BACKGROUND:Osteoblasts are the main cell types responsible for bone formation and remodeling,and the normal performance of their function is precisely regulated by various signaling pathways.Among them,the bone morphogenetic protein and Wnt signaling pathways play a key role in osteogenesis. OBJECTIVE:To review the role of bone morphogenetic protein/Wnt signaling pathway in the regulation of osteoblast function and analyze its changes in different physiological and pathological conditions in order to further reveal the molecular mechanism of bone formation and remodeling. METHODS:The Chinese and English search terms"BMP signaling pathway,Wnt signaling pathway,and osteogenesis"were searched in CNKI,Wanfang,and PubMed databases for original researches published from the inception to June 2023.Totally 61 articles were finally selected for analysis and summary.Using the method of the literature review,the studies of the bone morphogenetic protein/Wnt signaling pathway in regulating osteogenesis were sorted out and analyzed. RESULTS AND CONCLUSION:(1)Bone morphogenetic protein and Wnt signaling pathways play important roles in the differentiation,proliferation,and maturation of osteoblasts.Bone morphogenetic protein signaling pathway mainly regulates the expression of osteogenesis-related genes through the activation of Smad protein.Smad protein enters the nucleus and regulates the expression of genes related to osteogenesis.Different Wnt signaling pathway from bone morphogenetic protein mainly depends on the activation of β-catenin to exert its biological effects.(2)The regulatory effect of bone morphogenetic protein/Wnt signaling pathway will be affected by many factors in different physiological and pathological states.Growth factors,hormones,and mechanical stress can affect the activity of bone morphogenetic protein/Wnt signaling pathway to some extent.(3)Bone morphogenetic protein/Wnt signaling pathway interacts with other signaling pathways in the regulation of osteogenesis,and they together constitute a complex regulatory network.(4)Chinese medicine and natural compounds can promote bone health by regulating signaling pathways,providing new possibilities for treating bone diseases.(5)Future studies can further explore the interaction of bone morphogenetic protein/Wnt signaling pathway and other signaling pathways and its changes in different physiological and pathological conditions,resolve the key nodes and regulation mechanism in the complex network,to provide more precise targets for the treatment of bone-related diseases,and also provide new ideas to reveal the molecular mechanism of bone formation and remodeling.

BACKGROUND:Osteonecrosis of the femoral head is a common complication in patients with systemic lupus erythematosus.The prediction and validation of the risk in advance will help to avoid or delay the progression of osteonecrosis of the femoral head.OBJECTIVE:To analyze risk factors for the occurrence of osteonecrosis of the femoral head in systemic lupus erythematosus patients and to construct and validate a nomogram prediction model of systemic lupus erythematosus patients with osteonecrosis of the femoral head.METHODS:A retrospective study was conducted to analyze the medical records of 914 systemic lupus erythematosus patients who first visited First Affiliated Hospital of Henan University of Chinese Medicine between January 2013 and December 2022.All patients were divided into osteonecrosis of the femoral head(n=100)and non-osteonecrosis of the femoral head(n=814)groups according to whether they had suffered from osteonecrosis of the femoral head or not.Univariate,LASSO regression,and multifactorial logistic regression analyses were used to screen and identify the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head.The dataset was also randomly divided into training and test sets in a ratio of 7:3.A nomogram prediction model of the risk of systemic lupus erythematosus complicating osteonecrosis of the femoral head was constructed based on the results of the multifactorial logistic regression analysis.The performance of the nomogram was evaluated using the receiver operating characteristic curve,Hosmer-Lemeshow calibration curve,and decision curve analysis.RESULTS AND CONCLUSION:(1)There were significant differences in disease duration of systemic lupus erythematosus,systemic lupus erythematosus disease activity,lupus nephritis,respiratory involvement,gastrointestinal involvement,Sj?gren's syndrome,osteoporosis,anti-ribonucleoprotein,complement C3 decrease,cyclophosphamide,mycophenolate mofetil,biologics,maximum daily dose of glucocorticosteroids,and pulses of intravenous methylprednisolone between the osteonecrosis of the femoral head and non-osteonecrosis of the femoral head groups(P＜0.05).(2)Ten predictor variables related to the risk of osteonecrosis of the femoral head in patients with systemic lupus erythematosus were screened using LASSO regression analysis.Multivariate logistic regression analysis further confirmed disease duration of systemic lupus erythematosus,respiratory involvement,Sj?gren's syndrome,osteoporosis,anti-ribonucleoprotein,cyclophosphamide,mycophenolate mofetil,biologics,and maximum daily dose of glucocorticosteroids were independent risk factors for osteonecrosis of the femoral head in systemic lupus erythematosus patients(P＜0.05).(3)The area under the receiver operating characteristic curve for predicting the risk of occurrence of osteonecrosis of the femoral head in systemic lupus erythematosus patients was 0.802(95％CI=0.742-0.862)in the training set and 0.811(95％CI=0.745-0.876)in the testing set.The Hosmer-Lemeshow calibration curve fit was well(P=0.447 in raining set;P=0.870 in testing set).Decision curve analysis showed that it was beneficial in predicting the risk of osteonecrosis of the femoral head in systemic lupus erythematosus patients using the nomogram prediction model.(4)Menstrual abnormalities were one of the risk factors for osteonecrosis of the femoral head in female systemic lupus erythematosus patients.(5)The results suggest that the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head are multi-factorial,and a nomogram prediction model containing nine risk factors was also developed,which could be used to predict the risk of osteonecrosis of the femoral head in systemic lupus erythematosus patients.In addition,we reported for the first time that menstrual abnormalities were one of the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head in female.

