Objective:To study the effects of cathepsin K(CTSK)on the healing process of tooth extraction socket and type H blood vessel angiogenesis in mice.Methods:Ctsk knockout(Ctsk-/-)mice were generated by CRISPR/Cas9 technology,and genotype sequen-cing,general observation,Micro-CT and immunohistochemistry were performed to confirm successful knockout of Ctsk.Then 8 week-old WT and Ctsk-/-mice were used to establish the tooth extraction modle by extracting the left maxillary first molars,and the mice were sac-rificed at the day 7,10,14,21,28 and 35 respectively(n=3)after tooth extraction.Then samples were subjected to stereo microscope and Micro-CT examination.Immunofluorescence staining was used to study the effect of Ctsk knockout on type H blood vessel angiogene-sis.Results:Ctsk knockout did not affect the soft tissue healing of tooth extraction socket,but significantly promoted the bone healing process,and Ctsk deficency significantly enhanced type H blood vessel angiogenesis in the tooth extraction socket.Conclusion:Ctsk knockout can enhance type H vessel angiogenesis,and promote bone healing process of tooth extraction socket in mice.

Objective:To observe the efficacy of hypertonic dextrose injection(prolotherapy)at retrodiscal tissue in the treatment of chronic joint pain in patients with temporomandibular disorders(TMD).Methods:From June 2012 to March 2022,244 patients(aged 16 to 75 years)underwent the treatment were included and classified according to DC/TMD.The treatment started from an anesthetic in-jection of 2％lidocaine(1.5-2 mL)into the retrodiscal tissue.The patients were then instructed to perform mandibular condylar exercise for 5-10 min,prior to the therapeutic injection of 50％dextrose(1-1.5 mL)by using the same method.Assessment of TMJ pain and jaw function was performed at 2 weeks,2,6 and 12 months after injection.Results:By March 2022,221 cases completed the final sur-vey(the rate of loss of follow-up was 9.4％),the average follow-up time was(75.7±25.1)months.2 weeks after treatment,there was significant relief of joint pain,and mandibular function was significantly improved in most patients by 2 month after treatment.Of these,186 cases achieved profound pain relief and faily normal jaw function,17 cases with recurrence of joint pain and jaw dysfunction and op-ted for occlusal splint treatment due to fear of injection,16 cases claimed no obvious therapeutic effect but rejected any further tratment,2 cases subsequently accepted TMJ surgery.There was no worsening of TMD or other complication as a result of the treatment.Conclu-sion:Hypertonic dextrose injection in retrodiscal tissue attachment is straightforward,safe and effective in the treatment of chronic joint pain and TMD.

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

OBJECTIVE To study the effects of the curcumin derivative bisdemethoxycurcumin （BC） promoting neuronal differentiation of neuroblastoma cells Neuro-2a （N2a） in mice and its mechanism. METHODS The effects of BC （1， 2， 4， 6， 8， 10 μmol/L） on the viability of N2a cells were detected by MTT assay to determine the concentration range of drug treatment. The control group， retinoic acid （RA） group （10 μmol/L） and BC groups （1， 2 and 4 μmol/L） were set up， and the length of neural protrusions of the differentiated cells was measured and the cell differentiation rate was calculated after 48 h and 72 h of culture. Compared with 0 min group， Western blot was used to detect the phosphorylation levels of protein kinase B （Akt）， extracellular- signal regulated kinase 1/2 （ERK1/2）， and p38 mitogen-activated protein kinase （p38） proteins in cells treated by 4 μmol/L BC for 5， 15， 30， 60， 120 min. After intervention with inhibitors LY294002 （LY） and PD98059 （PD）， the effects of BC on Akt and ERK1/2 protein phosphorylation levels and promoting neural differentiation were further validated. RESULTS According to the MTT experiment， the BC concentrations for subsequent induction of cell differentiation were determined to be 1， 2， and 4 μmol/L. After 48 hours of differentiation， compared with the control group， the cell differentiation rate in RA group and BC 1， 2 and 4 μmol/L groups， the length of cellular neural processes wjxhhxx413@163.com in the BC 4 μmol/L group significantly increased （P＜0.05 or P＜0.01）；after inducing differentiation of BC for 72 hours，compared with the control group， the cell differentiation rate and the length of cellular neural processes in the RA group， the cell differentiation rate in the BC 4 μmol/L group， and the length of cellular neural processes in the BC 2 μmol/L group all significantly increased （P＜0.05 or P＜0.01）.Compared with the 0 min group， the phosphorylation levels of Akt， ERK1/2， and p38 proteins in cells of the 5， 15， 30， 60 and 120 min groups increased to varying degrees after treated by 4 μmol/L BC， and some differences were statistically significant （P＜0.05 or P＜0.01）. After adding the inhibitor LY/PD， compared with the BC group， the phosphorylation level of ERK1/2 protein in the PD+BC group cells were significantly reduced （P＜0.01）， and the cell differentiation rates in the LY group， LY+BC group， PD group， and PD+BC group was significantly reduced （P＜0.01）. CONCLUSIONS BC promotes N2a cell differentiation mainly by increasing cell differentiation rate and neural protrusion length. The mechanism may be related to the activation of mitogen-activated protein kinase/ ERK and PI3K/Akt signaling pathways.

