ObjectiveTo explore the mechanism by which Banxia Xiexin Tang （BXT） regulates the advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia （VD）. MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry（UPLC-Q-Orbitrap-MS/MS）， and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries （2-VO） method. The successfully modeled rats were randomly allocated into the model， low-， medium-， and high-dose （3.748 5， 7.497， 14.994 g·kg^-1） BXT （BXT-L， BXT-M， and BXT-H）， and nimodipine （NMP， 0.002 7 g·kg^-1） groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage， and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze， Y-maze， and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin （HE） staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE， RAGE， and phosphorylated nuclear factor-kappa B p65 （p-NF-κB p65） in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry （IHC）. The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze， Y maze， and novel object recognition tests showed that compared with the sham group， the model group demonstrated prolonged successful latency and decreases in number of platform crossings， alternation rate， number of entries into the new arm， preference index， and discrimination index （P0.01）. Compared with the model group， the BXT-H and BXT-M groups showed shortened successful latency （P0.01） and increases in number of platform crossings （P0.05）， alternation rate （P0.01）， number of entries into the new arm （P0.05）， preference index （P0.01）， and discrimination index （P0.01）. HE results showed that compared with the sham group， the cells of model rats were loosely and disorderly arranged， and the nuclei were condensed. Compared with the model group， the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group， the model group presented up-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 in the hippocampus （P0.01）， and compared with the model group， the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 （P0.01）. Western blot results showed that compared with the sham group， the model group presented up-regulated expression of AGE， RAGE， p-NF-κB p65， and tumor necrosis factor-α （TNF-α） （P0.05）， and compared with the model group， the BXT-H group presented down-regulated expression of AGE， RAGE， p-NF-κB p65， and TNF-α （P0.05）. IHC results showed that compared with the sham group， the model group had increased expression of RAGE （P0.01）， and compared with the model group， the BXT-H and BXT-M groups had reduced expression of RAGE （P0.01）. ELISA results showed that compared with the sham group， the model group exhibited elevated levels of TNF-α and Interleukin-1β （IL-1β） and declined levels of acetylcholine （ACh） and dopamine （DA） in the serum （P0.01）. Compared with the model group， the BXT-L， BXT-M， and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum （P0.05） and elevated levels of ACh and DA （P0.05）. ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway， reducing neuroinflammatory responses， and regulating neurotransmitter levels.

ObjectiveTo explore the mechanism by which Banxia Xiexin Tang （BXT） regulates the advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia （VD）. MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry（UPLC-Q-Orbitrap-MS/MS）， and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries （2-VO） method. The successfully modeled rats were randomly allocated into the model， low-， medium-， and high-dose （3.748 5， 7.497， 14.994 g·kg^-1） BXT （BXT-L， BXT-M， and BXT-H）， and nimodipine （NMP， 0.002 7 g·kg^-1） groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage， and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze， Y-maze， and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin （HE） staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE， RAGE， and phosphorylated nuclear factor-kappa B p65 （p-NF-κB p65） in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry （IHC）. The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze， Y maze， and novel object recognition tests showed that compared with the sham group， the model group demonstrated prolonged successful latency and decreases in number of platform crossings， alternation rate， number of entries into the new arm， preference index， and discrimination index （P<0.01）. Compared with the model group， the BXT-H and BXT-M groups showed shortened successful latency （P<0.01） and increases in number of platform crossings （P<0.05）， alternation rate （P<0.01）， number of entries into the new arm （P<0.05）， preference index （P<0.01）， and discrimination index （P<0.01）. HE results showed that compared with the sham group， the cells of model rats were loosely and disorderly arranged， and the nuclei were condensed. Compared with the model group， the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group， the model group presented up-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 in the hippocampus （P<0.01）， and compared with the model group， the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 （P<0.01）. Western blot results showed that compared with the sham group， the model group presented up-regulated expression of AGE， RAGE， p-NF-κB p65， and tumor necrosis factor-α （TNF-α） （P<0.05）， and compared with the model group， the BXT-H group presented down-regulated expression of AGE， RAGE， p-NF-κB p65， and TNF-α （P<0.05）. IHC results showed that compared with the sham group， the model group had increased expression of RAGE （P<0.01）， and compared with the model group， the BXT-H and BXT-M groups had reduced expression of RAGE （P<0.01）. ELISA results showed that compared with the sham group， the model group exhibited elevated levels of TNF-α and Interleukin-1β （IL-1β） and declined levels of acetylcholine （ACh） and dopamine （DA） in the serum （P<0.01）. Compared with the model group， the BXT-L， BXT-M， and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum （P<0.05） and elevated levels of ACh and DA （P<0.05）. ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway， reducing neuroinflammatory responses， and regulating neurotransmitter levels.