BACKGROUND:Osteonecrosis of the femoral head is a common complication in patients with systemic lupus erythematosus.The prediction and validation of the risk in advance will help to avoid or delay the progression of osteonecrosis of the femoral head.OBJECTIVE:To analyze risk factors for the occurrence of osteonecrosis of the femoral head in systemic lupus erythematosus patients and to construct and validate a nomogram prediction model of systemic lupus erythematosus patients with osteonecrosis of the femoral head.METHODS:A retrospective study was conducted to analyze the medical records of 914 systemic lupus erythematosus patients who first visited First Affiliated Hospital of Henan University of Chinese Medicine between January 2013 and December 2022.All patients were divided into osteonecrosis of the femoral head(n=100)and non-osteonecrosis of the femoral head(n=814)groups according to whether they had suffered from osteonecrosis of the femoral head or not.Univariate,LASSO regression,and multifactorial logistic regression analyses were used to screen and identify the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head.The dataset was also randomly divided into training and test sets in a ratio of 7:3.A nomogram prediction model of the risk of systemic lupus erythematosus complicating osteonecrosis of the femoral head was constructed based on the results of the multifactorial logistic regression analysis.The performance of the nomogram was evaluated using the receiver operating characteristic curve,Hosmer-Lemeshow calibration curve,and decision curve analysis.RESULTS AND CONCLUSION:(1)There were significant differences in disease duration of systemic lupus erythematosus,systemic lupus erythematosus disease activity,lupus nephritis,respiratory involvement,gastrointestinal involvement,Sj?gren's syndrome,osteoporosis,anti-ribonucleoprotein,complement C3 decrease,cyclophosphamide,mycophenolate mofetil,biologics,maximum daily dose of glucocorticosteroids,and pulses of intravenous methylprednisolone between the osteonecrosis of the femoral head and non-osteonecrosis of the femoral head groups(P＜0.05).(2)Ten predictor variables related to the risk of osteonecrosis of the femoral head in patients with systemic lupus erythematosus were screened using LASSO regression analysis.Multivariate logistic regression analysis further confirmed disease duration of systemic lupus erythematosus,respiratory involvement,Sj?gren's syndrome,osteoporosis,anti-ribonucleoprotein,cyclophosphamide,mycophenolate mofetil,biologics,and maximum daily dose of glucocorticosteroids were independent risk factors for osteonecrosis of the femoral head in systemic lupus erythematosus patients(P＜0.05).(3)The area under the receiver operating characteristic curve for predicting the risk of occurrence of osteonecrosis of the femoral head in systemic lupus erythematosus patients was 0.802(95％CI=0.742-0.862)in the training set and 0.811(95％CI=0.745-0.876)in the testing set.The Hosmer-Lemeshow calibration curve fit was well(P=0.447 in raining set;P=0.870 in testing set).Decision curve analysis showed that it was beneficial in predicting the risk of osteonecrosis of the femoral head in systemic lupus erythematosus patients using the nomogram prediction model.(4)Menstrual abnormalities were one of the risk factors for osteonecrosis of the femoral head in female systemic lupus erythematosus patients.(5)The results suggest that the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head are multi-factorial,and a nomogram prediction model containing nine risk factors was also developed,which could be used to predict the risk of osteonecrosis of the femoral head in systemic lupus erythematosus patients.In addition,we reported for the first time that menstrual abnormalities were one of the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head in female.

