Objective:To explore the effectiveness of applying the ADDIE (analysis, design, develop, implement, evaluate) Model in clinical teaching for nursing interns in spine surgery department.Methods:Using a convenience sampling method, 44 nursing interns in the Department of Orthopedics at Peking Union Medical College Hospital were selected as the control group from July 2021 to May 2022, and were taught using traditional methods. From July 2022 to May 2023, 45 nursing interns were selected as the observation group, and a teaching team was formed to design a training program based on the five stages of the ADDIE instructional design model. This program was tailored to improve the overall clinical competence of the spinal surgery nursing interns. After training, the teaching effects were evaluated based on knowledge test scores, skills test scores, overall clinical competence, and teaching satisfaction.Results:After the training, the skills test scores in specialized nursing for the observation group were (94.87±1.10) points, higher than the control group's (93.98±1.41) points, with a statistically significant difference ( P<0.01). The observation group also scored higher than the control group in clinical judgment, organizational effectiveness, overall performance, and total score in the Mini-Clinical Evaluation Exercise, with statistically significant differences ( P<0.01). Additionally, the observation group reported higher satisfaction with the teaching plan and methods compared to the control group ( P<0.05) . Conclusions:Clinical teaching for spinal surgery nursing interns based on the ADDIE instructional design model can improve their specialized practical skills and overall clinical competence. The interns also expressed a high level of acceptance for this teaching design model.

Objective To explore the role of transcription factor EB(TFEB)induced by aerobic exer-cise in improving insulin resistance(IR)of skeletal muscles in high-fat diet mice.Method Eighteen male SPF C57BL/6 mice aged 6 weeks were randomly divided into a common diet group(CON),a high-fat diet group(HFD),and a high-fat diet exercise group(HFDE),each of 6.Both high-fat groups were on high-fat diet for 12 weeks.Then the HFDE group underwent daily 60-minute tread-mill exercise with the slope of 0°,at a speed of 12 m/min,5 times per week for 12 weeks.Finally,the glucose tolerance and insulin sensitivity were detected using the intraperitoneal injection glucose tol-erance test(IPGTT)and intraperitoneal injection insulin tolerance test(IPITT).The fasting blood glu-cose and insulin contents were measured by biochemical method,and the IR level was calculated by using the homeostatic model assessment of insulin resistance(HOMA-IR).Moreover,Western blotting was employed to detect the expression of phosphorylated transcription factor EB(pTFEB)and TFEB in skeletal muscle,glucose transporter 4(GLUT4)in cytoplasm and membrane,phosphorylated insulin re-ceptor substrates1(pIRS1),phosphorylated protein kinase B(pAKT),phosphoinositide 3-kinase(PI3K),and phosphorylated akt substrate of 160 kD(pTBC1D4)in skeletal muscle.The correlation of pTFEB and TFEB to insulin signaling pathway-related proteins was analyzed.Results(1)Compared with the CON group,there was a significant increase in the average body weight,IPGTT,blood glucose at each time point of IPGTT,area under curve(AUC),serum insulin,HOMA-IR,protein expressions of pTFEB,total-TFEB and GLUT4 in cytoplasm of the HFD group(P<0.01),but a significant decrease in the average protein expressions of pIRS1,pAKT,PI3K,pTBC1D4 and GLUT4 in cell membrane of skeletal muscles(P<0.01).However,no significant differences were found between the two groups in the average expression of pTFEB and T-TFEB proteins.(2)Compared to the HFD group,a signifi-cant increase was found in the average body weight,blood glucose at each time point of IPGTT,blood glucose of IPITT at 0 min,30 min and 60 min and AUC,serum insulin,HOMA-IR,expres-sions of pTFEB,T-TFEB and GLUT4 in cytoplasm of HFDE group(P<0.05 or P<0.01),with a signifi-cant decrease in the average protein expressions of pIRS1,pAKT,PI3K,pTBC1D4 and GLUT4 in cell membrane and T-TFEB in nucleus(P<0.01).