BACKGROUND:In orthodontic treatment,full-mouth treatment is usually used to treat single-root severely twisted teeth,and single-tooth treatment is less common.OBJECTIVE:To design a personalized orthodontic device based on biomechanical principles to address the rotation of teeth 11,12,13,21,22,and 23,and evaluate the device's impact on tooth movement using three-dimensional finite element method.METHODS:Based on the biomechanical principle of tooth rotation and movement,a personalized orthodontic device was made by digital design combined with three-dimensional printing,so that the personalized orthodontic device and the tooth formed an anchorage system.The absolute anchorage of the micro-implant was used to precisely control the single-root twisted tooth in the three-dimensional direction.The CBCT data of the maxillary alveolar bone and tooth tissue of a female volunteer were collected.The three-dimensional finite element models of the twisted tooth-periodontal ligament-maxillary bone-personalized orthodontic device were established using Mimics,Geomagic Wrap,SolidWorks,3-matic Research 15.0,and Ansys Workbench software.The equivalent stress distribution characteristics of the personalized orthodontic device,the movement trend of the tooth,and the equivalent stress distribution characteristics of the periodontal ligament were calculated under a thrust of 60 g.RESULTS AND CONCLUSION:(1)The maximum equivalent stress observed on the personalized orthodontic device was 47.71 MPa.(2)The initial tooth displacement under the device demonstrated a rotational trend.The peak equivalent stress in the periodontal ligament was concentrated at the neck,while lower stress was observed in the apex region.(3)The safety and feasibility of the personalized orthodontic device designed in this study for severely rotated single-rooted teeth were preliminarily verified through finite element analysis.

Objective To explore the regularity of prescriptions for epidemic disease in Taiping Huimin Heji Ju Fang based on the latent structure model and association rules analysis,and to provide references for modern epidemic treatment.Methods Prescriptions for epidemic diseases were extracted from Taiping Huimin Heji Ju Fang.A high-frequency herb matrix(frequency≥10)was constructed,and high-frequency herbs were analyzed using MicrosoftExcel 2016,Lantern 5.0,and IBM SPSS Modeler 18.0 for efficacy classification,property/flavor/channel tropism statistics,latent structure modeling,and association rule analysis.Results Among the 200 collected herbal prescriptions,46 high-frequency medicinal materials were identified,such as licorice,fresh ginger,dried ginger,poriae,and ginseng.The top 3 drugs efficacy were tonifying deficiency,relieving surface and warming inner.The medicinal properties were mainly warm,and the medicinal flavors were pungent,bitter,and sweet.The meridian tropisms mainly included the spleen meridian,lung meridian and stomach meridian.The analysis of latent structure model suggested that there were 8 types of common symptoms of epidemic disease,such as wind evil attack exterior,wind-cold-dampness,wind-heat,excess-heat in triple energizer,dampness inhibits qi stagnation,yang deficiency,blockage and spleen-qi deficiency.Theanalysis of association rules obtained licorice-ephedra and licorice-atractylodes,which with a core of licorice medicine,and the 16 association rules such as dried ginger-cinnamon,pericarpium citri reticulatae-mangnolia officinalis and poriae-ginseng-atractylodes macrocephala after eliminating ginger,jujube and licorice.Conclusion Most of the medicines used in the treatment of epidemic diseases in Taiping Huimin Heji Ju Fang are pungent,bitter and dispelling evil,the treatment should follow the principle of dispelling evil,warming yang to dissipate cold,dispelling dampness,clearing heat and expelling fire,inducing resuscitation,supporting the right and supplementing deficiency,which embodies the treatment principle of dispelling evil and supporting right,and provides reference and ideas for the treatment of clinical diseases based on syndrome differentiation.

