ObjectiveTo evaluate the efficacy and possible mechanism of Wei's Huoxue Tongluo Formula （韦氏活血通络方，WHTF） in treating atrophic-stage non-arteritic anterior ischemic optic neuropathy （NAION） with qi deficiency and blood stasis. MethodsA total of 82 atrophic-stage NAION patients with qi deficiency and blood stasis were randomly divided into a treatment group and a control group， with 41 cases in each group. The treatment group was given oral administration of WHTF twice a day plus acupoint injection of distilled water 2 ml at Taiyang （EX-HN5） once daily， while the control group received injection of compound anisodine injection 2 ml at Taiyang （EX-HN5） once daily and oral administration of WHTF placebo twice a day. Both groups received treatment for a course of 14 days. The best-corrected visual acuity （BCVA）， optic disc perfusion density （PD）， flux index （FI）， macular superficial PD， vascular density （VD）， and traditional Chinese medicine （TCM） syndrome scores were compared between groups before treatment and on day 7 and day 14 of treatment. Additionally， mean defect （MD） and mean sensitivity （MS） of visual fields were measured before treatment and on day 14， along with safety evaluation. ResultsAfter treatment， both groups showed significant improvement in BCVA， visual field MD and MS， and TCM syndrome scores （P＜0.05 or P＜0.01）. On day 14 of treatment， the TCM syndrome score in the treatment group was significantly lower than that in the control group （P＜0.05）. There was no significant improvement in optic disc PD and FI， and macular superficial PD and VD after treatment in either group （P＞0.05） except that on day 7 the macular superficial foveal PD in the control group was significantly better than that in the treatment group （P＜0.05）. During the treatment period， no serious adverse events occurred in either group. ConclusionWHTF can improve the visual function indicators including visual acuity and visual field， as well as TCM syndrome scores in atrophic-stage NAION patients with qi deficiency and blood stasis. It shows clinical safety， although it does not appear to have a significant effect on optic disc or macular blood flow.

Ulcerative colitis （UC） is a common digestive disease characterized by recurrence and remission alternation，which seriously affects the life quality and physical and mental health of patients. The pathogenesis of UC is complex，and studies have shown that the occurrence and development of UC are closely related to the transduction of multiple signaling pathways. The current western medicine treatment has many problems，such as single action target，more adverse reactions，poor patient tolerance，and easy recurrence after stopping the medicine. Traditional Chinese medicine has the advantages such as multi-targets，multi-pathways， and fewer adverse reactions， elucidating that the action mechanism of traditional Chinese medicine in the treatment of UC is the focus of current research. Therefore， this paper conducted a systematic review on how traditional Chinese medicine exerts therapeutic effects by regulating the signaling pathways related to UC in recent years，and it was found that traditional Chinese medicine can regulate nuclear factor-κB （NF-κB），adenylate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR），Janus tyrosine protein kinase （JAK）/signal transducer and activator of transcription （STAT），phosphatidylinositol 3-kinase （PI3K） /protein kinase B （Akt），NOD-like receptor thermoprotein structural domain-related protein 3 （NLRP3）/cysteine protease-1 （Caspase-1），nuclear respiratory factor 2 （Nrf2）/heme oxygenase-1 （HO-1）， and several other pathways，thereby inhibiting oxidative stress and cellular pyroptosis，regulating the Tregs/Th17 cellular balance， promoting autophagic response and M2-type macrophage polarization，restoring the diversity and abundance of intestinal flora，promoting the repair of intestinal mucosal barrier function，and alleviating the inflammatory damage of UC colonic tissues. The holistic concept and evidence-based treatment of traditional Chinese medicine were combined with the modern molecular mechanism research of traditional Chinese medicine， and the traditional Chinese medicine combinations with different mechanisms， following regulation， were formulated into compound formulas or pairs of medicines according to the pattern of evidence. It is expected to achieve better therapeutic efficacy and to provide ideas and references for the modification of classic compound formulae of traditional Chinese medicine in UC treatment and clinical translation.