(3)TFEB was negatively correlated with the expres-sion of pIRS1,PI3K,pAKT,and pTBC1D4 proteins(r=-0.8642,r=-0.7789,r=-0.8946,r=-0.8040)but positively correlated with cytoplasmic GLUT4(r=0.8532,P<0.01).Moreover,TFEB in the nucleus was of positive correlation with GLUT4 in the cell membrane(r=0.7744,P<0.01).Conclusions High-fat diet can decrease the expression of insulin signaling pathway related proteins in skeletal mus-cles of mice and weaken their insulin action,leading to the disorder of glucose and lipid metabolism.However,aerobic exercise can significantly increase the expression of such proteins to promote insulin function and sensitivity,and relieve disorders in glucose and lipid metabolism.This effect may be achieved through the promotion of skeletal muscle TFEB nuclear translocation,which activates IRS1/PI3K/AKT/TBC1D4/GLUT4 signaling pathway and facilitates GLUT4 membrane translocation,ultimately enhancing glucose uptake in skeletal muscle cells.The authors speculate that the TFEB-mediated insu-lin signaling pathway may be an important molecular pathway for aerobic exercise to improve insulin re-sistance.

The pursuit of cosmetic effects in post-surgical wounds has led to the development of ultra-minimally invasive techniques in surgery. Minimal invasive surgery has replaced open surgery and has become the new gold-standard for treating diseases. One such technique is the single incision triangulated umbilicus surgery (SITUS), which offers several advantages over traditional laparoscopic and other scarless surgeries, including reduced trauma, faster recovery, and better cosmetic outcomes. SITUS also has a short learning curve, aligns with conventional instrumentation operating habits, and can be used for whole abdominal surgeries. Chinese scholars have made further improvements to the SITUS technology, including expanding its applicability in intra-abdominal surgery and refining its incision closure methods to achieve superior cosmetic results. Currently, SITUS technology is experiencing rapid development in urology applications and has demonstrated satisfactory results in both domestic and international reports. This review aims to discuss the effectiveness and development of the SITUS technique in urology.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory deficits and cognitive decline. Previous studies of peripheral blood biomarkers in AD have been focused on alterations of β-amyloid (Aβ) and phosphorylated (p)-tau. This article reviews the research progress of new biomarkers, such as inflammatory factors, metabolic indicators, and non-coding RNA, in peripheral blood of AD in recent years, in order to provide references for AD diagnosis.

Objective:To investigate the central mechanism of moxibustion in treating chronic inflammatory visceral pain(CIVP)and its analgesic effect from the perspective of the p38 mitogen-activated protein kinase(MAPK)/Ets-like transcription factor 1(ELK1)signaling pathway in the spinal cord. Methods:Clean-grade male Sprague-Dawley rats were randomly divided into a normal group,a model group,a herb-partitioned moxibustion(HPM)group,a sham-HPM group,a p38 MAPK inhibitor group,and a dimethyl sulfoxide(DMSO)group.CIVP rat models were prepared using an enema mixture of 2,4,6-trinitrobenzene sulfonic acid solution and 50%ethanol.The HPM group was treated with HPM;the sham-HPM group was treated the same as the HPM group,but the moxa cones were not ignited;rats in the p38 MAPK inhibitor group received L5-L6 intrathecal injection of p38 MAPK inhibitor(SB203580);rats in the DMSO group received L5-L6 intrathecal injection of 2%DMSO.Abdominal withdrawal reflex(AWR),mechanical withdrawal threshold(MWT),and thermal withdrawal latency(TWL)were used to observe pain-related behaviors in each group.Hematoxylin-eosin staining was used to observe the