BACKGROUND:Previous studies by the research group have shown that core proteoglycan in Cornus Cervi Col la can enter the bone,promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells,and has a good repair effect on steroid-induced osteonecrosis of the femoral head.OBJECTIVE:To investigate the therapeutic effect and potential mechanism of Cornus Cervi Colla on steroid-induced osteonecrosis of the femoral head in rats by fecal non-targeted fecal metabolomics.METHODS:Thirty SD rats were randomly divided into three groups using a random number table method:the control group(n=10)was injected with normal saline into the right gluteal muscle(injected on the first 3 days of each week for 3 consecutive weeks),and was given pure water gavage(once a day for 6 consecutive weeks).The model group(n=10)was injected with methylprednisolone sodium succinate into the right gluteal muscle(injected on the first 3 days of each week for 3 consecutive weeks)to establish a steroid-induced osteonecrosis of the femoral head model,and was given pure water gavage(once a day for 6 consecutive weeks).The Cornus Cervi Co I la group(n=10)was also established with a steroid-induced osteonecrosis of the femoral head model,and was given Cornus Cervi Col la gavage(once a day for 6 consecutive weeks).After gavage,cecal feces and femoral heads were collected for fecal metabolomics analysis and bone tissue Micro-CT and hematoxylin-eosin staining,respectively.RESULTS AND CONCLUSION:(1)Metabolomics analysis results showed that there were 233 differential metabolites between the Cornus Cervi Col la and model groups,with 65 significantly differing and clearly annotated metabolites.Lipid and amino acid metabolites were significantly increased,with bile acids,sulfated steroids,ephedrine,hypoxanthine,betaine,L-carnitine,B-mouse bile acid,cytidine,4-pyridoxic acid,taurine,N-acetyl-d-glucosamine,and butyric acid being the most impacted(variable weight value VIP＞5).The metabolic pathways of taurine and hypotaurine were crucial in the metabolic regulatory network(pathway impact=0.428 57).(2)Micro-CT scanning results of bone tissue showed that the femoral heads of rats in the model group and the Cornus Cervi Col la group had different degrees of damage;the femoral head contour was irregular;the trabeculae in the subchondral bone of the femoral head were missing and disordered,and some cystic structures were visible.Compared with the model group,the degree of trabecular damage in the rats of the Cornus Cervi Colla group was milder.Hematoxylin-eosin staining results showed that the trabeculae in the subchondral bone of the femoral heads of rats in the model group and the Cornus Cervi Colla group were sparse or interrupted,and the empty bone lacuna rate and adipocyte invasion were increased.Compared with the model group,the empty bone lacuna rate and adipocyte invasion in the subchondral bone of the femoral heads of rats in the Cornus Cervi Colla group were reduced.(3)These results conclude that Cornus Cervi Colla potentially mitigates steroid-induced osteonecrosis of the femoral head through the metabolic processes involving taurine and associated pathways.

BACKGROUND:Osteonecrosis is an orthopedic disease that severely limits joint function,with complex pathogenesis involving multiple risk factors.Cathepsins,as a class of enzymes that play a key role in bone metabolism,are closely related to the proliferation,differentiation of bone cells,and remodeling of the bone matrix.However,previous studies have mostly focused on descriptive analyses,lacking direct evidence of causal relationships.OBJECTIVE:To clarify the potential causal relationship between cathepsins and osteonecrosis and to explore their possible mechanisms by analyzing large-scale sample data from the FinnGen database.METHODS:We obtained osteonecrosis-related data from the FinnGen database,including R9(a total of 359 399 samples:1 385 cases and 358 014 controls)and R10 versions(a total of 392 580 samples:1 543 cases and 391 037 controls).Single nucleotide polymorphisms associated with nine cathepsins(cathepsin B,E,F,G,H,O,S,L2,and Z)were acquired from a previous study(3 301 individuals).Univariate Mendelian randomization,reverse univariate Mendelian randomization,and multivariate Mendelian randomization analyses were conducted using the inverse variance weighted method,MR-Egger method,weighted median method,simple mode method,and weighted mode method.Initially,Mendelian randomization analysis was performed using osteonecrosis data from R9.Additionally,sensitivity analyses were conducted using Cochran's Q test,MR-Egger intercept,MR-PRESSO global test,and leave-one-out analysis to check for horizontal pleiotropy and heterogeneity.Subsequently,a validation analysis study was carried out on the R10 dataset,and a meta-analysis was conducted to combine the two datasets to explore the joint effect.RESULTS AND CONCLUSION:Univariate Mendelian randomization analysis results showed that higher levels of cathepsin B were significantly associated with a reduced risk of osteonecrosis(inverse variance weighted:odds ratio(OR)=0.865,95％confidence interval(CI):0.762-0.982,P=0.025),and no reverse causal relationship was found between the nine cathepsins and osteonecrosis(P＞0.05).These associations were validated by meta-analysis.Multivariate analysis,using the nine cathepsins as covariates,revealed a reverse causal relationship between the levels of cathepsin Band the risk of osteonecrosis(inverse variance weighted:OR=0.8710,95％CI:0.761-0.997,P=0.045),consistent with the results before adjustment.Sensitivity analyses based on heterogeneity and horizontal pleiotropy suggested that the results were relatively robust.This study suggests that there is a causal relationship between high levels of cathepsin B and the reduced risk of osteonecrosis,and it may serve as a biomarker for osteonecrosis,providing new directions and insights for the diagnosis and treatment of osteonecrosis.Although this study is based on data analysis of European populations,these findings have important implications for Chinese biomedical research,especially in understanding disease mechanisms,developing biomarkers,and formulating treatment strategies.They also encourage similar studies conducted on Chinese populations to explore the impact of racial and genetic background differences on the occurrence of osteonecrosis.

