Objective To systematically analyze the characteristics of the disease burden of hypertensive heart disease (HHD) in the elderly (≥60 years) globally and in China from 1990 to 2021, and to predict its future trends from 2022 to 2040, with the aim of providing data support for optimizing comprehensive prevention and control strategies for HHD. Methods Based on the Global Burden of Disease (GBD) 2021 database, the number of prevalent cases and disability-adjusted life years (DALYs) of HHD in the elderly were extracted for the world, China, and five regions categorized by sociodemographic index (SDI). Joinpoint regression was used to analyze the temporal trends of age-standardized prevalence rate and age-standardized DALYs rate of HHD in the elderly. A three-factor decomposition method was applied to evaluate the relative contributions of aging, population growth, and epidemiological changes to the variations in the elderly HHD burden. Additionally, a Bayesian age-period-cohort model was used to predict the elderly HHD burden from 2022 to 2040. Results In 2021, the number of prevalent elderly HHD cases reached 10 283 000 globally and 3 412 400 in China, representing increases of 179.20% and 159.20% respectively, compared with 1990. The DALYs of elderly HHD were 18 812 700 person-years globally and 4 731 400 person-years in China, rising by 76.08% and 29.45% respectively from 1990. Meanwhile, the growth rates of the number of prevalent cases and DALYs of elderly HHD varied across different SDI regions. From 1990 to 2021, the age-standardized prevalence rate of elderly HHD in China, as well as the age-standardized DALYs rate of elderly HHD both globally and in China, showed significant downward trends (all average annual percentage changes<0, all P<0.001). In 2021, the 70-74 years age group accounted for the highest proportion of prevalent cases and DALYs of elderly HHD, both globally and in China. Decomposition analysis revealed that population growth was the dominant factor driving the increase in the elderly HHD burden across all regions. The prediction model results indicated that the number of prevalent cases and DALYs of elderly HHD would continue to rise globally and in China from 2022 to 2040, with the growth rate of the elderly HHD burden in China between 2021 and 2040 expected to exceed the global average. Conclusion Over the past 32 years, although the age-standardized disease rates of elderly HHD have mainly shown a downward trend globally and in China, the absolute number of the disease burden has increased substantially. The projection model indicates a continued upward trajectory, with the growth rate in China higher than the global average. Therefore, there is an urgent need to implement precise prevention and control strategies to effectively mitigate the disease burden of elderly HHD.

Idiopathic pulmonary fibrosis （IPF） is a chronic and fibrotic lethal interstitial lung disease with poor prognosis. It is mainly treated by organ transplantation and administration of chemical drugs， which have poor efficacy and induce side effects， failing to meet the clinical needs. Therefore， it is urgent to develop more safe and effective drugs to treat IPF. Traditional Chinese medicine （TCM） has garnered increasing attention in recent years in the treatment of IPF due to its unique advantages. Increasing studies have shown that TCM has remarkable therapeutic effects on IPF and thus demonstrate broad application prospects. Modern medical research shows that the pathogenesis of IPF can be discussed from inflammation （macrophage polarization）， oxidative stress， epithelial-mesenchymal transition （EMT）， autophagy inhibition and other related signaling pathways， while few studies systematically explain the relationship between the signaling pathways and TCM theory. According to the theory of TCM， lung collateral obstruction is the basic pathogenesis of IPF. Therefore， according to the principle of dredging and replenishing lung collaterals， IPF can be treated with the methods of reinforcing healthy qi and eliminating pathogen， replenishing qi and activating blood， and detoxifying and dredging collaterals， which demonstrate definite curative effect and can effectively relieve clinical symptoms， restore the lung function and blood oxygen partial pressure， improve the quality of life of patients， and reduce adverse reactions. Experimental studies have found that dredging and replenishing lung collaterals have significant effects on IPF inflammation （macrophage polarization）， oxidative stress， EMT， autophagy inhibition and other signaling pathways. Therefore， from the perspective of impediment， this article reviews pathogenesis of IPF， the research progress in TCM treatment of IPF， and the treatment of IPF from active components， single herbs， and compound prescriptions of TCM， with the aim of revealing the scientific connotation of the treatment of IPF from impediment and providing a new theoretical basis for enriching the TCM methods of treating IPF.

