BACKGROUND:Treadmill training is one of the effective ways to promote the recovery of motor function after spinal cord injury.Treadmill training can promote neurogenesis,but the effect of different intensities of treadmill training on the activation of endogenous stem cells is still unclear. OBJECTIVE:To analyze the activation effect of different intensities of treadmill training on endogenous neural stem cells in the spinal cord of mice after spinal cord injury. METHODS:Fifty female C57BL/6J mice were divided into control group,spinal cord injury group,low-,moderate-,and high-intensity exercise groups with 10 mice in each group by random number table method.T10 segment spinal cord injury model was constructed by the clamp method in spinal cord injury group,low-,moderate-,and high-intensity exercise groups.On day 7 after spinal cord injury,mice in the low-,moderate-,and high-intensity exercise groups were respectively trained on the treadmill with corresponding intensity,3 times/d,10 min/times,6 times a week for 28 consecutive days.At 3,7,14,21,and 28 days after treadmill training,the hind limb motor function was evaluated by BMS score.At 28 days after treadmill training,the spinal cord tissue of the injured area was obtained,and the expression of epidermal growth factor receptor,glial fibrillary acidic protein,and 5-Ethynyl-2'-deoxyuridine(EdU),a proliferative marker,was detected.Hematoxylin-eosin staining was used to observe the morphology of spinal cord. RESULTS AND CONCLUSION:(1)The BMS score of mice in the spinal cord injury group was lower than that in the control group(P<0.05).With the extension of treadmill training time,the BMS scores of mice with spinal cord injury gradually increased,and the BMS scores of mice in moderate-intensity exercise group on days 14 and 21 after treadmill training were higher than those in spinal cord injury group and low-and high-intensity exercise groups(P<0.05).The BMS score of mice in moderate-and high-intensity exercise group was higher than that in spinal cord injury group and low-intensity exercise group at 28 days after treadmill training(P<0.05).(2)Compared with the control group,the proportion of epidermal growth factor receptor and EdU positive cells was increased in spinal cord injury group(P<0.05).Compared with spinal cord injury group,the proportion of epidermal growth factor receptor and EdU positive cells was increased in low-,moderate-,and high-intensity exercise groups(P<0.05),and the highest was found in moderate-intensity exercise group.Compared with control group,the proportion of glial fibrillary acidic protein positive cells was increased in spinal cord injury group(P<0.05).Compared with spinal cord injury group,the proportion of glial fibrillary acidic protein positive cells was lower in low-,moderate-,and high-intensity exercise groups(P<0.05),and the moderate-intensity exercise group was the lowest.(3)Hematoxylin-eosin staining showed that a large cavity was formed in the injured area of mice with spinal cord injury,and the cavity in the injured area of mice with spinal cord injury decreased after different intensities of treadmill training,and the decrease was most obvious in the moderate-intensity exercise group.(4)These results indicate that low-,moderate-,and high-intensity treadmill training can promote the recovery of motor function of mice with spinal cord injury by activating endogenous neural stem cells,and the effect of moderate-intensity exercise training is the most obvious.

The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

The incidence of knee osteoarthritis(KOA)is in-creasing year by year,seriously affecting patients'health.Mes-enchymal stem cells are multipotent cells with multiple differen-tiation functions.The extracellular vesicles released by these cells can carry various"cargo"to corresponding cells and tis-sues,exerting biological functions.They have shown great clini-cal potential in the treatment of KOA.This study reviews the therapeutic effects and mechanisms of extracellular vesicles se-creted by mesenchymal stem cells from different tissues such as bone marrow,adipose tissue,and synovium in KOA.It is found that miRNA is an important biological component in exerting therapeutic effects.The study also discusses the research pro-gress of engineered extracellular vesicles in KOA,pointing out the current challenges in clinical application,such as standard-ized acquisition of extracellular vesicles and difficulties in targe-ted action,aiming to provide a certain reference for the basic re-search and clinical application of extracellular vesicle therapy for KOA.

