The clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR /Cas9) immune system is an adaptive immune system widely distributed in bacteria and archaea. It precisely defends against invasion by exogenous phages, viruses, and plasmids through sequence-specific endogenous immune response mechanisms. As the most prominent member of this family, the CRISPR/Cas9 system has evolved into the most widely applied, flexible, and efficient technical platform in the field of genome engineering due to its exceptional genome modification capabilities. Within the CRISPR/Cas9 system, the Cas9 protein, precisely guided by a single-stranded guide RNA (gRNA), can specifically recognize target DNA sequences and induce double-strand breaks. This activates the cell’s DNA repair mechanisms, enabling gene knockout, knock-in, or modification. Demonstrating significant advantages in specificity, flexibility, and operability, CRISPR/Cas9 technology has shown immense potential in the medical field, opening new avenues for modernizing traditional Chinese medicine (TCM) research. On one hand, this technology can be used to construct precise disease models and tailor personalized treatment plans. It enables in-depth elucidation of the molecular mechanisms underlying the action targets and signaling pathways of TCM formulas and active components, thereby unraveling the scientific secrets of their complex mechanisms of action. On the other hand, it demonstrates powerful tool value in improving TCM germplasm resources, identifying and screening superior varieties, evaluating the controllability of TCM quality, and producing innovative drugs, providing technical support for the standardization and precision of TCM. Simultaneously, the high-throughput omics data generated by CRISPR technology is driving artificial intelligence (AI) to construct virtual disease models and drug prediction systems. This empowers the intelligent screening of effective TCM components, the precise prediction of potential targets, and the exploration of “reducing toxicity while enhancing efficacy” through formula combinations. This synergistic innovation between CRISPR and AI aligns perfectly with precision medicine’s urgent demand for personalized, efficient drug development, injecting new momentum into the modernization and transformation of TCM. This paper first systematically reviews and explains the developmental trajectory, structural basis, and action mechanisms of the CRISPR/Cas9 system, tracing its scientific evolution from a bacterial immune system to a gene-editing tool. It then comprehensively outlines the current state of convergence between precision medicine concepts and modernization research in TCM, analyzing the synergistic points and potential spaces for their integration. Against the backdrop of rapid precision medicine advancement, this paper emphasizes how CRISPR/Cas9 gene editing technology empowers in-depth analysis of TCM mechanisms—including specific applications in disease model construction, therapeutic target validation, and multi-target network regulation studies. It further elaborates on its multidimensional practical contributions to modernizing TCM, spanning key domains such as germplasm resource innovation, bioactive compound biosynthesis, quality standardization control, and novel TCM drug development. Finally, this paper envisions the future landscape of deep integration between CRISPR technology and AI: from data-driven intelligent drug screening to high-throughput precision discovery of effective TCM components, and further to intelligent model construction based on “reducing toxicity while enhancing efficacy” mechanisms. The synergistic convergence of these multidimensional technologies will pioneer new scientific paradigms and translational pathways for TCM modernization, propelling TCM toward leapfrogging development in the era of precision medicine.

BACKGROUND:Upper lumbar spinal stenosis is a multifactorial degenerative disorder of the spine.For narrowing of the spinal canal in the upper lumbar region(L1-L4),surgical decision-making is particularly complex.Existing minimally invasive surgeries each have their own advantages and limitations.Currently,there are few reports on biomechanical comparison and finite element analysis of different surgical methods for the treatment of high lumbar spinal stenosis.OBJECTIVE:To analyze the biomechanical impact of endoscopic unilateral laminotomy for bilateral decompression,transforaminal endoscopic lumbar decompression,and cross-overtop decompression in the treatment of upper lumbar spinal stenosis using endoscopy,and to verify the reliability and effectiveness of these three surgical techniques in treating upper lumbar spinal stenosis,providing a biomechanical basis for clinical decision-making.METHODS:The CT images of the lumbar spine of a healthy volunteer were selected,and the finite element model M0 of the normal lumbar L1-L5 segments was established using Mimics,Geomagic,Solid works,and Ansys software.The L2-L3 segment,representing upper lumbar characteristics,was chosen.Based on this model,the surgical models for endoscopic unilateral laminotomy for bilateral decompression(M1),transforaminal endoscopic lumbar decompression(M2),and cross-overtop decompression(M3)were established.Using software,the changes in the range of motion of the entire lumbar segment and the maximum Von Mises stress of the intervertebral discs were simulated and evaluated for each group of models under six loading conditions:flexion,extension,left lateral bending,right lateral bending,left rotation,and right rotation.RESULTS AND CONCLUSION:(1)Compared with model MO,the range of motion in M1,M2,and M3 increased under all six conditions,with M1 showing a greater increase.(2)M1 and M2 demonstrated significant increases in range of motion under forward bending,extension,and right rotation,while the increase under other conditions remained below 7％.(3)Compared with model M3,model M1 exhibited slightly increased overall joint range of motion during extension and left bending,while no significant changes were observed in other aspects,and the L1-L5 lumbar segments did not reach an unstable state.(4)In model M1,the maximum Von Mises stress of the intervertebral discs increased most significantly under flexion and extension loading conditions.However,under left lateral bending,right lateral bending,left rotation,and right rotation loading conditions,the increase did not exceed 5％.(5)These findings suggest that due to the sagittal anatomical characteristics of the facet joints,the unilateral laminotomy for bilateral decompression technique,while decompressing,involves resection of more facet joints,which impacts overall segmental stability.The transforaminal endoscopic lumbar decompression technique is suitable for patients with foraminal stenosis but cannot achieve complete decompression for those with severe ventral central stenosis.The Cross-Overtop technique effectively enlarges the volume of the central canal and lateral recess,optimizing decompression,and shows unique advantages in treating upper lumbar spinal stenosis.