BACKGROUND:The elastic modulus of traditional solid titanium alloy implants is higher than that of human bone,and the resulting"stress shielding"phenomenon may affect the osseointegration of implants.Simultaneously,the wettability of 3D printed titanium alloy surface needs to be improved.OBJECTIVE:To prepare hydrophilic Gyroid implants with excellent biomechanical properties.METHODS:The 3D models of Gyroid implant,solid implant,mandibular bone and crown were established,and the mechanical properties of different implants were analyzed by finite element analysis.The Gyroid structure implant model was imported into the 3D printer to make the Gyroid structure implant materialized,and then the hydrophilic Gyroid structure implant with excellent mechanical properties and surface activity was prepared by sandblasting acid etching and ultraviolet functionalization.The morphology and hydrophilicity of 3D printed Ti6Al4V specimens before and after surface modification were analyzed by scanning electron microscopy and contact angle test.RESULTS AND CONCLUSION:(1)The finite element analysis results showed that under the vertical average bite force,the Gyroid structure could uniformly disperse the load acting on the implant into the entire structure.The load on the solid structure implant could only be dispersed on its outer surface and concentrated in the neck.The maximum equivalent stress of the Gyroid structure implant was 200.67 MPa,which did not exceed 50%of the yield strength of Ti6Al4V material.The maximum equivalent stress of the Gyroid structure implant on the surrounding bone tissue was 24.27 MPa,which was slightly higher than the maximum equivalent stress of the solid structure implant 17.32 MPa,and in the range of 20-60 MPa.The stimulation effect of the Gyroid structure implant on new bone formation was better than that of the solid structure implant.(2)The 3D printing technology could materialize the Gyroid structure implant model.Scanning electron microscopy showed that there were many unmelted spherical metal particles on the surface of the 3D printed Ti6Al4V specimens.After sandblasting and acid etching,a micron-scale mesh pore structure was formed on the surface,and no protruding metal particles were seen.The surface morphology of the superimposed UV functional treatment group was basically consistent with that after sandblasting and acid etching.The contact angle test results showed that the surface hydrophilicity of the specimens treated with ultraviolet functionalization plus sandblasting and acid etching was better than that of the sandblasting and acid etching and non-surface treatment groups.(3)The sandblasting and acid etching technology can remove the weakly connected metal particles on the 3D printed specimen and improve the similarity between the solid model and the design model.On this basis,the ultraviolet functionalization treatment can significantly improve the hydrophilicity of the 3D printed Gyroid structure implant surface without affecting its structure.

Objective To investigate the mechanism of modified Guizhi Fuling Pills in treating diabetic kidney disease(DKD)through autophagy regulation based on network pharmacology and experimental validation.Methods Active components and action targets of modified Guizhi Fuling Pills were screened via the TCMSP database.DKD-related autophagy targets were obtained from GeneCards,TTD,DrugBank and PharmGKB.A protein-protein interaction network was constructed using STRING,followed by GO functional and KEGG pathway enrichment analyses via DAVID.Molecular docking of key components and core targets was performed using AutoDock Tools 1.5.7.DKD model rats were prepared.The rats were randomly divided into normal group,model group,valsartan group(50 mg/kg),and modified Guizhi Fuling Pills low-,medium-and high-dosage group(9.9,19.8 and 39.6 g/kg).After 8-week interventions,body mass and water intake were recorded;fasting blood glucose,24 h urinary total protein(24 hUTP),urinary albumin-to-creatinine ratio(UACR)were monitored.Renal histopathology was evaluated via HE and Masson staining.Western blot was used to detect protein expressions of AMPK/FOXO1 pathway(p-AMPK,AMPK,FOXO1)and autophagy markers(Beclin-1,p62),while quantitative real-time PCR was used to assess AMPK and FOXO1 mRNA expressions.Results A total of 146 active components of Guizhi Fuling Pills and 33 main targets for treating DKD were screened,with the core targets including FOXO1,BCL2,TP53 and PTEN.KEGG pathway enrichment analysis suggested that AMPK/FOXO1 signaling pathway,AGE-RAGE and insulin signaling pathways may play a core regulatory role.Guizhi Fuling Pills could significantly reduce the body mass of DKD rats,reduce water intake,decrease renal index,decrease fasting blood glucose,24 hUTP and UACR(P<0.05,P<0.01),improve renal tissue pathology,increase AMPK,FOXO1,Beclin-1 protein expressions and AMPK,FOXO1 mRNA expressions(P<0.05),and reduce p62 protein expression(P<0.05).Conclusion Modified Guizhi Fuling Pills may exert therapeutic effects on DKD by regulating the AMPK-FOXO1-autophagy axis.

