Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Objective The study aimed to elucidate the population composition and seasonal distribution characteristics of mosquitoes in Laoshan District, Qingdao City, providing a scientific basis for the prevention and control of mosquito-borne infectious diseases. Methods Mosquito surveillance was conducted in Laoshan District in Qingdao City using light traps from April to November 2020-2022. Dominant mosquito species were identified using the Berger-Parker dominance index(I)and mosquito density was compared using the Kruskal-Wallis H test. The seasonal distribution characteristics of adult mosquitoes were analyzed using concentration and circular distribution method. Spearman rank correlation analysis was used to study the relationship between mosquito populations and meteorological factors with mean monthly temperature, mean monthly relative humidity, and mean monthly rainfall. Results The mean mosquito density for the trapping period was 9.771 females/(trap·night)in 2020,9.771 in 2021, and 9.427 in 2022. There was no statistically significant difference in mosquito density between different years(H = 0.095, P = 0.954). In total, 2 781 adult female mosquitoes comprising five species from four genera were captured over three years. Culex pipiens(I = 0.654), Aedes albopictus(I = 0.202), and Aedes aegypti(I = 0.118)were identified as dominant species. Seasonal fluctuations in the adult mosquitoes were unimodal, and primarily concentrated from June to September. The peak period of adult mosquito varied between years with statistical significance. (F = 3.838, P ＜ 0.05). Mosquito density was highly correlated with mean monthly temperature, mean monthly relative humidity and mean monthly precipitation(P＜ 0.05). Conclusions Cx. pipiens pallens, Ae. albopictus, and Ar. inamoratus are the dominant mosquito species in the Laoshan District of Qingdao City. The activity of adult mosquitoes is seasonal, and primarily concentrated in summer and autumn, during which the risk of mosquito-borne diseases such as dengue fever is increased.

Dysphagia is a common complication of stroke. Combining the principles of traditional Chinese medicine with modern research findings， it is proposed that "latent pathogen in the cerebral collaterals" constitutes the core pathogenesis of post-stroke dysphagia （PSD）. In clinical practice， treatment is tailored according to the location of PSD. During the oral stage， when the pathogen invades the face and mouth， resulting in excessive salivation， acupoints are primarily selected from the foot shaoyin （少阴） kidney channel， in combination with ren mai （任脉） ， du mai （督脉）， chong mai （冲脉） and the spleen channel， to replenish essence and fill the marrow， dispel dampness and unblock the channels. In the pharyngeal stage， as the pathogen obstructs the throat， disrupting normal swallowing， the therapy emphasizes dredging the shaoyang （少阳） channel and warming and tonifying the jueyin （厥阴） channel， by taking acupoints mainly from the hand and foot shaoyang channels， along with the jueyin channels， so as to soothe the liver and promote bile secretion， regulate and harmonize qi and blood. During the esophageal stage， where the pathogen damages the esophagus， impeding food passage， the treatment emphasizes activating the yangming （阳明） channels and regulating taiyin （太阴） channels； acupoints are mainly selected from the foot yangming stomach channel， along with the taiyin channels， aiming to warm yang， unblock the channels and dispel stasis.

Alzheimer's disease (AD), a prototypical neurodegenerative disorder, encompasses multifaceted pathological processes. As pivotal cellular structures within the central nervous system, ion channels play critical roles in regulating neuronal excitability, synaptic transmission, and neurotransmitter release. Extensive research has revealed significant alterations in the expression and function of ion channels in AD, implicating an important role of ion channels in the pathogenesis of abnormal Aβ deposition, neuroinflammation, oxidative stress, and disruptions in calcium homeostasis and neural network functionality. This review systematically summarizes the crucial roles and underlying mechanisms of ion channels in the onset and progression of AD, highlighting how these channel abnormalities contribute to AD pathophysiology. We also discuss the therapeutic potential of ion channel modulation in AD treatment, emphasizing the importance of addressing multifactorial nature and heterogeneity of AD. The development of multi-target drugs and precision therapies is proposed as a future direction of scientific research.
Alzheimer Disease/therapy* ; Humans ; Ion Channels/physiology* ; Oxidative Stress ; Animals ; Amyloid beta-Peptides/metabolism* ; Synaptic Transmission ; Calcium/metabolism*