BACKGROUND:Previous studies by the research group have shown that core proteoglycan in Cornus Cervi Col la can enter the bone,promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells,and has a good repair effect on steroid-induced osteonecrosis of the femoral head.OBJECTIVE:To investigate the therapeutic effect and potential mechanism of Cornus Cervi Colla on steroid-induced osteonecrosis of the femoral head in rats by fecal non-targeted fecal metabolomics.METHODS:Thirty SD rats were randomly divided into three groups using a random number table method:the control group(n=10)was injected with normal saline into the right gluteal muscle(injected on the first 3 days of each week for 3 consecutive weeks),and was given pure water gavage(once a day for 6 consecutive weeks).The model group(n=10)was injected with methylprednisolone sodium succinate into the right gluteal muscle(injected on the first 3 days of each week for 3 consecutive weeks)to establish a steroid-induced osteonecrosis of the femoral head model,and was given pure water gavage(once a day for 6 consecutive weeks).The Cornus Cervi Co I la group(n=10)was also established with a steroid-induced osteonecrosis of the femoral head model,and was given Cornus Cervi Col la gavage(once a day for 6 consecutive weeks).After gavage,cecal feces and femoral heads were collected for fecal metabolomics analysis and bone tissue Micro-CT and hematoxylin-eosin staining,respectively.RESULTS AND CONCLUSION:(1)Metabolomics analysis results showed that there were 233 differential metabolites between the Cornus Cervi Col la and model groups,with 65 significantly differing and clearly annotated metabolites.Lipid and amino acid metabolites were significantly increased,with bile acids,sulfated steroids,ephedrine,hypoxanthine,betaine,L-carnitine,B-mouse bile acid,cytidine,4-pyridoxic acid,taurine,N-acetyl-d-glucosamine,and butyric acid being the most impacted(variable weight value VIP＞5).The metabolic pathways of taurine and hypotaurine were crucial in the metabolic regulatory network(pathway impact=0.428 57).(2)Micro-CT scanning results of bone tissue showed that the femoral heads of rats in the model group and the Cornus Cervi Col la group had different degrees of damage;the femoral head contour was irregular;the trabeculae in the subchondral bone of the femoral head were missing and disordered,and some cystic structures were visible.Compared with the model group,the degree of trabecular damage in the rats of the Cornus Cervi Colla group was milder.Hematoxylin-eosin staining results showed that the trabeculae in the subchondral bone of the femoral heads of rats in the model group and the Cornus Cervi Colla group were sparse or interrupted,and the empty bone lacuna rate and adipocyte invasion were increased.Compared with the model group,the empty bone lacuna rate and adipocyte invasion in the subchondral bone of the femoral heads of rats in the Cornus Cervi Colla group were reduced.(3)These results conclude that Cornus Cervi Colla potentially mitigates steroid-induced osteonecrosis of the femoral head through the metabolic processes involving taurine and associated pathways.

