BACKGROUND:Careful regulation of bone immune response during repair of bone scaffold is important for bone regeneration. OBJECTIVE:To review the influence of bone immune response on bone repair and the design of bone tissue engineering scaffold with regulating bone immune function and its application in bone repair. METHODS:Relevant articles published from 1973 to 2023 were retrieved from Science Direct,PubMed,Web of Science,and CNKI databases.English search terms were"osteoimmunology,macrophages,bone repair materials,bone scaffold,bone defects,bone regeneration".Chinese search terms were"bone immunity,macrophages,bone repair material,bone stent,bone defect,bone regeneration".Totally 80 articles of the latest research progress in this field were summarized and analyzed. RESULTS AND CONCLUSION:(1)A detailed review was conducted on the important time points in the origin and development process of bone immunity,and it was explained that macrophages,as important members of the bone immune regulatory system,can be divided into two phenotypes:M1(pro-inflammatory)and M2(anti-inflammatory),and play a key role in different stages of bone regeneration.During the inflammatory phase,M1 type macrophages can activate osteoclasts,initiate tissue repair processes,and participate in the reconstruction of bone microvascular networks.On the other hand,during the bone tissue regeneration process in the later stages of inflammation,sustained high expression of M1 type macrophages can hinder the formation of new bones.During the repair phase,M2 macrophages can secrete osteogenic cytokines,stimulate osteogenic differentiation and mineralization of bone marrow mesenchymal stem cells,and promote bone formation.On the other hand,long-term activation of M2 macrophages can increase the secretion of fibrogenic molecules,leading to excessive formation of scar tissue and delaying the healing process.Therefore,regulating macrophages to undergo phenotype transformation at appropriate stages and constructing an immune microenvironment beneficial for osteogenesis has great significance for bone regeneration.(2)In the process of designing bone scaffolds with bone immune regulation characteristics,the physical and chemical properties such as scaffold roughness,pore structure,stiffness,hydrophilicity,surface charge,and surface functional groups can be changed to affect non-specific protein and cell adhesion,thereby affecting the interaction between bone scaffolds and the immune system.By designing surface functional coatings of bioactive substances such as hydroxyapatite,bioactive glass,metal ions,extracellular matrix,drugs,cytokines,and exosomes,the immune microenvironment can be actively regulated by releasing bioactive substances after implantation into the body,affecting macrophage polarization and crosstalk between macrophages and bone cells,and promoting more M2 polarization of macrophages,so as to build a bone immune microenvironment that is conducive to bone regeneration.(3)Based on the research and development of bone tissue engineering scaffolds,in addition to focusing on the direct regulatory factors of stem cell osteogenic differentiation,this article also proposes that attention should be paid to the management of the immune microenvironment of stem cell differentiation.By regulating the appropriate bone immune microenvironment,more stem cell osteogenic differentiation can be induced;the osteogenic efficiency of the scaffold can be enhanced,and the concept of"bone immune regulatory characteristics"can be condensed;deeply elucidated the multi-directional regulatory role of the bone immune microenvironment and introduced the existing strategies for changing the physicochemical properties and surface functional coating of scaffolds to endow them with bone immune regulatory potential,providing new ideas for guiding the development of a new generation of bone tissue engineering scaffolds with bone immune regulatory characteristics.However,the bone immune microenvironment is a dynamic equilibrium state,and most of the existing regulatory strategies do not consider the dynamic matching of regulation.Therefore,the research and development of intelligent bone immune regulatory scaffolds with efficient and targeted regulation of the immune microenvironment will be a key focus of attention for scholars in future.

