Objective To analyze the spatiotemporal distribution characteristics of and trends in the disease burden of dengue fever in China from 2005 to 2024, so as to provide insights into formulation of dengue fever control strategies. Methods Data pertaining to dengue fever cases in China from 2005 to 2024 were retrieved from the Infectious Disease Reporting Information System of Chinese Center for Disease Control and Prevention, and city population, gross domestic product (GDP), GDP per capita, and consumer price index in China were captured from the China Statistical Yearbook, National Bureau of Statistics of China, the China City Statistical Yearbook, and bureaus of statistics in each city. The disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) due to dengue fever were calculated in China from 2005 to 2024. The direct and indirect economic burdens of dengue fever were estimated to calculate the total economic burden. The trends in the disease burden of dengue fever were estimated in China from 2005 to 2024 using a Joinpoint regression model with the software Joinpoint 4.9.0.0, and the average annual percent change (AAPC) and its 95% confidence interval (CI) were calculated. In addition, the DALYs rate and economic burden of dengue fever in China were subjected to global and local spatial autocorrelation analyses using the software ArcGIS 10.8. Results The gross DALYs due to dengue fever were 5 558 person-years in China from 2005 to 2024, and the DALYs of dengue fever increased from 36 person-years in 2005 to 899 person-years in 2024, with an increase of 23.97 folds. The average annual DALYs rate of dengue fever was 0.02 person-years/10⁵ in China during the 20-year study period from 2005 to 2024, and the DALYs rate peaked in 2014 (0.13 person-years/10⁵) and reduced during the COVID-19 pandemic from 2020 to 2022. YLDs were the main contributor of DALYs due to dengue fever in China from 2005 to 2024, with a total of 5 354 person-years, accounting for 96.33% (5 354 person-years/5 558 person-years) of the gross DALYs. The gross DALYs of dengue fever were 2 982 person-years among men (53.66%) and 2 575 person-years among women (46.34%) in China from 2005 to 2024, and high DALYs of dengue fever were measured among residents at ages of 15 to 30 years (1 639 person-years), 30 to 45 years (1 857 person-years), and 45 to 60 years (1 204 person-years), respectively, accounting for 84.56% (4 700 person-years/5 558 person-years) of total DALYs due to dengue fever in China. The total economic burden of dengue fever was estimated to be 612 million Yuan in China from 2005 to 2024, with an average annual economic burden of 30.584 million Yuan. The economic burden of dengue fever increased from 196 000 Yuan in 2005 to 121 million Yuan in 2024 in China, with an increase of 616.35 folds, and the per capita economic burden increased from 3 322.21 Yuan in 2005 to 4 940.01 Yuan in 2024, with an increase of 48.70%. Dengue fever cases were reported in 274 cities (counties) across 31 provinces (autonomous regions, municipalities) in China from 2005 to 2024, with relatively higher DALYs in Guangdong Province and Yunnan Province. Spatial autocorrelation analysis revealed that the disease burden of dengue fever appeared positive aggregation in Chinese cities (counties) from 2005 to 2024 (global Moran’s I = 0.045, Z = 2.24, P < 0.05), with high-high clusters mainly concentrated in the Pearl River Delta region in Guangdong Province and Xishuangbanna Dai Autonomous Prefecture and Pu’er City in Yunnan Province, and the total economic burden (global Moran’s I = 0.032, Z = 9.55, P < 0.001), per capita economic burden (global Moran’s I = 0.208, Z = 27.34, P < 0.001), and the proportion of total economic burdens in GDP in 2024 (global Moran’s I = 0.017, Z = 5.91, P < 0.001) all presented positive aggregation, with relatively higher total economic burdens mainly concentrated in Guangdong Province and Yunnan Province. Joinpoint regression analysis showed that the gross DALYs rates of dengue fever appeared an overall tendency towards a rise in China from 2005 to 2024 (AAPC = 16.24%, P = 0.029), and the DALYs rate presented an overall tendency towards a rise among both men (AAPC = 14.75%, P = 0.028) and women (AAPC = 14.93%, P = 0.037) during the study period. The per capita direct economic burden appeared an overall tendency towards a rise among dengue fever patients in China from 2005 to 2024 (AAPC = 2.16%, P = 0.012); however, there was no significant difference in the trends in the per capita indirect economic burden (AAPC = 0.46%, P = 0.470). In addition, the DALYs rate of dengue fever appeared a tendency towards a rise in 84.67% (232/274) of cities (counties) in China from 2005 to 2024, and the per capita economic burden appeared a tendency towards a rise in 85.40% (234/274) of cities (counties), while the DALYs rate and per capita economic burden of dengue fever appeared a tendency towards a rise in 77.01% (211/274) of cities (counties). Conclusions The disease burden of dengue fever significantly increased in China from 2005 to 2024. It is recommended to reinforce integrated dengue fever control in high-risk areas and among high-risk populations, and to improve the surveillance of imported dengue fever cases and vector control.

