ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

ObjectiveTo observe the effects of Qingxin Jieyu granules （QXJYG） on FeCl₃-induced carotid artery thrombosis in rats and on the expression of thrombosis-related proteins tissue factor （TF） and tissue factor pathway inhibitor （TFPI） as well as the protein kinase B （Akt）/nuclear factor-κB （NF-κB） signaling pathway in EA.hy926 cells exposed to tumor necrosis factor-α （TNF-α）， thus preliminarily exploring the mechanism of QXJYG in inhibiting thrombosis. MethodsThirty-six SD rats were randomized into normal control， model， positive control （aspirin， 9 mg·kg^-1）， and low-， medium-， and high-dose （0.99， 1.98， 3.96 g·kg^-1， respectively） QXJYG groups （n=6）. The rats in the drug treatment groups were administrated with corresponding drugs， and those in the normal control group and model group were given an equal volume of distilled water. After 14 consecutive days of prophylactic gavage， the rat model of common carotid artery thrombosis was established with 45% FeCl₃ solution， and the blood vessels were collected and the wet weight of thrombus was weighed by an electronic balance （precision of 1/10 000）. The thrombosis in the common carotid artery of each group of rats was observed by hematoxylin-eosin staining. The plasma levels of von Willebrand factor （vWF）， platelet endothelial cell adhesion molecule-1 （PECAM-1）， tissue-type plasminogen activator （t-PA）， and plasminogen activator inhibitor-1 （PAI-1） were determined by enzyme-linked immunosorbent assay. An endothelial cell injury model was established by treating EA.hy926 human umbilical vein endothelial cells with TNF-α. The cell counting kit-8 method was used to screen the intervention concentrations of QXJYG. Western blot was employed to determine the protein levels of TF， TFPI， Akt， p-Akt， NF-κB p65， and p-NF-κB p65 in each group of cells. ResultsThe animal experiment showed that compared with the normal control group， the model group showed an increase in carotid artery thrombus weight （P<0.05）， with unclear vascular structure and extensive thrombosis in the lumen. In addition， the plasma levels of vWF， PECAM-1， and PAI-1 were elevated， while the t-PA level became lowered （P<0.05） in the model group. Compared with the model group， the aspirin and QXJYG groups showed reductions in the weight of FeCl₃-induced carotid artery thrombi （P<0.05） and thrombosis in the lumen， declines in plasma levels of PECAM-1 and PAI-1， and an elevation in the t-PA level （P<0.05）. Moreover， the QXJYG groups showed reductions in the plasma level of vWF （P<0.05）， which， however， had no significant difference between the aspirin group and the model group. The cell experiments indicated that 31.25， 62.5， 125， 250， 500 mg·L^-1 QXJYG had no effect on the viability of EA.hy926 cells. Therefore， 250， 500 mg·L^-1 QXJYG were selected as the intervention concentrations for subsequent experiments. Western blotting results showed that compared with the control group， the TNF-α stimulation downregulated the expression of TFPI （P<0.05）， upregulated the expression of TF， and increased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05） in EA.hy926 cells. Compared with the model group， the intervention with QXJYG upregulated the expression of TFPI （P<0.05）， inhibited the expression of TF， and decreased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05）. ConclusionQXJYG has the effect of inhibiting thrombosis and regulating the expression of TF and TFPI in endothelial cells exposed to TNF-α by suppressing the abnormal activation of the Akt/NF-κB signaling pathway.

Objective To explore the effectiveness of an integrated laparoscopic simulation training course (best essential surgical technique training, BEST) in enhancing laparoscopic peritoneal suturing techniques in surgical residents.Methods As an integrated two-stage program, the BEST course applied basic laparoscopic training system with simple molds in phase Ⅰ training, and then adopted advanced laparoscopic training system, 3D Laparoscope and ex-vivo animal models in phase Ⅱ training. The laparoscopic suturing techniques were practiced in phase Ⅱ training. From August 2021 to July 2024, surgical residents in the second year of the national standardized training program were divided into pilot and control groups based on whether they had undergone the BEST course. Two cases of laparoscopic peritoneal suture were performed by the surgical residents under supervision in the department of gastrointestinal surgery. The operative time, quality of suture, and independent completion rate were compared between the two groups.Results A total of 33 surgical residents (19 in pilot group and 14 in control group) were included in this study, and a total of 66 cases of laparoscopic peritoneal suture were performed (38 in pilot group and 28 in control group). The operative time was significantly shorter in pilot group than that in control group (15.7 min vs. 17.5 min, P=0.025). The quality of suture was significantly better in pilot group compared to control group (P=0.023). In pilot group, all peritoneal sutures were performed by residents independently, whereas in control group, 3 cases (10.7%) were assisted by the supervisor, and the independent completion rate was different significantly (P=0.039).Conclusions The BEST course can help improve surgical residents′ laparoscopic peritoneal suturing techniques and could be promoted in the national standardized training program for surgical residents.