ObjectiveMyelodysplastic syndromes （MDS） is a group of clonal hematopoietic stem cell disorders，and this study aims to investigate the expression of hypoxia-inducible factor-1α（HIF-1α） in the bone marrow cells of patients with MDS and its correlation with the clinical features of MDS，the therapeutic efficacy of arsenic-containing Chineseherbal compound，and the survival prognosis. MethodAccording to the inclusion and exclusion criteria，27 MDS patients treated with arsenic-containing Chinese herbal compound in the Department of Hematology，Xiyuan Hospital，China Academy of Chinese Medical Sciences from January 2022 to September 2022 were included，and their bone marrow samples were collected by myelotomy. HIF-1α expression level in bone marrow cells was detected by real-time polymerase chain reaction （PCR） to analyze its correlation with clinical features，and logistic and Cox regression was used to analyze the risk factors affecting the efficacy and prognostic survival of MDS patients. ResultThe HIF-1α mRNA expression level was lower in bone marrow cells of MDS patients than in healthy subjects. HIF-1α was positively correlated with the degree of myelodysplasia（r=0.384，P<0.05） and bone marrow granulocytic system%（G%）（r=0.560，P<0.01）. Logistic regression showed that HIF-1α was a risk factor for the prognosis in the follow-up of the efficacy of treatment（P<0.05）and Cox regression showed that HIF-1α was an independent factor affecting the survival prognosis of MDS patients ［odds ratio（OR）=398.968，95% confidence interval（CI）（1.281，116 858.743），P<0.05］. ConclusionThe level of HIF-1α expression in bone marrow cells of MDS patients was closely related to the degree of clinical myelodysplasia and G%，and HIF-1α was a risk factor for the efficacy for and survival prognosis of MDS patients.

Objective To observe the feasibility of T1 mapping technique for evaluating myocardial gadolinium deposition in patients with apical hypertrophic cardiomyopathy(AHCM).Methods Data of 60 AHCM patients were retrospectively analyzed.The patients were divided into enhanced group and control group according to underwent gadolinium-based contrast agent(GBCA)enhanced examination or not(each n=30).Myocardial T1 value at the basal,middle and apical myocardium of the left ventricle as well as spleen T1 at the same layers were measured.T1 relative-value(T1R)was calculated and then compared between groups and among different parts of left ventricle in enhanced group.T1R in enhanced group were further analyzed based on gender,age,body mass index,cardiac function,hypertension,hyperlipidemia,diabetes,apical thickness,ejection fraction,delayed enhancement and interval time from the first enhanced examination to the last review and total dose of GBCA.Results No significant difference of T1Rbasal,T1Rmiddle nor T1Rapical was found between groups(t=0.329,1.484,0.720,all P＞0.05),nor of T1R in different parts of left ventricle within enhanced group(F=0.765,P＞0.05).In enhanced group,significant differences of myocardial T1R was found between different genders as well as patients with or without hypertension(both P＜0.05).Conclusion T1 mapping technology could be used for evaluating myocardial gadolinium deposition in patients with AHCM.

ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure （HBV-ACLF） at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients， including 618 in the early stage， 355 in the middle stage， and 85 in the late stage， were collected from 18 clinical centers across 12 regions nationwide from January 1， 2012 to February 28， 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients， like the four diagnostic information （including symptoms， tongue， pulse） of traditional Chinese medicine （TCM）， and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients， and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries， including 36 symptom information， 12 tongue information， and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF， which were liver-gallbladder damp-heat pattern， qi deficiency and blood stasis pattern， liver-kidney yin deficiency pattern， and spleen-kidney yang-deficiency pattern. In the early stage， heat （39.4%， 359/912） and dampness （27.5%， 251/912） were most common， and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern （74.6%， 461/618）； in the middle stage， dampness （30.2%， 187/619） and blood stasis （20.7%， 128/619） were most common， and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern （53.2%， 189/355）， and qi deficiency and blood stasis pattern （27.6%， 98/355）； and in the late stage， the pattern of the disease was dominated by qi deficiency （26.3%， 40/152） and yin deficiency （20.4%， 31/152）， and the patterns were dominated by qi deficiency and blood stasis pattern （36.5%， 31/85）， and liver-gallbladder damp-heat pattern （25.9%， 22/85）. ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF， presenting an overall trend of evolving patterns as "from excess to deficiency， transforming from excess to deficiency"， which is damp-heat → blood stasis → qi-blood yin-yang deficiency.