ObjectiveTo prepare a recombinant PETase with a dual-catalytic-triad and to evaluate its efficiency in the biodegradation of polyethylene terephthalate （PET）. MethodsBased on the crystal structure of wild-type PETase， point mutations （T88H/L117D） were introduced via site-directed mutagenesis. The recombinant protein was prepared using prokaryotic expression and chromatography purification techniques. The enzymatic hydrolysis of the mutant PETase was assessed by relatively quantifying the products mono （2-hydroxyethyl） terephthalate （MHET） and terephthalic acid （TPA）. ResultsBoth wild-type and mutant PETases accumulated as inclusion bodies， accounting for approximately 20% of the total bacterial protein. After solubilization in urea， the proteins were eluted at 300 mmol/L imidazole during affinity chromatography purification， with concentrations of 1.824 and 1.833 mg/mL and purities of 83.11% and 84.32%， respectively. Subsequent anion-exchange chromatography yielded highly pure enzymes in the 200 mmol/L NaCl fraction： 2.776 mg/mL （96.86% purity） for the wild type and 1.967 mg/mL （95.13% purity） for the mutant. Following refolding， the final concentrations were 0.484 mg/mL for the wild type and 0.991 mg/mL for the mutant. Hydrolysis assays revealed that the mutant released MHET and TPA at （237.67±17.00）% and （197.33±12.01）% of the wild-type levels， respectively. ConclusionThe T88H/L117D dual-catalytic-triad PETase is successfully prepared and it significantly enhanced PET-degrading activity， thus， it′s a promising biocatalyst for PET bioremediation.

[摘 要] 目的：探讨lncRNA CYTOR靶向miR-488-3p/Pumilio RNA结合家族成员2（PUM2）对子宫内膜癌（EC）细胞增殖、侵袭及上皮-间充质转化（EMT）的影响。方法：RT-qPCR检测EC细胞及hEM15A细胞中的基因表达情况；将HEC-1-A细胞随机分为空白组、sh-NC组、sh-lncRNA CYTOR组、mimic NC组、miR-488-3p mimic组、sh-lncRNA CYTOR + inhibitor NC组、sh-lncRNA CYTOR + miR-488-3p inhibitor组、miR-488-3p mimic + vector组、miR-488-3p mimic + PUM2组，检测各组HEC-1-A细胞增殖、侵袭、基因表达及EMT相关蛋白E-cadherin、N-cadherin、增殖蛋白（Ki-67）表达；双萤光素酶及RNA免疫沉淀（RIP）实验验证miR-488-3p与lncRNA CYTOR、PUM2的靶向关系。结果：EC细胞中miR-488-3p表达降低，lncRNA CYTOR、PUM2 mRNA表达增加（P < 0.05），以HEC-1-A细胞中的变化最为明显；沉默lncRNA CYTOR可降低细胞增殖、侵袭能力及Ki-67、N-cadherin、lncRNA CYTOR、PUM2表达水平，上调E-cadherin、miR-488-3p表达（P < 0.05）；过表达miR-488-3p可降低细胞增殖、侵袭能力及Ki-67、N-cadherin、PUM2表达水平，增加E-cadherin、miR-488-3p表达（P < 0.05）；抑制miR-488-3p逆转沉默lncRNA CYTOR对细胞增殖、侵袭、EMT的抑制作用；过表达PUM2逆转过表达miR-488-3p对细胞增殖、侵袭、EMT的抑制作用；miR-488-3p与lncRNA CYTOR、PUM2具有靶向关系。结论：沉默lncRNA CYTOR通过调控miR-488-3p/PUM2抑制EC细胞增殖、侵袭和EMT。

Tongxieyao Prescription is a classic prescription for the treatment of liver-spleen disharmony, which is widely used in the treatment of gastrointestinal diseases such as inflammatory bowel disease, functional diarrhea and chronic colitis. This article explored the correlation between the properties, chemical components, and pharmacological effects of Chinese materia medica in the treatment of gastrointestinal diseases based on the theory of drug delivery in Tongxieyao Prescription. It can be preliminarily inferred that the overall medicinal properties of Tongxieyao Prescription are warm, bitter, sweet, pungent and sour, and belong to the liver and spleen meridians. The ascending, descending, floating and sinking properties have a "rising" trend, which has the effects of gastrointestinal mucosal protection, intestinal flora regulation, gastrointestinal motility improvement and so on. Combined with the concept of "five principles" of TCM quality marker (Q-marker), the potential Q-marker of Tongxieyao Prescription was predicted and analyzed. It was considered that atractylenolide Ⅰ, atractylenolide Ⅱ, atractylenolide Ⅲ, paeoniflorin, synephrine, hesperidin, tangeretin, nobiletin, prim-O-glucosylcimifugin, 5-O-methylvisammioside, etc. could be used as Q-markers and quality control indicators of this prescription.

