ObjectiveThis study aims to investigate the effect of Dictamni Cortex on intestinal barrier damage in rats and its mechanism by untargeted metabolomics and targeted metabolomics for short-chain fatty acids （SCFAs）. MethodsRats were randomly divided into a control group， a high-dose group of Dictamni Cortex （8.1 g·kg^-1）， a medium-dose group （2.7 g·kg^-1）， and a low-dose group （0.9 g·kg^-1）. Except for the control group， the other groups were administered different doses of Dictamni Cortex by gavage for eight consecutive weeks. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in the ileal tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to detect the level of cytokines， including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）， in the ileal tissue of rats. Quantitative real-time fluorescence polymerase chain reaction （Real-time PCR） technology was used to detect the expression level of tight junction proteins， including zonula occludens-1 （ZO-1）， Occludin， and Claudin-1 mRNAs， in the ileal tissue of rats to preliminarily explore the effects of Dictamni Cortex on intestinal damage. The dose with the most significant toxic phenotype was selected to further reveal the effects of Dictamni Cortex on the metabolic profile of ileal tissue in rats by non-targeted metabolomics combined with targeted metabolomics for SCFAs. ResultsCompared with the control group， all doses of Dictamni Cortex induced varying degrees of pathological damage in the ileum， increased TNF-α （P<0.01）， IL-6 （P<0.01）， and IL-1β （P<0.01） levels in the ileal tissue， and decreased the expression level of ZO-1 （P<0.05， P<0.01）， Occludin （P<0.01）， and Claudin-1 （P<0.05） in the ileal tissue， with the high-dose group showing the most significant toxic phenotypes. The damage mechanisms of the high-dose group of Dictamni Cortex on the ileal tissue were further explored by integrating non-targeted metabolomics and targeted metabolomics for SCFAs. The non-targeted metabolomics results showed that 21 differential metabolites were identified in the control group and the high-dose group. Compared with that in the control group， after Dictamni Cortex intervention， the level of 14 metabolites was significantly increased （P<0.05， P<0.01）， and the level of seven metabolites was significantly decreased （P<0.05， P<0.01） in the ileal contents. These metabolites collectively acted on 10 related metabolic pathways， including glycerophospholipids and primary bile acid biosynthesis. The quantitative data of targeted metabolomics for SCFAs showed that Dictamni Cortex intervention disrupted the level of propionic acid， butyric acid， acetic acid， caproic acid， isobutyric acid， isovaleric acid， valeric acid， and isocaproic acid in the ileal contents of rats. Compared with those in the control group， the level of isobutyric acid， isovaleric acid， and valeric acid were significantly increased， while the level of propionic acid， butyric acid， and acetic acid were significantly decreased in the ileal contents of rats after Dictamni Cortex intervention （P<0.05， P<0.01）. ConclusionDictamni Cortex can induce intestinal damage by regulating glycerophospholipid metabolism， primary bile acid biosynthesis， and metabolic pathways for SCFAs.

Objective To investigate the expansion margins of the planning target volume (PTV) and the planning organ at risk volume (PRV) in nasopharyngeal carcinoma patients immobilized with Styrofoam and head-neck-shoulder mask. Methods A convenient sample of 33 nasopharyngeal carcinoma patients who received radiotherapy at Huanggang Central Hospital from January to October 2024 were selected as the research subjects. All patients underwent cone beam CT scans during the first three treatments and weekly thereafter. After registration and calibration, the setup errors in the X (LAT), Y (LNG), and Z (VRT) directions were recorded. Statistical analysis was performed on the setup errors in each direction to determine differences, and the expansion margins for PTV and PRV were calculated using empirical formulas. Results A total of 229 cone beam CT images were collected. Statistical analysis found that the setup errors (systematic error ± random error) of the patients in the X, Y, and Z directions were 1.05 ± 0.72, 1.30 ± 0.80, and 1.29 ± 0.82 mm, respectively. The expansion margins for PTV in the left-right, superior-inferior, and anterior-posterior directions were 1.40, 1.76, and 1.8 mm, respectively. The expansion margins for PRV in these directions were 0.83, 1.02, and 1.05 mm, respectively. Conclusion For patients immobilized using Styrofoam and head-neck-shoulder mask, it is recommended that the expansion margins for PTV and PRV be set at 2 mm and 1 mm, respectively, in the left-right, superior-inferior, and anterior-posterior directions, and the PRV margin for the spinal cord be set at 3 mm in all directions.