Objective:To evaluate the effect of inhibition of interleukin-6 (IL-6) trans-signaling on sepsis-associated encephalopathy (SAE) in mice.Methods:Eighty healthy male C57BL/6J mice, aged 8-10 weeks, weighing 22-24 g, were divided into 4 groups using a random number table method: sham operation group (Sham group, n=10), SAE group ( n=35), SAE plus sgp130Fc group ( n=25) and sgp130Fc group ( n=10). Sepsis was induced by cecal ligation and puncture (CLP) in anesthetized animals.Sham and sgp130Fc groups received no CLP.In group sgp130Fc and group SAE+ sgp130Fc, sgp130Fc 0.5 mg/kg was intraperitoneally injected at 1 h after sham operation or CLP.The survival rates, body weight and neurological function scores were recorded within 1-10 days after sham operation or CLP.Four mice in each group were selected at 24 h after sham operation or CLP to detect the expression of occlusin in hippocampus by Western blot.Five mice in each group were selected to measure cognitive function using Morris water maze test at day 4 after sham operation or CLP. Results:Compared with group Sham, the survival mice, body weight and neurological function scores on days 2-10 after CLP were significantly decreased, the expression of occludin was down-regulated, the frequency of crossing the original platform was decreased, and the time spent in target quadrant was shortened in group SAE ( P<0.05), and no significant change was found in the indexes mentioned above in group sgp130Fc ( P>0.05). Compared with group SAE, the survival rate and neurological function scores on days 3-10 after CLP were significantly increased, the expression of occludin was up-regulated, the frequency of crossing the original platform was increased, and the time spent in target quadrant was prolonged ( P<0.05), and no significant change was found in body weight in group SAE+ sgp130Fc ( P>0.05). Conclusions:Inhibition of IL-6 trans-signaling can reduce the damage to the blood brain barrier and SAE in mice.

Mycoplasma pneumoniae pneumonia (MPP) complicated with cerebral venous sinus thrombosis (CVST) is rare.We retrospectively analyzed the clinical data of two patients with refractory mycoplasma pneumoniae pneumonia (RMPP) complicated with CVST who were hospitalized in Xi′an children′s Hospital from December 2018 to April 2019, inquired the relevant literature, analyzed the clinical diagnosis and treatment characteristics, and discussed the diagnosis and treatment measures of RMPP complicated with CVST.Two cases were 6-year-old girls with fever and cough as the main symptoms.After physical examination, the respiratory sounds of the affected lung decreased, and the sounds of phlegm and dampness could be heard in both lungs.Mycoplasma pneumoniae (MP) antibody and RNA were positive.Chest CT showed lobar pneumonia with a large number of pleural effusion.The effect of macrolide antibiotics anti infection treatment was not good.Headache symptoms occurred during the course of the disease, and serum D-dimer increased significantly.Brain MRI showed CVST, including 1 case with lower extremity pain, and B-ultrasound showed right lower extremity arterial embolism.After anti infection, thrombectomy, anticoagulation and symptomatic treatment, 2 cases were discharged.When children with MPP, especially those with RMPP, have extracranial thrombosis and/or neurological symptoms, accompanied by elevated serum D-dimer, the possibility of CVST should be considered, and brain MRI examination should be performed in time to confirm and actively treat, which can reduce or avoid the occurrence of sequelae.Thrombosis may be related to excessive inflammatory reaction and vascular endothelial injury caused by MP infection.

