OBJECTIVE: To summarize the research progress on the role of macrophage-mediated osteoimmune in osteonecrosis of the femoral head (ONFH) and its mechanisms. METHODS: Recent studies on the role and mechanism of macrophage-mediated osteoimmune in ONFH at home and abroad were extensively reviewed. The classification and function of macrophages were summarized, the osteoimmune regulation of macrophages on chronic inflammation in ONFH was summarized, and the pathophysiological mechanism of osteonecrosis was expounded from the perspective of osteoimmune, which provided new ideas for the treatment of ONFH. RESULTS: Macrophages are important immune cells involved in inflammatory response, which can differentiate into classically activated type (M1) and alternatively activated type (M2), and play specific functions to participate in and regulate the physiological and pathological processes of the body. Studies have shown that bone immune imbalance mediated by macrophages can cause local chronic inflammation and lead to the occurrence and development of ONFH. Therefore, regulating macrophage polarization is a potential ONFH treatment strategy. In chronic inflammatory microenvironment, inhibiting macrophage polarization to M1 can promote local inflammatory dissipation and effectively delay the progression of ONFH; regulating macrophage polarization to M2 can build a local osteoimmune microenvironment conducive to bone repair, which is helpful to necrotic tissue regeneration and repair to a certain extent. CONCLUSION At present, it has been confirmed that macrophage-mediated chronic inflammatory immune microenvironment is an important mechanism for the occurrence and development of ONFH. It is necessary to study the subtypes of immune cells in ONFH, the interaction between immune cells and macrophages, and the interaction between various immune cells and macrophages, which is beneficial to the development of potential therapeutic methods for ONFH.
Humans ; Femur Head/pathology* ; Osteonecrosis/therapy* ; Macrophages/pathology* ; Inflammation ; Femur Head Necrosis/pathology*

Objective To investigate the effect of compound betamethasone adjuvant on break-through pain after unicompartmental knee arthroplasty under sciatic nerve combined with femoral nerve block.Methods A total of 100 patients underwent unicondylar knee arthroplasty,32 males and 68 females,aged 55-75 years,BMI 18.5-35.0 kg/m2,ASA physical status Ⅰ-Ⅲ,were divided into three groups according to random number table method:no adjuvant group(group C,n=34),dexamethasone adjuvant group(group D,n=33)and compound betamethasone adjuvant group(group B,n=33).The patients in the three groups received sciatic nerve block and 0.4％ropivacaine 15 ml before anesthesia in-duction,then femoral nerve block,0.4％ropivacaine 15 ml in group C,0.4％ropivacaine 15 ml in group D(containing dexamethasone 5 mg),and 0.4％ropivacaine 15 ml in group B(containing compound beca-methasone 4 mg).The occurrence of breakthrough pain,the number of effective analgesic pump compres-sions,opioid dosage,and the number of remedial analgesia cases were recorded.The ground movement dis-tance was recorded 0-24 hours,24-48 hours,and 48-72 hours after operation.The sleep quality scores and adverse events were also recorded.Results Compared with group C,the incidence rate of breakthrough pain was lower(P＜0.05),the number of effective analgesia pump compressions,the dosage of opioid,and the sleep quality score on the first night after operation were significantly decreased in group B(P＜0.05).Compared with group D,the incidence rate of breakthrough pain and breakthrough pain score were lower(P＜0.05),the number of effective analgesia pump compressions,the dosage of opioid,and the sleep quality score on the 1 st night after operation were significantly decreased in group B(P＜0.05).There was no significant difference in the ground movement distance of in different time periods and inci-dence of adverse events among the three groups.Conclusion Compound betamethasone adjuvant can reduce the incidence of breakthrough pain after unicompartmental knee arthroplasty under sciatic nerve com-bined with femoral nerve block,provide perfect analgesic effect,reduce postoperative opioid consumption,and improve the sleep quality of patients on the first night after surgery.