Objective To explore the influencing factors of cognitive impairment in non-dialysis patients with chronic kidney disease(CKD).Methods A total of 60 hospitalized non-dialysis patients with CKD in the Department of Nephrology of Northern Jiangsu People's Hospital Affiliated to Yangzhou University from September 2022 to September 2023 were enrolled as research objects.According to the estimated glomerular filtration rate(eGFR),they were divided into stage 1 to 2 of CKD group[eGFR ≥60 mL/(min·1.73 m2)]with 23 cases,the stage 3 of CKD group[eGFR 30～＜60 mL/(min·1.73 m2)]with 20 cases,and stage 4 to 5 of CKD group[eGFR＜30 mL/(min·1.73 m2)]with 17 cases.The Montreal Cognitive Assessment Scale(MoCA)was used to evaluate the cognitive function of the patients.Basic data and common clinical laboratory in-dicators on hospital admission were collected to analyze the differences in cognitive function levels under different renal function statuses and to explore the influencing factors of cognitive impairment.Results The incidence rates of cognitive impairment in the stage 1 to 2 of CKD group,stage 3 of CKD group,and stage 4 to 5 of CKD group were 47.8％,85.0％,and 94.1％respectively,the median MoCA scored 26,24 and 20 respectively,with statistically significant between-group differ-ences(P＜0.05).Cognitive function was significantly negatively correlated with age(r=-0.634,P＜0.001),blood urea nitrogen(BUN)(r=-0.574,P＜0.001),serum creatinine(Cr)(r=-0.417,P＜0.001),cystatin C(Cys-C)(r=-0.327,P=0.011),serum β2-microglobulin(β2-MG)(r=-0.259,P=0.046),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(r=-0.474,P＜0.001),and was significantly positively correlated with hemoglobin(HB)(r=0.401,P=0.001)and eGFR(r=0.485,P＜0.001).Multivariate Logistic regression analysis showed that age(P=0.006)and NT-proBNP(P=0.041)were influencing factors of cognitive im-pairment in non-dialysis patients with CKD.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of age for prediction were 0.860,0.864 and 0.812 respectively,the AUC,sensitivity,and specificity of NT-proBNP for pre-diction were 0.808,0.795 and 0.875 respectively,and the combined prediction of age and NT-proBNP had an AUC,sensitivity,and specificity of 0.893,0.955,and 0.750,respectively.Conclusion As renal function deteriorates,the incidence rate and severity of cognitive impairment in non-dialysis patients with CKD tend to increase.Advanced age,renal function deterioration,high NT-proBNP level,and anemia are associated with the occurrence of cognitive impairment in non-di-alysis patients with CKD,among which age and NT-proBNP are influencing factors for cognitive im-pairment.

Objective To evaluate the predictive value of different anthropometric indices in as-sessing body fat content in patients with chronic kidney disease(CKD).Methods Bioelectrical im-pedance analysis was used to measure body fat percentage and visceral fat area in 279 non-dialysis CKD patients.Height and body mass were measured to calculate body mass index(BMI).Waist and hip circumferences were measured to calculate waist-to-hip ratio.Skinfold thickness(triceps skinfold thickness and subscapular skinfold thickness)was also measured.Pearson correlation analysis was employed to explore the correlations between anthropometric indices and body fat percentage as well as visceral fat area.Receiver operating characteristic(ROC)curves were plotted,and the DeLong test was conducted to compare the differences in the area under the curve(AUC)of the ROC curves.Results Pearson correlation analysis revealed significant correlations between body fat percentage and BMI(r=0.419,P＜0.001),hip circumference(r=0.450,P＜0.001),triceps skinfold thickness(r=0.229,P＜0.001),and subscapular skinfold thickness(r=0.324,P＜0.001).Significant correlations were also observed between visceral fat area and BMI(r=0.658,P＜0.001),hip circumference(r=0.648,P＜0.001),triceps skinfold thickness(r=0.194,P=0.001),and subscapular skinfold thickness(r=0.333,P＜0.001).ROC curve analysis demonstrated that the triceps skinfold thickness had the largest AUC value(0.732)for diagnosing obesity in CKD patients,with a sensitivity of 62.1％and specificity of 78.8％,indicating a moderate diagnostic performance.BMI and hip circumference had AUC values of 0.806 and 0.804,respectively,for as-sessing visceral obesity in CKD patients,showing good diagnostic performance.In contrast,the waist-to-hip ratio exhibited poor diagnostic value for both overall obesity and visceral obesity.Conclusion Measuring BMI and hip circumference is valuable for diagnosing visceral fat accumula-tion in CKD patients.However,when assessing overall obesity in CKD patients,multiple anthropo-metric indices should be combined for comprehensive evaluation.Additionally,our results indicate that different anthropometric indices have varying diagnostic values for different types of obesity,ne-cessitating appropriate selection based on actual circumstances.