OBJECTIVE: To explore clinical effect of bone cement-strengthened pedicle screw technique in the correction of stage Ⅲ asymptomatic Kümmell disease with kyphosis. METHODS: A retrospective analysis was conducted on clinical data of 40 asymptomatic stage Ⅲ Kümmell disease patients admitted between March 2019 and December 2021, including 15 males and 25 females, aged from 61 to 81 years old with an average of (67.4±5.2) years old;according to different surgical methods, they were divided into percutaneous kyphoplasty group (PKP) and reinforced screw group. There were 18 patients in PKP group, including 7 males and 11 females, aged from 61 to 78 years old with an average of (66.2±5.5) years old;the courses of disease ranged from 5 to 12 months with an average of (7.33±1.78) months;bone mineral density(BMD) T values ranged from -2.45 to -4.00 with an average of (-3.08±0.46);2 patients with T₈-T₉, 10 patients with T₁₀-T₁₂, and 6 patients with L₁-L₂;treated with PKP. There were 22 patients in reinforced screw group, including 8 males and 14 females, aged from 65 to 81 years old with an average of (68.5±3.8) years old;the courses of disease ranged from 4 to 15 months with an average of (7.86±2.73)months;bone mineral density(BMD) T values ranged from -2.40 to -4.50 with an average of (-3.18±0.54);3 patients with T₈-T₉, 12 patients with T₁₀-T₁₂, and 7 patients with L₁-L₂;treated with bone cement reinforced pedicle screw internal fixation combined with kyphoplasty. Cobb angle and anterior margin height of the injured vertebra were compared before operation, 3 d and 12 months after operation. Visual analogue scale (VAS) and Oswestry disability index (ODI) were compared between two groups before operation and 12 months after operation. The incidence of postoperative complications was compared between two groups. RESULTS: All patients were followed up, PKP group followed up for 11 to 14 months with an average of (11.97±0.96) months and 10 to 14 months with an average of (12.05±1.09) months in reinforced screw group;there was no significant difference between two groups (P>0.05). Postoperative Cobb angle at 3 days and 12 months in reinforced screw group were (7.34±2.26) ° and (18.86±1.96) °, while in PKP group were (18.88±1.89) ° and (23.28±1.90) °;there were statistical difference between two groups (P<0.05). The anterior margin height of the injured vertebra in reinforced screw group were (25.28±1.33) mm and (19.62±2.22) mm at 3 days and 12 months after operation, while in PKP group were (18.61±2.16) mm and(15.93±1.34) mm;there were statistical difference between two groups (P<0.05). Cobb angle and the anterior margin height of the injured vertebra were significantly improved at 3 days and 12 months after operation between two groups (P<0.05). Postoperative VAS and ODI at 12 months in PKP group were (2.00±0.69) score and (13.44±4.02)%, while in reinforced screw group were(1.91±0.61) score and (10.18±4.26)%;which were significantly lower than (6.89±0.76) score and (36.33±3.40)% in PKP group, (7.23±0.75) score and (37.09±3.73) % in reinforced screw group before operation. There were no difference in postoperative VAS between two groups at 12 months (P>0.05);postoperative ODI in reinforced screw group at 12 months was lower than that in PKP group(P<0.05). There was no significant difference in complications between two groups (χ²=0.071, P>0.05). CONCLUSION PKP and bone cement reinforced nail combined with PKP could improve kyphotic deformity and postoperative function, and relieve pain. The application of bone cement-reinforced nail fixation technology could provide a more stable support, more obvious functional recovery, lower the risk of re-collapse of the injured vertebra, and maintain the long-term stability of spine.
Humans ; Male ; Female ; Aged, 80 and over ; Kyphosis/surgery* ; Aged ; Bone Cements ; Middle Aged ; Retrospective Studies ; Pedicle Screws ; Spinal Fractures/surgery* ; Fracture Fixation, Internal/methods* ; Bone Screws ; Kyphoplasty