Objective:To explore the effect and safety of endoscopic tubular musculoskeletal tumor surgery (ETMS) technology in spinal tumors.Methods:Clinical data were retrospectively collected from 18 spinal tumor patients who were treated with ETMS technology at Tianjin Medical University Cancer Institute and Hospital ( n=16) or the Affiliated Hospital of Qingdao University ( n=2) from November 2022 to December 2023. The total cohort included 11 males and 7 females, with the age at 60.3±8.6 years (range of 41-76). Two cases were diagnosed with benign tumors, four patients were diagnosed with spinal hematologic malignancies while other 12 cases were patients with spinal metastases. After localization under the C-arm X-ray machine, the spinal endoscopic channel is established using dilators. Soft tissue is dissected under endoscopic guidance to create an artificial cavity. Subsequently, the saline medium relied upon by the spinal endoscopic technique is removed, and posterior decompression and tumor curettage are performed using tubular techniques. Frankel grade classification and paraplegia index were used to evaluate the improvement of postoperative function and the VAS score was performed in pain scoring. The surgical complications and tumor evaluation were observed by postoperative outpatient and telephone follow-up. Results:The ETMS technology was successfully completed in all 18 patients with the mean operation time of 240.3±80.2 min. The median of intraoperative bleeding was 200.0(172.5, 350.0) ml and the mean postoperative drainage was 131.4±69.5 ml. The median value of postoperative hospitalization days was 6.0(4.0, 10.25) d. The paraplegia index decreased from 1.5(0, 3.0) preoperatively to 0(0, 1.25) postoperatively ( Z=-2.599, P=0.009). All the patients presented an improvement in Frankel grading after surgery except for one patient (downgrading from grade E to grade D). There was significantly difference in Frankel grading between preoperative and postoperative groups ( Z=2.812, P=0.005). The median value of preoperative VAS score was up to 5.5(4.0, 7.0) while the median value at postoperative, one month after surgery and three months after surgery were 1.5(1.0, 2.25), 1.0(0, 1.0) and 0(0, 1.0), respectively (χ 2=44.641, P<0.001). The 3-month postoperative VAS improvement rate was 91.2% (range 75%-100%). During a mean follow-up period of 7.6±6.2 months, none of the 18 patients presented surgical complications or tumor recurrence at surgical region. Only one patient died at 3.2 months after surgery until the last follow-up due to respiratory failure after lung tumor progression. The mean survival of the total cohort was up to 13.3 [95% CI (11.5, 15.0)] months. The 16 cases with spinal metastases or spinal hematological malignancies had a mean survival of 13.2 [95% CI (11.3, 15.0)] months. Conclusion:The ETMS technology presented good efficacy and safety in treatment of spinal tumors with low blood supply and with diameter less than 5cm.

Objective:This study aimed to explore the clinical value of myostatin(MST) and follistatin(FST) as biological biomarkers in evaluating sarcopenia in elderly women.Methods:This was a retrospective cross-sectional study that enrolled 350 females aged 20-89 years who underwent physical examinations in Shanghai Huadong Hospital in 2021. Demographic characteristics, muscle mass, fat mass, bone mineral density, hand grip strength, gait speed, and serum indices of MST and FST were collected.Results:The serum levels of MST did not change significantly with age. However, the serum levels of FST increased with age. In women aged≥60 years, MST was positively correlated with total lean mass and appendicular skeletal muscle index(ASMI; r=0.236, P=0.041; r=0.289, P=0.014), while FST was negatively correlated with ASMI( r=-0.265, P=0.030). In multivariate stepwise regression analysis, after adjusting for age, body mass index, hip bone mineral density, and total fat mass, only FST was independently correlated with ASMI( β=-0.238, P=0.006), while MST was not correlated with ASMI. The receiver operating characteristic curve was plotted using muscle mass reduction as the state variable and serum FST level as the test variable. The area under the curve was 0.753. And when the FST cutoff value was 17.49 ng/mL, the maximum Jordan index was 0.46, with a sensitivity of 77.3% and a specificity of 68.7%. Women aged ≥60 years were divided into three groups based on serum FST levels. Compared to the upper third of the serum FST level group, the low third of the FST level group had a significantly reduced risk of suffering from sarcopenia( OR=0.098, P =0.036). Conclusions:Serum FST lever has a better correlation with muscle mass among elderly women, making it a promising biomarker for evaluating muscle mass.