OBJECTIVE: To explore the clinical characteristics and genetic variants underlying Hereditary coagulation factor V (FV) deficiency in two Chinese pedigrees. METHODS: Seventeen individuals from three generations of the two pedigrees affected with FV deficiency whom had visited Taizhou Hospital of Zhejiang Province respectively in March and June 2024 were recruited as study subjects. One hundred healthy individuals undergoing physical examinations have served as the controls. Relevant coagulation parameters were measured. Thrombin generation was assessed using the calibrated automated thrombogram (CAT) assay. All exons and flanking regions of the F5 gene were amplified by PCR and directly sequenced. Candidate variants were analyzed for evolutionary conservation and potential pathogenicity, and their effects on protein structure were predicted. This study was approved by the Medical Ethics Committee of Taizhou Hospital of Zhejiang Province (Ethics No.: 20230722). RESULTS: The FV activity (FV: C) and antigen levels (FV: Ag) of both probands showed concurrent decrease. By thrombin generation assay, both the lag time ratio and time to peak ratio were significantly increased. Genetic analysis revealed that proband A carried compound heterozygous missense variants c.911G>A (p.Gly304Glu) and c.1238T>C (p.Met413Thr), whilst Proband B carried compound heterozygous missense variants c.1258G>T (p.Gly420Cys) and c.1538G>A (p.Arg513Lys) of the F5 gene. Conservation analysis revealed that the amino acid residues p.Gly304, p.Gly420, and p.Arg513 are highly conserved across various species. Online bioinformatics tools predicted that both the p.Gly304Glu and p.Gly420Cys variants are pathogenic. Protein modeling demonstrated that all four variants can result in alterations of protein structure or disruption of hydrogen bonding. CONCLUSION FV deficiency in these two pedigrees can be attributed to the compound heterozygous variants p.Gly304Glu/p.Met413Thr and p.Gly420Cys/p.Arg513Lys of the F5 gene.
Adult ; Female ; Humans ; Male ; Middle Aged ; China/ethnology* ; Factor V/chemistry* ; Factor V Deficiency/genetics* ; Heterozygote ; Pedigree ; East Asian People/genetics*