OBJECTIVES: To study the incidence and disease burden of congenital birth defects in children under five in China from 1990 to 2021 and to predict the incidence of congenital birth defects in this population from 2022 to 2036, providing a reference for the prevention of congenital birth defects in children. METHODS: Using the Global Burden of Disease Study 2021 (GBD 2021) database, the incidence and disability-adjusted life years (DALY) were employed to describe the disease burden. The Joinpoint regression model was used to analyze the trends in incidence and DALY rates of congenital birth defects in children under five. A grey prediction model GM(1,1) was applied to fit the trend of incidence rates of congenital birth defects in this age group and to predict the incidence from 2022 to 2036. RESULTS: In 2021, the incidence rate of congenital birth defects among children under five in China was 737.28 per 100 000. Among these, congenital musculoskeletal and limb deformities had the highest incidence rate at 307.15 per 100 000, followed by congenital heart defects (223.53 per 100 000), congenital urinary and genital tract malformations (74.99 per 100 000), and congenital gastrointestinal malformations (62.61 per 100 000). From 1990 to 2021, the incidence rate and DALY rate of congenital birth defects in children under five in China decreased at an average annual rate of 1.73% and 5.42%, respectively. The prediction analysis indicated a decreasing trend in the incidence of congenital birth defects among children under five in China from 2022 to 2036, with the incidence rate dropping from 892.36 per 100 000 in 2022 to 783.35 per 100 000 in 2036. CONCLUSIONS The incidence and disease burden of congenital birth defects in children under five in China showed a significant declining trend from 1990 to 2021. It is predicted that this incidence will continue to decrease until 2036.
Humans ; Congenital Abnormalities/epidemiology* ; China/epidemiology* ; Incidence ; Infant ; Infant, Newborn ; Child, Preschool ; Female ; Male ; Forecasting ; Disability-Adjusted Life Years

OBJECTIVE: To explore the predictive value of age, D-Dimer and fibrinogen (FIB) for non-thrombotic. METHODS: A retrospective analysis was conducted on a total of 1 384 coagulation test cases from January to August 2024 at Nanning No. 8 People's Hospital. Among them, the control group comprised 400 non-thrombotic cases with D-Dimer test results within the reference range. The thrombotic group comprised 57 clinically diagnosed thrombotic patients. The research group comprised 927 non-thrombotic cases with D-Dimer levels exceeding the reference range. The diagnosis treatment records, age information, plasma D-Dimer, and FIB test results of each group were collected. The changes and correlations of age, D-Dimer, and FIB indicators were compared and analyzed among the three groups. A new combination factor was generated by fitting a Logistic binary regression model. ROC curves were used to evaluate the predictive value of each index for non-thrombotic disease in both the research group and the thrombotic group. RESULTS: Compared with the control group, the thrombotic group and the research group had significantly higher age, D-Dimer, and FIB levels (P < 0.001). Further comparative analysis showed that the research group had significantly lower age and D-Dimer levels than the thrombotic group, the FIB level was significantly higher than that of the thrombotic group (P < 0.001). Spearman correlation analysis showed that the correlation coefficient between age and D-Dimer in the research group was higher than that in the control group and thrombotic group (P < 0.01), the thrombotic group had the highest negative correlation coefficient between FIB and D-Dimer (P < 0.01). The ROC curve analysis results showed that the AUC values of age, plasma D-dimer, and FIB independently predicted non-thromb diseases were 0.726, 0.735, and 0.611, respectively. A new combined factor was generated by fitting age, D-dimer, and FIB with a logistic binary regression model. The AUC value of the combined prediction of non-thrombotic diseases was the maximum at 0.832, which had high diagnostic value, and its sensitivity and specificity were 0.572 and 0.070. CONCLUSION Elevated D-dimer levels were associated with age, increased FIB, and a variety of non-thrombotic diseases, and combination of age, D-dimer, and FIB had a certain predictive value for non-thrombotic diseases, but the combined model had a low specificity, other information needs to be combined in the clinic to improve diagnostic accuracy.
Humans ; Fibrin Fibrinogen Degradation Products ; Retrospective Studies ; Fibrinogen ; Predictive Value of Tests ; Thrombosis ; Age Factors ; ROC Curve ; Male ; Female ; Middle Aged ; Adult

