ObjectiveTo investigate the mechanism by which Jianpi Xiao'ai prescription （JPXAP） inhibits colorectal cancer progression by regulating the inducible nitric oxide synthase-arginase 1 （iNOS-ARG1） metabolic axis and inducing mitochondrial reactive oxygen species （mito-ROS）-mediated mitochondrial structural and functional impairment. MethodsAn arginine metabolism disorder model of human colorectal cancer HCT116 cells was established by combined treatment with recombinant human interferon-γ （IFN-γ， 10 μg·L^-1） and N（ω）-hydroxy-L-arginine （Nor-NOHA， 200 μmol·L^-1） for 24 h， followed by intervention with 5%， 10%， or 20% JPXAP-containing serum. Cell proliferation was assessed using cell counting kit-8 （CCK-8）， 5-ethynyl-2′-deoxyuridine （EdU） staining， and colony formation assays. Cell invasion and migration were evaluated using Transwell chamber and wound healing assays. Mitochondrial membrane potential （MMP） and ROS levels were assessed by JC-1 and MitoSOX staining， respectively. Mitochondrial ultrastructure was observed by transmission electron microscopy （TEM）. The expression of iNOS， ARG1， and mitochondrial dynamics-related proteins， including mitofusin 2 （MFN2） and dynamin-related protein 1 （DRP1）， was analyzed by Western blot and immunofluorescence. The levels of L-arginine， citrulline， and urea were determined by colorimetric methods and enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the blank group， the model group exhibited significantly upregulated iNOS expression， downregulated ARG1 expression， a decreased ARG1/iNOS ratio， reduced L-arginine and urea levels， and increased citrulline levels （P<0.05）. Meanwhile， mito-ROS accumulation was significantly increased， the JC-1 red/green fluorescence ratio was decreased， and mitochondria showed swelling and cristae disruption， indicating that metabolic disorder induced mitochondrial injury. Compared with the model group， all JPXAP-treated groups further decreased the ARG1/iNOS ratio， enhanced nitric oxide （NO） and reactive nitrogen species accumulation， further reduced L-arginine and urea levels， and increased citrulline levels （P<0.01）. EdU-positive rate， colony formation rate， wound healing rate， and Transwell invasion number all decreased significantly with increasing serum concentration （P<0.01）. Mito-ROS levels were further elevated， and the JC-1 red/green ratio further decreased. TEM revealed aggravated mitochondrial swelling and vacuolization. MFN2 expression was downregulated and DRP1 expression was upregulated （P<0.01），in a dose-dependent manner. ConclusionJPXAP further activates NO-mediated oxidative/nitrosative stress under arginine metabolism imbalance， inducing mito-ROS accumulation， MMP collapse， and mitochondrial dynamics imbalance， thereby inhibiting colorectal cancer cell proliferation and migration. These findings reveal an antitumor mechanism of JPXAP based on coordinated targeting of the "metabolism-mitochondria" axis.

BACKGROUND: Physical activity, sedentary behavior (SB), and sleep duration are associated with brain health. Effects of those on developing Parkinson's disease (PD) are poorly investigated. This study aimed to examine the independent and joint associations of physical activity, SB, sleep with PD risk. METHODS: We analyzed data on 401,697 participants from the UK Biobank cohort, which was enrolled in 2006-2010. Physical activities were measured based on a questionnaire. Sleep and SB time were defined through self-reported total number of hours. Models fitted with restricted cubic spline were conducted to test for linear and non-linear shapes of each association. Cox proportional hazards regression models were used to estimate the association of three modifiable behaviors. RESULTS: Our analytic sample included 401,697 participants with 3030 identified cases of PD (mean age, 63 years; 62.9% male). PD risk was 18% lower in the high total physical activity group (95% CI, 0.75-0.90), 22% lower in the high leisure-time physical activity (LTPA) group (95% CI, 0.71-0.86) compared with the low level and 14% higher in the high sleep duration group (95% CI, 1.05-1.24) compared to moderate group. Total SB time was irrelevant with PD risk, while high TV viewing showed a 12% increase of PD risk compared to the low group (95% CI, 1.02-1.22). Low computer use (0 h/day) was associated with a 14% higher risk compared to 1 h/day use (95% CI, 1.04-1.26). Those associations were independent. A combination of 7 h/day sleep, moderate-to-high computer use, and moderate-to-vigorous intensity of LTPA showed lowest PD risk (HR, 0.70; 95% CI, 0.57-0.85). CONCLUSIONS Physical activity, SB, and sleep were associated with PD risks separately. Our findings emphasize the possibility for changing these three daily activities concurrently to lower the risk of PD. These findings may promote an active lifestyle for PD prevention.
Humans ; Parkinson Disease/physiopathology* ; Male ; Sedentary Behavior ; Female ; Middle Aged ; Exercise/physiology* ; Prospective Studies ; Sleep/physiology* ; Aged ; Surveys and Questionnaires ; Proportional Hazards Models ; Risk Factors

