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.

Dry eye disease is a multifactorial chronic ocular surface disorder that is challenging to manage because its pathogenesis is not well understood. The gut-eye axis theory provides insights into its pathogenesis to guide prevention and treatment. Intestinal flora dysbiosis induces dry eye disease through complex mechanisms involving inflammation, ocular surface microbiota, nerve damage, and microbial metabolites. This article reviews the immunometabolic regulation of the gut-eye axis and summarizes gut flora-targeted interventions(fecal microbiota transplantation, probiotic supplementation, and dietary modification)to provide a theoretical basis for dry eye disease prevention and treatment.

ObjectiveTo identify the rate， population characteristics， and vaccination history of repeat infections among previously infected people in the current epidemic based on the rate of repeat infection and population characteristics of different mutant strains at different times in Pudong New Area of Shanghai， and to provide reference for the prevention and control strategies of novel coronavirus repeat infections. MethodsA total of 9 250 investigated subjects were randomly selected from the new cases of asymptomatic infection and confirmed cases reported by Pudong New Area from March to May 2022. The investigation mainly focused on demographic characteristics， nucleic acid or antigen test results， and symptoms after infection. The repeat infection rates among different populations were compared， and logistic regression was used to analyze the impact of gender， age， and vaccination status on repeat infections. ResultsThe survey sample of 9 250 people had a response rate of 81.85%. There were 4 043 males （53.40%） and 3 528 females （46.60%）， with a median age of 34 years old （P₂₅， P₇₅： 7， 61）. The overall vaccine uptake rate was 59.44% （4 500/7 571）. In December of 2022， there were 563 cases of repeat infection， with an infection rate of 7.44%. The lowest rate of repeat infection was seen in the 3‒ year-old group （2.86%） and the highest rate in the 30‒ year-old group （12.42%）， with significant differences between different age groups. The repeated infection rate for those who had completed their vaccinations was significantly lower （6.57%） compared to those who had not （7.11%）. The age groups of 3‒ years， 70‒79 years， as well as individuals who completed full vaccination and received booster shots were protective factors against repeat infections. ConclusionThe overall rate of reinfection among the infected in Shanghai during the spring of 2022 was low in the outbreak of the Omicron variant， and the rate of reinfection in the 3‒ year-old group was significantly lower than in other age groups. Completing the full course of vaccination significantly reduces the risk of reinfection. Although the reinfection rate is high in individuals who received booster shots， it remains a mitigating factor compared to those who do not receive the vaccine. It is recommended to continue monitoring reinfections in key populations and further strengthen immunization efforts.