Objective:To explore the clinical efficacy of percutaneous balloon compression (PBC) in the treatment of trigeminal neuralgia (TN) based on the double difference (DID) model.Methods:A retrospective case - control study method was adopted to analyze the general data of 130 patients with trigeminal neuralgia (TN) who were treated in the Department of Neurosurgery of Hebei General Hospital from January 2022 to October 2023. Among them, 49 were males and 81 were females. The age was (53.28±11.67) years, ranging from 25 to 80 years old. According to different treatment methods, the patients were divided into an experimental group ( n=63) and a control group ( n=67). Patients in the experimental group were given percutaneous balloon compression (PBC) treatment, while those in the control group were treated with conservative drug therapy. Propensity score matching method was used for 1∶1 matching. After matching, there were 52 cases in each group. The general data of the two groups were compared. The visual analogue scale (VAS), 36-item short form health survey (SF-36) score, Hamilton depression rating scale (HAMD) score, Hamilton anxiety rating scale (HAMA) score, 5-hydroxytryptamine, neuropeptide P, inflammatory factor interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α) before and after treatment, as well as the clinical efficacy of the two groups of patients were comparatively analyzed. Meanwhile, the incidence of postoperative complications in the two groups was compared. The generalized estimating equation (GEE) model was used to analyze the influencing factors of clinical efficacy, and the difference-in-differences (DID) model was used to evaluate the efficacy before and after treatment. Measurement data conforming to the normal distribution were expressed as mean±standard deviation ( ± s), and the t-test was used for comparison between groups; the chi- square test was used for comparison between count data. Results:After treatment, the VAS, SF-36 score, HAMD score, HAMA score, 5-hydroxytryptamine level, neuropeptide P level, IL-1 level, and TNF-α level in the experimental group were (2.98±0.83) points, (75.56±1.18) points, (7.2±0.83) points, (7.15±0.85) points, (76.34±5.47) ng/mL, (50.95±11.01) pg/mL, (29.45±7.08) ng/L, and (21.18±3.55) ng/L respectively. In the control group, there were (3.63±0.95) points, (73.23±1.13) points, (7.98±0.80) points, (8.04±0.84) points, (186.31±11.61) ng/mL, (86.52±13.32) pg/mL, (34.47±6.58) ng/L, and (26.36±5.80) ng/L, respectively. The differences between the two groups were statistically significant ( P<0.05).The cure rate and the total incidence of postoperative complications in the experimental group were 55.77% and 13.46% respectively, while in the control group, they were 40.38% and 30.77% respectively. The differences between the two groups were statistically significant ( P<0.05).The results of the GEE model analysis showed that age, course of disease, VAS, SF-36 score, HAMA score, HAMD score, 5-hydroxytryptamine level, neuropeptide P level, IL-1 level, TNF-α level, treatment method, and the long - diameter ratio of FO significantly affected the clinical efficacy of patients ( P<0.05).The results of the DID model showed that the experimental group was superior to the control group in improving the VAS, SF-36 score, HAMD score, HAMA score, 5-hydroxytryptamine level, neuropeptide P level, IL-1 level, and TNF-α level( P<0.05). Conclusion:PBC can significantly improve the VAS, SF-36 score, HAMD score, HAMA score, 5-hydroxytryptamine, neuropeptide P, IL-1, TNF-α, and incidence of complications in patients with TN. It can also improve the psychological status and quality of life of patients.

BACKGROUND:Previous studies found that the proliferative scar-specific long non-coding RNA lncRNA HSFAS is a novel biomarker that can be used in the diagnosis of hypertrophic scar,but how it functions in hypertrophic scar is not clear. OBJECTIVE:To investigate the role and mechanism of lncRNA HSFAS in hypertrophic scar.METHODS:Fresh scar tissue and surrounding normal skin tissue samples from three patients with hypertrophic scar were collected,and tissue immunofluorescence was used to detect the expression of lncRNA HSFAS in frozen sections of two skin tissues. Primary fibroblasts were isolated from proliferative scarred skin tissue and normal skin tissue and cultured by enzyme digestion method. Quantitative real-time PCR was used to detect the mRNA expression of lncRNA HSFAS in cells. The proteins bound to lncRNA HSFAS were detected by RNA pull-down combined mass spectrometry. GO and KEGG were used to analyze the main functions and pathways of lncRNA HSFAS involved in hypertrophic scar progression. The targeted binding of lncRNA HSFAS to proteins was determined by catRAPID and RPISeq website analysis. RESULTS AND CONCLUSION:Compared with normal skin tissue and fibroblasts from normal skin tissue,the expression of lncRNA HSFAS in human hypertrophic scar tissue and primary fibroblasts from hypertrophic scar tissue was significantly increased (P<0.05). There were 510 proteins clearly bound to lncRNA HSFAS by RNA pull-down combined mass spectrometry. The results of GO and KEGG analyses showed that these proteins were mainly involved in RNA splicing and processing,chromosome synthesis and separation,and cell cycle. Among them,the proteins involved in RNA splicing and processing included scaffold attachment factor B2 and DICER1,and the binding fraction with lncRNA HSFAS was higher. The results of bioinformatics analysis showed that lncRNA HSFAS was bound to scaffold attachment factor B2 and DICER1 proteins. To conclude,lncRNA HSFAS may affect gene expression by interacting with scaffold attachment factor B2 and DICER1 proteins to regulate RNA splicing and processing modification,thus promoting the occurrence and development of hypertrophic scar.