ObjectiveTo investigate the effects of atorvastatin （ATV） on the proliferation and differentiation of rat bone marrow mesenchymal stem cells （BMSCs）， periodontal ligament stem cells （PDLSCs）， and dental pulp stem cells （DPSCs） in vitro， and to validate the regulatory effect of ATV on periodontal bone formation and tooth movement using a rat orthodontic tooth movement （OTM） model. MethodsThe effects of ATV on the proliferation and osteogenic/odontogenic differentiation of rat BMSCs， PDLSCs， and DPSCs were assessed in vitro. CCK-8 assay was used to detect the proliferation of the three types of cells. Alkaline phosphatase （ALP） staining and Alizarin Red staining were employed to evaluate osteogenic differentiation capacity. Western blot was used to detect the expression of osteogenesis-related proteins ［collagen type I （COL-I）， Runt-related transcription factor 2 （Runx2）， bone morphogenetic protein-2 （BMP-2）， osteocalcin （OCN）］ and the odontogenesis-related protein dentin sialophosphoprotein （DSPP） in BMSCs， PDLSCs and DPSCs. An OTM rat model was established， with rats randomly assigned to an ATV gavage group and a control group. The ATV gavage group received daily oral administration of ATV at a dose of 20 mg/kg， while the control group received an equal volume of solvent by gavage. Tooth movement distance was measured via Micro-CT on days 7， 14， and 21. Histomorphology of periodontal tissues was observed using Hematoxylin and Eosin （HE） staining and Masson staining. The gene and protein expression levels of osteogenic markers （BMP-2， Runx2， OCN） on the tension side of the first molar were detected by qRT-PCR and immunohistochemistry， respectively. ResultsATV at concentrations of 1×10⁻⁶ mol/L and 1×10⁻⁷ mol/L significantly promoted the proliferation and osteogenic/odontogenic differentiation of BMSCs， PDLSCs， and DPSCs， manifested as enhanced ALP activity， increased mineralized nodule formation， and up-regulated expression of osteogenic/odontogenic proteins COL-I， Runx2， BMP-2， OCN， and DSPP （P<0.001）. In the OTM model， compared with the control group， the ATV gavage group showed a significant reduction in tooth movement distance （P<0.05）， enhanced osteogenic activity in periodontal tissues， and significantly increased gene （P<0.001） and protein （P<0.05） expression of BMP-2， Runx2， and OCN on the tension side of the first molar. ConclusionATV enhances periodontal osteogenesis by promoting osteogenic/dentinogenic differentiation， thus inhibiting tooth movement.

Objective To investigate the regulatory effects and molecular mechanisms of extracellular vesicles(EVs)secreted by adri-amycin(ADR)-resistant breast cancer cells on vascular endothelial cells related to tumor microenvironment.Methods The ADR-sen-sitive breast cancer cell line(MCF-7)and its ADR-resistant counterpart(MCF-7-ADR)were established in vitro.Then,the EVs were isolated from the supernatant of cell culture using a commercial kit.The fluorescence labeling and tracking technology using PKH67 was used to validate the internalization of EVs by human umbilical vein endothelial cell(HUVEC).The effects of EVs on the proliferation,migration,and angiogenesis of HUVEC were assessed by the colony formation,scratch wound healing,and tube formation assays,re-spectively.The expression level of CD31 protein was detected by Western blot,and the levels of vascular endothelial growth factor(VEGF)in cell supernatant were determined by ELISA.The microRNA(miRNA)sequencing technology was utilized to identify the differentially expressed miRNAs in EVs secreted by ADR-resistant cells.Results Compared with the ADR-sensitive strain,the EVs secreted by the ADR-resistant strain significantly enhanced the proliferation(colony number increased by 38.7%,P=0.011),migra-tion(scratch healing rate improved by 42.3%,P=0.004),and tube formation ability(tube formation rates increased by 1.8 times and 2.3 times at 4 h and 16 h,respectively,P=0.044 and 0.010)of HUVEC.Western blot analysis showed that the expression level of CD31 in the EVs secreted by the ADR-resistant strain increased by 1.85 times compared with the ADR-sensitive strain(P=0.039).The results of ELISA showed that the expression level of VEGF increased by 2.12 times(P=0.012).The miRNA sequencing identified a differentially expressed miRNA profile.Conclusion The ADR-resistant breast cancer cells significantly enhance the proliferation,migration,and angiogenesis of vascular endothelial cells by secreting EVs rich in specific miRNA,and its mechanism may be related to the up-regulation of CD31/VEGF protein levels mediated by EVs,suggesting that the drug-resistant cells reshaping the tumor vascular microenvironment through EVs may become a new therapeutic target of chemotherapy resistance in breast cancer.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Objective To investigate the regulatory effects and molecular mechanisms of extracellular vesicles(EVs)secreted by adri-amycin(ADR)-resistant breast cancer cells on vascular endothelial cells related to tumor microenvironment.Methods The ADR-sen-sitive breast cancer cell line(MCF-7)and its ADR-resistant counterpart(MCF-7-ADR)were established in vitro.Then,the EVs were isolated from the supernatant of cell culture using a commercial kit.The fluorescence labeling and tracking technology using PKH67 was used to validate the internalization of EVs by human umbilical vein endothelial cell(HUVEC).The effects of EVs on the proliferation,migration,and angiogenesis of HUVEC were assessed by the colony formation,scratch wound healing,and tube formation assays,re-spectively.The expression level of CD31 protein was detected by Western blot,and the levels of vascular endothelial growth factor(VEGF)in cell supernatant were determined by ELISA.The microRNA(miRNA)sequencing technology was utilized to identify the differentially expressed miRNAs in EVs secreted by ADR-resistant cells.Results Compared with the ADR-sensitive strain,the EVs secreted by the ADR-resistant strain significantly enhanced the proliferation(colony number increased by 38.7%,P=0.011),migra-tion(scratch healing rate improved by 42.3%,P=0.004),and tube formation ability(tube formation rates increased by 1.8 times and 2.3 times at 4 h and 16 h,respectively,P=0.044 and 0.010)of HUVEC.Western blot analysis showed that the expression level of CD31 in the EVs secreted by the ADR-resistant strain increased by 1.85 times compared with the ADR-sensitive strain(P=0.039).The results of ELISA showed that the expression level of VEGF increased by 2.12 times(P=0.012).The miRNA sequencing identified a differentially expressed miRNA profile.Conclusion The ADR-resistant breast cancer cells significantly enhance the proliferation,migration,and angiogenesis of vascular endothelial cells by secreting EVs rich in specific miRNA,and its mechanism may be related to the up-regulation of CD31/VEGF protein levels mediated by EVs,suggesting that the drug-resistant cells reshaping the tumor vascular microenvironment through EVs may become a new therapeutic target of chemotherapy resistance in breast cancer.

