medical University. According to the differentiation degree and E-cadherin protein expression of gastric cancer, all patients were divided into the moderately well differentiated group ( n=82) and the poorly differentiated group ( n=101), as well as the E-cadherin-negative group ( n=80) and the E-cadherin-positive group ( n=103). The CT images in arterial and venous phases were used to reconstruct the virtual monoenergetic images (VMI) at 40, 50, 60, 70, 80, 90, and 100 keV, effective atomic number (Z eff) images and iodine concentration (IC) images. The CT values (CT keV) from VMI, Z eff and IC were measured, and the normalized Z eff (NZ eff) and the normalized IC (NIC) were calculated. Independent-sample t test or Mann-Whitney U test were used to compare the differences in quantitative parameters between groups. The logistic regression analysis was used to screen for the independent predictors, after which a combined prediction model was constructed. The receiver operating characteristic curves were used to evaluate the predictive efficiency of the parameters for the differentiation degree and the E-cadherin protein expression of gastric cancer. Results:There were statistically significant differences in CT 40 keV to CT 70 keV, NZ eff and NIC in dual-phase, as well as Z eff and IC in the venous phase between the moderately well differentiated group and the poorly differentiated group ( P<0.05). The combined prediction model was constructed by CT 40 keV ( OR=1.03, 95% CI 1.02-1.05, P<0.001) in arterial phase and CT 40 keV ( OR=1.05, 95% CI 1.03-1.07, P<0.001) and Z eff ( OR=1.32, 95% CI 1.06-1.65, P=0.015) in venous phase, of which the area under the curve (AUC) for the prediction of the moderately-well group and the poor group was 0.932 (95% CI 0.897-0.967), with a sensitivity of 90.1% and a specificity of 85.4%. Between the E-cadherin-negative group and the E-cadherin-positive group, CT 40 keV and NZ eff in arterial phase, as well as CT 40 keV to CT 70 keV, Z eff, NZ eff, IC and NIC in venous phase, had statistically significant differences ( P<0.05). The AUC for the combined prediction model established by CT 40 keV ( OR=1.02, 95% CI 1.01-1.04, P<0.001) and Z eff ( OR=1.33, 95% CI 1.09-1.63, P=0.006) in venous phase was 0.800 (95% CI 0.736-0.864), with a sensitivity of 95.0% and a specificity of 60.2%. Conclusion:The combined prediction model from the quantitative parameters of dual-layer spectral detector CT can be used to predict the differentiation degree and the E-cadherin protein expression of gastric cancer preoperatively.

A 68-year-old male patient with malignant left lung tumor was treated with gefitinib(250 mg,po,qd)for 29 days.Liver function test results showed AST 310 U·L-1,ALT 493 U·L-1,AKP 100 U·L-1,TBil 18 μmol·L-1,GGT 60 U·L-1,INR 1.81.Several liver function indicators of the patient showed abnormal,which was consistent with the clinical manifestations of moderate liver injury.The liver function index of the patient improved after the doctor adopted the suggestion of clinical pharmacists to protect the liver.Clinical pharmacists made a comprehensive and dynamic assessment of the patient's condition,analyzed the correlation between the patient's liver injury and gefitinib,and judged that the patient's liver injury was likely caused by gefitinib.Clinical pharmacists analyzed the drug use of a blind trial patient,proposed the follow-up treatment plan,and discussed the blind trial drugs,which provided references for clinical safe and rational drug use and had important reference significance.