BACKGROUND:Dental follicle cells are widely used in periodontal tissue regeneration engineering because of their excellent characteristics.With the development of biological scaffold materials,their relationship with periodontal tissue regeneration technology is increasingly close.OBJECTIVE:To review the performance of ivory follicle cells under the influence of internal and external biological factors by different experiments,and analyze their effects on the biological characteristics of dental follicle cells with scaffold materials.METHODS:Using"dental follicle cell,scaffolds,material,periodontal tissue regeneration,tissue engineering,review"as English and Chinese key words,the articles published in PubMed,Sciencedirect,and CNKI from 2013 to 2023 were searched,and finally 95 articles were included for analysis and discussion.RESULTS AND CONCLUSION:(1)Dental follicle cells originate from dental follicle tissue,which has certain stem cell differentiation potential.Because of its excellent performance,it is actively used in periodontal tissue regeneration engineering research.(2)The proliferation and osteogenic differentiation of dental follicle cells are affected by many biological factors,and both endogenous and exogenous factors can promote the proliferation and osteogenic differentiation of dental follicle cells to a certain extent.(3)3D printing technology and nanotechnology enable researchers to manufacture more suitable scaffold materials.(4)Polymer materials show us their flexibility and plasticity in periodontal tissue regeneration.We can manufacture targeted scaffold materials according to different defect sites to achieve efficient tissue regeneration.The good biocompatibility of inorganic materials makes them widely used in periodontal tissue regeneration engineering.By adjusting the content of nanoscale inorganic materials or improving the performance of scaffolds,scaffolds with better biocompatibility can be prepared.(5)There are many new synthetic(composite)materials,which show us excellent characteristics.However,because the mechanism of biological factors in scaffold materials on dental follicle cells is complicated,and the research on dental follicle cells is mostly concentrated on in vitro culture,so how to make scaffold materials more suitable for the growth and development of dental follicle cells and apply them safely and effectively in clinical treatment is the future research direction.

Objective:To investigate the effects of two anastomosis methods on perioperative and pathological outcomes during totally laparoscopic right hemicolectomy (TLRH).Methods:In a national multicenter snapshot study, 1,854 patients who underwent laparoscopic right hemicolectomy were enrolled from 52 tertiary hospitals across China. The post-hoc analysis based on this study compared the data of 303 patients who underwent TLRH. Patients were divided into the antiperistaltic group (33 cases) and the isoperistaltic group (270 cases) according to type of anastomosis. Due to the significant difference in sample size between the two groups, propensity score matching (PSM) was performed to eliminate the influence of baseline characteristic discrepancies. The matching was based on the following known confounding factors: age, gender, body mass index (BMI), history of abdominal surgery, and history of diabetes, with a caliper value of 0.2. Perioperative and pathological outcomes were compared between the two groups.Results:After PSM, 33 patients were included in the antiperistaltic group and 65 patients in the isoperistaltic group. There were no statistically significant differences in baseline data between the two groups (all P>0.05). No significant differences were observed between the two groups in terms of operation time, blood loss, time to first defecation, time to first oral intake, or the incidence and grading of complications either (all P>0.05). However, length of postoperative hospital stay in the isoperistaltic group was significantly shorter than that in the antiperistaltic group, however (7.0 [6.0, 9.0] days vs. 8.0 [7.0, 10.5] days, P=0.049). In terms of pathological outcomes, there were also no statistically significant differences between the two groups in the number of harvested lymph nodes or the number of positive lymph nodes (all P>0.05). Conclusions:The two digestive tract reconstruction modalities, antiperistaltic and isoperistaltic anastomosis, have comparable perioperative safety and efficacy in TLRH. The isoperistaltic group had better outcomes in terms of postoperative hospital stay.