Breast cancer (BC) is one of the most prevalent malignant tumors affecting women worldwide, with its incidence rate continuously increasing. As a result, treatment strategies for this disease have received considerable attention. Research has highlighted the crucial role of the Hedgehog (Hh) signaling pathway in the initiation and progression of BC, particularly in promoting tumor growth and metastasis. Therefore, molecular targets within this pathway represent promising opportunities for the development of novel BC therapies. This study aims to elucidate the therapeutic mechanisms by which natural compounds modulate the Hh signaling pathway in BC. By conducting a comprehensive review of various natural compounds, including polyphenols, terpenes, and alkaloids, we reveal both common and unique regulatory mechanisms that influence this pathway. This investigation represents the first comprehensive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC. Furthermore, by exploring the structure-activity relationships between these compounds and their molecular targets, we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway. These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics. Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.

Objective To explore the differences of coronary computed tomography-derived fractional flow reserve(CT-FFR)and dynamic stress computed tomography myocardial perfusion imaging(CT-MPI)parameters in obstructive coronary artery disease(CAD),and their correlation with coronary computed tomography angiography(CCTA)vessel stenosis.Methods A retrospective analysis was conducted on 37 patients with obstructive CAD who underwent combined CCTA and dynamic stress CT-MPI scans.Based on the CCTA results,the patients were divided into moderate CAD group(22 cases)and severe CAD group(15 cases).The lowest CT-FFR value and perfusion parameter values between the two groups were analyzed.A total of 111 vessels including the left anterior descending branch(LAD),left circumflex branch(LCX),and right coronary artery(RCA)were classified into the mild vessel stenosis group(＜25％)with 42 vessels,moderate vessel stenosis group(25％-69％)with 49 vessels,and severe vessel stenosis group(≥70％)with 20 vessels.The lowest CT-FFR value and lowest perfusion parameter value among these three groups were analyzed.The correlation between CT-FFR value and CT-MPI perfusion parameter values and their diagnostic efficacy were analyzed.Results At the patient level,the relative myocardial blood flow(rMBF),myocardial blood flow(MBF),myocardial blood volume(MBV),flow extraction product(FEP)in the severe CAD group were significantly lower than those in the moderate CAD group(P＜0.05),while there was no significance in CT-FFR and perfusion capillary blood volume(PCBV)between these two groups(P=0.061,0.098).At the vascular level,there were significant differences in rMBF and MBV among mild,moderate,and severe vessel stenosis groups(P＜0.05).CT-FFR showed significant difference between mild vs moderate vessel stenosis groups and mild vs severe vessel stenosis groups(P＜0.001),and no significant difference between moderate and severe vessel stenosis groups(P=0.355).rMBF had the highest correlation with the degree of vessel stenosis(r=-0.674).CT-MPI combined with CT-FFR had a high efficacy in diagnosing CCTA vessel stenosis,area under the curve(AUC)≥0.90.Conclusion rMBF is more effective than CT-FFR in evaluating the degree of vessel stenosis in CCTA.CT-FFR combined with CT-MPI is helpful to evaluate functional vascular stenosis.