BACKGROUND: Neuroticism has been associated with numerous health outcomes. However, most research has focused on a single specific disorder and has produced controversial results, particularly regarding mortality risk. Here, we aimed to examine the association of neuroticism with morbidity and mortality and to elucidate how neuroticism affects trajectories from a healthy state, to one or more neuroticism-related disorders, and subsequent mortality risk. METHODS: We included 483,916 participants from the UK Biobank at baseline (2006-2010). Neuroticism was measured using the Eysenck Personality Questionnaire. Three clusters were constructed, including worry, depressed affect, and sensitivity to environmental stress and adversity (SESA). Cox proportional hazards regression and multistate models were used. Linear regression was used to examine the association between neuroticism and immune parameters and neuroimaging measures. RESULTS: High neuroticism was associated with 37 non-overlapping diseases, including increased risk of infectious, cardiometabolic, neuropsychiatric, digestive, and respiratory diseases, and decreased risk of cancer. After adjustment for sociodemographic variables, physical measures, healthy behaviors, and baseline diagnoses, moderate-to-high neuroticism was associated with a decreased risk of all-cause mortality. In multistate models, high neuroticism was associated with an increased risk of transitions from a healthy state to a first neuroticism-related disease (hazard ratio [HR] [95% confidence interval (CI)] = 1.09 [1.05-1.13], P  <0.001) and subsequent transitions to multimorbidity (1.08 [1.02-1.14], P  = 0.005), but was associated with a decreased risk of transitions from multimorbidity to death (0.90 [0.84-0.97], P for trend = 0.006). The leading neuroticism cluster showing a detrimental role in the health-illness transition was depressed affect, which correlated with higher amygdala volume and lower insula volume. The protective effect of neuroticism against mortality was mainly contributed by the SESA cluster, which, unlike the other two clusters, did not affect the balance between innate and adaptive immunity. CONCLUSION This study provides new insights into the differential role of neuroticism in health outcomes and into new perspectives for establishing mortality prevention programs for patients with multimorbidity.
Humans ; Neuroticism/physiology* ; Male ; Female ; Middle Aged ; Aged ; Proportional Hazards Models ; Surveys and Questionnaires ; Adult ; Risk Factors

Objective:To reveal the coupling mechanism of beam temporal profile and tissue oxygen content on radical kinetics, further explain the potential biological basis of the FLASH effect, and provide a reference for beam optimization and treatment planning design of FLASH radiotherapy (FLASH-RT).Methods:TOPAS-nBio v3.0 was used to simulate the physical and chemical processes of electron beams in water, and a full-scale kinetic model was established covering the generation, diffusion, reaction, and quenching of free radicals such as hydroxyl radical (·OH) and hydrated electrons (e aq-). Under different beam temporal profiles (single pulse, multi-pulses, continuous wave irradiation) and different oxygen concentration conditions, the evolution dynamics of free radicals were systematically simulated. At the same time, the data on e aq- content were obtained by experimental measurement of laser absorption spectroscopy to verify the accuracy of the model prediction. Results:The changing trend of e aq- concentration measured in the experiment was highly consistent with the simulation result, verifying the reliability of the constructed model. The beam time structure had a significant impact on the peak value and duration of free radical concentration. The single-pulse structure can cause the free radicals to rapidly increase and then quickly quench in a short time, while the continuous or long-pulse structure can cause the radical concentration to remain at a high level for a long time. The evolution of ·OH was not sensitive to the oxygen environment, while e aq- are greatly affected by the oxygen environment. The scavenging efficiency of free radicals in a hypoxic environment was significantly decreased, leading to an enhanced accumulation of oxidative damage to biological macromolecules. The lifespan of e aq- in an oxygen-rich environment decreased rapidly. Conclusions:Radical kinetics are regulated by both the beam temporal profile and oxygen content. FLASH-RT can utilize single-pulse or multi-pulses intervals to form periodic windows, reducing normal tissue damage by efficiently scavenging free radicals through antioxidants, while free radicals in tumor tissues continuously accumulate and amplify damage, thus generating a selective protective effect.