Objective To investigate the effect and mechanism of Efferocytosis Relatived LncRNA (EFRL) on homocysteine-induced atherosclerosis in macrophage efferocytosis. Methods RAW264.7 cells were cultured in vitro, and the Control group (0 μmol/L Hcy) and Hcy intervention group (100 μmol/L Hcy) were set up. After GapmeR transfection of macrophages with Hcy intervention, EFRL knockdown negative control group (Hcy combined with LNA-NC) and EFRL knockdown group (Hcy combined with LNA-EFRL) were set up. High-throughput sequencing was applied for different expression of LncRNA MSTRG. 88917.16 (EFRL), UCSC was used to analyze its conservation, CPC and CPAT were used to analyze its ability to encode proteins, and GO and KEGG were used to analyze related biological functions. The localization of LncRNA EFRL in macrophages was analyzed by nucleoplasmic separation and RNA-FISH. Quantitative real-time PCR was used to detect the expression levels of LncRNA EFRL and its target gene SPAST in Hcy-treated macrophages. The apoptosis rate of Jurkat cells induced by UV was detected by flow cytometry. In vitro efferocytosis assay combined with immunofluorescence technique was used to analyze macrophage efferocytosis. ELISA was used to detect the levels of interleukin 1β(IL-1β) and IL-18. Results The new LncRNA MSTRG.88917.16 was identified and named EFRL(Efferocytosis Relatived LncRNA). UCSC, CPC and CPAT analyses showed that LncEFRL is highly conserved and does not have the ability to encode proteins. GO and KEGG analyses suggested that LncEFRL may be involved in macrophage efferocytosis. LncRNA EFRL was localized in the nucleus of macrophages as determined by nucleoplasmic separation and RNA-FISH. In comparison to the Control group, the expression levels of LncRNA EFRL and its target gene SPAST in the Hcy group were increased. In comparison to the Control group (0 min), the apoptosis rate of the experimental group (15, 30 min) Annexin V is more than 85%. Compared with Hcy combined with LNA-NC group, Hcy combined with LNA-EFRL group had enhanced macrophage efferocytosis and reduced levels of inflammatory factors. Compared with Hcy combined with LNA-NC group, the expression level of SPAST in Hcy combined with LNA-EFRL group was decreased. Conclusion Inhibition of EFRL expression can alleviate the process of Hcy inhibiting macrophage efferocytosis, and the mechanism is related to the regulation of the downstream target gene SPAST by EFRL.
RNA, Long Noncoding/physiology* ; Animals ; Homocysteine ; Mice ; Macrophages/drug effects* ; Humans ; RAW 264.7 Cells ; Atherosclerosis/chemically induced* ; Apoptosis/genetics* ; Phagocytosis/genetics* ; Jurkat Cells ; Interleukin-1beta/genetics* ; Efferocytosis

The red doctor spirit is the advanced culture of the Communist Party of China formed under a specific historical and cultural background. It can be summarized as “political firmness， excellent technology， working hard， and healing the wounded and rescuing the dying.” This content has many hidden similarities and integrations with the goal of cultivating humanistic literacy for medical students in military medical universities. This paper aimed to identify the important connection points between the red doctor spirit and the contents and goals of medical humanities teaching， as well as integrate the red doctor spirit into medical humanities teaching by various dimensions， including systematic reconstruction of textbook content， immersive innovation in teaching form， three-dimensional support in resource construction， and innovative implementation of narrative medicine teaching. It also further explored the extension of the red doctor spirit in military medical humanistic literacy， namely， revolutionary humanism and revolutionary heroism， thereby enhancing the effectiveness of medical humanistic teaching.

Kirsten rat sarcoma viral oncogene homolog (KRAS) protein inhibitors are a promising class of therapeutics, but research on molecules that effectively penetrate the blood-brain barrier (BBB) remains limited, which is crucial for treating central nervous system (CNS) malignancies. Although molecular generation models have recently advanced drug discovery, they often overlook the complexity of biological and chemical factors, leaving room for improvement. In this study, we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug efficacy and drug absorption properties. Our approach utilizes a variational autoencoder (VAE) generative model integrated with reinforcement learning for multi-objective optimization. This method specifically aims to enhance BBB permeability (BBBp) while maintaining high-affinity substructures of KRAS inhibitors. To support this, we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models. Additionally, we introduce two novel metrics, the knowledge-integrated reproduction score (KIRS) and the composite diversity score (CDS), to assess structural performance and biological relevance. Retrospective validation with KRAS inhibitors, AMG510 and MRTX849, demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications. This study provides a robust framework for accelerating the structural enhancement of lead compounds, advancing the drug development process across diverse targets.