BACKGROUND:Socket-shield technique can effectively maintain labial soft and hard tissues,but the incidence of postoperative complications such as exposure and displacement of root shield is relatively high.It is speculated that the root shield may be exposed and displaced due to excessive load after long-term function of dental implants. OBJECTIVE:Through three-dimensional finite element analysis,we aim to study the influence of varying root shield thicknesses on the stress distribution,equivalent stress peaks,and displacement in the root shield,periodontal ligaments,implant,and surrounding alveolar bone under normal occlusal loading.We also attempt to analyze the correlation between the thickness of the root shield and occurrence of mechanical events such as root shield exposure,displacement,and fracture. METHODS:Cone-beam CT data of a patient who met the indication standard of socket-shield technique for maxillary central incisor were retrieved from database.Reverse engineering techniques were used to build models of the maxillary bone and root shield,while forward engineering was used to create models for the implant components based on their parameters.Models depicting various root shield thicknesses(0.5,1.0,1.5,and 2.0 mm)were created using Solidworks 2022 software.ANSYS Workbench 2021 software was then used to simulate and analyze the effects of varying root shield thicknesses on stress distribution,equivalent stress peaks,and displacement of the root shields,periodontal ligaments,implants,and surrounding alveolar bone under normal occlusion. RESULTS AND CONCLUSION:(1)In all root shield models,the stress was concentrated on the palatal cervical side,both sides of the edges and the lower edge of the labial side.As the thickness of the root shield increased,the equivalent stress peak and displacement showed a decreasing trend.The 0.5 mm thickness model produced a stress concentration of 176.20 MPa,which exceeded the yield strength(150 MPa)of tooth tissue.(2)The periodontal ligament stress in each group was concentrated in the neck margin and upper region.With the increase of root shield thickness,the equivalent stress peak and displacement of periodontal ligament showed a decreasing trend.(3)Implant stress in all models was concentrated in the neck of the implant and the joint of the implant-repair abutment,and the labial side was more concentrated than the palatal side.With the increase of root shield thickness,the equivalent stress peak of the implant in the model showed an increasing trend.(4)In each group of models,stress of cortical bone concentrated around the neck of the implant and the periphery of the root shield,and the labial side was more concentrated than the palatal side.With the increase of the thickness of the root shield,the equivalent stress peak around the root shield decreased;the peak value of the equivalent stress of the bone around the neck of the implant showed an increasing trend.In the model,the stress of cancellous bone was mainly concentrated around the neck of the lip of the implant,the top of the thread,the root tip and the lower margin of the root shield,and the labial side was more concentrated than the palatal side.With the increase of the thickness of the root shield,the peak value of the equivalent stress of the bone around the root shield in the model showed a decreasing trend.The minimum principal stress of cortical bone in each group of models was concentrated around the neck of the implant,exhibiting a fan-shaped distribution.As the thickness of the root shield increased,the minimum principal stress of cortical bone showed an increasing trend.(5)These results indicate that different thicknesses of the root shield have different biomechanical effects.The root shield with a thickness of 0.5 mm is easy to fracture.For patients with sufficient bone width,the root shield with a thickness of 2.0 mm is an option to reduce the risk of complications such as root shield exposure,fracture,and displacement.Meanwhile,it should be taken into account to protect the periodontal ligament in the preparation process,and rounding treatments ought to be carried out on both sides and the lower edge of the root shield.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Atherosclerosis(AS)is the major pathologic basis of cardiovascular disease,and its complications,such as myocardial infarction and stroke,are primarily triggered by rupture of atherosclerotic vulnerable plaques(VASPs).Conventional imaging techniques rely on anatomical changes,making it difficult to assess plaque vulnerability at an early stage.In recent years,molecular imaging combined with nanoprobe technology has enabled precise visualization at the cellular and molecular levels by targeting pathological features of plaques(e.g.,lipid core,inflammation,thin fibrous cap,etc.).This article reviews the pathological features of VASPs,the limitations of existing imaging techniques,and the design principles and application progress of molecular imaging probes and discusses the challenges and future directions for their clinical translation.

Atherosclerosis(AS)is the major pathologic basis of cardiovascular disease,and its complications,such as myocardial infarction and stroke,are primarily triggered by rupture of atherosclerotic vulnerable plaques(VASPs).Conventional imaging techniques rely on anatomical changes,making it difficult to assess plaque vulnerability at an early stage.In recent years,molecular imaging combined with nanoprobe technology has enabled precise visualization at the cellular and molecular levels by targeting pathological features of plaques(e.g.,lipid core,inflammation,thin fibrous cap,etc.).This article reviews the pathological features of VASPs,the limitations of existing imaging techniques,and the design principles and application progress of molecular imaging probes and discusses the challenges and future directions for their clinical translation.