Fabry disease, a rare genetic disorder affecting multiple organs, has understudied correlations among enzyme activity, genotype, and clinical manifestations in patients of different sexes with classical and late-onset phenotypes. In this study, clinical data, α-Gal A activity, and GLA gene test results of 311 patients, who were categorized by classical and late-onset phenotypes, ⩽5% and > 5% of the normal mean value of enzyme activity, and truncated and nontruncated mutation groups, were collected. The common clinical manifestations of Fabry disease included acroparesthesia, hypohidrosis/anhidrosis, neuropsychiatric system, and renal and cardiovascular involvement. Multiorgan involvement was higher in males and classical phenotype patients. In both sexes, classical patients commonly presented with acroparesthesia and multiorgan involvement, whereas late-onset patients showed renal, neuropsychiatric, and cardiovascular involvement. Male and classical patients had lower enzyme activity than female and late-onset patients, respectively. Classical males with enzyme activity of ⩽5% of the normal mean level showed higher multiorgan involvement frequency than those with enzyme activity of > 5%, whereas no significant difference was observed among females. Ninety-five gene mutation sites were detected, with significant phenotype heterogeneity in patients with the same mutation. No significant difference in enzyme activity or clinical manifestations was observed between truncated and nontruncated mutations. Overall, male patients with Fabry disease, regardless of classical or late-onset phenotype, have a higher frequency of multiple-organ involvement and lower α-Gal A activity than female patients. α-Gal A activity was closely correlated with clinical symptoms in males but weakly correlated with clinical manifestations in females. The clinical manifestations of patients with the same mutation are heterogeneous, and the correlation between gene mutation and enzyme activity or clinical manifestation is weak.
Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Age of Onset ; alpha-Galactosidase/metabolism* ; China ; Fabry Disease/enzymology* ; Genotype ; Mutation ; Phenotype ; Sex Factors ; East Asian People/genetics*

Objective:Drug safety assessments based on real-world data are often challenged by both treatment switching and rare events. In this study, we used statistical simulations to investigate the effects of switching rates and treatment effects on the statistical performance of commonly used analytical strategies and methods under overlapping scenarios of treatment switching and rare events.Methods:The simulation scenario was set up as a bidirectional treatment switching (allowing the control group to switch to the treatment group and the treatment group to switch to the control group), and the event rates were set at approximately 2%, 5%, and 20%. Different simulation scenarios were generated with sufficient sample size to consider switching rate and relative treatment effect. The simulated datasets were analyzed using three types of analysis strategy, i.e. intention to treat (ITT), per protocol (PP), and as treated (AT). The performance of five indicators, namely percentage bias, mean square error, empirical standard error, coverage, and rejection rate, were compared among the different methods in different scenarios, and recommendations for method selection were given.Results:In terms of analytical strategies and methods, AT analysis were relatively optimal in terms of percentage bias and accuracy, followed by PP analysis and ITT analysis. When the relative treatment effects converged (e.g. HR=1.0), both the ITT analysis and the time-dependent AT approaches (marginal structural model, time-dependent Cox regression model or time-dependent propensity score matching) performed well; when the relative treatment effects were small (e.g. HR=0.8), the marginal structural model was the most optimal; when the relative treatment effects were large (e.g. HR=0.6 or 0.4), the approaches of using a censored treatment for switchers in the AT analysis were more accurate. In addition, the time-dependent AT approaches had the highest rejection rate when there was a difference in treatment effect between the two groups, and the ITT analysis had the lowest rejection rate. Conclusions:For the dual challenges of bidirectional switching and rare events in real-world drug safety evaluations, adequate sample size is a prerequisite for accurate estimation of treatment effects, while switching rates and effect sizes of switched drugs might also affect estimation accuracy. Appropriate strategies and methods should be selected for the analysis. It is necessary to consider whether the event is rare or not, the switching rate and the expected treatment effect size of the two types of treatment to select appropriate analysis strategies and methods.

Objective To investigate the diagnostic value of transforming growth factor-β1(TGF-β1),cal-granulin A8(S100-A8)and interleukin-17(IL-17)in spinal tuberculosis and their relationship with erythro-cyte sedimentation rate(ESR)and C-reactive protein(CRP).Methods A total of 103 patients diagnosed with spinal tuberculosis in the Second Hospital of Lanzhou University from July 2017 to December 2023 were se-lected as the study group,and 109 healthy people were selected as the control group during the same period.The general data of the two groups were collected,and the levels of TGF-β1,S100-A8,IL-17,ESR and CRP were compared between the two groups.The receiver operating characteristic(ROC)curve was used to ana-lyze the diagnostic value of TGF-β1,S100-A8 and IL-17 for spinal tuberculosis.Pearson correlation analysis was used to study the correlation between the levels of TGF-β1,S100-A8,IL-17 and ESR,CRP in patients with spinal tuberculosis.Results The proportion of hypertension and tuberculosis in the study group was higher than that in the control group(P<0.05),and there was no significant difference in other indicators between the two groups(P>0.05).Compared with the control group,the levels of TGF-β1,S100-A8,IL-17,ESR and CRP in the study group were increased(P<0.05).The levels of TGF-β1,S100-A8 and IL-17 were positively correlated with ESR and CRP(P<0.05).ROC curve analysis showed that the area under the curve,sensitivi-ty and specificity of TGF-β1,S100-A8 and IL-17 in the diagnosis of spinal tuberculosis were 0.907,97.1%and 74.3%,respectively,and the diagnostic efficiency was high.Conclusion The combination of TGF-β1,S100-A8 and IL-17 has a better diagnostic efficacy,and it is positively correlated with ESR and CRP in patients with spinal tuberculosis.

