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 explore the application value of ¹⁸F-PSMA PET/CT on the detection of metastatic lesions of prostate cancer with serum total prostate specific antigen (tPSA) ≤20 ng/mL and the predictive variables affecting the imaging results, and to establish a predictive nomogram for the metastasis of prostate cancer. 【Methods】 The imaging, pathological, serum and clinical data of 175 pathologically confirmed prostate cancer patients who underwent ¹⁸F-PSMA PET/CT examination during Jan.2020 and Oct.2021 were retrospectively collected.The patients were divided into metastatic group and non-metastatic group according to PET/CT imaging results, and the positive detection rate of metastatic lesions was calculated.The independent influencing factors of ¹⁸F-PSMA PET/CT in the positive detection of metastatic lesions were determined with univariate and multivariate logistic regression analyses.The predictive nomogram was established. 【Results】 Of the 175 patients, metastatic lesions were detected in 78 cases and not detected in 97 cases, with a detection rate of 44.6% (78/175).There were statistically significant differences between the metastatic group and the non-metastatic group in urinary tract symptoms, androgen deprivation treatment (ADT) at the time of PET/CT examination and the risk level of Gleason score (GS) (P<0.05).Univariate logistic regression showed that urinary tract symptoms(OR=3.64, P<0.001), GS risk (OR=3.96, P<0.001) and concurrent ADT treatment (OR=3.71, P<0.001) were associated with the positive detection rate of metastatic lesions.Multivariate Logistic regression showed that urinary tract symptoms (OR=3.19, P=0.002), GS high-risk group (OR=2.95, P=0.005) and concurrent ADT treatment (OR=3.27, P=0.001) were independent predictors of positive detection rate. 【Conclusion】 The probability of metastasis in newly diagnosed prostate cancer patients with tPSA≤20 ng/mL is high.¹⁸F-PSMA PET/CT is of high value for the early detection of metastasis.Urinary tract symptoms, GS high-risk group and concurrent ADT treatment are independent predictors of metastatic lesions.The predictive nomogram can help assist clinical optimization of imaging examination path.

Objective To explore the safety and efficacy of neoadjuvant chemotherapy(NAC)combined with immunotherapy before radical cystectomy plus pelvic lymph nodes dissection(RC-PLND)for muscle-invasive bladder cancer(MIBC).Methods The clinical data of 101 patients with MIBC who underwent neoadjuvant therapy followed by RC-PLND in the Department of Urology,the First Affiliated Hospital of Xi'an Jiaotong University during Jan.2019 and Dec.2023 were retrospectively analyzed,including 71 patients(70.3％)who received NAC(NAC group)and 30(29.7％)who received NAC combined with immunotherapy(NAC combine immunotherapy group).The clinical and pathological data and adverse events during neoadjuvant therapy were compared.Logistic regression analysis was used to explore the independent predictors of pathological complete response(pCR)and pathological partial response(pPR).Results There were no significant differences in the baseline data between the two groups(P＞0.05).However,the proportion of multiple tumors in patients receiving NAC before surgery was significantly higher than that in the NAC combined immunotherapy group(69.0％vs.46.7％,P=0.034).Compared with NAC group,NAC combined with immunotherapy group had significantly improved rate of pathological downstaging and pPR(60.6％vs.83.3％,P=0.026;45.1％vs.70.0％,P=0.022).Furthermore,the rate of pCR in patients undergoing NAC combined immunotherapy was higher than those undergoing NAC,but the difference was not significant(53.3％vs.33.8％,P=0.067).Logistic regression analysis revealed that clinical T-stage and tumor diameter were independent predictors of pCR and pPR(P＜0.05).In addition,the most common adverse events during neoadjuvant therapy were anemia,decreased white blood cells,nausea,and vomiting,but most of them were grade 1-2 and could be relieved through symptomatic treatment.Conclusion NAC combined with immunotherapy is safe and effective,which can improve the rate of pathological downstaging,pPR and pCR,without increasing the incidence of adverse reactions.

Objective: To investigate the factors affecting depression and anxiety symptoms among the elderly, so as to provide the basis for promoting mental health among the elderly. Methods: The elderly aged 60 years and above in Ningbo City, Zhejiang Province were recruited using the multistage stratified random sampling method from June to August 2022, and demographic information, lifestyle and self-rated health status were collected by questionnaires. The symptoms of depression and anxiety were assessed by the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7), respectively. The presence of depressive and anxiety symptoms was determined when both the PHQ-9 score and the GAD-7 score were 10 points and higher. Factors affecting depressive and anxiety symptoms were identified using a multivariable logistic regression model. Results: A total of 7 771 individuals were surveyed, including 3 490 males (44.91%) and 4 281 females (55.09%), and had a mean age of (72.11±6.79) years. The prevalence of depression and anxiety symptoms was 2.05%. Multivariable logistic regression analysis identified residence (urban area, OR=0.316, 95%CI: 0.201-0.498), sedentary duration (<3 h/d, OR=0.349, 95%CI: 0.232-0.525; 3-5 h/d, OR=0.458, 95%CI: 0.313-0.671), physical activity (≥3 times/week, OR=0.551, 95%CI: 0.373-0.815), sleep quality (poor, OR=2.491, 95%CI: 1.738-3.571), social isolation (OR=1.688, 95%CI: 1.148-2.481) and self-rated health (poor, OR=5.857, 95%CI: 3.547-9.671; normal, OR=1.903, 95%CI: 1.234-2.937) as the influencing factors for depression and anxiety symptoms among the elderly. Conclusion The prevalence of depression and anxiety symptoms among the elderly is associated with residence, sedentary duration, sleep quality, physical activity, social interactions and self-rated health status.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Bladder cancer is one of the most common urinary tumors, and human urinary tract has been proved to be non-sterile. The significance of urinary tract flora in pathophysiology and treatment of urothelial carcinoma remains to be studied. Meanwhile, intestinal flora has also become an important clinical factor, which has been proved to play a variety of roles in body metabolism, local and systemic inflammation and immunity. Microorganisms can affect the clinical course of cancer, efficacy of chemotherapy and immunotherapy drugs, bioavailability and side effects. This review will explore the relationship between bladder cancer and urinary tract and intestinal microbiome, and explore reliable disease predictors, prognostic indicators and therapeutic targets through a better understanding of the interaction between the microbiome and tumor cells.