Objective To identify factors associated with gastrointestinal heat retention in preschool children,and to provide a foundational understanding for future clinical investigations. Methods A case-control study was performed,which involved children from kindergartens in the Longgang District of Shenzhen City,Guangdong Province,from May to July 2021. Using the Children's Gastrointestinal Heat Retention Diagnostic Self-assessment Scale,subjects were allocated into a case group (children diagnosed with gastrointestinal heat retention) and a control group (children without this condition). An online survey was used to collect data on dietary behaviors,caregivers' feeding behaviors,early antibiotic use,daily routines,and birth conditions. SPSS 27.0 software was used to facilitate precise sociodemographic matching and paired logistic regression analysis to explore the association between gastrointestinal heat retention and the above factors. Results From the analysis of 51,252 matched cases,the study found that several factors contributed to an increased risk of gastrointestinal heat retention. These factors included reduced food intake compared to peers,reports of picky eating by caregivers,distractions during meals,pronounced dietary preferences,disinterest in food,meal durations ≥ 25 min,reluctance to sample new foods,consistent refusal of specific food types for over one month,irregular meal locations,coercive feeding practices,use of micronutrient supplements,allowing children too much freedom in food choice,persuading children to eat,infrequent encouragement to experiment with new foods,early antibiotic introduction,inadequate sleep,and premature birth (P<0.05). In contrast,exclusive breastfeeding in the first six months,engagement in moderate to massive physical activity,and regular napping patterns were associated with a reduced risk of gastrointestinal heat retention (P<0.05). Conclusion The suboptimal dietary habits,improper feeding practices,insufficient physical activity,inadequate sleep,and premature antibiotic exposure may be significant risk factors for gastrointestinal heat retention. Future research dedicated to unraveling the cause of gastrointestinal heat retention should prioritize these elements.

Objective To systematically review the evidence from systematic reviews of the application models and health benefits of virtual reality(VR)technology in physical activities and health domains in children and adolescents with cere-bral palsy(CP). Methods PubMed,Embase,CINAHL,SPORTDiscus,Google Scholar,PsycINFO and CNKI were searched to collect and screen systematic reviews published from January,2020 to March,2024 on the application of VR technology in physical activities and health for children with CP.The relevant evidence was reported following PRISMA guidelines. Results A total of eight English researches from China,Saudi Arabia,Indonesia and Brazil were included,involving 5 692 children and adolescents with CP,came primarily from interdisciplinary journals in clinical medicine,thera-py and clinical risk management,games and gamification,and physical movement therapy.The subjects aged four to 18 years,with spastic hemiplegia and spastic diplegia.The VR technologies featured five typical applica-tion models:immersive environment simulation;interactive motion gamification;virtual training and coaching;AI-based activity data tracking and analysis,and motion capture and feedback,biofeedback integration and wear-able technology applications;and augmented reality integration.Interventions lasted 15 to 90 minutes a time,one to 15 times a week,with intensities ranging from moderate to vigorous and durations from one to 24 weeks.The application of VR technology might increase the interest in participating in physical activities,enhance the interactive experience,through integration with wearable and biofeedback technologies,enable timely monitor-ing,tracking,analysis and feedback on children's activity statuses,improving their physical and functional abili-ties. Conclusion VR technology including immersive environment simulation and interactive motion gamification may im-prove interest in physical activities,physical quality and functional abilities,promoting behavioral health,and en-hancing overall health levels and quality of life of children and adolecents with CP.

Objective To investigate the application effect of fiberoptic bronchoscopy and alveolar lavage therapy in the diagnosis and treatment of recurrent wheezing diseases in children. Methods A total of 151 children with recurrent wheezing diseases were enrolled, and divided into control group (n=84) and study group (n=67) based on different diagnostic and therapeutic methods. The control group received conventional diagnosis and treatment, while the study group underwent fiberoptic bronchoscopy combined with alveolar lavage therapy. The time to resolution of symptoms and length of hospital stay were compared between the two groups. Additionally, lung function [forced expiratory volume in 1 second (FEV₁), FEV₁/forced vital capacity (FEV₁/FVC) and peak expiratory flow (PEF)], exhaled nitric oxide (FeNO), serum inflammatory mediator levels [C-reactive protein (CRP), procalcitonin (PCT) and white blood cell (WBC) count] and clinical efficacy were compared. Results The absence time of wheezing and pulmonary rales and hospital stay in the study group were significantly shorter than those in the control group (P < 0.05). After treatment, FEV₁, FEV₁/FVC and PEF in two groups were significantly higher than before treatment, and the study group was significantly higher than the control group (P < 0.05). After treatment, FeNO, CRP, PCT and WBC in two groups were significantly lower than before treatment, and the study group was significantly lower than the control group (P < 0.05). The total effective rate of the study group was 94.03%, which was significantly higher than 77.38% of the control group (P < 0.05). Conclusion Fiberoptic bronchoscopy and alveolar lavage are effective in the diagnosis and treatment of recurrent asthmatic diseases in children, which can effectively relieve symptoms, shorten hospital stay, and improve lung function, FeNO and serum inflammatory mediators.