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:The occurrence and development of osteoarthritis is strongly associated with immune abnormalities,and the importance of various immune cells and immune mediators in the pathogenesis of osteoarthritis has been continuously elucidated. OBJECTIVE:To review the role of immune cells and related cytokines in osteoarthritis disease,and provide new ideas for future research and prevention of osteoarthritis. METHODS:Taking"osteoarthritis,knee,macrophages,T cells,B cells,natural killer cells,dendritic cells,cytokines,inflammatory factors,immune cells"as search terms,relevant published literature was searched on CNKI,WanFang,VIP,PubMed and Web of Science databases.After reading the title and abstract for preliminary screening,98 articles were selected for review after reading the full text again. RESULTS AND CONCLUSION:In the past,it was believed that the pathogenesis of osteoarthritis was associated with cartilage wear.In recent years,studies have suggested that osteoarthritis is a chronic inflammatory state in which immune cells are widely involved.With the in-depth study of the pathogenesis of osteoarthritis,scholars believe that the pathogenesis of osteoarthritis is driven by early innate immune response,which will gradually catalyze degenerative changes and eventually lead to changes in the joint microenvironment.Various immune cells and cytokines are the key factors affecting the repair of osteoarthritis.Macrophages and natural killer cells participate in synovial inflammatory reaction,and T cell immune reaction participates in the degradation of osteoarthritis cartilage and aggravates the condition of osteoarthritis.Interleukin-1β secreted by immune cells,interleukin-6,tumor necrosis factor α,interleukin-17 and interleukin-37 play an important role in the pathophysiology of osteoarthritis,among which interleukin-1β is the most important inflammatory factor causing articular cartilage damage.Assessing immunological risk factors at the early stage of osteoarthritis can effectively treat the disease at an early stage,which can significantly reduce disability,morbidity and costs associated with osteoarthritis.At present,the immunomodulatory effect of stem cells and their derived secretions and biomaterials on the treatment of osteoarthritis has been confirmed in different experimental models,but there is still a lot of research to be done before they are used in clinical practice.With the discovery of new therapeutic targets,targeted treatment will bring new hope for the repair of clinical osteoarthritis.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective : To analyze the clinical characteristics of patients with abdominal type allergic purpura(HSP), to improve their diagnostic level, and to explore the risk factors for gastrointestinal bleeding in HSP patients. Methods : A retrospective analysis was conducted on the clinical manifestations, laboratory data, imaging, endoscopic, and pathological characteristics of 98 patients with abdominal type HSP. Based on the occurrence of gastrointestinal bleeding, 98 patients were divided into a bleeding group and a non-bleeding group, and the risk factors for gastrointestinal bleeding in HSP patients were analyzed. Results : Abdominal HSP often presented with abdominal pain, vomiting, vomiting blood, black stools, and bloody stools. Imaging often showed edema and thickening of the duodenum and jejunum, as well as enlargement of surrounding lymph nodes. Under endoscopy, the descending part of the duodenum and jejunum mucosa were commonly congested and edematous with erosion, and ulcers were seen in the distal ileum. Pathology commonly involved acute and chronic inflammation of the mucosa with congestion, edema, and local erosion. Patients with gastrointestinal bleeding had significantly higher levels of white blood cell count(WBC), neutrophil count(NEUT), C-reactive protein(CRP), D-dimer(D-D), and fibrinolytic products(FDP) compared to non-bleeding patients(P<0.05), while levels of red blood cell count(RBC), hemoglobin(HGB), and albumin(ALB) were significantly lower than those of non bleeding patients(P<0.05). Logistic regression analysis showed that decreased ALB and increased FDP were independent risk factors for gastrointestinal bleeding in patients with abdominal HSP(P<0.05). The areas under the ROC curves of ALB and FDP were(AUC=0.877, 95%CI:0.794-0.960,P<0.01) and(AUC=0.806, 95%CI:0.722-0.890,P<0.01), respectively. The maximum value of the Jordan index for ALB was 0.734, with sensitivity and specificity of 89.6% and 83.9%, respectively, and had a critical value of 38.2 g/L. The maximum value of the Jordan index for FDP was 0.577, with sensitivity and specificity of 64.2% and 93.5%, respectively, and had a critical value of 18.14 μg/ml. There was no statistically significant difference in the ROC curves between ALB and FDP. Conclusion For HSP with abdominal pain as the initial symptom, imaging and endoscopic examination are helpful for early diagnosis. Decreased ALB and elevated FDP are independent risk factors for gastrointestinal bleeding in adult patients with abdominal HSP.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical bacterial isolates from bloodstream infections in China in 2021.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2021 to December 2021. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 11 013 bacterial strains were collected from 51 hospitals, of which 2 782 (25.3%) were Gram-positive bacteria and 8 231 (74.7%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.6%), Klebsiella pneumoniae (18.9%), Staphylococcus aureus (9.8%), coagulase-negative Staphylococci (6.3%), Pseudomonas aeruginosa (3.6%), Enterococcus faecium (3.6%), Acinetobacter baumannii (2.8%), Enterococcus faecalis (2.7%), Enterobacter cloacae (2.5%) and Klebsiella spp (2.1%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 25.3% and 76.8%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci was detected; more than 95.0% of Staphylococcus aureus were sensitive to ceftobiprole. No vancomycin-resistant Enterococci strains were detected. The rates of extended spectrum B-lactamase (ESBL)-producing isolated in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 49.6%, 25.5% and 39.0%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.2% and 15.8%, respectively; 7.9% of carbapenem-resistant Klebsiella pneumoniae was resistant to ceftazidime/avibactam combination. Ceftobiprole demonstrated excellent activity against non-ESBL-producing Escherichia coli and Klebsiella pneumoniae. Aztreonam/avibactam was highly active against carbapenem-resistant Escherichia coli and Klebsiella pneumoniae. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii (5.5% and 4.5%). The prevalence of carbapenem-resistance in Pseudomonas aeruginosa was 18.9%. Conclusions:The BRICS surveillance results in 2021 shows that the main pathogens of blood stream infection in China are gram-negative bacteria, in which Escherichia coli is the most common. The MRSA incidence shows a further decreasing trend in China and the overall prevalence of vancomycin-resistant Enterococci is low. The prevalence of Carbapenem-resistant Klebsiella pneumoniae is still on a high level, but the trend is downwards.