Aim To investigate the role of tryptophan 2,3-dioxygenase(TDO2)in cisplatin-acute kidney in-jury(Cis-AKI)and to explore the mechanism of TDO2 in relation to apoptosis in tubular epithelial cells(TECs)to investigate the mechanism of TDO2 associ-ated with apoptosis.Methods An AKI model was es-tablished by intraperitoneal injection of cisplatin(Cis).Colorimetric assay was used to detect CRE and BUN levels,and PAS staining was employed to observe renal injury in mice.Immunohistochemistry was used to detect TDO2 protein expression and distribution and macrophage(F4/80+)infiltration;immunofluores-cence was used to detect the co-localization of TDO2 with the tubular marker LTL;TUNEL staining was used to detect apoptosis in mouse kidney;flow cytome-try was used to detect overexpression of human renal cortical proximal tubular epithelial cells(HK2)and apoptosis after administration of the TDO2 inhibitor 680C91;Western blot was used to detect TDO2 and NF-κB pathway protein levels in HK2 cells after over-expression and inhibition of TDO2.Results In the o-verall animal experiments,Cis-AKI mice showed signif-icantly higher levels of CRE and BUN and obvious tu-bular damage compared with the control group;at the same time,the renal tissues of Cis-AKI mice showed increased expression of F4/80,and the proportion of apoptotic cells in kidney cells was increased.Immuno-histochemistry and immunofluorescence showed that the expression of TDO2 increased,mainly localized in TECs.In cellular experiments,HK2 cells overexpress-ing TDO2 increased the proportion of apoptosis,and the expression of TDO2,p-IKBα,and p-p65 proteins was elevated,and p-IKBα/IκBα and p-p65/p65 were ele-vated;furthermore,the proportion of apoptosis was re-duced by the administration of 680C91,and the expres-sion of p-IκBα,and p-p65 proteins decreased,and the expression of p-IKBα/IKBα,and p-p65/p65 de-creased.Conclusions Elevated TDO2 in TECs is in-volved in the pathological mechanism of Cis-AKI,which may be related to its induction of apoptosis in TECs and activation of the NF-κB signaling pathway and consequently renal injury.

Objective To investigate the needs of the main caregivers of patients with spinal cord injury following neurogenic bowel dysfunction to participate in the whole process of intestinal management.Methods Nine main caregivers of patients with spinal cord injury in Jiangsu Province Hospital from January to Decem-ber,2024 were selected with objective sampling method.They were investigated face-to-face semi-structured in-depth interviews,and the data were analyzed,summarized and extracted by Colaizzi 7-step analysis method.Results Three themes and eight sub-themes were extracted:the needs of professional knowledge and skills standards in intestinal management(lack of intestinal training knowledge,lack of ability to acquire knowledge and different standards of medical institutions);the needs of physical ability and decision making ability participating in intesti-nal training(lack of participation,single decision-making behavior,excessive dependence on medical personnel);the desire for therapeutic benefits and the needs for building psychological confidence(concerns about the pa-tient's prognosis,overdependence on medication).Conclusion Clinical medical staff should pay attention to the actual needs and difficulties faced by the main caregivers of patients with neurogenic bowel dysfunction to participate in the entire intestinal management,and construct targeted training programs,strengthen the skills and knowledge training,to enhance their autonomy and responsi-bility,to achieve the rehabilitation goal better.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective To investigate the impacts of epidural anesthesia with ropivacaine combined with dezocine on lower limb motor nerve block and maternal and infant outcomes in primipara undergoing painless delivery.Methods A total of 159 primiparas who delivered in Nanjing Jiangbei Hospital were selected as the research objects,and divided into the blank group(53 cases),the ropivacaine group(53 cases)and the combined group(53 cases)by the random number table method.Parturients in the blank group were given natural delivery mode,parturients in the ropivacaine group were given ropivacaine epidural anesthesia,and parturients in the combined group were given dezocine anesthesia on the basis of ropivacaine.Analgesic effect at different time points,time of the first,second and third stage of labor,pressing times of analgesic pump,lower limbs motor nerve block,maternal and infant outcomes,and adverse reactions of parturients were compared among the three groups.Results At 10 minutes after analgesia,60 minutes after analgesia,when the cervix was fully dilated and when the fetus was delivered,the VAS scores of the parturients in the ropivacaine group and the combined group were lower than those in the blank group(P<0.05),and the VAS scores of the parturients in the combined group were significantly lower than those in the ropivacaine group(P<0.05).There was no significant difference in the time of the first,second or third stage of labor of parturients among the three groups(P>0.05);The pressing times of analgesic pump of parturients in the combined group was significantly less than that in the ropivacaine group(P<0.05).There was no statistically significant difference in terms of low limb motor nerve block after painless labor of parturients among the three groups(P>0.05).There were no statistically significant differences in the perineal incision rate or the Apgar scores of newborns at 1 minute and 5 minutes after birth among the three groups(P>0.05).The usage rate of forceps and the rate of conversion to cesarean section in the combined group were significantly lower than those in the ropivacaine group and the blank group(P<0.05).There was no statistically significant difference in the incidence of total adverse reactions among the blank group,the ropivacaine group and the combined group(P>0.05).Conclusion The combination of ropivacaine and dezocine for epidural anesthesia has a better analgesic effect on primiparas with painless delivery,has a smaller impact on lower limb motor nerve block in parturients,and can achieve better maternal and infant outcomes.