BackgroundAdverse childhood experiences （ACEs） are strong predictors of psychopathology across the lifespan， exerting extensive adverse effects on physical and mental health during early development. While ACEs increase the risk of childhood psychopathology， sleep quality and impair cognitive function， the early neurobiological mechanisms mediating ACE-induced cognitive impairment remain unclear. ObjectiveTo explore the association between ACEs exposure and the risk of psychopathology， sleep disorders， and cognitive function， and to examine the mediating role of the putamen volume in the relationship between ACEs and cognitive function from a neurodevelopment perspective. MethodsData were obtained from the Adolescent Brain Cognitive Development （ABCD） study， comprising 10 572 children aged 9 to 10. Participants were categorized into five groups based on the cumulative score of ACEs reported by their parents and the children themselves： no-exposure group （0 types of ACEs）， the one-exposure group， the two-exposure group， the three-exposure group， and the high-risk exposure group （≥ 4 types of ACEs）. Logistic regression analysis was employed to evaluate the association between ACEs and psychopathological symptoms ［T score of the Child Behavior Checklist （CBCL） ≥ 65］. Multiple linear regression analysis was ultilized to analyze the correlations between ACEs and the scores of the Sleep Disturbance Scale for Children （SDSC）， the NIH Toolbox Cognition Battery （NIHTB-CB）， as well as the multiple structures in the cerebral cortex and subcortex. The Bootstrap method was applied to test the mediating effect of the putamen volume between ACEs and neurocognitive function. ResultsAfter adjusting for confounders， ACEs cumulative score was correlated with children's psychopathological symptoms in a dose-response manner. Compared with the no-exposed group， the high-risk exposure group had a 2.08-fold （OR=2.080， 95% CI： 1.401–3.088） increased risk of internalizing problems and a 3.13-fold （OR=3.132， 95% CI： 1.703–5.760） increased risk of externalizing problems， and the risk of conduct problems was 4.68 times that of the no-exposed group （OR=4.681， 95% CI： 2.528–8.669）. ACEs cumulative score positively predicted the total score of SDSC （β=0.080， 95% CI： 0.059–0.102）， with relatively stronger predictive effects on sleep-wake transition disorder （β=0.086， 95% CI： 0.063–0.109） and sleep onset and maintenance disorder （β=0.066， 95% CI： 0.043–0.089）. In terms of neurocognition and brain structure， ACEs cumulative score negatively predicted the overall cognitive composite score （β=-0.025， 95% CI： -0.050–-0.001）， the crystallized cognitive composite score （β=-0.035， 95% CI： -0.060–-0.010）， the volume of the left putamen nucleus （β=-0.025， 95% CI： -0.046– 0.003）， and the volume of the right putamen nucleus （β=-0.023， 95% CI： -0.044– 0.003）. The total putamen volume played a partial mediating role between ACEs and the overall cognitive composite score， the effect value was -0.002 （95% CI： -0.004–-0.001）， accounting for 7.49% of the total effect. ConclusionACEs exposure may increase the risk of psychopathological and sleep disturbances in children and may impair neurocognitive function. Reduced putamen volume may serve a potential neurobiological pathway underlying the impact of ACEs on childhood cognition. ［Funded by National Natural Science Foundation of China-Young Scientists Program （number， 82401763）； Sichuan University West China Hospital Full-time Postdoctoral Research and Development Fund Project （number， 2023HXBH084）］