Background and Aims:Tumor deposits(TDs)may influence prognosis beyond the current 8th edition AJCC pTNM nodal classification in gastric cancer(GC).This study investigates the prognostic value of TD number and proposes an improved pN staging(mpN)that classifies patients with TD number>1 as pN3b.We validated the mpN staging against the 8th AJCC pN staging.Methods:A dual-center retrospective cohort study was performed,including 1 327 patients who underwent radical gastrectomy at Sun Yat-sen University Cancer Center(2011-2015;test cohort)and 340 patients from Guangdong Provincial People's Hospital(2015-2022;validation cohort).Patients were dichotomized into low-TD(≤1)and high-TD(>1)groups.Outcomes were overall survival(OS)and disease-free survival(DFS).Survival analyses used Kaplan-Meier curves,IPTW,and Cox regression.Predictive performance of staging systems was assessed by time-dependent ROC(tROC)/tAUC,concordance index(C-index)and Akaike information criterion(AIC).Results:TDs were present in 435/1 327(32.7%)in the test cohort.Presence of TD was associated with worse OS(IPTW-adjusted HR=2.69,95%CI=2.18-3.31,P<0.01)and DFS(HR=2.82,95%CI=2.32-3.42,P<0.01).In multivariable models,TD remained an independent adverse factor for OS(HR=1.65,95%CI=1.34-2.05;P<0.01)and DFS(HR=1.74,95%CI=1.43-2.11,P<0.01).Increasing TD number correlated with progressively poorer survival;X-tile identified>1 as an optimal cutoff,with high-TD patients showing markedly worse outcomes(OS:adjusted HR=3.65,95%CI=2.74-4.88;DFS:adjusted HR=3.74,95%CI=2.85-4.91;both P<0.01).Incorporation of TD number into the mpN staging(assigning TD>1 to pN3b)improved prognostic discrimination:in the test cohort 5-year OS tAUC was 0.746 for mpN vs.0.703 for AJCC pN(C-index 0.738 vs.0.721,AIC 5 805.27 vs.5 849.30);similar improvements were observed in the validation cohort.Conclusion:TD presence and number exert significant negative prognostic impact in GC.Classifying patients with TD number>1 as pN3b enhances prognostic accuracy.Routine reporting of TD counts and further prospective multicenter validation of mpN staging are warranted.

Oral and maxillofacial CBCT(cone beam computed tomography)as a kind of oral imaging techniques,can accurately show the tooth pulp in an all-round way.Especially for showingthe morphologyof special root canals,it has incomparable advantages over two-dimensional X ray film.With the development of digital technology and artificial intelligence technology,CBCT has been widely used in stomatology.In this paper,we will systematically review the applicationprogress of CBCT combined with oral digital technology and arti-ficial intelligence technology,with a view to providing references for clinical diagnosis and treatmentand technical development of the discipline.

Objective:Drug safety assessments based on real-world data are often challenged by both treatment switching and rare events. In this study, we used statistical simulations to investigate the effects of switching rates and treatment effects on the statistical performance of commonly used analytical strategies and methods under overlapping scenarios of treatment switching and rare events.Methods:The simulation scenario was set up as a bidirectional treatment switching (allowing the control group to switch to the treatment group and the treatment group to switch to the control group), and the event rates were set at approximately 2%, 5%, and 20%. Different simulation scenarios were generated with sufficient sample size to consider switching rate and relative treatment effect. The simulated datasets were analyzed using three types of analysis strategy, i.e. intention to treat (ITT), per protocol (PP), and as treated (AT). The performance of five indicators, namely percentage bias, mean square error, empirical standard error, coverage, and rejection rate, were compared among the different methods in different scenarios, and recommendations for method selection were given.Results:In terms of analytical strategies and methods, AT analysis were relatively optimal in terms of percentage bias and accuracy, followed by PP analysis and ITT analysis. When the relative treatment effects converged (e.g. HR=1.0), both the ITT analysis and the time-dependent AT approaches (marginal structural model, time-dependent Cox regression model or time-dependent propensity score matching) performed well; when the relative treatment effects were small (e.g. HR=0.8), the marginal structural model was the most optimal; when the relative treatment effects were large (e.g. HR=0.6 or 0.4), the approaches of using a censored treatment for switchers in the AT analysis were more accurate. In addition, the time-dependent AT approaches had the highest rejection rate when there was a difference in treatment effect between the two groups, and the ITT analysis had the lowest rejection rate. Conclusions:For the dual challenges of bidirectional switching and rare events in real-world drug safety evaluations, adequate sample size is a prerequisite for accurate estimation of treatment effects, while switching rates and effect sizes of switched drugs might also affect estimation accuracy. Appropriate strategies and methods should be selected for the analysis. It is necessary to consider whether the event is rare or not, the switching rate and the expected treatment effect size of the two types of treatment to select appropriate analysis strategies and methods.