Objective To investigate the expression of TSR2 in gastric cancer and explore its correlation with progression of gastric cancer and the possible mechanism.Methods We retrospectively analyzed TSR2 expression in clinical specimens from 105 gastric cancer patients and the impact of TSR2 expression level on disease progression and 5-year postoperative survival of the patients.GO and KEGG enrichment analyses were used to predict the biological functions and mechanisms of TSR2.In gastric cancer MGC-803 cells with lentivirus-mediated TSR2 overexpression or knockdown,the changes in cell proliferation,invasion,and migration were assessed with CCK-8 and Transwell assays,and the expressions of p-PI3K and p-AKT were detected using Western blotting.Results TSR2 expression was significantly lower in gastric cancer tissues than in the adjacent tissues with significant correlations with CEA level,CA19-9 level,and T and N staging(P<0.05).A low TSR2 expression,CEA≥5 μg/L,CA19-9≥37 kU/L,T3-T4 stages,and N2-N3 staged were identified as independent risk factors affecting 5-year survival rate of the patients following radical surgery(P<0.05),and a high TSR2 expression was associated with a higher 5-year survival rate of the patients(P<0.001).Bioinformatics analysis suggested the functional involvement of TSR2 with the PI3K/AKT signaling pathway.MGC-803 cells overexpressing TSR2 showed significantly lowered proliferation,migration,and invasion capacities(P<0.05),while TSR2 knockdown produced the opposite effects(P<0.05).Western blotting showed that TSR2 overexpression reduced the phosphorylation of PI3K and AKT,and TSR2 knockdown caused the opposite changes in MGC-803 cells(P<0.05).Conclusion TSR2 is lowly expressed in gastric cancer tissues to adversely affect the patients'prognosis,and its overexpression inhibits gastric cancer cell proliferation,invasion,and migration possibly by downregulating the PI3K/AKT pathway.

Objective:To investigate the optimal serum antibody titer in acute stage for the diagnosis of Mycoplasma pneumoniae (MP) infection by passive agglutination, and to evaluate the clinical diagnostic value of different antibody titers.Methods:A cross-sectional study.Eighty-eight pairs of clinical serum samples were collected from children with MP infection treated at the Department of Pediatrics in Shengjing Hospital of China Medical University from December 2016 to February 2017 and Children′s Hospital of Baotou in November 2019.The four-fold change of the double serum specific antibody titer was used as the gold standard, and the receiver operating characteristic (ROC) curve was plotted.When detecting the single serum in acute stage, different antibody titers were used as positive criteria to evaluate their clinical application value in the diagnosis of MP infection and find the most appropriate serum antibody titer as the diagnostic cut-off value.Results:(1)When the serum specific antibody titer ≥1∶40 was used as the positive criterion, the sensitivity was 72.9%, the area under the ROC curve was 0.817, and the specificity was 87.5%, which might cause overdiagnosis.When the serum specific antibody titer ≥1∶160 was used as the positive criterion, the specificity was 97.5%, the area under the ROC curve was 0.775, and the sensitivity was 52.1%, which might cause missed diagnosis.When the serum specific antibody titer ≥1∶80 was used as the positive criterion, the sensitivity was 60.4%, the specificity was 97.5%, and the area under the ROC curve was 0.823, overall performing better compared with the said two criteria.(2)After the disease lasted at least 5 days, blood samples were collected.About 72.5% of the children had antibodies, and 60.0% of the children had antibody titers ≥1∶80.Conclusions:(1)When the passive agglutination method is used to detect MP infection, antibody titer ≥1∶80 is recommended as the diagnostic standard.However, in clinical practice, the diagnosis of MP infection depends on clinical and other laboratory test results.(2) It is appropriate to collect blood samples on 5-7 days of illness.If MP infection is clinically suspected, and an antibody titer of 1∶40 is also suggestive, it can perform cooperative diagnosis based on molecular biology lab results or retest at a shorter interval.