BACKGROUND:Upper lumbar spinal stenosis is a multifactorial degenerative disorder of the spine.For narrowing of the spinal canal in the upper lumbar region(L1-L4),surgical decision-making is particularly complex.Existing minimally invasive surgeries each have their own advantages and limitations.Currently,there are few reports on biomechanical comparison and finite element analysis of different surgical methods for the treatment of high lumbar spinal stenosis.OBJECTIVE:To analyze the biomechanical impact of endoscopic unilateral laminotomy for bilateral decompression,transforaminal endoscopic lumbar decompression,and cross-overtop decompression in the treatment of upper lumbar spinal stenosis using endoscopy,and to verify the reliability and effectiveness of these three surgical techniques in treating upper lumbar spinal stenosis,providing a biomechanical basis for clinical decision-making.METHODS:The CT images of the lumbar spine of a healthy volunteer were selected,and the finite element model M0 of the normal lumbar L1-L5 segments was established using Mimics,Geomagic,Solid works,and Ansys software.The L2-L3 segment,representing upper lumbar characteristics,was chosen.Based on this model,the surgical models for endoscopic unilateral laminotomy for bilateral decompression(M1),transforaminal endoscopic lumbar decompression(M2),and cross-overtop decompression(M3)were established.Using software,the changes in the range of motion of the entire lumbar segment and the maximum Von Mises stress of the intervertebral discs were simulated and evaluated for each group of models under six loading conditions:flexion,extension,left lateral bending,right lateral bending,left rotation,and right rotation.RESULTS AND CONCLUSION:(1)Compared with model MO,the range of motion in M1,M2,and M3 increased under all six conditions,with M1 showing a greater increase.(2)M1 and M2 demonstrated significant increases in range of motion under forward bending,extension,and right rotation,while the increase under other conditions remained below 7％.(3)Compared with model M3,model M1 exhibited slightly increased overall joint range of motion during extension and left bending,while no significant changes were observed in other aspects,and the L1-L5 lumbar segments did not reach an unstable state.(4)In model M1,the maximum Von Mises stress of the intervertebral discs increased most significantly under flexion and extension loading conditions.However,under left lateral bending,right lateral bending,left rotation,and right rotation loading conditions,the increase did not exceed 5％.(5)These findings suggest that due to the sagittal anatomical characteristics of the facet joints,the unilateral laminotomy for bilateral decompression technique,while decompressing,involves resection of more facet joints,which impacts overall segmental stability.The transforaminal endoscopic lumbar decompression technique is suitable for patients with foraminal stenosis but cannot achieve complete decompression for those with severe ventral central stenosis.The Cross-Overtop technique effectively enlarges the volume of the central canal and lateral recess,optimizing decompression,and shows unique advantages in treating upper lumbar spinal stenosis.

[摘 要] 目的：探讨环指蛋白8（RNF8）对子宫内膜癌（EC）细胞顺铂（CDDP）敏感性的影响及可能机制。方法：基于在线数据库分析RNF8在EC组织中的表达及拷贝数变异；采用慢病毒介导shRNA稳定敲低Ishikawa细胞中RNF8表达并进行CDDP处理，按sh-NC+溶剂对照、sh-RNF8+溶剂对照、sh-NC + CDDP、sh-RNF8 + CDDP分组处理，并设置sh-RNF8 + CDDP + KU60019抑制实验。采用CCK-8、克隆形成、Annexin V-FITC/PI流式细胞术、Hoechst 33258/PI染色、WB及γ-H2AX免疫荧光检测细胞活力、克隆形成、凋亡、DNA损伤累积及ATM/CHK2通路相关蛋白表达。结果：RNF8在EC组织和细胞中表达升高。RNF8敲低降低细胞存活率和IC50，抑制克隆形成，并进一步增强CDDP诱导的凋亡；同时BAX、Cleaved-Caspase-3和γ-H2AX表达升高，BCL-2、p-ATM、p-CHK2和RAD21表达降低。KU60019处理进一步促进DNA损伤累积和细胞凋亡，并降低细胞活力。结论：RNF8可能通过ATM/CHK2轴促进DNA损伤应答并降低EC细胞对CDDP的敏感性；敲低RNF8可增加DNA损伤累积并增强CDDP敏感性。