Objective To analyze the epidemiological characteristics of other-infectious diarrhea (OID) in Shaanxi Province from 2006 to 2015 to further clarify the prevention and control strategies.Methods We collected data from the Infectious Disease Report Information System in China for Disease Prevention and Control and made a statistical description of the epidemiological characteristics of incidence distribution in Shaanxi from 2006 to 2015.Results Totally 207 437 cases of other-infectious diarrhea were reported in Shaanxi Province during 2006 -2015,with the average yearly incidence rate of 52.43/105.The incidence number was higher in males (126 673 cases) than in females (80 764 cases),with male-female ratio of 1.57 ∶ 1.The diseases were most serious in age groups 0-and 1-4 years,accounting for 72.48％.The top-three careers of reported cases were scattered children (74.88 ％),farmers (10.75 ％) and students (5.75 ％),respectively.The cities with the highest incidence in Shaanxi Province were Baoji,Yan'an and Ankang.Two high-incidence seasons were summer (July to August) and winter (November to December).The main pathogen of viral diarrhea was rotavirus,but laboratory-confirmed proportion was low (4.60％).Conclusion Other-infectious diarrhea,especially infection caused by rotavirus in autumn and winter,mainly occurred in children younger than 5 years old.Etiological diagnosis should be strengthened because of the poor laboratory diagnosis reporting rate.

Objective: To analyze the epidemiological characteristics and the molecular types of human adenovirus (HAdV) from influenza-like illness (ILI) samples with negative influenza virus in Xi'an from January 2013 to December 2015. Methods: Samples from patients with ILI were collected from two national influenza sentinel surveillance hospitals during 2013—2015 in Xi′an. HAdV was detected by real-time PCR, and then the positive samples were inoculated into Hep-2 cells to isolate the viruses. The amplified products were purified and sequenced of hexon gene, and the sequences were compared with the Genebank data and phylogenetic trees were constructed. Results: In 2367 samples, 88 samples were positive for HAdV, the positive rate was 3.72%. There were 7 subtypes detected, and the rates of each subtype are as follows: HAdV-1 was 9.09%, HAdV-2 was 22.73%, HAdV-3 was 23.86%, HAdV-4 was 5.68%, HAdV-5 was 7.95%, HAdV-6 was 3.41% and HAdV-7 was 1.14%. Males had higher infection rate than females, but there was no significant difference. The patients were divided into 6 groups according to age. There were 3 positive samples among those under 1 year of age, 36 positive samples among those 1 to 3 years old, 26 positive samples among those 4 to 6 years old, 16 positive samples in those 7 to 18 years old, 5 positive samples in 19 to 59 years old and 2 positive samples in those older than sixty years of age. HAdV infection was primarily confined to children under 7 years of age. Conclusions HAdV-3 and HAdV-2 were the dominant epidemic strains during 2013—2015 in Xi′an. Children younger than 7 years were the main susceptible population. HAdV infections circulate all year-round and there was no considerable seasonal variation.