Objective:To investigate the relationship between lipid levels and cognitive impairment in the elderly Chinese population using prospective cohort data.Methods:Based on the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) cohort, this study included 24 380 individuals aged ≥60 years who participated in the cognitive function follow-up survey from 2018 to 2019. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with cognitive impairment defined according to different educational levels: MMSE ≤17 for illiterate individuals, MMSE ≤20 for those with primary education and MMSE ≤24 for those with secondary education or above. Multivariable linear regression and logistic regression models were employed to examine the associations between six baseline lipid indicators and cognitive scores, as well as cognitive impairment. Additionally, restricted cubic splines were used to explore the exposure-dose relationship between lipid levels and cognitive function.Results:The study population had a median follow-up time of 11.6 years, with a baseline age of (59.7±6.8) years. Among the participants, 9 510 (39.0%) were males, and the mean MMSE score was 24.7±6.8. A total of 3 887 individuals (15.9%) were identified as cognitively impaired. The results of multivariable linear regression and logistic regression indicated that total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were not only significantly positively associated with cognitive scores but also significantly associated with a lower risk of cognitive impairment. Each 1 mmol/L increase in these lipid levels corresponded to β values (95% CI) of 0.267 (0.173-0.361), 0.385(0.271-0.499) and 0.331(0.231-0.431), respectively. Each 1 mmol/L increase in these lipid levels corresponded to odds ratio ( OR) (95% CI) values of 0.915 (0.876-0.956), 0.875 (0.830-0.923) and 0.886 (0.848-0.927), respectively. The dose-response curve demonstrated that the negative association was primarily observed within the guideline-recommended optimal lipid level range. Specifically, when LDL-C was less than 3.4 mmol/L and non-HDL-C was less than 4.1 mmol/L, the corresponding OR (95% CI) values were 0.859 (0.796-0.926) and 0.876 (0.818-0.939). Conclusion:Lipid levels exhibit a certain linear negative association with cognitive impairment in elderly Chinese adults, with LDL-C and non-HDL-C demonstrating a stronger effect, particularly within the guideline-recommended optimal range.

To satisfy the growing healthcare demands of the public, it is essential to develop a public service platform for vaccination. This initiative aligns with national policies, optimizes resource allocation, innovates service models, enhances service efficiency, and reduces service costs. Drawing on relevant national policies and regulatory requirements, as well as the notable achievements and practical experiences gained through the exploration and innovation of vaccination service models across various regions, this paper proposes expert recommendations. It defines the essential components and functional specifications for public service platforms, focusing on public needs such as electronic vaccination record management, appointment management, the promotion of electronic vaccination certificates, vaccination certificate verification for school enrollment, vaccination site navigation, and science communication and public engagement. The recommendations aim to serve as a reference for the development of vaccination public service platforms nationwide.