Objective To explore the differences of coronary computed tomography-derived fractional flow reserve(CT-FFR)and dynamic stress computed tomography myocardial perfusion imaging(CT-MPI)parameters in obstructive coronary artery disease(CAD),and their correlation with coronary computed tomography angiography(CCTA)vessel stenosis.Methods A retrospective analysis was conducted on 37 patients with obstructive CAD who underwent combined CCTA and dynamic stress CT-MPI scans.Based on the CCTA results,the patients were divided into moderate CAD group(22 cases)and severe CAD group(15 cases).The lowest CT-FFR value and perfusion parameter values between the two groups were analyzed.A total of 111 vessels including the left anterior descending branch(LAD),left circumflex branch(LCX),and right coronary artery(RCA)were classified into the mild vessel stenosis group(＜25％)with 42 vessels,moderate vessel stenosis group(25％-69％)with 49 vessels,and severe vessel stenosis group(≥70％)with 20 vessels.The lowest CT-FFR value and lowest perfusion parameter value among these three groups were analyzed.The correlation between CT-FFR value and CT-MPI perfusion parameter values and their diagnostic efficacy were analyzed.Results At the patient level,the relative myocardial blood flow(rMBF),myocardial blood flow(MBF),myocardial blood volume(MBV),flow extraction product(FEP)in the severe CAD group were significantly lower than those in the moderate CAD group(P＜0.05),while there was no significance in CT-FFR and perfusion capillary blood volume(PCBV)between these two groups(P=0.061,0.098).At the vascular level,there were significant differences in rMBF and MBV among mild,moderate,and severe vessel stenosis groups(P＜0.05).CT-FFR showed significant difference between mild vs moderate vessel stenosis groups and mild vs severe vessel stenosis groups(P＜0.001),and no significant difference between moderate and severe vessel stenosis groups(P=0.355).rMBF had the highest correlation with the degree of vessel stenosis(r=-0.674).CT-MPI combined with CT-FFR had a high efficacy in diagnosing CCTA vessel stenosis,area under the curve(AUC)≥0.90.Conclusion rMBF is more effective than CT-FFR in evaluating the degree of vessel stenosis in CCTA.CT-FFR combined with CT-MPI is helpful to evaluate functional vascular stenosis.

As the foremost among the four examinations in traditional Chinese medicine （TCM）， inspection and related equipment research face challenges in landing and transformation due to variations in evidence quality， lack of standardization， insufficient algorithm transparency， and poor reliability and stability of decision-making. Against the backdrop of rapid development of emerging technologies such as big data， the internet of things， and artificial intelligence， coupled with macro policy support from the government， digital and intelligent generalized inspection in TCM has emerged， with the aim of utilizing digital technologies to overcome the limitations of naked-eye inspection and comprehensively perceive and analyze facial and bodily expressions. The research in this field intelligently correlates Zang-fu organ functions with health conditions and disease progression and establishes a technical system for digital and intelligent inspection， multi-dimensional and multimodal perception， fusion analysis， and decision-making. This system aims to enhance the accuracy of disease risk warning and diagnosis， bridging the gap between inspection equipment and assistance in clinical decision-making. From an evidence-based perspective， this paper systematically examines the research ideas of digital and intelligent inspection and the development of related equipment， deeply explores how to propose clinical practice-oriented key scientific issues， comprehensively acquire and co-apply multi-dimensional data， establish precise inspection models driven by digital intelligence， optimize standards to enhance equipment interoperability and reliability， construct post-effect evaluation mechanisms to promote improvement， and actively address potential risks such as the black box nature and information security in the application of intelligent technology. This paper not only demonstrates the tremendous potential of digital technologies in improving the accuracy and clinical application efficiency of inspection but also provides new perspectives and ideas for the modernization of inspection in TCM， paving the way for the application of inspection in the global medical and health field.

Objective　To investigate the relationship between exosomal microRNA (miR)-335-5p and the severity of cirrhosis in patients with chronic hepatitis B (CHB), in order to provide more clinical information for early intervention and treatment. Methods From February to August 2019, 6 healthy controls, 8 cases of compensated cirrhosis (CLC), and 8 cases of decompensated cirrhosis (DLC) were recruited from the physical examination outpatient department and the hepatology department of Peking University Third Hospital Qinhuangdao Hospital as a discovery cohort, and serum samples were collected for exosome extraction and miRNA microarray analysis. A validation cohort of 229 CHB patients with cirrhosis, including 94 CLC and 135 DLC patients, was selected from those diagnosed and treated in the hepatology department of the hospital from December 2019 to May 2022. Exosomes were extracted and identified, and the expression level of serum exosomal miR-335-5p was detected by real-time fluorescence quantitative PCR. The model for end-stage liver disease (MELD) score and the combined formula of serum sodium with MELD (MELD-Na) score were used to evaluate the severity of cirrhosis. Results In the discovery cohort, the expression of miR-335-5p in the DLC group was significantly down-regulated compared to the control group and CLC group (P<0.05). In the validation cohort, the level of exosomal miR-335-5p in the DLC group was significantly lower than that in the CLC group (P<0.001). Spearman correlation analysis showed a negative correlation between the expression of exosomal miR-335-5p and both MELD and MELD-Na scores in patients with cirrhosis (P<0.05). After adjusting for other confounding factors in the multiple linear regression model, the expression of exosomal miR-335-5p was still negatively correlated with MELD score (β=-0.103, 95%CI:-3.692 to -1.149, P<0.001) and MELD-NA score (β=-0.109, 95%CI:-4.007 to -1.270, P<0.001). ROC curve analysis indicated that serum exosomal miR-335-5p could differentiate DLC with an area under the ROC curve of 0.905 (95%CI: 0.867 to 0.944), corresponding to a cutoff value of 0.158, with a specificity of 87.2%, and a sensitivity of 83.7%. Conclusions The low expression of exosomal miR-335-5p is associated with the aggravation of cirrhosis in CHB patients, and may serve as a useful biomarker for the early diagnosis of DLC.