Objective: To investigate the outbreak of mumps in a remote village school of Zhaoqing City, to evaluate and vaccine effectiveness ( VE ) of mumps containing vaccine (MuCV), so as to provide reference for the formulation of epidemic prevention and control strategies. Methods: Through on site case investigations and interviews, case data and epidemic related epidemiological information were obtained. Descriptive and retrospective cohort studies were used to analyze the epidemic characteristics, explore risk factors, and evaluate the protective effect of vaccines. Results: Totally 166 cases of mumps were found, and all of them were students. The total attack rate was 7.79% and the outbreak lasted for 60 days. The first case occurred on October 11th and the last case occurred on December 9th in 2018. Most of the cases aged from 10 to 13 years old, accounting for 66.27%. There were 96 male patients and 70 female patients, with no statistically significant sex difference in the incidence rate ( χ 2=2.40, P >0.05). Involving 28 classes, 11 of which had an incidence rate more than 10%, mainly distributed in grades 2, 4 and 6. There were statistically significant differences in incidence rates among different grades ( χ 2=96.89, P <0.01) and different floors ( χ 2=67.35, P < 0.01 ), with the third floor higher than the other floors. Twelve out of 58 boarding pupils were cases, and boarding pupils were 1.89 times higher in risk of contracting mumps than day students ( RR=1.89, 95%CI =1.10-3.23). Pupils without being given the shot of MuCV were higher in the infection rate than those having the shot ( χ 2=5.70, P <0.05), and the VE % was 35% (95% CI = 7%- 55%). The VE % of one dose was 34% (4%-54%), while the effectiveness of protection was declined with time ( χ 2 trend =6.53, P < 0.05). The effectiveness of vaccine almost diasappeared six years after the shot ( χ 2=1.12, P >0.05). Conclusion Delayed case report and isolation, low rate of receiving MuCV, and decreasing effectiveness of one shot MuCV are closely assocaited with the outbreak and ongoing spread of the epidemic.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.

Objective:To analyze the predictive value of enhanced MRI in the outcome of prolapsed and sequestrated lumbar disc herniation through a retrospective analysis.Methods:A retrospective analysis of the data of 64 patients with prolapsed and sequestrated lumbar disc herniation from January 2015 to December 2018, including 38 males and 26 females; age 35.72±12.44 years (range, 22-64 years) ; 43 cases of prolapsed type, 21 cases of sequestrated type. Conservative treatment was the first choice for all patients, in case of surgical indications during the treatment, percutaneous endoscopic lumbar discectomy or fenestration discectomy will be performed. Enhanced MRI was performed at the first and last inspections, the volume of the protrusion, the thickness of rim enhancement (Tr), and the extent of rim enhancement (Er) were measured and calculated at the same time. According to the ring around the protrusion, the size of the rim-enhancement area was divided into type I-III; then compared the relationship between the rim-enhancement signal differentiation and the resorption rate of protrusions, and the correlation between Tr, Er values and the resorption rate of protrusions during the initial inspection.Results:Among the 64 patients, 42 patients completed conservative treatment, and 22 received surgical treatment. According to the rim-enhancement signal differentiation, 23 cases were treated conservatively for type I, 3 cases were treated by surgery; 16 cases were treated for type II conservatively, 7 cases were treated by surgery; 3 cases were treated for type III conservatively, and 12 cases were treated by surgery. All patients were followed up for 12 to 34 months. Among 42 conservatively treated patients, The volume of the protrusion before treatment was 2 645.67±690.86 mm 3, and the volume of the protrusion after treatment was 842.76±573.35 mm 3. The volume of protrusions before and after treatment was statistical significance ( t=11.897, P<0.001), Tr was 1.38±0.83 mm, and Er was 73.08%±34.39%, the resorption rate of protrusions was 65.10%±24.50%, and 39 cases (92.86%, 39/42) reached the standard for protrusion resorption (resorption rate ≥30%); 23 cases of type I , the resorption rate was 76.54%±18.62%; 16 cases of type II had an resorption rate of 56.81%±21.44%; 3 cases of type III had an resorption rate of 21.58%±12.19%. The resorption rate of type III were compared by single factor analysis of variance, and the difference was statistically significant ( F=12.885, P<0.001); 32 cases of both type I and II (82.05%, 32/39) had significant resorption (resorption rate ≥50%), and no case of type Ⅲ had significant resorption, comparing with type I and II, the difference was statistically significant ( P=0.010); Tr was positively correlated with resorption rate ( r=0.569, P<0.001), Er was positively correlated with resorption rate ( r=0.677, P<0.001). Conclusion:Under close clinical observation, parts of the prolapsed or sequestrated lumbar disc herniations can be conservatively treated, and the herniated disc can be resorption in many people and the clinical symptoms were alleviated. Rim-enhancement signal differentiation by enhanced MR has a better predictive value for the outcome of the herniation, type I is more prone to resorption, preferred conservative treatment, type Ⅲ is not easy to resorption, preferred surgery treatment, and the higher thickness of rim enhancement, the greater extend the rim-enhancement, the more prone to resorption phenomenon.

