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:For thoracolumbar spine fractures with developmental stenosis of the vertebral arch,accurate nail placement is difficult using traditional fluoroscopy-assisted techniques.O-arm navigation assistance systems offer higher precision in general vertebral arch nail placement,but there is scarce literature on the application of O-arm navigation-assisted nail placement in thoracolumbar spine fractures with developmental stenosis of the vertebral arch both domestically and abroad. OBJECTIVE:To explore the accuracy of percutaneous vertebral arch nail placement assisted by O-arm navigation in patients with thoracolumbar spine fractures complicated by developmental stenosis of the vertebral arch. METHODS:A retrospective analysis was conducted on 53 patients who underwent percutaneous vertebral arch screw fixation surgery at Department of Orthopedics,General Hospital of Central Theater Command of PLA for thoracolumbar spine fractures complicated by developmental stenosis of the vertebral arch from January 2021 to March 2023.Totally 208 cases of vertebral arch developmental stenosis were found(cases with multiple vertebral arch developmental stenosis were counted separately).Based on the surgical approach,the patients were divided into two groups:O-arm navigation group(n=98)and C-arm fluoroscopy group(n=110).Postoperative imaging data were compared between the two groups,including anatomical perforation score,functional perforation score,actual vs.expected nail trajectory in the horizontal plane,and sagittal plane angle differences. RESULTS AND CONCLUSION:(1)There was no significant difference in the narrowest width of the pedicle isthmus(pow)between the two groups of patients(P>0.05).The proportions of different degrees of narrowing(mild:6 mm≤pow<7 mm,moderate:5 mm≤pow<6 mm,severe:pow<5 mm)were also not significantly different between the two groups(P>0.05).(2)The overall grade and scores of anatomical perforation and functional perforation were lower in the O-arm group compared to the C-arm group,and these differences were statistically significant(P<0.001).In terms of the angular deviation between the actual and planned screw trajectories,the O-arm group had smaller deviations,and these differences were statistically significant(P<0.05).(3)In the mild and moderate narrowing groups,the O-arm group showed significant advantages in anatomical perforation,functional perforation,and angular deviation between actual and planned screw trajectories,and these differences were statistically significant(P<0.001).(4)The O-arm group demonstrated better performance in anatomical perforation and functional perforation,especially in the T12-L2 segment,with more significant advantages.Additionally,the O-arm group had better angular deviations in actual and planned screw trajectories in all segments compared to the C-arm group.(5)Therefore,the use of O-arm navigation-assisted percutaneous screw placement for the treatment of thoracolumbar fractures with developmental pedicle isthmal narrowing provides higher accuracy and safer surgery.

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional

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:To detect the levels of sex hormones and insulin in follicular fluid(FF)and the expression level of phosphatase and tensin homolog deleted on chromosome ten(PTEN)in granulosa cells in the infertile patients with polycystic ovary syndrome(PCOS),and to preliminarily explain the correlations between the insulin level and the expression level of PTEN mRNA.Methods:Seventy infertile patients were selected as the subjects and divided into PCOS group and control group(tubal obstruction or infertility due to male factors)according to infertility factors.All patients received in vitro fertilization-embryo transfer(IVF-ET)treatment.FF and ovarian granulosa cells were collected on the day of ovulation.The expression levels of PTEN mRNA in ovarian granulosa cells of the patients in two groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.The levels of sex hormone and insulin in FF were measured by electrochemiluminescence.The correlations of the PTEN mRNA expression level in ovarian granulosa cells and testosterone(T)in FF with the level of insulin in FF were analyzed by Spearman correlation analysis method.Results:There were no significant differences in age,infertility years,body mass index(BMI),basic sex hormone,total dose of gonadotropin(Gn)and days of ovulation induction in two groups(P＞0.05).Compared with control group,the anti-Mullerian hormone(AMH)and antral follicle counting(AFC)of the patients in PCOS group were significantly increased(P＜0.05).The RT-qPCR results showed that the PTEN mRNA expression level in ovarian granulosa cells of the patients in the PCOS group was higher than that in control group(P＜0.001).The electrochemiluminescence results showed that the levels of T and insulin in FF of the patients in PCOS group were higher than those in control group(P＜0.05),whereas the estrogen and progesterone levels were lower than those in control group(P＜0.05).The Spearman correlation analysis showed that that T level in FF was positively correlated with the insulin level of the patients in PCOS group(r=0.577,P＜0.001),and the PTEN mRNA expression level in ovarian granulosa cells was positively correlated with the insulin levels in FF(r=0.616,P＜0.001);in control group,there was no correlation between T level and insulin level in FF(r=0.266,P=0.123),and there was no correlation between the expression level of PTEN mRNA in granulosa cells and the insulin level in FF in control group(r=-0.214,P=0.216).Conclusion:The high expression of PTEN in granulosa cells of the infertile patients with PCOS may be related to the local hyperinsulin level in the ovary,and PTEN participates in the occurrence and development of PCOS.

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 investigate the effect of triply periodic minimal surfaces (TPMS) structure and ceramic volume fraction on the mechanical properties of polymer-infiltrated ceramic network (PICN) composite and reveal its strengthening and toughening mechanism.Methods:In this study, TPMS structures with gyroid (G), primitive (P), diamond (D), and ceramic volume fraction (40%, 55%, 70%, 85%) were designed. Porous zirconia scaffolds were prepared using stereolithography technology, and resin was infiltrated into the scaffolds through a vacuum. Then, the PICN composites were obtained after curing. The bending strength, elastic modulus and fracture toughness of PICN were tested using an electronic universal testing machine, with commercial PICN as the control group. The micromorphology of PICN was observed through stereomicroscope and scanning electron microscope. The cytocompatibility of PICN was verified by using cell counting kit, live/dead cell staining and phalloidin staining.Results:The bending strength values of PICN with different ceramic volume fractions ranged from 82.0 MPa to 376.0 MPa, and they gradually increased as the ceramic volume fraction rised. The elastic modulus values of PICN with different ceramic volume fractions ranged from 12.1 GPa to 56.1 GPa. The fracture toughness values of PICN with different ceramic volume fractions ranged from 1.7 MPa·m 1/2 to 6.5 MPa·m 1/2. The bending strength of 85G PICN reached 306.0 MPa, and it had the highest fracture toughness (6.5 MPa·m 1/2) and an appropriate elastic modulus between that of the control group and that of enamel. Under scanning electron microscopy, it could be observed that the cracks branch and deflect at the interface and eventually terminate within the resin phase. After co-culture with PICN, the survival rate of mouse fibroblasts exceeded 80%, indicating that PICN had no cytotoxicity. Conclusions:The PICN composite with TPMS structure can satisfy the mechanical properties and cytocompatibility of dental prosthesis.

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.