Objective: To investigate the current status of benefit finding among young and middle-aged patients with type 2 diabetes mellitus (T2DM) and analyze its influencing factors, so as to provide a reference for improving the level of benefit finding in this population. Methods: From November 2022 to May 2023, young and middle-aged patients with T2DM aged 18-59 years hospitalized in the endocrinology departments of 2 tertiary hospitals in Hengyang City, Hunan Province were selected as survey subjects by a convenience sampling method. Basic demographic information was collected using a general questionnaire survey. Benefit finding, resourcefulness, and stigma were evaluated using the Benefit Finding Scale, the Chinese Version of the Resourcefulness Scale, and the Type 2 Diabetes Stigma Assessment Scale, respectively. A multiple linear regression model was used to analyze the influencing factors of benefit finding among young and middle-aged patients with T2DM. Results: A total of 305 young and middle-aged patients with T2DM were investigated, including 222 males (72.79%) and 83 females (27.21%). There were 231 cases aged 45-59 years, accounting for 75.74%. The scores for benefit finding, resourcefulness, and stigma were (42.86±6.06), (75.12±11.30), and (41.20±10.10), respectively. Multiple linear regression analysis showed that young and middle-aged patients with T2DM who were male (β′=0.088), aged 18-<45 years (β′=0.083), absence of diabetes complications (β′=0.124), and had higher resourcefulness scores (β′=0.679) had higher levels of benefit finding, while patients with higher stigma scores (β′=-0.097) had lower levels of benefit finding. Conclusion The level of benefit finding among young and middle-aged patients with T2DM was moderate, and was related to gender, age, diabetes complications, resourcefulness, and stigma.

Objective: To evaluate the radiation dose, operational standardization, and image quality of computed tomography (CT) Ningbo City Medical Imaging Cloud Platform, so as to provide references for optimizing the quality of CT examinations. Methods: Six CT devices were randomly selected from the Ningbo City Medical Imaging Cloud Platform. Digital Imaging and Communication in Medicine (DICOM) image data from CT examinations of the head, neck, chest, and abdomen in males aged 36 to 60 years were collected from January 2023 to December 2024. The radiation dose levels were evaluated using the volume CT dose index (CTDIvol) and dose length product (DLP). The coefficient of variation (CV) of CTDIvol and scan length were calculated to assess scan stability. Operational standardization was evaluated using the redundancy rate of scan length and protocol matching degree. Imaging quality was assessed using the signal to noise ratio (SNR) and contrast to noise ratio (CNR). Results: A total of 28 897 DICOM images were collected, including 6 730 axial scans of the skull, 2 778 plain scans of the neck, 15 496 plain scans of the chest, and 3 893 plain scans of the abdomen. The typical values of CTDIvol and DLP radiation doses for the head, neck, and chest were all lower than the diagnostic reference levels. The maximum typical values of CTDIvol and DLP for the abdomen were 22.49 mGy and 941.45 mGy·cm, respectively, which were higher than the diagnostic reference levels. The CV values of CTDIvol and scan length ranged from 14.59% to 37.88% and from 8.27% to 44.96%, respectively. The scan stability of head CT was relatively poor, with CV values ranging from 21.74% to 37.88% and from 12.66% to 44.96%, respectively. The redundancy rate of scan length ranged from 6.02% to 74.40%, and the protocol matching degree ranged from 79.80% to 100.00%. The operational standardization of neck CT was relatively poor, with redundancy rates ranging from 45.70% to 74.40% and protocol matching degrees ranging from 79.80% to 95.36%. The mean SNR and mean CNR of the pulmonary arteries in the chest were relatively high, ranging from 15.81 to 17.65 and from 6.33 to 7.41, respectively. Conclusions The radiation doses from abdominal CT examinations on some CT devices exceed the diagnostic reference levels. The scan stability of head CT examinations and the operational standardization of neck CT examinations represent weak points in quality control. It is recommended to carry out targeted quality control training to enhance the overall quality level of CT examinations.