OBJECTIVE To investigate the efficacy of Ningmitai Capsules combined with cefoperazone/sulbactam on the treatment of type 2 diabetes mellitus(T2DM)complicated with urinary tract infections(UTIs)and its impact on soluble triggering receptor expressed on myeloid cells-1(sTREM-1),microRNA(miRNA)-34 b and Toll-like receptor-4(TLR4),so as to provide a new combined regimen for clinical treatment of such patients.METHODS From May 2022 to May 2024,122 patients with T2DM complicated with UTIs treated at the Affiliated People's Hospital of Shandong First Medical University were randomly divided into a conventional group and a combination group by the odd-even randomization method,with 61 cases in each group.The conventional group was treated with cefoperazone/sulbactam,whereas the combination group received Ningmitai capsules in combination with cef-operazone/sulbactam.The efficacy,improvement time of related symptoms,T lymphocyte subsets(CD3+,CD4+,CD4+/CD8+),sTREM-1,miRNA-34b,TLR4 levels and occurrence of adverse reactions were compared between the two groups.RESULTS The total effective rate in the combination group was higher than that in the conventional group after treatment(93.44%vs.80.33%,χ2=4.604,P=0.032).There were statistically signifi-cant differences between the two groups in the time for urine routine to return to normal,disappearance of urinary irritation symptoms,conversion of urine pathogens to negative and defervescence(P<0.05).After treatment,the levels of CD3+,CD4+and CD4+/CD8+in both groups were lower than those before treatment(P<0.05),and the levels in the combination group were higher than those in the conventional group(P<0.05).Moreover,the levels of sTREM-1,miRNA-34b and TLR4 in both groups decreased after treatment(P<0.05),and the levels in the combination group were lower than those in the conventional group(P<0.05).During the treatment period,no severe adverse reactions were observed in either group,and laboratory test results for blood routine and hepatic and renal functions showed no abnormalities.CONCLUSION The application of Ningmitai capsules combined with cef-operazone/sulbactam in the treatment of T2DM complicated with UTIs has good efficacy,can effectively control infec-tions,shorten the time for symptom relief,improve immune function and attenuate inflammation level with high safety.

Objective To investigate the current status and characteristics of registered clinical trials on TCM interventions for sepsis;To provide references for relevant clinical trial registrations.Methods Clinical trials on TCM interventions for sepsis registered in the World Health Organization International Clinical Trials Registry Platform(WHO ICTRP)and the Chinese Clinical Trial Registry(ChiCTR)from inception to June 2024 were retrieved.Data on registration time,registry centers,regions,institutions,participating centers,funding sources,trial design,phase,sample size,randomization methods,blinding,interventions,disease types,and outcome measures were analyzed using Excel 16.0.Results A total of 118 TCM intervention trials for sepsis were included,registered regions involving Guangdong,Jiangsu,and Shanghai,with institutions including Guangdong Provincial Hospital of Chinese Medicine,Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,and Jiangsu Provincial Hospital of Traditional Chinese Medicine.Most trials were single-center studies(94,79.66%),funded primarily by hospitals(38)and local governments(36).The majority were interventional studies(105,88.98%),with phases concentrated in pilot/exploratory studies and Phase Ⅳ trials(52).Sample sizes were mostly 60-99 cases(51).Randomized controlled trials predominantly used simple randomization(65)and double-blinding(22).Interventions mainly included empirical formulas,Chinese patent medicines,and classical prescriptions,targeting conditions such as gastrointestinal dysfunction and lung injury,with primary outcomes including SOFA,APACHE Ⅱ,and mortality rate.Conclusion The number of TCM registered clinical trials for sepsis has generally increased.There are some problems,such as uneven distribution of test areas,poor standardization and integrity of registration information,and the advantages and characteristics of TCM need to be further highlighted.