morphological changes in rat colon tissue.Western blotting and real-time quantitative reverse-transcription polymerase chain reaction were used to detect the phosphorylated protein and mRNA expression of apoptosis signal-regulating kinase 1(ASK1),MAPK kinase(MKK)3/6,p38 MAPK,ELK1,and mitogen and stress-activated protein kinase 1(MSK1)in the spinal cord. Results:Compared with the normal group,CIVP rats had severe colonic inflammatory injuries,and the pathological injury scores increased significantly,along with increased AWR scores under different colorectal distension(CRD)stimulation pressures and decreased MWT and TWL;the mRNA and phosphorylated protein expression of p38 MAPK,ELK1,MSK1,ASK1,MKK3,and MKK6 all increased in the spinal cord(P<0.01).After HPM treatment,the colon injuries were repaired,and the pathological injury scores decreased;under different CRD stimulation pressures,the AWR scores decreased,and the MWT and TWL increased;the mRNA and phosphorylated protein expression of p38 MAPK,ELK1,ASK1,and MKK3 in the spinal cord also decreased,with statistically significant differences compared with the model group and the sham-HPM group(P<0.01).There were no significant differences in the above indicators between the HPM group and the p38 MAPK inhibitor group(P>0.05),and the same was true regarding the comparisons between the model group and the DMSO group. Conclusion:HPM exerted analgesic effects via downregulating the mRNA and phosphorylated protein expression of ASK1,MKK3,p38 MAPK,and ELK1 in the spinal cord of CIVP rats.The inhibition of spinal p38 MAPK/ELK1 signaling pathway activation may be one of the mechanisms by which HPM relieves pain in CIVP.

Objective:To explore the therapeutic mechanism of electroacupuncture(EA)in treating Parkinson disease(PD)using Tandem mass tag(TMT)quantitative proteomics technology. Methods:Forty-eight PD patients were randomly divided into a control group and an observation group,with 24 patients in each group.The control group received routine drug treatment,while the observation group received EA in addition to the routine drug treatment.EA was administered for 30 min per session,3 times a week,for a total of 12 weeks.Nine patients from each group were randomly selected to provide peripheral blood serum samples before and after treatment for TMT quantitative proteomics analysis.Differentially expressed proteins between the two groups were compared,and bioinformatics analysis was performed.The screened differentially expressed proteins were validated using enzyme-linked immunosorbent assay(ELISA). Results:In the observation group,scores on the unified Parkinson disease rating scale(UPDRS),UPDRS Ⅱ,and UPDRS Ⅲ were significantly reduced after treatment(P<0.05).In the control group,these scores tended to increase,but the changes were not statistically significant(P>0.05).After treatment,the UPDRS and UPDRS Ⅲ scores in the observation group were significantly lower than those in the control group(P<0.05).The observation group showed 62 differentially expressed proteins,while the control group had 36.Compared to the control group,the observation group had 142 differentially expressed proteins.These proteins were primarily involved in the cyclic adenosine monophosphate(cAMP)signaling pathway,T helper(Th)1 and Th2 cell differentiation,ATP-binding cassette transporter,vascular endothelial growth factor signaling pathway,and high-affinity immunoglobulin E receptor(FcεRI)signaling pathway.ELISA verification indicated that after EA treatment,the levels of α-Synuclein(αSyn)and heat shock protein beta 1(HSPB1)in the observation group were significantly lower than those in the control group(P<0.05),while the regulator of G-protein signaling 10(RGS10)level was significantly higher(P<0.05). Conclusion:EA,combined with routine drug therapy,can significantly improve clinical symptoms of PD,potentially through the regulation of the cAMP signaling pathway and the contents of differentially expressed proteins of αSyn,HSPB1,and RGS10.