Objective:To prepare the bacterial outer membrane vesicles(OMV)that can express programmed death ligand 1(PD-L1)nanobody on surface,and to discuss its structural characteristics,cell compatibility,intracellular distribution,and its blocking effect on the programmed cell death protein-1(PD-1)/PD-L1 signaling axis.Methods:The pET28a-ClyA-PD-L1nb prokaryotic expression vector was constructed and transformed into Escherichia coli BL21(DE3)competent cells;the OMV was isolated from the BL21(DE3)monoclonal colonies transformed with the PD-L1nb expression vector by ultracentrifugation;the protein purification was performed using the histidine(His)tag;transmission electron microscope and nanoparticle size analyzer were used to analyze and identify the OMV;the OMV isolated from the BL21(DE3)monoclonal colonies transformed with the PD-L1nb expression vector was used as experimental group;the OMV isolated from the untransformed BL21(DE3)monoclonal colonies was used as control group;Western blotting method was used to detect the expression levels of ClyA-PD-L1nb fusion protein in the OMV in two groups;cell counting kit-8(CCK-8)assay was used to detect the activities of mouse macrophage RAW 264.7 cells,mouse triple-negative breast cancer 4T1 cells,and human embryonic kidney HEK293T cells after treated with OMV;fluorescence imaging technology was used to observe the tumor cell endocytosis of OMV;flow cytometry was used to detect the binding effect of OMV to the PD-L1 on surface of the tumor cells in PBS group,OMV-PD-L1nb group,and aPD-L1+OMV-PD-L1nb group.Results:The sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)results showed that after induction of Escherichia coli,significantly thickened protein bands appeared near the predicted relative molecular mass(about 49 000),and after purification,no obvious impurity proteins existed in the lanes;the OMV-PD-L1nb with a size of about 120 nm was isolated by ultracentrifugation,and it presented a uniform spherical structure under transmission electron microscope;the Western blotting results showed that the specific band of ClyA-PD-L1nb was detected in the OMV in experimental group;the CCK-8 assay results showed that after treated with different concentrations of OMV,the viabilities of the RAW 264.7 cells,4T1 cells,and HEK293T cells were all close to 100％;the fluorescence imaging results showed that OMV-PD-L1nb was endocytosed by 4T1 cells and dispersed in the cytoplasm;compared with OMV-PD-L1nb group,the average fluorescence intensity in the cells in aPD-L1+OMV-PD-L1nb group was significantly decreased(P＜0.001).Conclusion:The OMV surface-displaying PD-L1nb,OMV-PD-L1nb,is successfully prepared and isolated;OMV-PD-L1nb shows good compatibility on mouse macrophage cells,tumor cells,and human embryonic kidney cells,can be endocytosed by tumor cells,and successfully blocks the PD-1/PD-L1 signaling pathway.