【Objective】 To compare the efficacy and safety of blue laser en bloc enucleation and traditional plasmakinetic electrocautery in the treatment of non-muscle invasive bladder cancer (NMIBC). 【Methods】 A total of 50 NMIBC patients treated in our hospital during Oct.2018 and Dec.2019 were enrolled. A randomized, incomplete blinding, parallel control design and non-inferior test method was adopted. The control group (electrocautery group) used plasmakinetic electrocautery for transurethral resection, and the experimental group (blue laser group) used semiconductor blue laser for transurethral en bloc enucleation. The effective resection rate, operation time, postoperative catheter indwelling time, length of hospital stay, perioperative hemoglobin changes and obturator nerve reflex were compared. 【Results】 There were 24 patients in the blue laser group and 26 in the electrocautery group. The effective dissection rate and hemostasis rate in both groups reached 100%. The blue laser group had slightly longer operation time than the electrocautery group (55 min vs.42 min, P=0.009), but lesser hemoglobin decrease (5.7 g/L vs. 10.4 g/L, P=0.007). There were no significant differences in urinary catheter indwelling time, length of hospital stay and reoperation rate between the two groups. The electrocautery group had 3 cases of obturator nerve reflex, while the blue laser group had none. 【Conclusion】 Compared with the traditional electrocautery, blue laser has good vaporization cutting and coagulation hemostatic effects on bladder tumor tissue, and can completely enucleate tumors in a front-firing model with less bleeding and no obturator nerve reflex, which can be used as a new, efficient, safe and easy-to-learn method for NMIBC surgery. However, its effects on postoperative recurrence rate and progression rate still need further studies.

【Objective】 To investigate the feasibility and safety of semiconductor blue laser in the treatment of non-muscle invasive bladder cancer (NMIBC) in the day surgery model. 【Methods】 The clinical data of 22 NMIBC patients (average age 55.8 years and tumor size 1.4 cm) who underwent outpatient screening and accepted blue laser ambulatory surgery in our hospital during Jun.2022 and Sep.2022 were retrospectively analyzed. On the day of admission, transurethral resection of cancer was performed using blue laser en bloc enucleation. On the day of surgery or in the morning of next day, bladder irrigation was stopped, the catheter was removed, and patients were discharged. The baseline data, pre-hospital waiting time, operation time, length of hospital stay, hemoglobin decrease, complications and management, follow-up, medical costs, and patients’ satisfaction rate were recorded. 【Results】 The pre-hospital waiting time was 2 to 7 days, average (4.1±1.3)days. The operation time was 29 to 50 minutes, average (40.8±5.5)minutes. The length of hospital stay was 0.6 to 1.2 days, average (0.9±0.2)days. Hemoglobin decrease was 1 g/L to 8 g/L, average (3.8±1.8)g/L. The catheter was indwelt for 0.5 to 1 day, average (0.7±0.1)day. The medical costs were 13 790 to 16 811 Yuan, average (14 941.5±690.2) Yuan. Patients’ satisfaction rate was 100.0%. Mild intraoperative and postoperative complications occurred in 2 cases. One patient developed symptoms of cystitis which disappeared after 2 days of oral antibiotic cefixime, and another patient developed bladder spasm which was relieved after oral solifenacin succinate tablets. No adverse events such as obturator nerve reflex or bladder perforation occurred. After removal of the catheter, no urinary retention was observed. 【Conclusion】 This study was the first to apply blue laser ambulatory surgery in the treatment of bladder cancer, confirming that it is a safe, feasible, economical and efficient model for selected patients, which can be promoted in suitable hospitals.

Uncovering the alterations of neural interactions within the brain during epilepsy is important for the clinical diagnosis and treatment. Previous studies have shown that the phase-amplitude coupling (PAC) can be used as a potential biomarker for locating epileptic zones and characterizing the transition of epileptic phases. However, in contrast to the θ-γ coupling widely investigated in epilepsy, few studies have paid attention to the β-γ coupling, as well as its potential applications. In the current study, we use the modulation index (MI) to calculate the scalp electroencephalography (EEG)-based β-γ coupling and investigate the corresponding changes during different epileptic phases. The results show that the β-γ coupling of each brain region changes with the evolution of epilepsy, and in several brain regions, the β-γ coupling decreases during the ictal period but increases in the post-ictal period, where the differences are statistically significant. Moreover, the alterations of β-γ coupling between different brain regions can also be observed, and the strength of β-γ coupling increases in the post-ictal period, where the differences are also significant. Taken together, these findings not only contribute to understanding neural interactions within the brain during the evolution of epilepsy, but also provide a new insight into the clinical treatment.
Humans ; Scalp ; Epilepsy/diagnosis* ; Brain ; Electroencephalography