Objective To construct and identify the recombinant retroviral vector containing five copies of hypoxia responsive elements (5HRE)and neurotrophin-3 (NT-3 ).Methods Using PCR,enzyme digestion and DNA ligase,5HRE and human derived NT-3 were cloned into the retroviral vector plasmid (pLNCX)to construct the recombinant retroviral vector plasmid pLNCX-5HRE-SV40-NT3-IRES-EGFP.The retrovirus RV-5HRE-NT3 was packaged in the PT67 cells,and then it was purified and concentrated by high-speed centrifugation.After infected for 48 h with the concentrated retrovirus,the number of the EGFP positive cells in the NIH 3T3 cells was counted by fluorescence activated cells and sorted to calculate the retrovirus titer.Results The retroviral vector plasmid,pLNCX-5HRE-SV40-NT3-IRES-EGFP,was successfully constructed,and the retrovirus was packaged and defined as RV-5HRE-NT3.After purification and concentration,the retrovirus titer reached 9.1 × 10 6 cfu/mL. Conclusion The recombinant retroviral vector which carried out hypoxia-regulated expression of NT-3 was successfully constructed.It may provide basis for studies on hypoxia-regulated expression of the exogenous genes.

OBJECTIVETo observe the morphological changes during development of the ventricular zone (VZ) and subventricular zone (SVZ) of human fetus and the distribution pattern of neural stem cells in the VA and SVZ.

METHODSHuman fetuses at the gestational ages of 9-11 weeks, 14-16 weeks, 22-24 weeks and 32-36 weeks were collected, and the brain sections of the VZ/SVZ under the frontal lobe were examined for cytoarchitecture and distribution of nestin-positive cells with HE staining, immunohistochemistry or immunofluorescence.

RESULTSThe thickness of VZ underwent no significant changes at the gestational ages of 9-24 weeks (P>0.05) and became obviously thinner at 32 weeks (P<0.05), while the thickness of SVZ increased during 9-24 weeks (P<0.05) without obvious thinning at 32 weeks (P>0.05). VZ was thicker than SVZ at 9-11 weeks but became markedly thinner than SVZ after 14 weeks (P<0.05). The VZ contained denser cells than SVZ and showed a distinct boundary between the VZ and SVZ. Large numbers of nestin-positive cells were detected in the VZ and SVZ, and nestin immunoreactivity was found primarily in the cell processes and occasionally in the soma. Some nestin-positive cells in the SVZ had 1-3 processes. Nestin immunoreactivity in the VZ and SVZ gradually grew weak with development. The cells positive for both nestin and Ki67 were located mainly in the inner zone of the VZ and throughout the SVZ, where some nestin-positive but Ki67-negative cells were also found.

CONCLUSIONThe SVZ fully extends and the neural stem cells in the VZ/SVZ can be morphologically heterogeneous during the development of fetal human brain.

Fetus ; Frontal Lobe ; cytology ; embryology ; metabolism ; Humans ; Nestin ; metabolism ; Neural Stem Cells ; metabolism ; Neurons ; metabolism

OBJECTIVETo investigate the expression of metabotropic glutamate receptor 5 (mGluR5) and its cellular distribution in the frontal cortex, ventricular zone (VZ) and subventricular zone (SVZ) in human fetuses.

METHODSAccording to the gestational age, the collected fetuses were divided into 4 groups, namely 9-11 weeks, 14-16 weeks, 22-24 weeks and 32-36 weeks. Brain tissue blocks including the frontal lobe or VZ/SVZ were prepared into slices, and the expression pattern and cellular distribution of mGluR5 in the frontal cortex and VZ/SVZ were observed by immunohistochemistry or immunofluorescence.

RESULTSmGluR5 immunoreactivity was present in the cell membrane in the frontal cortex, VZ and SVZ from the 9th to 36th weeks and the immunoreactivity in the marginal zone (MZ) and cortical plate (CP) was markedly stronger than that in VZ and SVZ. The cells expressing mGluR5 included neural stem/progenitor cells in the VZ and SVZ, immature neurons in the VZ and MZ, and numerous mature neurons in the CP.

CONCLUSIONmGluR5 is expressed by a variety of cells such as neural stem cells in the frontal cortex, VZ and SVZ in human fetus, suggesting a role of mGluR5 in the development of human cerebral cortex.

Cerebral Cortex ; cytology ; Cerebral Ventricles ; cytology ; metabolism ; Fetus ; cytology ; metabolism ; Frontal Lobe ; cytology ; metabolism ; Humans ; Neural Stem Cells ; cytology ; metabolism ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate ; metabolism