Intravascular large B cell lymphoma (IVLBCL) is a rare, aggressive subtype of diffuse large B cell lymphoma, with nasal turbinate involvement being uncommon. We report a 51-year-old woman with a 1-month history of fever of unknown origin. Laboratory findings showed cytopenia, hypertriglyceridemia, elevated ferritin, increased soluble CD25, and bone marrow hemophagocytosis. No infectious cause was identified. PET-CT revealed abnormal 18F-fluorodeoxyglucose (FDG) uptake in the nasal turbinates. Turbinate biopsy revealed tumor cells localized predominantly within vascular lumens, positive for CD20, BCL6, PAX5, and MUM1, with a Ki-67 index >60%, confirming a diagnosis of IVLBCL with hemophagocytic lymphohistiocytosis (HLH). The patient received one cycle of the DEP regimen (liposomal doxorubicin, etoposide, and methylprednisolone) for HLH, followed by five cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and consolidation with auto-HSCT, achieving sustained complete remission. IVLBCL outcomes are heterogeneous; early diagnosis and prompt treatment improve survival, and R-CHOP plus auto-HSCT may be an effective strategy.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objective:This study aimed to investigate the role of heat shock protein family A member 5 (HSPA5) in ferroptosis at its regulatory mechanisms in ulcerative colitis (UC), using both a dextran sulfate sodium (DSS)-induced mouse model of acute colitis and in vitro cell experiments.Methods:Differentially expressed genes in UC were identified using the GSE87466 dataset from the Gene Expression Omnibus, cross-referenced with the ferroptosis-related gene database FerrDB (version 2). A protein-protein interaction (PPI) network was constructed, identifying HSPA5 as a core hub gene. To validate its role in vivo, acute colitis was induced in C57BL/6 mice using DSS, followed by treatment with the ferroptosis inhibitor Ferrostatin-1 (Fer-1). Lipid peroxidation and ferroptosis levels were assessed by measuring malondialdehyde (MDA) and iron content in colon tissues. The expression of ferroptosis-related proteins, including prostaglandin-endoperoxide synthase 2 (PTGS2), glutathione peroxidase 4 (GPX4), ferritin light chain (FTL), activating transcription factor 4 (ATF4), and HSPA5, in addition to tight junction proteins ZO-1 and Occludin, were evaluated using immunohistochemistry and Western blotting. In vitro, an inflammatory model was established using lipopolysaccharide (LPS)-stimulated Caco-2 cells. Lentiviral knockdown of HSPA5 was performed to assess its regulatory effects on ferroptosis by assessing MDA levels, GPX4 activity, and the expression of related proteins. Statistical analyses were conducted with SPSS (version 29.1), with t-tests or one-way ANOVA for normally distributed data and the Mann-Whitney U test for ordinal data. Statistical significance was set at P<0.05. Results:Based on the PPI analysis and previous research, HSPA5 emerged as a key gene linking UC and ferroptosis. In DSS-treated mice, colonic injury was accompanied by elevated MDA levels ( t=5.72, P<0.001) and iron accumulation ( t=6.32, P<0.001). DSS also increased the expression of PTGS2 and proteins in the ATF4-HSPA5 pathway, while reducing the levels of GPX4, FTL, ZO-1, and Occludin. These findings could be partially reversed by Fer-1 (MDA: t=2.92, P<0.05; iron: t=5.84, P<0.001). In Caco-2 cells, LPS treatment elevated the expression of PTGS2, ATF4, and HSPA5, and elevated the MDA content ( t=9.63, P<0.001), while reducing the expression of FTL, GPX4, ZO-1, and Occludin, as well as GPX4 enzyme activity ( t=-11.20, P<0.001). Knockdown of HSPA5 further exacerbated these changes, significantly increasing MDA levels ( t=4.15, P<0.01), decreasing GPX4 activity ( t=-9.81, P<0.001), and altering ferroptosis-related protein expression. Conclusion:HSPA5 appears to protect against intestinal damage in UC by enhancing GPX4 expression and activity, thereby reducing ferroptosis and preserving epithelial barrier integrity through the maintenance of tight junction proteins.

Objective:To explore the influence of non-motor symptoms on the change trajectory of early activities of daily living in patients with Parkinson disease, and to provide a reference for medical staff to implement intervention measures for people with low levels of activities of daily living in the preclinical stage.Methods:The longitudinal follow-up data of 431 patients with Parkinson disease in the Parkinson's progression Markers Initiative from baseline to five consecutive years after enrollment were selected by convenience sampling method in July 2024, including the scores of aceivities of daily living, the Rapid Eye Movement Sleep Behavioral Disorder Screening Questionnaire, etc. A latent class growth model classified change trajectory of activities of daily living, and the influencing factors were analyzed by univariate and binary Logistic regression.Results:Among the 431 patients, 260 were male and 171 were female, with an average age of (61.30 ± 9.60) years. The scores of activities of daily living of the patients at baseline, 12 months after enrollment, 36 months after enrollment, and 60 months after enrollment were (5.97 ± 4.30), (7.20 ± 4.61), (8.90 ± 5.60), and (10.57 ± 6.93) points, respectively. The model identified two types of trajectories: rapid decline in low activities of daily living group (25.3%, 109/431) and slow decline in lower activities of daily living group (74.7%, 322/431). The binary Logistic regression results showed that apathy ( OR=0.374, 95% CI 0.189-0.739), fatigue ( OR=0.261, 95% CI 0.138-0.495), University of Pennsylvania Smell Identification Test ( OR=1.039, 95% CI 1.005-1.074), the Rapid Eye Movement Sleep Behavioral Disorder Screening Questionnaire ( OR=0.880, 95% CI 0.795-0.973), and the gastrointestinal score of the Scales for Outcomes in PD-Autonomic ( OR=0.724, 95% CI 0.630-0.832) were independent influencing factors for the classification of the change trajectory of activities of daily living in patients with Parkinson disease (all P<0.05). Conclusions:Patients with Parkinson disease exhibit a decreasing trend in early activities of daily living, emphasizing the need for targeted interventions in those with fatigue, apathy, and high Rapid Eye Movement Sleep Behavioral Disorder Screening Questionnaire and Scales for Outcomes in Parkinson disease-Autonomic gastrointestinal scores to possibly decelerate disease advancement.