Objective To evaluate the performance of lightweight Chinese large language models (LLMs) in answering specialized lung cancer questions, and to explore the impact of retrieval-augmented generation (RAG) on model performance. Methods Eleven lightweight Chinese LLMs with parameter sizes ranging from 7B to 32B were included. A lung cancer-specific evaluation dataset consisting of 200 questions [100 A1-type (basic knowledge) and 100 A2-type (clinical case) questions], constructed based on clinical guidelines and thoracic surgery textbooks, was used for assessment. Model performance was evaluated under two conditions (with and without RAG). Accuracy was used to assess model performance, and response latency was recorded to reflect inference efficiency. An accuracy–latency scatter plot was constructed for descriptive analysis of overall model performance. Results All models successfully completed the evaluation. With the introduction of RAG, the overall average accuracy improved from 61.68% to 76.36%. Smaller models demonstrated the most significant improvement (e.g., the accuracy of DeepSeek-7B increased from 32.50% to 60.00%, P<0.001). The average response latency increased from 12.58 s to 13.80 s. The Qwen3 series showed the best overall performance, and Qwen3-32B achieved the highest accuracy under both conditions (76.50% and 84.00%, respectively). After RAG integration, performance differences among model families were markedly reduced. Based on the accuracy-latency trade-off, Qwen3-32B achieved the best balance between accuracy and response latency under the baseline condition, whereas Qwen3-14B demonstrated superior overall performance in terms of accuracy, latency, and computational cost after RAG integration. Conclusion The integration of RAG technology improves the ability of lightweight Chinese LLMs to answer specialized lung cancer questions. Under the dual practical constraints of limited computational resources and medical data security requirements, the "lightweight model+RAG" technical framework may represent a promising deployment solution.

ObjectiveTo investigate the regulatory mechanism of peptidylarginine deiminase 4 （PADI4） on matrix metalloproteinase （MMPs） expression and its potential role in the development of systemic lupus erythematosus （SLE）. MethodsThe mRNA expression levels of MMP-14/17/25 in SLE patients and healthy controls （HC） were measured by real-time fluorescence quantitative reverse transcription polymerase chain reaction （RT-qPCR）， and their serum protein levels were measured by enzyme-linked immunosorbent assay （ELISA）. Spearman's rank correlation analysis was used to evaluate the correlations between MMPs levels and clinical parameters in SLE patients. Primary neutrophils were treated with the PADI4 inhibitor GSK484， or MMPs expression levels were examined in PADI4-knockdown neutrophil-like HL-60 （dHL-60） cells， and cell migration ability was assessed by wound healing assay. ResultsThe mRNA expression levels of MMP-14/17/25 in neutrophils from SLE patients were lower than those in the HC （all P<0.01）. Serum levels of these three MMPs were also lower than those in the HC （all P<0.01）. MMP-14 levels were negatively correlated with immunoglobulin G （IgG） （r=-0.266）， immunoglobulin A （IgA） （r=-0.286）， and globulin （GLB）（r=-0.269） （all P<0.05）， while both MMP-17 （r=-0.269） and MMP-25（r=-0.244） levels were negatively correlated with urinary protein （UTP） （all P<0.05）. After treatment with GSK484 （10 μmol/L） to inhibit PADI4 activity， the protein expression levels of MMP-14/17/25 in neutrophils were higher than those in the Vehicle group （all P<0.05）， and the cell migration rate in wound healing assay was also greater than that in the Vehicle group （P<0.01）. Furthermore， after knockdown of PADI4 expression， the mRNA expression levels of MMP-14/17/25 were higher than those in the Vehicle group （all P<0.05）. ConclusionMMP-14/17/25 are downregulated in SLE and negatively regulated by PADI4. PADI4 may contribute to SLE progression by suppressing MMPs expression and neutrophil migration. These findings suggest that MMPs may serve as novel biomarkers and therapeutic targets for SLE.