Objective To explore the value of T2*mapping in quantitatively evaluate changes in knee joint cartilage and subchon-dral bone of new recruits before and after intensive training.Methods MRI scans of the right knee joint were performed three times on 20 new recruits:before intensive training,after one week of intensive training,and after one month of rest.The knee joint cartilage was divided into six regions:lateral femur(LF),medial femur(MF),lateral tibia(LT),medial tibia(MT),patella cartilage(PC),and trochlea cartilage(TC).Using the posterior angle of the meniscus as a boundary,LF and MF were divided into the cLF/cMF and pLF/pMF.Divid-ed into superficial zone(SZ)cartilage and deep zone(DZ)cartilage based on a thickness of 1/2 of the cartilage.The subchondral bone was divided into superficial bone(SB)within 5 mm of the joint cartilage,and deep bone(DB)within 6-10 mm of the joint cartilage.The T2*values of each region of cartilage and subchondral bone were evaluated through region of interest(ROI)analysis.Single fac-tor analysis of variance was used to compare the changes in T2*values.The LSD test method was used for inter-group comparison.Results After one week of intensive training,MT-SZ,cMF-SZ,PC-SZ,TC-SZ were significantly higher than before intensive training(P＜0.05).After one month of rest,there was no statistically significant difference in the T2*value of the cartilage area compared with before intensive training(P＞0.05).There was a trend of"rising first and then falling".There was no statistically signifi-cant difference in the T2*value of subchondral bone of the knee joint before intensive training and after one week of intensive training(P＞0.05).Compared with after one month of rest,except for cLF-DB,pLF-DB,trochlea cartilage-deep bone(TC-DB),the T2*value of the subchondral bone of the remaining knee joint increased before intensive training and after one week of intensive training,with sta-tistically significant differences(P＜0.05).Conclusion T2*mapping can display the changes in the ultrastructure and biochemical components of joint cartilage and subchondral bone after the new recruits intensive training,detect early injuries and conduct non-invasive quantitative evaluation.

Objective To investigate the expression of TSR2 in gastric cancer and explore its correlation with progression of gastric cancer and the possible mechanism.Methods We retrospectively analyzed TSR2 expression in clinical specimens from 105 gastric cancer patients and the impact of TSR2 expression level on disease progression and 5-year postoperative survival of the patients.GO and KEGG enrichment analyses were used to predict the biological functions and mechanisms of TSR2.In gastric cancer MGC-803 cells with lentivirus-mediated TSR2 overexpression or knockdown,the changes in cell proliferation,invasion,and migration were assessed with CCK-8 and Transwell assays,and the expressions of p-PI3K and p-AKT were detected using Western blotting.Results TSR2 expression was significantly lower in gastric cancer tissues than in the adjacent tissues with significant correlations with CEA level,CA19-9 level,and T and N staging(P<0.05).A low TSR2 expression,CEA≥5 μg/L,CA19-9≥37 kU/L,T3-T4 stages,and N2-N3 staged were identified as independent risk factors affecting 5-year survival rate of the patients following radical surgery(P<0.05),and a high TSR2 expression was associated with a higher 5-year survival rate of the patients(P<0.001).Bioinformatics analysis suggested the functional involvement of TSR2 with the PI3K/AKT signaling pathway.MGC-803 cells overexpressing TSR2 showed significantly lowered proliferation,migration,and invasion capacities(P<0.05),while TSR2 knockdown produced the opposite effects(P<0.05).Western blotting showed that TSR2 overexpression reduced the phosphorylation of PI3K and AKT,and TSR2 knockdown caused the opposite changes in MGC-803 cells(P<0.05).Conclusion TSR2 is lowly expressed in gastric cancer tissues to adversely affect the patients'prognosis,and its overexpression inhibits gastric cancer cell proliferation,invasion,and migration possibly by downregulating the PI3K/AKT pathway.