The PRR11 gene (Proline Rich 11) has been implicated in lung cancer; however, relationship between PRR11 and immune infiltration is not clearly understood. In this study, we used The Cancer Genome Atlas (TCGA) data to analyze the lung adenocarcinoma patients; PRR11 gene expression, clinicopathological findings, enrichment, and immune infiltration were also studied. PRR11 immune response expression assays in lung adenocarcinoma (LUAD) were performed using TIMER, and statistical analysis and visualization were conducted using R software. All data were verified using Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA). We found that PRR11 was an important prognostic factor in patients with LUAD. PRR11 expression was correlated with tumor stage and progression. Gene Set Enrichment Analysis (GSEA) showed that PRR11 was enriched in the cell cycle regulatory pathways. Immune infiltration analysis revealed that the number of T helper 2 (Th2) cells increased when PRR11 was overexpressed. These results confirm the role of PRR11 as a prognostic marker of lung adenocarcinoma by controlling the cell cycle and influencing the immune system to facilitate lung cancer progression.
Humans ; Prognosis ; Adenocarcinoma of Lung/genetics* ; Lung Neoplasms/genetics* ; Biological Assay ; Cell Cycle

AIM: To compare the accuracy of different intraocular lens(IOL)calculation formulas in cataract patients with axial length longer than 28mm and a history of radial keratotomy(RK).METHODS: Retrospective study. The medical records of 19 cataract patients(29 eyes)after RK and with axial length longer than 28mm who underwent cataract surgery from January 2011 to July 2020 in Beijing Tongren Hospital were analyzed. The absolute error(AE)of the difference among three different formulas was calculated. AE refers to the absolute value between the actual spherical equivalent after cataract surgery and the spherical equivalent predicted by the IOL formula. The AE values of the three formulas and the percentages of eyes with AE≤0.5, 0.75, 1.0, and 2.0D were calculated and compared.RESULTS: The AE values of the three formulas were significantly different(χ2=8.759, P=0.013). The Barrett True-K formula had the smallest median AE, which was only 0.62(0.20, 1.15)D, followed by the Haigis formula 0.76(0.34, 1.26)D, and the Holladay 1(D-K)formula had the largest 1.01(0.49, 1.62)D. The percentages of affected eyes with AE ≤0.5, 0.75, 1.0, and 2.0D for the Barrett True-K formula were 48%, 59%, 69%, and 93%, which were equal to or higher than the other two formulas.CONCLUSION: The Barrett True-K formula is more recommended among the three formulas for cataract patients after RK and with axial length longer than 28 mm.

Objective: To investigate the regulatory relationship of Protein Phosphatase 2 Regulatory Subunit B"Alpha ( PPP2R3A) and hexokinase 1 ( HK1) in glycolysis of hepatocellular carcinoma (HCC). Methods: In HepG2 and Huh7 cells, PPP2R3A expression was silenced by small interfering RNA (siRNA) and overexpression by plasmid transfection. The PPP2R3A-related genes were searched by RNA sequencing. Glycolysis levels were measured by glucose uptake and lactate production. QRT-PCR, ELISA, western blot and immunofluorescence assay were performed to detect the changes of PPP2R3A and HK1. Cell proliferation, migration and invasion assay were used to study the roles of HK1 regulation by PPP2R3A. Results: RNA sequencing data revealed that PPP2R3A siRNA significantly downregulated the expression of HK1. PPP2R3A gene overexpression promotes, while gene silencing suppresses, the level of HK1 and glycolysis in HCC cells. In HCC tissue samples, PPP2R3A and HK1 were colocalized in the cytoplasm, and their expression showed a positive correlation. HK1 inhibition abrogated the promotion of glycolysis, proliferation, migration and invasion by PPP2R3A overexpression in liver cancer cells. Conclusion Our findings showed the correlation of PPP2R3A and HK1 in the glycolysis of HCC, which reveals a new mechanism for the oncogenic roles of PPP2R3A in cancer.
Carcinoma, Hepatocellular/pathology* ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glycolysis ; Hexokinase/metabolism* ; Humans ; Liver Neoplasms/pathology* ; Protein Phosphatase 2/metabolism* ; RNA, Small Interfering/metabolism*