BACKGROUND: It remains unclear whether sleep duration and physical activity (PA) trajectories in middle-aged and older adults are associated with different risks of cardiovascular diseases (CVDs). This study aimed to explore the trajectories of total sleep duration and PA among middle-aged and older Chinese adults and their impact on CVD risk. METHODS: This study was based on the China Health and Retirement Longitudinal Study. 12009 adults aged 45 years and older from five waves were included. CVD events were measured by self-reports of heart disease and stroke. We first used group-based trajectory modeling to identify total sleep duration and PA trajectories from 2011 to 2020, and then employed logistic regression models to analyze their risk for CVD. RESULTS: We identified three sleep duration and PA trajectories. The risk of heart disease increased by 33% (OR = 1.31, 95% CI: 1.12-1.53) for the short sleep duration trajectory (vs. moderate sleep duration trajectory), by 40% (OR = 1.40, 95% CI: 1.06-1.84) for the high decreasing PA trajectory, and by 20% (OR = 1.20, 95% CI: 1.01-1.42) for the low stable PA trajectory (vs. high stable PA trajectory), respectively. Similar results for stroke and CVD as the outcomes were also observed, but the higher risk of stroke in the high decreasing PA trajectory group was not statistically significant. The joint effects of sleep and PA showed lower risks of heart disease and stroke in trajectories with moderate or long sleep duration and high stable PA compared with short sleep duration and a low stable PA trajectory. CONCLUSIONS Short total sleep duration, high decreasing PA, and low stable PA trajectories could increase the risk of CVDs among middle-aged and older adults. Long-term moderate to long total sleep durations and high stable PA trajectories might be optimal for preventing CVDs.

Objective To analyze the factors influencing the occupational health literacy (OHL) level among workers in key industries from the perspectives of both individual workers and enterprises. Methods A total of 32 336 front-line workers from 12 key industries in the secondary industry in Guangdong Province were selected as the research subjects by a stratified cluster random sampling method. Their OHL level was investigated using Occupational Health Literacy Questionnaire of National Key Populations, and the influencing factors were analyzed. Results The OHL level of the research subjects was 48.5%. The OHL level of the research subjects in four dimensions from high to low was basic knowledge of occupational health protection, occupational health practice and behavior, legal knowledge of occupational health, and basic skills of occupational health protection (80.7%, 61.2%, 48.3% and 29.5%, respectively). The multivariable logistic regression analysis showed that the OHL level of female workers was lower than that of males (P<0.05). Lower OHL was also associated with older age, lower education level, lower personal monthly income of workers (all P<0.01). The workers with length of service < 3 years and ≥ 20 years had lower OHL level than those with length of service 3-<10 years and 10-<20 years, respectively (all P<0.05). Workers in larger enterprises had higher OHL levels (all P<0.01). The OHL level of workers in the sixth category of industries with occupational injuries had higher occupational injury risks than those in the third and fourth categories (all P<0.05). The OHL levels of workers in state-owned enterprises, private enterprises, foreign-funded enterprises, and other enterprises were higher than that of workers in public institutions (all P<0.05). Conclusion The influencing factors of workers′ OHL in key industries of the secondary industry include individual factors (gender, age, education level, personal monthly income, length of service) and enterprise factors (enterprise size, enterprise nature and industry injury risk category). Female, older workers, those with lower education or income, and those with short length of service represent priority groups for OHL interventions, while small and micro enterprises are priority units for future workplace health promotion intervention.