BACKGROUND:Osteonecrosis is an orthopedic disease that severely limits joint function,with complex pathogenesis involving multiple risk factors.Cathepsins,as a class of enzymes that play a key role in bone metabolism,are closely related to the proliferation,differentiation of bone cells,and remodeling of the bone matrix.However,previous studies have mostly focused on descriptive analyses,lacking direct evidence of causal relationships.OBJECTIVE:To clarify the potential causal relationship between cathepsins and osteonecrosis and to explore their possible mechanisms by analyzing large-scale sample data from the FinnGen database.METHODS:We obtained osteonecrosis-related data from the FinnGen database,including R9(a total of 359 399 samples:1 385 cases and 358 014 controls)and R10 versions(a total of 392 580 samples:1 543 cases and 391 037 controls).Single nucleotide polymorphisms associated with nine cathepsins(cathepsin B,E,F,G,H,O,S,L2,and Z)were acquired from a previous study(3 301 individuals).Univariate Mendelian randomization,reverse univariate Mendelian randomization,and multivariate Mendelian randomization analyses were conducted using the inverse variance weighted method,MR-Egger method,weighted median method,simple mode method,and weighted mode method.Initially,Mendelian randomization analysis was performed using osteonecrosis data from R9.Additionally,sensitivity analyses were conducted using Cochran's Q test,MR-Egger intercept,MR-PRESSO global test,and leave-one-out analysis to check for horizontal pleiotropy and heterogeneity.Subsequently,a validation analysis study was carried out on the R10 dataset,and a meta-analysis was conducted to combine the two datasets to explore the joint effect.RESULTS AND CONCLUSION:Univariate Mendelian randomization analysis results showed that higher levels of cathepsin B were significantly associated with a reduced risk of osteonecrosis(inverse variance weighted:odds ratio(OR)=0.865,95％confidence interval(CI):0.762-0.982,P=0.025),and no reverse causal relationship was found between the nine cathepsins and osteonecrosis(P＞0.05).These associations were validated by meta-analysis.Multivariate analysis,using the nine cathepsins as covariates,revealed a reverse causal relationship between the levels of cathepsin Band the risk of osteonecrosis(inverse variance weighted:OR=0.8710,95％CI:0.761-0.997,P=0.045),consistent with the results before adjustment.Sensitivity analyses based on heterogeneity and horizontal pleiotropy suggested that the results were relatively robust.This study suggests that there is a causal relationship between high levels of cathepsin B and the reduced risk of osteonecrosis,and it may serve as a biomarker for osteonecrosis,providing new directions and insights for the diagnosis and treatment of osteonecrosis.Although this study is based on data analysis of European populations,these findings have important implications for Chinese biomedical research,especially in understanding disease mechanisms,developing biomarkers,and formulating treatment strategies.They also encourage similar studies conducted on Chinese populations to explore the impact of racial and genetic background differences on the occurrence of osteonecrosis.

Objective:To investigate the hard and soft tissue changing trend and contributing factors of skeletal class Ⅱ hyperdivergent patients before and after orthodontic camouflage treatment by analyzing the cephalogram and the three dimensional(3D)facial scan data.Methods:Eighteen skeletal class Ⅱhyperdivergent adult female patients who finished camouflage orthodontic treatment were selected.Skele-tal and dental measurements were carried out with the cephalometric analysis before and after the treat-ment.3D facial data before and after orthodontic treatment were acquired and the anatomical landmarks were set after the repositioning and superimposition process.Hard tissue measurement included 17 mea-surement indicators(sella-nasion-subspinale angle,sella-nasion-supramental angle,subspinale-nasion-supramental angle,facial angle,angle of convexity,Frankfort horizontal plane-mandibular plane angle(FH-MP),Y axis angle,sella-nasion plane-mandibular plane angle(MP-SN),pogonion-nasion-supra-mental distance,upper incisor-nasion-subspinale distance,upper incisor to sella-nasion,lower incisor-nasion-supramental distance,lower incisor-nasion-supramental angle,upper incisor to lower incisor,up-per incisor to sella-nasion,lower incisor-mandibular plane angle,and Z angle),and the changes before and after treatment were measured for 11 of them.Twenty soft tissue landmarks(left/right cheekbone,left/right chelion,left/right crista philtra,soft tissue gnathion,left/right gonion,glabella,labrale infe-rius,labrale superius,soft tissue menton,left/right mid-mandibular border,soft tissue pogonion,stomi-on superius,sublabial,subnasale,and supralabial)and 9 soft tissue indicators(lower lip height,facial convexity,lower vermilion height,mandibular contour,nasolabial angle,philtral length,philtral width,upper lip height,and upper vermilion height)were measured and recorded for treatment changes.Linear-regression analysis and correlation analysis were carried out for analyzing the relationship between hard and soft tissue changes before and after the treatment.Results:Significant differences were noticed for 18 out of the 20 cephalometric measurements and facial measurements before and after the treatment(P＜0.05),which mainly represented the sagittal retraction of lip area after the treatment.Significant vertical displacements were revealed for soft tissue menton after treatment[(1.88±2.61)mm,P＜0.05].Significant sagittal displacements were revealed for left/right cheilion[(-2.95±1.9)mm,(-2.90±1.92)mm],labrale inferius[(-4.94±1.95)mm],labrale superius[(-3.25±1.44)mm],sublabial[(-3.10±3.5)mm],and subnasale[(-1.23±1.06)mm]after treatment(P＜0.05).An average of 4.10°±2.57° increasement was noticed for Z angle after treatment.High correla-tion(r＞0.7)was noticed for the displacement of menton after treatment with FH-MP,with the rate of-0.183:1,and MP-SN,with the rate of-0.157:1.Moderate correlations(0.7≥r＞0.4)were no-ticed for the other measurements with correlations(P＜0.05).Conclusion:A certain extent of facial improvements could be achieved with orthodontic camouflage treatment for skeletal class Ⅱ hyperdiver-gent patients,which were mostly represented by the improvement of sagittal relationship of nose,lips,and chin.Certain correlations were noticed for the hard and soft tissue changes.