Objectives:To explore the independent and combined effects of sleep duration and physical activity(PA)on the incidence of cardiovascular disease(CVD).Methods:The study subjects were derived from three sub-cohorts of the China-PAR project.Information on sleep and PA was collected from the surveys conducted in 2007-2008,and the incidence and mortality data of CVD were obtained during the follow-up survey from 2012 to 2015.Sleep duration was categorized into≤6 h/d,>6-8 h/d,and>8 h/d,and the PA level was classified according to the tertiles of PA volume(MET-h/d).The Cox proportional hazards model stratified by cohort source was applied to estimate the associations of PA and sleep duration with CVD incidence,coronary heart disease(CHD)incidence,and stroke incidence.Results:A total of 93 933 participants were included.During an average follow-up of(5.82±0.98)years,3 862 CVD events were documented.Compared with the low PA group,the hazard ratios(HRs)and 95%confidence intervals(CIs)of the CVD incidence,CHD incidence,and stroke incidence for the high PA group were 0.73(0.65-0.82),0.62(0.49-0.77)and 0.88(0.76-1.01),respectively.A U-shaped relation between sleep duration and incidence of CVD and stroke was observed.Compared with those who slept for>6-8 h/d,the risk of CVD(HR[95%CI]:1.10[1.00-1.21],P=0.04)and stroke(HR[95%CI]:1.33[1.18-1.49],P<0.01)was higher among participants slept>8 h/d.The risk of CVD,CHD and stroke tended to be higher in the≤6 h/d sleep group.Compared with the high PA combined with>6-8 h/d,the risk of stroke was highest in the high PA combined with>8h/d sleep group(HR[95%CI]:1.74[1.37-2.22],P<0.05),while the risks of CVD(HR[95%CI]:1.69[1.39-2.04],P<0.05)and CHD(HR[95%CI]:1.99[1.41-2.81],P<0.05)were highest in the low PA combined with≤6 h/d sleep group.Conclusions:Adequate physical activity and appropriate sleep duration are associated with lower risk of morbidity from CVD,CHD and stroke.

Objective To investigate the dosimetric effects of tumor treating fields(TTFields)patches on different radiotherapy modes for glioblastoma(GBM)patients who wear TTFields patches during radiotherapy,thereby providing dosimetric guidance for determining the appropriate radiotherapy mode.Methods With the TTFields data from GBM patients,artifact-free radiotherapy CT images were obtained utilizing 3D-printed TPU TTFields patches(3D-Print-TTFields)and anthropomorphic phantoms,and then a TTFields-synchronized radiotherapy image model was constructed.Furthermore,the treatment planning system was used to construct a dosimetric calculation model for TTFields-synchronized radiotherapy by simulating and fitting the ray attenuation rate of TTFields patches measured by accelerators.Using these models,3 kinds of radiotherapy plans were simulated and developed.Specifically,P1 simulated the conventional radiotherapy mode;P2 simulated the TTFields-combined radiotherapy mode(TTF-Com-RT),in which patients underwent radiotherapy using the P1 plan while wearing TTFields patches;and P3 simulated the TTFields-synchronized radiotherapy(TTF-Syn-RT)mode where the TTFields patches were worn throughout the entire radiotherapy process.The paired t-test was used to analyze dosimetric parameters such as target dose(D95),average scalp dose(D-skin),conformity index(CI)and homogeneity index(HI)in 3 plans(P1,P2,and P3),as well as the D95 and D-skin parameters for intensity-modulated radiotherapy(IMRT)and volumetric modulated arc therapy(VMAT)techniques in the P3 plan.Results The D95 simulated by P2 decreased by 1.35%as compared with P1(P<0.05),and the D95 simulated by P3 was 1.31%higher than that in P2(P<0.05).Compared with P1,P2 and P3 increased the D-skin by 12.56%and 14.30%,respectively(P<0.05),and the D-skin simulated by P3 increased by 1.55%as compared with P2(P<0.05).However,there were trivial differences in D95 between P3 and P1,CI and HI among all plans,D95 and D-skin between IMRT and VMAT techniques in P3 plan(P>0.05).Conclusion Based on GBM patient data,CT simulation images obtained from 3D-Print-TTFields combined with anthropomorphic phantom are artifact-free and meet radiotherapy requirements.The target and scalp dose differences between TTF-Com-RT and TTF-Syn-RT are less than 2%,and the dosimetric difference of TTF-Syn-RT using IMRT/VMAT techniques is insignificant.Therefore,clinicians can choose radiotherapy modes and techniques according to actual needs.