Objective To explore the influencing factors of frailty among the health check-up elder-ly participants from our outpatient clinic.Methods A total of 710 elderly individuals(≥60 years old)who taking health check-up in our outpatient department between April and August 2022 were consecutively enrolled,and according to the results of Fried Frailty Phenotype Scale,they were divided into non-frailty group(422 cases),pre-frailty group(225 cases)and frailty group(63 cases).Their general clinical data,laboratory indicators and echocardiographic parameters were collected,and multivariate logistic regression analysis was applied to identify the independent in-fluencing factors for pre-frailty and frailty.Results The overall prevalence of pre-frailty and frail-ty was 31.7％and 8.9％,respectively.The pre-frailty and frailty groups had obviously larger left atrial anterior-posterior diameter and left ventricular end diastolic diameter and lower left ventric-ular ejection fraction when compared with the non-frailty group(P＜0.05).Multivariate logistic regression analysis showed that Hb was a protective factor for pre-frailty in the elderly partici-pants(OR=0.984,95％CI:0.966-0.992,P=0.048),while age(OR=1.064),CCI(OR=1.387)and LAAP(OR=1.059)were risk factors for pre-frailty in them(P＜0.05,P＜0.01).Serum albumin was a protective factor for frailty(OR=0.823,95％CI:0.728-0.931,P=0.002),but age(OR=1.081),CCI(OR=1.458),left atrial anterior-posterior diameter(OR=1.249)and NT-proBNP(OR=1.652)were independent risk factors for frailty(P＜0.05,P＜0.01).Conclusion There are differences in influencing factors for frailty of different severity,and the status of frailty is related to factors such as age,comorbidity,cardiac function and nutritional sta-tus.Therefore,comprehensive interventions should be implemented as early as possible for the elderly occurrence of pre-frailty so as to prevent and reverse frailty at the same time.

Background and Aims:Tumor deposits(TDs)may influence prognosis beyond the current 8th edition AJCC pTNM nodal classification in gastric cancer(GC).This study investigates the prognostic value of TD number and proposes an improved pN staging(mpN)that classifies patients with TD number>1 as pN3b.We validated the mpN staging against the 8th AJCC pN staging.Methods:A dual-center retrospective cohort study was performed,including 1 327 patients who underwent radical gastrectomy at Sun Yat-sen University Cancer Center(2011-2015;test cohort)and 340 patients from Guangdong Provincial People's Hospital(2015-2022;validation cohort).Patients were dichotomized into low-TD(≤1)and high-TD(>1)groups.Outcomes were overall survival(OS)and disease-free survival(DFS).Survival analyses used Kaplan-Meier curves,IPTW,and Cox regression.Predictive performance of staging systems was assessed by time-dependent ROC(tROC)/tAUC,concordance index(C-index)and Akaike information criterion(AIC).Results:TDs were present in 435/1 327(32.7%)in the test cohort.Presence of TD was associated with worse OS(IPTW-adjusted HR=2.69,95%CI=2.18-3.31,P<0.01)and DFS(HR=2.82,95%CI=2.32-3.42,P<0.01).In multivariable models,TD remained an independent adverse factor for OS(HR=1.65,95%CI=1.34-2.05;P<0.01)and DFS(HR=1.74,95%CI=1.43-2.11,P<0.01).Increasing TD number correlated with progressively poorer survival;X-tile identified>1 as an optimal cutoff,with high-TD patients showing markedly worse outcomes(OS:adjusted HR=3.65,95%CI=2.74-4.88;DFS:adjusted HR=3.74,95%CI=2.85-4.91;both P<0.01).Incorporation of TD number into the mpN staging(assigning TD>1 to pN3b)improved prognostic discrimination:in the test cohort 5-year OS tAUC was 0.746 for mpN vs.0.703 for AJCC pN(C-index 0.738 vs.0.721,AIC 5 805.27 vs.5 849.30);similar improvements were observed in the validation cohort.Conclusion:TD presence and number exert significant negative prognostic impact in GC.Classifying patients with TD number>1 as pN3b enhances prognostic accuracy.Routine reporting of TD counts and further prospective multicenter validation of mpN staging are warranted.