Objective: To investigate individualized therapeutic strategy for bilateral carotid body tumors. Methods: Clinical data of 16 patients with bilateral carotid body tumor treated from January 2003 to August 2016 were retrospectively studied. Of the 16 patients, 9 were males and 7 were females; 5 were sporadic and 11 were familial; 8 cases were observed, 1 cases was malignant and treated with chemotherapy, and 7 cases were treated with surgery. The treatment course, perioperative complications and clinical efficacy were assessed. Comprehensive evaluation of bilateral carotid body tumors was performed based on the size of bilateral tumor, clinical manifestations, genetic tests and other indicators. Individual treatment strategies included observation, surgery and observation, bilateral surgery, radiotherapy or chemotherapy. Surgical resection of carotid body tumor was unilateral in 3 cases and bilateral in 3 cases; removal of bilateral carotid body tumors plus unilateral jugular bulb in 1 case; and the internal carotid artery was reconstructed with autologous greater saphenous vein in 1 case. Results: All patients were followed up for 3 months to 12 years. There was no patient death during perioperative period. Superior laryngeal nerve injury occurred in 2 case. Baroreceptor failure syndrome occurred in one patient, but it gradually recoverd with medical treatments. Conlusion It is important to identify whether bilateral carotid body tumors are hereditary and to make an individualized therapeutic strategy for each patient with bilateral carotid body tumors, focusing on the improvement in the quality of life of patient.

OBJECTIVEThe plasmid construction and validation of RET point mutation in vitro.METHODS The RET gene exon in the mainland familial medullary thyroid carcinoma family was analized with muon capture two generation sequencing of. In vitro, the RET relative point mutationswere reconstructed in NIH3T3 cells and the expression levels were studied.RESULTSThe corresponding lentiviral plasmids of RET point mutations were successfully obtained after point mutating the wild RET plasmids, it was verified that the target genes were expressed in NIH3T3 cells stably by Western Blot. CONCLUSIONSStable cell lines carrying RET point mutations were reconstructedsuccessfully, which provide a good platform for studying various point mutations.

Objective To analyze retrospectively the therapeutic effect and safety of minimally invasive transthoracic device closure of perimembranous ventricular septal defect (PVSD).Methods One hundred and twenty-nine patients with PVSD from January 2011 to December 2011 in our hospital were selected and a 3 to 5 cm incision was made in the inferior sternum,which performed minimally invasive transthoracic device closure of ventricular septal defect (VSD).Right ventricular free wall was punctured and guided by transthoracic echocardiography (TEE),and then the occluder was released after a delivery sheath passed through the VSD.Location of occluder,effect on heart valve,fastness and residual shunt were evaluated by TEE instantly during operation.All patients were followed up intimately after operation,echocardiogram and electrocardiogram were rechecked regularly.Results One hundred and fourteen cases were successfully occluded.Fifteen cases were performed VSD repair operation with cardiopulmonary bypass.The amounts of concentric occluder and eccentric occluder were 96 and 20,respectively.The patients performed minimally invasive transthoracic device closure of VSD had no severe complications after operation.Conclusion Although the short-term therapeutic effect of minimally invasive transthoracic device closure of PVSD is definitely and has favourable prospect of application,the long-term follow-up remains to be studied.

It has been a major topic for the reform on higher medical education and teaching to cultivate medical students' professional information literacy so asto make them equipped with the information competence required for disease control or medical research.In this thesis,the concept of professional information literacy for medical students was introduced,and by analyzing the relationship of information literacy education and medical education modes,countermeasures and methods of cultivating medical students' professional information literacy by combining the reform on medical education and teaching were put forward.

Introducing the PBL teaching mode in regional anatomy teaching accords with the need of 21centuries social development for the highquality medical science personnel training and the regional anatomy course characteristic, and is beneficial to the students’ changing their study concept and raising their learning ability. It is also an effective way for allaround quality education.