Objective:To investigate the effect of oral administration of vitamin D3 on intestinal barrier function in patients after gastric cancer surgery,and to provide a reference for perioperative nutritional therapy in patients with gastric cancer.Methods:The conve-nience sampling method was used to select 80 patients with gastric cancer who were admitted to Department of Gastrointestinal Surgery in a grade A tertiary hospital in Xiamen,China,from June 2021 to May 2023,and the patients were divided into intervention group and control group using a random number table.The patients in the intervention group were given oral administration of vitamin D3 800 IU/d for 14 consecutive days before surgery.ELISA was used to measure the serum levels of 25-hydroxyvitamin D3[25(OH)D3],intestinal barrier indicators(D-lactate,Zonulin),and inflammatory indicators(C-reactive protein,interleukin-6)within 24 hours after admis-sion and on days 1,4,and 7 after surgery,and the changes in these indicators were compared between the two groups.Results:A total of 71 patients were enrolled finally,with 34 in the intervention group and 37 in the control group.On days 1,4,and 7 after surgery,the intervention group had a significantly lower level of D-lactate than the control group(F=3.978,P=0.026;F=9.649,P=0.005;F=4.389,P=0.021).On day 4 after surgery,the intervention group had a significantly lower level of Zonulin than the control group(F=3.198,P=0.035).Conclusion:Oral administration of vitamin D3 before surgery may accelerate the recovery of intestinal barrier function in pa-tients with gastric cancer.

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*

BackgroundCognitive function is closely related to an individual's quality of life and social functioning， with approximately 20%~35% of patients with depressive disorder experiencing some degree of cognitive impairment even after clinical symptom remission. Existing evidence suggests that tACS can improve specific cognitive domains， such as memory function， while its effects on other cognitive dimensions， such as executive functioning， attention， and information processing speed， remain unclear. ObjectiveTo explore the effects of tACS on the multidimensional cognitive functions and emotional problems of patients with depressive disorder， thus to provide references for the treatment of depressive disorder. MethodsForty-nine patients with depressive disorder who were hospitalized in the Fourth People's Hospital of Wuhu from November 2022 to October 2024 and met the diagnostic criteria for depressive disorder outlined in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， were selected as study participants. Subjects were randomly divided into study group （n=23） and control group （n=26） based on Microsoft Excel. Both groups received sertraline treatment. The initial dose was 50 mg/day， which gradually titrated upward based on individual variability， drug tolerance， and therapeutic response， with a maintenance dose ranging from 100 to 200 mg/day. In addition， the study group underwent tACS therapy for 4 weeks， with 5 sessions per week， each lasting 20 minutes. The control group received sham stimulation， in which the stimulus was interrupted after the first 30 seconds. At baseline， the 4^th week， and the 12^th week of treatment， patients were assessed using the Hamilton Depression Scale-17 item （HAMD-17）， Hamilton Anxiety Scale （HAMA）， and MATRICS Consensus Cognitive Battery （MCCB）. ResultsRepeated measures analysis of variance indicated that both the time effect and the time×group interaction effect for HAMD-17 scores were statistically significant between the two groups （F=260.437， 25.309， P<0.01）. At week 12 of treatment， the HAMD-17 score in the study group was lower than that in the control group （t=4.236， P<0.01）. For HAMA scores， the time effect， group effect， and time×group interaction effect were all statistically significant between the two groups （F=248.082， 4.506， 9.500， P<0.05 or 0.01）. At weeks 4 and 12， study group reported lower HAMA scores compared with control group （t=4.580， 2.608， P<0.05 or 0.01）. Regarding the MCCB scores for attention/vigilance， verbal learning， and overall composite， the time effect， group effect， and time×group interaction effect were all statistically significant between the two groups （F=70.331， 27.882， 51.679， 5.560， 10.948， 7.860， 8.490， 3.874， 5.025， P<0.05 or 0.01）. After intervention， the study group showed significantly higher MCCB scores for attention/vigilance， verbal learning， and overall composite at both week 4 （t=-2.149， -3.530， -2.740， P<0.05） and week 12 （t=-3.534， -3.576， -3.838， P<0.01） when compared to the control group. ConclusionThe combined tACS and sertraline therapy may demonstrate superior efficacy to pharmacotherapy alone in the short term for improving attention/vigilance， verbal learning， overall cognitive function， and anxiety symptoms in patients with depressive disorders. Based on the 12-week outcomes， the combined tACS and sertraline therapy not only sustaine its previously observed advantages in improving cognitive domains and anxiety symptoms， but also demonstrate potentially superior efficacy over monotherapy in alleviating depressive symptoms. ［Fund by Clinical Medical Research Transformation Special Project of Anhui Province （number， 202204295107020065）］