ObjectiveTo investigate the mRNA expression profile and clinical significance of the RAB24 gene in hepatocellular carcinoma （HCC） based on multi-source database including The Cancer Genome Atlas （TCGA） and clinical cohort validation. MethodsData from TCGA （n=424） were utilized to evaluate the prognostic value of RAB24 expression via Kaplan-Meier analysis and Cox regression models. An independent clinical cohort comprising 90 HCC and 30 paracancerous tissues was established to validate protein expression and histopathological features through immunohistochemistry （IHC） and routine histological staining. The TIMER database was employed to analyze the association between RAB24 and the tumor microenvironment （TME）. Furthermore， integrated with LinkedOmics， GSEA and GSVA algorithms were used to quantitatively characterize the core molecular pathways regulated by RAB24. ResultsThe mRNA expression level of RAB24 in HCC was significantly higher than that in non-tumor liver tissues （P<0.05）. Kaplan-Meier analysis revealed that the overall survival （OS） of patients in the RAB24 low-expression group was significantly longer compared to the high-expression group （HR=1.570， Log-rank P=0.01）. Cox proportional hazards regression analysis demonstrated that RAB24 expression （HR=1.480， P=0.028）， T stage （HR=2.949， P<0.001）， M stage （HR=4.077， P=0.017）， and tumor residual status （HR=2.317， P<0.001） were independent prognostic factors for HCC. RAB24 expression was highly correlated with alpha-fetoprotein （AFP） levels and immune infiltration levels （P<0.01）， and showed a significant， low-level positive correlation with the TP53 gene （Rho=0.31， P<0.01）. Quantitative analysis of the RAB24 protein in clinical samples validated that RAB24 expression in HCC tissues was significantly elevated compared to non-tumor liver tissues （P<0.05）. TIMER analysis confirmed that RAB24 expression was highly associated with the infiltration of multiple immune cells （such as B cells and NK cells）， as well as stromal and tumor purity scores in tumor tissues （P<0.01）. GSEA/GSVA enrichment revealed that the P53， MYC， and mTORC1 signaling pathways were activated in the RAB24 high-expression group； correlation analysis confirmed that the RAB24 expression level exhibited a significant， low-level positive correlation with the ribosome pathway activity score （r=0.23， P<0.01）. ConclusionsThe RAB24 gene， as a poor prognostic factor for HCC patients， is a potential biomarker for HCC diagnosis， treatment and prognosis. The study is expected to lay a theoretical foundation for the precise diagnosis and treatment of clinical HCC.

Objective To understand the distribution, species composition, seasonal fluctuations, and presence of Dabie bandavirus in ticks in Tai'an City, providing a basis for assessing tick-borne disease risks and formulating prevention strategies. Methods Free-living ticks were monitored using the flagging method, whereas parasitic ticks were monitored through host surface examination. Reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the presence of Bandavirus dabieense in tick specimens. Results The density of free-living ticks in Tai'an City showed a continuous decreasing trend over the 3 years from 2021 to 2023, with an average tick density of 0.43 ticks/(flag·100 m). The dominant habitats were scenic areas and forests, and the seasonal fluctuations exhibited a bimodal pattern, peaking in March and August. The only free-living tick species captured was Haemaphysalis longicornis. Over the 3 years, the average tick index for parasitic ticks was 1.85, with sheep as the primary host. Seasonal fluctuations also followed a bimodal pattern, peaking in March and August. The primary parasitic tick species captured were H. longicornis and Rhipicephalus sanguineus. No Dabie bandavirus was detected in the tick specimens. Conclusions Tick density in Tai'an City remains relatively high, necessitating continued efforts to enhance tick surveillance and implement targeted prevention measures in rural environments to further reduce the health risks posed by tick-borne diseases.

BACKGROUND:Zinc-based alloy medical implant materials have excellent mechanical properties,complete degradability and good biocompatibility,and are mainly used in orthopedic implants,cardiovascular stents,bile duct stents,tracheal stents,nerve catheters,etc. OBJECTIVE:To review the research progress of biodegradable zinc-based alloys in bone defect repair and prospect the promising research direction and achievements of zinc-based materials. METHODS:After searching PubMed,Web of Science,WanFang Data,and CNKI databases from the establishment of the database to June 2023,various relevant articles on biodegradable zinc-based alloys for bone implant material research were collected.The basic characteristics of biodegradable zinc based alloys were summarized,and the role of zinc-based alloys in promoting bone tissue repair was sorted and summarized.The current research hotspots and shortcomings were discussed. RESULTS AND CONCLUSION:(1)Zinc-based alloys have good biocompatibility.Using zinc-based alloys as the matrix material,with the help of scaffold structure construction technology and coating optimization process,the bone conductivity of zinc-based alloys will be effectively improved,and their degradation products will have efficient bone induction to regulate the gene expression of osteoblasts and osteoclasts,thereby promoting the repair and reconstruction of bone defects.(2)However,in the research on optimizing zinc-based alloys,the coating process is relatively insufficient,and additive loading technology is still lacking.(3)Zinc-based alloys have excellent mechanical and biological properties.Through special processes,their bone conductivity and osteoinductivity can be increased to effectively improve their ability to promote bone repair and reconstruction,and it is expected to further achieve the development of personalized transplant materials.Further research and development are needed to optimize the integration of coating and additive loading technologies into zinc-based alloys.