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 investigate the influencing of portal vein embolization (PVE) and PVE combined with transcatheter arterial chemoembolization (TACE) on secondary hepatectomy and prognosis of patients with initially unresectable hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 102 patients with initially unresectable HCC who were admitted to the Third Affiliated Hospital of Naval Medical University from October 26,2015 to December 31,2022 were collected. There were 82 males and 20 females, aged 52(range,25?73)years. Of 102 patients, 72 cases undergoing PVE combined with TACE were set as the PVE+TACE group, and 30 cases undergoing PVE were set as the PVE group. Observation indicators: (1) surgical resection rate of secondary hepatectomy and increase of future liver remnant (FLR); (2) situations of secondary hepatectomy; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Results:(1) Surgical resection rate of secondary hepatectomy and increase of FLR. The surgical resection rate of secondary hepatectomy in the PVE+TACE group and the PVE group were 72.2%(52/72) and 53.3%(16/30), respectively, showing no significant difference between the two groups ( χ2=3.400, P>0.05). The surgical waiting time, increasing volume of FLR, growth rate of FLR in the 52 patients of PVE+TACE group receiving secon-dary hepatectomy were 20(range, 14?140)days, 140(range, 62?424)mL, 9.8(range, 1.5?26.5)mL/day, respectively. The above indicators in the 16 patients of PVE group receiving secondary hepatectomy were 16(range, 12?35)days, 160(range, 95?408)mL, 10.5(range, 1.2?28.0)mL/day, respectively. There was no significant difference in the above indicators between the 52 patients of PVE+TACE group and the 16 patients of PVE group ( Z=1.830, 1.498, 1.266, P>0.05). (2) Situations of secondary hepatectomy. The operation time, rate of tumor necrosis (>90%, 60%?90%,<60%), cases with complications ≥ grade Ⅲa in the 52 patients of PVE+TACE group receiving secondary hepatectomy were 200(range, 125?420)minutes, 8, 4, 40, 28, respectively. The above indicators in the 16 patients of PVE group receiving secondary hepatectomy were 170(range, 105?320)minutes, 0, 0, 16, 4, respectively. There were significant differences in the above indicators between the 52 patients of PVE+TACE group and the 16 patients of PVE group ( Z=2.132, ?2.093, χ2=4.087, P<0.05). (3) Follow-up. Sixty-eight patients who completed the surgery were followed up for 40(range, 10?84)months. The 1-, 3-, 5-year recurrence free survival rate in the 52 patients of PVE+TACE group receiving secondary hepatectomy were 73.0%, 53.3%, 35.4%, respectively. The above indicators in the 16 patients of PVE group were 62.5%, 37.5%, 18.8%, respectively. There was a significant difference in the recurrence free survival rate between the 52 patients of PVE+TACE group and the 16 patients of PVE group ( χ2=4.035, P<0.05). The 1-, 3-, 5-year overall survival rate in the 52 patients of PVE+TACE group receiving secondary hepatectomy were 82.5%, 61.2%, 36.6%, respectively. The above indica-tors in the 16 patients of PVE group receiving secondary hepatectomy were 68.8%, 41.7%,20.8%, respectively. There was a significant difference in the overall survival rate between the 52 patients of PVE+TACE group and the 16 patients of PVE group ( χ2=4.767, P<0.05). Conclusion:Compared with PVE, PVE+TACE as stage Ⅰ surgery can increase the surgical resection rate of secondary hepatec-tomy and the recurrence free survival rate of patients with initially unresectable HCC, prolong the long-term survival time, but not influence the growth rate of FLR.