Objective To investigate the relationship between the levels of CD4+/CD8+and D-dimer(D-D)in peripheral blood and the outcome of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis(EBV-HLH).Methods Ninety patients with EBV-HLH who were treated in Beijing Friendship Hospital from September 2021 to August 2023 were included as observation group,and additional 90 patients with infectious mononucleosis(IM)treated in the hospital contemporarily were selected as the control group.The levels of CD4+/CD8+and D-D in peripheral blood were compared between the two groups of patients to examine the correlation between the levels of CD4+/CD8+and D-D in peripheral blood and EBV-DNA load in patients with EBV-HLH,compare the outcome of patients within 3 months in terms of the levels of CD4+/CD8+and D-D in peripheral blood,evaluate the effects of CD4+/CD8+and D-D levels in peripheral blood on the risk of death from EBV-HLH,and analyze the interaction between the levels of CD4+/CD8+and D-D in peripheral blood.Results The patients in observation group showed significantly lower peripheral blood CD4+/CD8+ratio and significantly higher D-D than the patients in control group(P＜0.05).The peripheral blood CD4+/CD8+ratio was negatively correlated with EBV-DNA load(P＜0.05),and D-D was positively correlated with EBV-DNA load(P＜0.05)in EBV-HLH patients.The patients with high peripheral blood CD4+/CD8+ratio were assocaited with lower 3-month mortality rate compared to the patients with low CD4+/CD8+ratio.The patients with high D-D level were associated with higher 3-month mortality rate compared to the patients with low D-D level(P＜0.05).In EBV-HLH patients with low levels of peripheral blood CD4+/CD8+,the risk of death was 6.125 times that of the patients with high levels of CD4+/CD8+.High level D-D was associated with 14.348 times risk of death compared to the patients with low level D-D.CD4+/CD8+and D-D had synergistic effect on death of EBV-HLH patients.Conclusions Peripheral blood CD4+/CD8+levels decreased and D-D levels increased in EBV-HLH patients.Peripheral blood CD4+/CD8+levels and D-D levels and their changes may be useful for predicting the outcome of patients.

Objective To establish a fast,stable,and sensitive zebrafish model of osteoporosis(OP)using different method.Methods OP models were induced by iron overload or prednisolone(Pred),and bone formation and mortality were observed.The groups were divided into:Control group,model group(include FAC group and Pred group),and positive control group(AC group).Ammonium ferric citrate was used as the model drug in the iron-overload induction method.For the Pred induction models,the modeling time for the Pred-3 days post-fertilization(dpf)method was 3～9 dpf,the modeling time for the Pred-5 dpf method was 5～10 dpf,and Pred was administered from 3 dpf and removed from 7～9 dpf for the Pred withdrawal method.To compare the anti-osteoporosis(OP)effects of commonly used drugs such as Alfacalcidol(AC),Calcitriol(CA),and Alendronate(AL),it's important to select a stable and sensitive positive control drug and to further optimize different staining methods and conditions.Results There was no significant effect of ammonium ferric citrate 500 μg/mL on bone formation.Bone formation and the length of the first vertebra were significantly decreased in the Pred group induced by Pred-3 dpf compared with those in the control group(P＜0.01,P＜0.05),but zebrafish mortality was higher.There was no significant difference between the Pred-5 dpf method,but bone formation was significantly reduced in the Pred withdrawal group(P＜0.01),with no mortality.Alfacalcidol,calcitriol,and alendronate all had anti-OP effects,with CA having the most sensitive and stable anti-OP effect.Alizarin red staining showed that the optimal dye parameters were 0.02%concentration for dyeing 2 h,with washing in 0.5%KOH and glycerol under the conditions of a 3∶1 ratio for 3 h followed by a 1∶1 ratio for 14 h.The result of staining showed that calcein was more sensitive for staining bone nodes and ARS staining was more sensitive for staining the first vertebra.Conclusions The Pred withdrawal method can be used to establish a rapid,stable,and sensitive OP model in zebrafish as a reliable model for studying OP.