Aim To investigate the role of tryptophan 2,3-dioxygenase(TDO2)in cisplatin-acute kidney in-jury(Cis-AKI)and to explore the mechanism of TDO2 in relation to apoptosis in tubular epithelial cells(TECs)to investigate the mechanism of TDO2 associ-ated with apoptosis.Methods An AKI model was es-tablished by intraperitoneal injection of cisplatin(Cis).Colorimetric assay was used to detect CRE and BUN levels,and PAS staining was employed to observe renal injury in mice.Immunohistochemistry was used to detect TDO2 protein expression and distribution and macrophage(F4/80+)infiltration;immunofluores-cence was used to detect the co-localization of TDO2 with the tubular marker LTL;TUNEL staining was used to detect apoptosis in mouse kidney;flow cytome-try was used to detect overexpression of human renal cortical proximal tubular epithelial cells(HK2)and apoptosis after administration of the TDO2 inhibitor 680C91;Western blot was used to detect TDO2 and NF-κB pathway protein levels in HK2 cells after over-expression and inhibition of TDO2.Results In the o-verall animal experiments,Cis-AKI mice showed signif-icantly higher levels of CRE and BUN and obvious tu-bular damage compared with the control group;at the same time,the renal tissues of Cis-AKI mice showed increased expression of F4/80,and the proportion of apoptotic cells in kidney cells was increased.Immuno-histochemistry and immunofluorescence showed that the expression of TDO2 increased,mainly localized in TECs.In cellular experiments,HK2 cells overexpress-ing TDO2 increased the proportion of apoptosis,and the expression of TDO2,p-IKBα,and p-p65 proteins was elevated,and p-IKBα/IκBα and p-p65/p65 were ele-vated;furthermore,the proportion of apoptosis was re-duced by the administration of 680C91,and the expres-sion of p-IκBα,and p-p65 proteins decreased,and the expression of p-IKBα/IKBα,and p-p65/p65 de-creased.Conclusions Elevated TDO2 in TECs is in-volved in the pathological mechanism of Cis-AKI,which may be related to its induction of apoptosis in TECs and activation of the NF-κB signaling pathway and consequently renal injury.

Objective:To investigate the current status of the implementation of home-based phototherapy (HBPT) in patients with vitiligo, and to analyze management needs among patients receiving HBPT.Methods:A questionnaire survey was conducted on the application of HBPT among patients with vitiligo who visited the outpatient clinic of the Hospital for Skin Diseases, Chinese Academy of Medical Sciences from December 2021 to November 2022. Additionally, the popularization and usage of HBPT as well as needs of patient management were investigated and analyzed in these vitiligo patients.Results:A total of 496 valid questionnaires were collected from 496 patients with vitiligo (241 males [48.5%] and 255 females [51.5%]) . Their ages at visit ranged from 2 to 67 (30.87 ± 12.36) years. The most commonly affected sites were the head and face (52.2%) , followed by hair (32.1%) , hands and feet (31.4%) , trunk (30.2%) , limbs (24.3%) , neck (19.5%) , and perineum (9.9%) . Among the participants, 320 (64.5%) were currently using or had used HBPT, and 352 (70.8%) expressed a willingness to learn more about HBPT usage guidelines and health education. Regarding the repigmentation outcomes after HBPT: among 312 patients, 54 (17.3%) reported complete recovery, 64 (20.5%) were markedly improved, 142 (45.5%) experienced improvement, and 52 (16.7%) showed no response. Adverse reactions occurred in 223 patients (71.5%) , of whom 28 (9.0%) experienced severe adverse reactions. The most desired guiding information was the adjustment method for phototherapy dosage and treatment duration (184/352, 52.3%) ; the most effective way to receive health education information was through verbal education by medical staff (177/352, 50.3%) .Conclusion:For vitiligo patients who were willing to accept and use HBPT, the most desired guiding information was the adjustment method for phototherapy dosage and treatment duration, and verbal health education by medical staff appeared to be the main way to obtain health education information.