Objective:To investigate the feasibility of ultra-low dose (ULD) CT pulmonary angiography (CTPA) combined with deep learning reconstruction (DLR) in the diagnosis of pulmonary embolism (PE).Methods:This cross-sectional study prospectively enrolled 100 patients with suspected PE who underwent CTPA examination in Zhongshan Hospital Fudan University, and Shanghai Geriatric Medical Center from April to July 2024, and were randomly divided into the routine dose (RD) group and ULD group according to block randomization. Effective dose (ED) were calculated. The noise index of RD group and ULD group was set to 10 and 20, respectively. Other scanning parameters and contrast agent injection protocol were the same. The CT images of RD group were reconstructed using hybrid iterative reconstruction (HIR), while ULD images were reconstructed with HIR and DLR (ULD-HIR subgroup and ULD-DLR subgroup). The image quality of the three groups of images was subjectively evaluated (overall image noise, pulmonary artery display) and objectively evaluated [signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) of the images] respectively. Finally, the diagnostic results of PE by the expert committee composed of three chief physicians were taken as the gold standard, and one physician with lower qualifications independently evaluated the diagnostic rate of PE in the three groups of images. Objective image quality parameters across the three groups were compared using ANOVA, with LSD post hoc test was used for multiple comparisons. Subjective scores among the three groups were analyzed using the Kruskal-Wallis H test, with Bonferroni corrected pairwise post hoc test was applied for multiple pairwise comparisons. Results:The ED in the RD group and ULD group were (2.7±0.5) mSv and (0.7±0.2) mSv, respectively, and the differences were statistically significant ( t=26.42, P<0.001). The overall differences in CT values of pulmonary arteries at all levels in the images of the RD group, the ULD-HIR subgroup, and the ULD-DLR subgroup were not statistically significant ( P>0.05).The RD group, ULD-HIR subgroup and ULD-DLR subgroup overall differences in SNR and CNR at all levels pulmonary arteries were statistically significant ( P<0.001), in which except for the differences in CNR and SNR values of the left pulmonary arterial trunk in the RD group and the ULD-HIR subgroup, and SNR values of basal segment pulmonary artery of the lower lobe of the left lung, which were not statistically significant ( P>0.05), the differences of the rest of the indexes in the pairwise comparisons between the groups were statistically significant ( P<0.05). The overall differences in the subjective scores of image pulmonary vascular display and image noise in the RD group, ULD-HIR subgroup and ULD-DLR subgroup were statistically significant ( P<0.001), except that the differences in the subjective scores of image pulmonary vascular display in the ULD-DLR subgroup were not statistically significant when compared with that of the RD group ( P>0.05) and that of the rest of the metrics in the between-groups two-by-two comparisons were all statistically significant ( P<0.05). The difference in diagnostic rates of PE in the pulmonary artery trunk, lobe and segmental levels in the images of the RD group, ULD-HIR subgroup and ULD-DLR subgroup was not statistically significant ( P>0.05). Conclusions:DLR can significantly reduce the radiation dose of CTPA examination. Even at ultra-low radiation dose, its image quality is still better than HIR reconstruction at conventional doses and preserve diagnostic accuracy of PE at the lobe level and segment level.

Objective:To investigate the current status of application of stereotactic body radiation therapy (SBRT) in China, aiming to provide reference for promoting the development of this technology.Methods:From January to March 2024, a questionnaire was designed and distributed online, targeting member units of the Professional Committee of Stereotactic Radiosurgery Treatment, which covers 175 radiotherapy units in 30 provinces and regions nationwide. The survey focused on the current application of SBRT technology and its utilization in the treatment of early-stage non-small cell lung cancer (NSCLC). A statistical description of the survey results was presented.Results:Of 175 questionnaires distributed, a total of 130 valid responses were collected, with an effective response rate of 74.3%. A total of 81.5% (106/130) of the units had implemented SBRT technology, and 99.1% of the respondents believed it was necessary to further promote SBRT technology, yet the actual training rate was only 67.0%. SBRT equipment configuration: there were a total of 267 SBRT equipment, featuring a diverse range of types, with traditional linear accelerators as the mainstays, accounting for 76.0% ( n=203), followed by 12.0% ( n=32) for TOMO, 6.4% ( n=17) for Cyber knife, 3.7% ( n=10) for Gamma knife, and proton/heavy ion equipment at 1.5% ( n=4), respectively. The percentage of units with multi-leaf collimator leaf widths ≤0.5 cm was 93.4% (99/106). The application of SBRT: the first radiotherapy unit commenced SBRT in 2000, and this technology entered a period of rapid growth after 2015, sustaining a steady increase over the past decade; SBRT technology was mainly applied in the brain, lung, liver, bone, adrenal gland, and kidney, with application rates of 97.2%, 94.3%, 86.8%, 71.7%, 56.6%, and 27.4%, respectively, while the application rates for the pancreas, metastatic lymph nodes, and other parts were less than 5%. Current status of SBRT technology application in early-stage NSCLC: 90.6% (96/106) of units had implemented SBRT; pre-treatment multi-disciplinary diagnosis and treatment accounted for 77% (74/96); the proportion of application units for peripheral and central type lung cancer lesions both exceeded 57.3%, whereas the application rate for ultra-central type and lesions > 5 cm lung cancer was less than 30%; there was significant variability in the selection of reference guidelines, dose fractionation patterns, and the concept of central type among units. Conclusions:The development of SBRT technology in China is in a period of steady growth, but several issues such as low training rate and lack of standardization still exist. The survey results provide important reference for clinical training and promotion of SBRT technology in China.