Objective To investigate the effect of acupuncture on the morphology of the dry eye rabbit's cornea and the nuclear factor κB(NF-κB)signaling pathway of the corneal tissue to analyze the mechanism of acupuncture on dry eyes.Methods Twenty-four healthy New Zealand rabbits,without restriction on sex,were randomly divided into four groups,including a blank group,a model group,an acupuncture group,and a sham acupuncture group,with 6 in each group.Rabbits in the blank group were not treated;rabbits in the other three groups were treated with scopolamine hydro-bromide 2.0 mg·kg-1 by subcutaneous injection at 8:00,11:00,14:00 and 18:00 each day for 35 consecutive days un-til the end of the experiment.Rabbits in the sham acupuncture group were treated with sham acupuncture on the 22nd day after successful modeling by quickly pricking acupoints(Jingming BL1,Cuanzhu BL2,Sizhukong SJ23,Taiyang EX-HN5 and Tongziliao GB1)with a blunt acupuncture needle,once a day,for a total of 14 days.Rabbits in the acupuncture group were treated with acupuncture at the same acupoints as the sham acupuncture group after successful modeling.The corneal fluorescence staining was conducted on Days 0,21,28 and 35 after modeling.On Day 35,corneal confocal microscope ex-aminations were conducted.Then,the rabbits were sacrificed,the corneal morphological changes were observed by light microscope and transmission electron microscope,and the expression of corneal NF-κB protein was detected by Western blot.Results Compared with the model group,the score of rabbit corneal fluorescein staining in the acupuncture group and blank group decreased on the 28th and 35th days after modeling,and the differences were statistically significant(all P＜0.05).The results of the confocal microscope examination on Day 35 after modeling showed that,compared with other groups,there were a large number of globular immune cells and activated stromal cells with unclear boundaries and irregu-lar sizes in the stromal layer and inflammation in the area with irregular intercellular space in the model group and the sham acupuncture group.In the acupuncture group,the morphology of stromal layer cells improved,the cells were slightly acti-vated,and there were no obvious abnormalities in the corneal nerve morphology.On the 35th day after modeling,the re-sults of the light microscope showed that,the surface of the corneal tissue in the model group and the sham acupuncture group showed hyperkeratinized flat epithelial cells,lymphocyte infiltration,increased number of focal epithelial cell layers,and epithelial cell detachment.In the acupuncture group,there were 4-6 layers of epithelial cells in the corneal epitheli-um,and epithelial shedding decreased.In addition,the lymphocyte infiltration decreased compared with the model group.On the 35th day after modeling,the results of the transmission electron microscope showed that abnormal microvilli oc-curred and epithelial cells were absent in the corneal epithelial cells of rabbits in the model group and the sham acupuncture group,the cell space was widened,the rough endoplasmic reticulum was severely expanded,and desmosomes were dis-banded with mitochondrial swelling.In the acupuncture group,the microvilli structure of epithelial cells was sparse and short,local deletion was still observed,the rough endoplasmic reticulum was slightly expanded,and no obvious swelling of mitochondria was observed.On the 35th day after modeling,the Western blot examination results showed that,compared with the blank group,the expression of p-NF-κB p65 was up-regulated in both the model group and sham acupuncture group(both P＜0.05);compared with the model group and sham acupuncture group,the expression of p-NF-κB p65 in the acupuncture group was down-regulated(both P＜0.05).Conclusion Acupuncture can inhibit the NF-κB signaling path-way to play an anti-inflammatory role and relieve corneal inflammation and injury of dry eye rabbit models.

Objective:To explore the predictive value of a regression model based on diffusion kurtosis imaging (DKI) parameters for prediction of the recurrence risk in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER-2)-negative early invasive breast cancer.Methods:A retrospective cross-sectional study was designed. The clinicopathological (age, histological grade, Ki-67 level, etc.) and imaging data of 50 patients (50 lesions) with ER-positive, HER-2 negative early invasive breast cancer who underwent treatment at Wuxi People′s Hospital from January 2016 to December 2018 were retrospectively analyzed. All patients were female, aged 29 to 81 years, and underwent pre-operation conventional MRI and DKI examinations. The volume of breast fibroglandular tissue (FGT), background parenchymal enhancement (BPE), and internal enhancement features were recorded; the peak enhancement (PH), peak enhancement rate, time to peak, mean kurtosis (MK), and mean diffusivity (MD) were calculated. Based on the 21-gene recurrence risk scores, patients were divided into low recurrence risk group and medium-high recurrence risk group. Independent sample t test, Mann-Whitney U test, χ2 test were used to compare the differences of various indicators between the two groups. Two logistic models were constructed with age, PH, MD, and MK as independent variables (Pre1), and with Ki-67, age, PH, MD, and MK as independent variables (Pre2), respectively. The efficacy of the models in predicting low recurrence risk in patients was assessed using receiver operating characteristic curve and area under the curve (AUC). Results:There were 25 cases in the low recurrence risk group and 25 cases in the medium-high recurrence risk group. The differences in age, FGT, PH, MD, MK, and Ki-67 between the low recurrence risk group and the medium-high recurrence risk group were statistically significant (all P<0.05), while other indexes showed no statistically significant differences (all P>0.05). The AUC of Pre1 in predicting low recurrence risk of ER-positive, HER-2 negative early invasive breast cancer was 0.87, with a sensitivity of 0.76 and specificity of 0.88. The AUC of Pre2 for predicting the low recurrence risk of ER-positive, HER-2 negative early invasive breast cancer was 0.92, with a sensitivity of 0.84, and specificity of 0.92. Conclusions:A multi-parameter model based on DKI can effectively predict the recurrence risk of ER-positive and HER-2 negative breast cancer. The model with combination of Ki-67 can further improve the predictive efficacy, and help effectively identify patients at low recurrence risk.