Objective To study the clinicopathological features of sarcomatoid hepatocellular carcinoma (SHC).Methods The clinical data of 42 patients with SHC who underwent surgical resection in the Peking University People's Hospital (n =33) and the Department of Pathology of the Peking University Health Science Center (n=9) from January 2008 to May 2017 were retrospectively analyzed.Results The average age was 58.3 (aged 32～84) years;the ratio of male to female was 2.2 ∶ 1;the average diameter of the lesions was 8.2 cm;the median AFP value was 45.2 ng/ml.The median survival time was 10.5 months,the average progression-free survival time was 2.9 months,and the 5-year survival rate was 25.0％.On histopathology,the tumor consisted of various degrees of different differentiated carcinomas with aligned sarcomatoid spindle cells.Immunohistochemical results in the sarcomatoid region expressed both mesenchymal markers and epithelial-derived markers.Conclusions SHC tumors were highly aggressive,with high rates of lymph node metastasis and poor prognosis.The diagnosis of SHC mainly depended on histopathology.Immunohistochemistry was very important for its diagnosis and differential diagnosis.Surgical resection was the treatment modality of choice to achieve prolonged survival time.

Objective To investigate the distribution and antimicrobial susceptibility of the bacteria isolated from bloodstream infections during 2013-2014 in Changhai Hospital for rational use of antibacterial agents.Methods The bacterial strains from blood samples were collected during the period from January 2013 through December 2014,and subjected to antimicrobial susceptibility testing by using automated system or Kirby-Bauer method.The results were interpreted according to CLSI M100-S24 breakpoints or FDA breakpoints.The data were analyzed by WHONET 5.6 software.Results A total of 1 048 nonduplicate isolates were collected,of which Escherichia coli,coagulase-negative Staphylococcus (CNS) and Klebsiella pneumoniae accounted for 29.5％,15.8％ and 13.8％,respectively.Gastroenterology,Hematology,General surgery,Urology and Department of Infectious Diseases are the top 5 departments according to their total number of bacterial isolates.The results of antimicrobial susceptibility testing showed that ESBLs-producing E.coli and K.pneumoniae accounted for 63.8％ and 38.6％,respectively.The prevalence of methicillinresistant CNS (MRCNS) was 77.6％.The E.coli strains isolated from Urology showed higher resistance rates to cephalosporins than the total E.coli strains,while the E.coli strains isolated from Gastroenterology showed higher resistance rates to betalactarn/beta-lactamase inhibitor combinations and carbapenems than the total E.coli strains.Higher prevalence of MRCNS was found in departments of Hematology,Urology and Neurosurgery.All the CNS strains isolated from Neurosurgery were resistant to methicillin.The K.pneumoniae strains isolated from Bum ICU had higher resistance rates to all the antibacterial agents tested than the total K.pneumoniae strains,while the K.pneumoniae strains isolated from Gastroenterology showed higher resistance rates to carbapenems and tigecycline than the total K.pneumoniae strains.Conclusions The pathogenic bacteria isolated from bloodstream infections vary with departments in terms of species distribution and antimicrobial susceptibility profile.It is necessary to strengthen the surveillance of antimicrobial resistance in hospital for rational use of antibiotics.