Objective: To examine the relationship between self-management behaviors and time perspective among patients with comorbid diabetes, so as to provide the evidence for improving self-management behaviors among patients with comorbid diabetes. Methods: The patients with comorbid diabetes who were registered in the chronic disease health management system of Minhang District, Shanghai Municipality in 2021, followed up regularly, and lived in Meilong Town were recruited. Demographic information and family history of diabetes were collected through questionnaire surveys. Time perspective and self-management behaviors were assessed using the Zimbardo Time Perspective Inventory and Diabetes Self-Management Behavior Scale, respectively. The relationship between self-management behaviors and time perspective was analyzed using a multivariable ordinal logistic regression model. Results: A total of 907 patients with comorbid diabetes were enrolled, including 472 males (52.04%) and 435 females (47.96%). There were 652 cases aged 65 years and above, accounting for 71.89%. In terms of the types of time perspective, 280 patients were future-oriented (30.87%), 236 were balanced (26.02%), 162 were sensation-seeking (17.86%), 123 were fatalistic (13.56%), and 106 were negative (11.69%). In terms of the self-management behaviors, 46 patients were good (5.07%), 643 were moderate (70.89%), and 218 were poor (24.04%). Multivariable ordinal logistic regression analysis showed that after adjusting for age, gender, educational level, marital status, occupation status, monthly income, and family history of diabetes, the patients with comorbid diabetes who had a future-oriented time perspective had better self-management behaviors (OR=1.874, 95%CI: 1.204-2.915). Conclusion The self-management behaviors among patients with comorbid diabetes are moderate to poor, and patients with a future-oriented time perspective can better engage in self-management behaviors.

Adenomyosis is a common gynecological disease characterized by the invasion of endometrial glands and stroma into the myometrium of uterus, the pathological mechanism of which remains unclear yet. Disturbed lipid metabolism extensively affects abnormal cell proliferation and invasion in various diseases. However, the lipidome signature of human myometrium, which could be crucial in the development of adenomyosis, remains unknown. In this study, we generated the first lipidome profiling of human myometrium using a high-coverage and quantitative lipidomics approach based on ultra-performance liquid chromatography (UPLC) coupled with triple quadrupole (QqQ)-mass spectrometry (MS). A total of 317 lipid species were successfully quantified in the myometrial tissues from women with (n = 38) or without (n = 65) adenomyosis who underwent hysterectomy at Peking Union Medical College Hospital (Bejing, China). Up to 83 lipid species showed significant alternations in content between the two groups. These lipid aberrations involved multiple metabolic pathways, and emphasized inflammation, cell migration, and immune dysregulation upon adenomyosis. Moreover, receiver operating characteristic (ROC) curve analysis found that the combination of five lipid species could accurately distinguished the myometrial samples from women with and without adenomyosis with an area under the curve (AUC) of 0.906. Desorption electrospray ionization MS imaging (MSI) further underscored the heterogeneous distributions of these lipid markers in the adenomyosis lesion and adjacent myometrial tissue. Collectively, these results extremely improved our understanding on the molecular basis of adenomyosis, and could shed light on developing potential biomarkers and new therapeutic directions for adenomyosis.