Objectives:To explore the independent and combined effects of sleep duration and physical activity(PA)on the incidence of cardiovascular disease(CVD).Methods:The study subjects were derived from three sub-cohorts of the China-PAR project.Information on sleep and PA was collected from the surveys conducted in 2007-2008,and the incidence and mortality data of CVD were obtained during the follow-up survey from 2012 to 2015.Sleep duration was categorized into≤6 h/d,>6-8 h/d,and>8 h/d,and the PA level was classified according to the tertiles of PA volume(MET-h/d).The Cox proportional hazards model stratified by cohort source was applied to estimate the associations of PA and sleep duration with CVD incidence,coronary heart disease(CHD)incidence,and stroke incidence.Results:A total of 93 933 participants were included.During an average follow-up of(5.82±0.98)years,3 862 CVD events were documented.Compared with the low PA group,the hazard ratios(HRs)and 95%confidence intervals(CIs)of the CVD incidence,CHD incidence,and stroke incidence for the high PA group were 0.73(0.65-0.82),0.62(0.49-0.77)and 0.88(0.76-1.01),respectively.A U-shaped relation between sleep duration and incidence of CVD and stroke was observed.Compared with those who slept for>6-8 h/d,the risk of CVD(HR[95%CI]:1.10[1.00-1.21],P=0.04)and stroke(HR[95%CI]:1.33[1.18-1.49],P<0.01)was higher among participants slept>8 h/d.The risk of CVD,CHD and stroke tended to be higher in the≤6 h/d sleep group.Compared with the high PA combined with>6-8 h/d,the risk of stroke was highest in the high PA combined with>8h/d sleep group(HR[95%CI]:1.74[1.37-2.22],P<0.05),while the risks of CVD(HR[95%CI]:1.69[1.39-2.04],P<0.05)and CHD(HR[95%CI]:1.99[1.41-2.81],P<0.05)were highest in the low PA combined with≤6 h/d sleep group.Conclusions:Adequate physical activity and appropriate sleep duration are associated with lower risk of morbidity from CVD,CHD and stroke.

Objective:The 5th edition of the WHO classification of central nervous system (CNS) tumors in 2021 made significant revisions to the nomenclature and grading system of solitary fibrous tumors (SFT). This study aimed to explore the changes in the grading of CNS SFT and its relationship with clinical pathological features and prognosis.Methods:This study retrospectively reviewed the clinical and pathological data of 82 patients with CNS SFT diagnosed at the First Affiliated Hospital of Fujian Medical University from March 2006 to June 2021, reassessed their grading according to the WHO 5th edition CNS tumor classification, and conducted a comprehensive analysis of their histological morphology, immunohistochemical characteristics, and clinical imaging data.Results:The age of the patients ranged from 21 to 83 years, with a median age of 48 years. Follow-up was completed for 82 patients, during which 10 patients died, 24 recurred, and 5 metastasized. MRI imaging showed that SFT exhibited isointense signals on T1-weighted imaging (T1WI) and complex signals on T2-weighted imaging (T2WI), with signal intensity decreasing as the content of collagen fibers increased. According to the 2021 grading criteria, there was a significant change in the grading of SFT, with the number of grade 1 SFT increasing from 10 cases under the 2016 standard to 39 cases, while the number of grade 2 and 3 SFT decreased accordingly. The 2016 grading system was significantly correlated with the overall survival (OS) of patients ( P=0.009), while the 2021 grading system did not reach statistical significance. Both grading systems were correlated with histological phenotype, Ki-67 index, mitotic figures, and necrosis ( P＜0.05). All cases expressed STAT6, and showed varying degrees of expression of vimentin, CD99, BCL-2, and CD34. The staining intensity of type Ⅳ collagen fibers, as analyzed semi-quantitatively, was correlated with the OS of the patients ( P=0.017). Conclusions:The new grading system for CNS SFT has undergone significant changes, and its association with OS requires further validation. In-depth study of the content and fine structure of collagen fibers in SFT may have important clinical significance for the prognosis assessment and the formulation of treatment plans for patients. Moreover, quantitative analysis of T2WI signal intensity may provide a new method for preoperative preliminary assessment of the collagen fiber content in SFT.