[Objective]To explore the combined diagnosis and treatment system of Chinese and western medicine for primary Sj?gren's syndrome(pSS),and to provide practical and standardized diagnostic and therapeutic directions for professional practice.[Methods]By reviewing the literature,summarizing the etiology and pathogenesis of pSS,the rules and treatments of pSS,combining the current situation of pSS diagnosis and treatment in Chinese and western medicine and our team's many years of clinical experience,this paper refers to the western medical standards for the diagnosis and evaluation of pSS and carries out typing according to different clinical manifestations or systemic involvement,and then carries out diagnosis and treatment according to the four diagnostic elements of Chinese medicine,so as to build up the combined diagnostic and treatment system of pSS of Chinese and western medicine,combining disease with type.[Results]The combined diagnosis and treatment system of Chinese and western medicine for pSS included 9 common clinical patterns of pSS,including Qi and Yin deficiency,dry heat and toxin,dry toxin stasis,dry heat injuring the lungs,kidney Qi failure,liver and Yin deficiency,Qi(Yin)deficiency and collateral stasis,Qi and blood deficiency,and Yin deficiency and heat and toxin,etc.,and each of which had been formulated into a detailed rationale,methodology,prescription and medicine.[Conclusion]The combined diagnosis and treatment system of Chinese and western medicine for pSS provides a good paradigm for clinical diagnosis and treatment of pSS,which will generate certain clinical value and practical implications.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Objectives To explore the expression, biological function, and mechanism of MKI67 in pancreatic cancer and its clinical significance. Methods The expression level, diagnosis, and prognostic value of MKI67 in pancreatic cancer were analyzed using public databases. We also investigated the association between the MKI67 with immune cell infiltration and immune checkpoint molecules. We analyzed the functional pathway enrichment to uncover the possible molecular mechanisms. qRT-PCR and Western blot assay were used to verify the expression of MKI67 mRNA and protein. Immunohistochemistry staining was used to detect the expression of MKI67 in tissue protein. Results The high expression of MKI67 was significantly associated with high histological grades and poor outcomes in pancreatic cancer. High MKI67 expression was correlated with poor prognosis of pancreatic cancer patients (P=0.009). MKI67 was an independent risk factor for the patient outcome (95%CI: 1.084-1.743, P<0.05). The MKI67 expression was positively correlated with the helper T cell 2 levels but negatively correlated with plasmacytoid DC, NK cells, mast cells, the T follicular helper, immune DC, and CD8 T cells. Conclusion MKI67 may serve as a biomarker for the diagnosis and prognosis of pancreatic cancer and the mechanism might be associated with immune escape or immunosuppression.

Objective:To study the risk factors of venous thromboembolism(VTE)and the predictive value of the improved VTE score model to identify the risk of VTE in gynecological surgery patients.Methods:From Janu-ary 1,2020 to December 31,2022,41 patients with VTE after gynecological surgery were selected as the VTE group,and a total of 164 patients with adjacent gynecological surgeries during the same period were selected as the non-VTE group with a ratio of 1 :4.Univariate and multivariate Logistic regression analysis were used to ana-lyze the risk factors of VTE after gynecological surgery,and a modified VTE risk factor rapid assessment model(referred to as the improved VTE score model)was constructed.The receiver operating characteristic(ROC)curve was used to study the predictive value for VTE for in gynecological surgery,and compared with the Caprini score model(Caprini table for short).Results:①Multivatiate Logistic regression analysis showed that there were independent risk factors for postoperative VTE in gynecology surgery(OR＞1,P＜0.05),including age≥60 years,BMI≥28 kg/m2,malignant tumors,surgery time＞3 hours,history of thrombosis,and the increased D-di-mer difference before and after surgery.②The Area under Curve(AUC)of ROC was 0.963 in the improved VTE score model with a Youden index 81.10％,sensitivity 87.80％and specificity 93.29％.The AUC of the Caprini score model was 0.888 with Youden index 63.41％,sensitivity 73.17％and specificity 90.24％.The improved VTE score model the Caprini score model identified 92.68％and 85.37％of VTE patients as high-risk or ex-tremely high-risk,respectively,but the difference was not statistically significant(P＜0.05).Conclusions:More attention should be paid to the six independent risk factors for postoperative VTE in gynecology surgery.The two score models showed a similar identified level.However,the improved VTE score model is more simple and easier to operate,has better practicality,and has certain clinical promotion value.