B-cell lymphomas account for 70％-80％of non-Hodgkin lymphomas(NHL)and exhibit significant heterogeneity in genetic profiles,phenotypic characteristics,and clinical manifestations,posing substantial challenges for clinical management.The B-cell receptor(BCR)is a transmembrane receptor on the surface of B cells that plays a central regulatory role in B-cell development,activation,and adaptive immune responses.As a core mechanism driving malignant transformation in various B-cell malignancies,aberrant activation of the BCR signaling pathway,plays a pivotal role in B lymphoma pathogenesis.Dysregulated BCR signaling not only promotes tumor cell proliferation,survival,and anti-apoptotic capacity but also accelerates malignant progression.Consequently,researchers are vigorously exploring therapeutic strategies targeting BCR and its downstream pathways,including inhibitors of Bruton's tyrosine kinase(BTK)and PI3K,as well as direct BCR-targeted approaches.The central role of BCR signaling in lymphoma pathogenesis and treatment underscores its potential as a critical focus for future therapeutic development,offering new directions and hope for improved clinical outcomes.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

AIM: To compare the agreement between the ARK Biometer Combo and OA 2000 in patients wearing orthokeratology lenses.METHODS: A prospective study. A total of 148 patients(148 eyes)who were wearing orthokeratology lenses and returned for follow-up at the Shanghai Eye Disease Prevention and Treatment Center from August to September 2024 were included. Biometric measurements were performed using both the ARK Biometer Combo and OA 2000. Parameters including axial length(AL), corneal central thickness(CCT), anterior chamber depth(ACD), lens thickness(LT), corneal curvature(Kf and Ks), astigmatism(AST), white-to-white corneal diameter(WTW)and pupil diameter(PD)were obtained. Differences in measurement parameters between the two biometers were compared, and agreement was assessed.RESULTS: There were no statistically significant differences in the measurements of Kf, Ks and AST between the two biometers(P>0.05). Statistically significant differences were found in the measurements of AL, CCT, ACD, LT, WTW and PD(t=2.559, P=0.012; t=16.771, P<0.0001; t=4.749, P<0.0001; t=-15.212, P<0.0001; t=-14.915, P<0.0001; t=-2.402, P=0.018). ICC ranged from 0.615 to 0.999. Bland-Altman analysis showed that the maximum absolute values of the 95% limits of agreement(LoA)of AL, CCT, ACD, LT, Kf, Ks, AST, WTW and PD were 0.07 mm, 35.07 μm, 0.07 mm, 0.12 mm, 0.66 D, 1.14 D, 1.00 D, 0.76 mm, and 0.98 mm, respectively.CONCLUSION: In orthokeratology patients, the ARK Biometer Combo and OA 2000 showed good agreement in measuring AL, CCT, ACD, Kf and LT, and can be used interchangeably.