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 provide reference for strengthening the standardized management of off-label drug use in cancer hospitals. METHODS The evaluation system for off-label drug use was established to standardize the application， approval， and filing process for off-label drug use in our hospital. The changes in off-label drug application quantity， proportion， disease category and drug category in our hospital were compared before （October 1st， 2021-September 30th， 2022） and after （October 1st， 2022- September 30th， 2023） the establishment of the evaluation system； drug items supported by high-level evidence screened by pharmacy department were analyzed statistically. RESULTS The number of off-label drug use applications in our hospital had gradually increased， from 306 pieces in the fourth quarter of 2021 to 3 828 pieces in the third quarter of 2023. In the year before the construction of the evaluation system， there were a total of 4 482 applications for off-label drug use， and in the year after the construction of the evaluation system， there were 11 840 applications for off-label drug use. After the construction of the evaluation system， the proportion of unregistered off-label drug use significantly decreased， compared to the same period last year （P＜0.05）. Among them， there were no unregistered applications for off-label drug use for digestive system tumors， head and neck tumors， and radioactive drugs； lymphoma， breast tumors，urogenital system tumors， cytotoxic drugs and new anti-tumor drugs all had a decrease of over 70% in unregistered off-label drug applications. Twenty-seven off-label drug use items related to 19 drugs supported by high-level evidence were screened by the pharmacy department of our hospital， among which 25 items were drug use beyond indication. CONCLUSIONS The establishment of off-label drug use evaluation system in cancer hospital is helpful to the rational use and refined management of clinical anti-tumor drugs.

ObjectiveTo demonstrate the long-term effect of Yishi Therapy for primary tinnitus and analyze the factors affecting the effectiveness. MethodsWe conducted long-term follow-ups of primary tinnitus cases treated with Yishi Therapy during 1 January 2017 to 30 June 2023 by face-to-face， online and telephone between 1 July 2023 and 31 January 2024， to understand the final regression of primary tinnitus and lifestyle changes. We retrospectively analysed the basic data of patients before treatment， and statistically analysed the recovery rate and overall effective rate of tinnitus treated by the Yishi Therapy， and the factors affecting the effectiveness such as lifestyle， age， duration of disease， gender， tinnitus location， severity of tinnitus， accompanying symptoms and complications on the overall effective rate. ResultsA total of 496 cases of primary tinnitus completed follow-ups successfully， and the total Tinnitus Evaluation Questionnaire （TEQ） at follow-up was significantly lower than that before treatment （P＜0.001）. Among the 496 cases， 101 （20.36%） cases cured， 189 （38.10%） cases showed significant improvement， 116 （23.39%） cases were effective， 90 （18.15%） cases were ineffective， and the overall effect rate was 81.85% （406/496）. At follow-up， the score of lifestyle was higher than that before treatment （P＜0.001）. Grouped by the score of lifestyle at follow-up， the effective rates of better lifestyle group and poor lifestyle group were 97.53% （237/243） and 66.80% （169/253）， respectively， with statistical significance （P＜0.001）. Grouped by the mean value of the difference in lifestyle scores before and after treatment， the effective rates of the group with greater lifestyle adjustment and the group with smaller adjustment were 97.55% （239/245） and 66.53% （167/251）， respectively， and the differences were statistically significant （P＜0.001）. Binary logistic regression showed that the better lifestyle， the greater lifestyle adjustment and the severity of tinnitus were positively correlated with the total effective rate of tinnitus （P＜0.001）， while older and hearing loss were negatively correlated with the total effective rate of tinnitus （P＜0.05）. ConclusionYishi Therapy on primary tinnitus shows good long-term effect， lifestyle， severity of tinnitus， hearing loss or not， age are the relevant factors affecting the efficacy of tinnitus， lifestyle is the main factor affecting clinical efficacy.