Objective:To analyze the clinical characteristics of patients of chronic active Epstein-Barr virus infection (CAEBV) with intestinal involvement misdiagnosed as inflammatory bowel disease (IBD).Methods:A retrospective analysis was conducted on the clinical characteristics, laboratory results, digestive endoscopic findings, histological results, treatment and prognosis of 10 patients with CAEBV intestinal involvement who were misdiagnosed as IBD and treated at the Department of Hematology, Beijing Friendship Hospital, Capital Medical University from February 2019 to November 2022. Epstein-Barr virus-encoded small RNA (EBER) was detected by in situ hybridization. Results:Among the 10 patients with CAEBV, eight were males and two were females. Seven patients had been misdiagnosed as ulcerative colitis and three misdiagnosed as Crohn′s disease. The median age of onset was 36 years (ranged from 26 to 52 years), and the median time from onset to CAEBV diagnosis was 18.5 months (ranged from 2.0 to 96.0 months). The main clinical characteristics of these patients included fever >38.5 ℃ in 10 cases, diarrhea in seven cases, abdominal pain in seven cases, abdominal lymph node enlargement in six cases and hematochezia in seven cases. Six patients primarily presented with gastrointestinal symptoms, and seven patients had involvement of extraintestinal organs, three patients developed hemorrhagic shock due to gastrointestinal bleeding. The laboratory findings included anemia in seven cases, elevated erythrocyte sedimentation rate in six cases, decreased natural killer cell activity in five cases, and elevated ferritin in three cases. Epstein-Barr virus (EBV) DNA were detected in the peripheral blood mononuclear cells (PBMCs) of nine patients, with a median viral load of 23 000 copies/mL. Seven patients were tested positive for anti-EBV viral capsid antigen IgG and nuclear antigen 1 IgG. The main endoscopy findings were hyperemia, edema of the affected intestinal wall mucosa, which could be accompanied by erosion, multiple scattered shallow ulcers with varying sizes. There were six patients with total colon involvement. The rectum was involved in three patients, and the esophagus, gastric antrum, duodenum and small intestine were each involved in one patient. Seven patients underwent follow-up colonoscopy after diagnosis, and four cases progressed. All 10 patients showed active chronic inflammation in the histopathological examinations of their intestinal tissue, with crypt changes in four cases and granulomatous changes in one cases. The intestinal tissues of eight patients were positive for EBER staining, and EBER positive cells≥50 cells/high-power field in seven patients. Seven patients were treated with 5-aminosalicylic acid before the correct diagnosis. Five patients had not improved or progressed upon the follow-up colonoscopy. Two patients died of uncontrolled massive hemorrhage of digestive tract.Conclusions:The clinical, endoscopic and pathological findings of patients with CAEBV intestinal involvement lack specificity. For IBD patients initially diagnosed accompanied by fever and evidence of extraintestinal organ involvement, it is recommended to simultaneously detect EBV DNA in PBMCs and blood plasma, EBER in intestinal tissue, and identify the main EBV-infected cells in peripheral blood and/or tissue, to distinguish CAEBV.

Objective:This study aimed to evaluate the global research landscape, identify trends, and determine hotspots concerning hepatoma recurrence post-liver transplantation.Methods:We conducted a bibliometric analysis usinga systematic search was conducted in the Web of Science Core Collection database from Jan. 1992 to Oct. 2023 to identify relevant articles on hepatoma recurrence after liver transplantation. Articles were selected based on inclusion and exclusion criteria and analyzed for publication trends by country/region, journal, author, institution, citation, and keyword. Visualization tools such as Citespace, VOSviewer, and Bibliometric.com were utilized for statistical analysis, identification of emerging trends, and clustering of keyword co-occurrence.Results:Out of 4,936 articles retrieved, 1,189 were included in the final analysis. There was a notable increase in publications on hepatoma recurrence following liver transplantation from 1992 to 2021, peaking in 2021 both globally (n=103) and nationally (n=32). China has the largest number of publications in this field (n=308), maintaining significant collaboration with the United States, South Korea, Japan, Canada. 'Liver Transplantation’ journal had the highest number of publications (n=113). Zhejiang University was the leading institution (n=74), with Academician Zheng Shusen being the most prolific scholar (n=76 publications). Citation emergence detection found that Italian scholar Mazzaferro's Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis published on The Lancet Oncology in 2009 had the highest burst strength (36.98). Five bursting keywords were identified: alpha fetoprotein, model, validation, sorafenib, and risk. Cluster analysis of keyword co-occurrence revealed five primary research themes: the medication for hepatocellular carcinoma recurrence after liver transplantation, recipient selection criteria, prognostic factors, development and validation of recurrence prediction model, and local treatments for hepatocellular carcinoma.Conclusions:The study underscores rapid advancements in the research on hepatocellular carcinoma recurrence post-liver transplantation over the past three decades, with significant contributions from Chinese scholars, particularly from Zhejiang University and Academician Zheng Shusen. The evolving research hotspots have shifted from transplantation experiences and recipient selection criteria to early post-transplant recurrence risk prediction and therapeutic strategy development.