Objective : To explore the general information，clinical features，imaging findings and outcome of pa- tients with drug-induced cholestatic． Methods : The clinical data of patients diagnosed as cholestatic drug-induced liver injury in recent 5 years were analyzed retrospectively，and followed up for at least 6 months. Results : There were 105 patients with drug-induced cholestatic liver injury in the hospital，the median age was 55 years old (54. 3% male) ，most of them had no specific clinical symptoms ; there were nearly 80 kinds of drugs involved，the top three were traditional Chinese medicine (34. 3% ) ，antineoplastic drugs (22. 9% ) and antibiotics ( 10. 5% ) . Among the 49 patients with magnetic resonance cholangiopancreatography ( MRCP) ，7 ( 14. 3% ) had sclerosing cholangitis-like changes ; most of the patients were combined with multiple liver-protecting and enzyme-lowering drugs ; there were 53 cured (50. 5% ) ，41 improved (39. 0% ) ，7 uncured (6. 7% ) ，and 4 died (3. 8% ) among 105 patients，and the total effective rate was 89. 5%． Conclusion Drug-induced cholestatic liver injury mainly oc- curs in elderly patients，involving many kinds of drugs，mainly traditional Chinese medicine．Drugs can also cause changes similar to sclerosing cholangitis，so drug-induced liver injury (DILI) should be used as one of the differen- tial diagnosis of cholestasis and abnormal cholangiography．Liver disease and the number of drugs have no effect on the prognosis of the patients，while low Roussel Uclaf causality assessment method (RUCAM) score and hemoglobin count，short hospitalization time and high white blood cell count are poor prognostic factors.

Objective: To detect the difference in the incidence of small intestinal bacterial overgrowth(SIBO) in patients with liver cirrhosis and chronic hepatitis fibrosis(CHF) with the lactulose hydrogen breath test(LHBT), and to explore the relationship between SIBO and inflammatory factors and oxidative stress related indicators. Methods: LHBT was performed on 38 CHF patients, 60 cirrhosis patients and 31 healthy controls to evaluate the incidence of SIBO. The patients were further divided into SIBO-positive and negative group. Then we compared related clinical symptoms and laboratory tests between the two groups and detected lipopolysaccharide(LPS), interleukin(IL)-6, tumor necrosis factor(TNF)-α, IL-10 level, and several kinds of oxidative stress indicators such as diamine oxidase(DAO), superoxide dismutase(SOD), glutathione(GSH), catalase(CAT). Statistical analysis was conducted to analyze the correlation between the concentration of LPS, IL-6, TNF-α, DAO, SOD, GSH, CAT and LHBT summation value. Results: (1) The positive rate of SIBO in CHF group, cirrhosis group and control group was 36.84%, 60.00% and 9.68%, respectively. The difference was statistically significant(P<0.01).(2) The differences in CTP classification and ascites were statistically significant between the two subgroups with and without SIBO(P<0.05).(3) The levels of LPS, IL-6, CAT, DAO and SOD in SIBO-positive group were higher than those in negative group(P<0.05). However, the concentrations of IL-10, TNF-α and GSH were similar between the two groups.(4) The LHBT summation value was positively correlated with the concentrations of LPS, IL-6, DAO, SOD and CAT in serum(P<0.05), but had no significant correlation with TNF-α, IL-10 and GSH. Conclusion Compared with healthy controls, CHF and cirrhosis patients are more likely to develop SIBO. It is also related to the increase of inflammatory factors and oxidative stress indexes in peripheral blood. SIBO may aggravate the inflammatory response of CHF and cirrhosis patients through intestinal flora dysregulation and oxidative stress, thus aggravating the disease change.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.