Aim To analyze serum exosome sequencing data from patients with coronary heart disease(CHD)and normal subjects by using bioinformatics-related methods to construct a competitive endogenous ln-cRNA-miRNA-mRNA(ceRNA)regulatory network,to mine the predicted potential Chinese medicines,and to perform preliminary validation of the biological processes and core Chinese medicines involved in the ceRNA network.Methods We used exoRbase data-base to obtain the expression matrix of differential genes,combined with the raw letter method to con-struct the ceRNA network,and performed GO analysis and KEGG analysis on the differential mRNAs in the network,and used COREMINE database to predict the biological processes and core target genes involved in the ceRNA network,and to screen the herbal medi-cines with potential therapeutic effects;AVECs oxida-tive damage cell model was constructed in vitro,and the cytoskeleton,tube-forming function,cell prolifera-tion,LDH leakage rate,ROS level and p-AKT,AKT,p-PI3K and AKT protein expression were examined to verify the action pathways and targets of the core Chi-nese medicine Salvia miltiorrhiza for the treatment of coronary heart disease.Results Compared with nor-mal subjects,395 mRNAs,80 miRNAs,60 lncRNA differential genes,and 80 miRNAs were predicted in serum exosomes of coronary heart disease,and the constructed ceRNA sub-network,mainly consisted of 21 lncRNAs,80 miRNAs,and 82 mRNAs;AKT1,VEGFA,IL1B and other genes in the network.The abnormally expressed mRNAs were involved in biologi-cal processes such as oxidative stress and signaling pathways such as PI3 K/Akt,and Dan Shen,Chuanx-iong and Panax notoginseng were most closely related to exosome-mediated biological processes and core genes in coronary heart disease.The active ingredients of tanshinone ⅡA,the core Chinese medicine,could pro-mote vascular endothelial cell proliferation,tube for-mation,skeleton formation and repair,reduce LDH leakage rate and ROS level,and promote the expres-sion of p-AKT and p-PI3K protein.Conclusion There is a complex ceRNA regulatory network trans-duction in coronary artery disease serum exosomes,and traditional Chinese medicine can be used to treat CHD through multi-target intervention,and Dan Shen,Chuanxiong and Panax notoginseng are expected to be candidate sources of traditional Chinese medicine,a-mong which the active ingredient of Dan Shen,tanshi-none ⅡA,activates PI3 K/Akt signaling pathway to play a protective role against oxidative stress-injured cells,and treats CHD.

This paper collects questionnaires from graduates and graduate students of clinical-related majors through economic experiments,and discusses the impact of different payment modes on the quantity and quality of medical services provided by doctors by simulating the decision of medical students to provide medical and health services to patients with different health conditions and disease types under two medical insurance payment methods:Fee-for-service(FFS)and Ambulatory Patient Groups(APG).The results showed that there were significant differences in the number of health services provided by doctors to patients with different health conditions and patients with different disease types under two different payment models.Physicians are motivated by the FFS model to provide too many medical and health services to patients,and APG can restrain doctors from providing excessive medical services,and the number of optimal health care service decisions made by doctors in the APG model is significantly higher than that of the FFS model.Compared with APG,the FFS model can better protect the medical needs of cases with poor health and complex conditions,and provide more comprehensive medical and health services.Finally,the paper puts forward suggestions such as using the APG payment mode as much as possible for routine outpatient clinics and common cases,and promoting FFS payment as a supplementary payment method for complex and severe cases.

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution’s experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution’s experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution’s experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.

Objective:To investigate the effects of naringin(NRG)on apoptosis,proliferation,migration and invasion of oral squa-mous cell carcinoma(OSCC)cells.Methods:NRG of 0,5,10,15,20,25 and 30 μmol/L was respectively used to treat OSCC CAL-27 cells,and CCK-8 assay was used to cell vitality.CAL-27 cells were divided into low,medium and high dose NRG groups(NRG-L,NRG-M and NRG-H),Compound C(AMPK inhibitor)group,NRG-H+Compound C group,and control group(NC group,normal cul-ture).Cell proliferation,apoptosis,migration and invasion were detected by CCK-8 assay,EdU staining,flow cytometry,scratch and Tr-answell assays.The expression of aspartate specific cysteine proteinase-3(Caspase-3),proliferating cell nuclear antigen(PCNA),matrix metalloproteinase-2(MMP-2),MMP-9,p-AMPK,sirtuin 1(SIRT1)and acetylated NF-κB p65(Ac-NF-κB p65)was detected by Western blot.Results:5,10 and 20 μmol/L NRG was selected as the low,medium and high dose for the treatment of CAL-27 cells,re-spectively.Compared with NC group,in NRG-L,NRG-M and NRG-H groups EdU positive rate,scratch healing rate,A450 value,num-ber of invasive cells,the protein expression of PCNA,MMP-2,MMP-9 and Ac-NF-κB p65 in CAL-27 cells decreased,the apoptosis rate,and the protein of Caspase-3,p-AMPK,and SIRT1 increased(P＜0.05);in Compound C group EdU positive rate,scratch healing rate,A450 value,the number of invasive cells,the protein expression of PCNA,MMP-2,MMP-9 and Ac-NF-κB p65 in CAL-27 cells in-creased,apoptosis rate and the protein expression of Caspase-3,p-AMPK and SIRT1 decreased(P＜0.05).Compound C reversed the effects of high dose NRG on the proliferation,migration,apoptosis and invasion of CAL-27 cells.Conclusion:The inhibitory effects of NRG on proliferation,migration and invasion of CAL-27 cells and the promotion of apoptosis may be related to activation of AMPK and inhibition of NF-κB pathway.

The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.