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.

In recent years, there has been increasing evidence that nonalcoholic fatty liver disease (NAFLD) is a manifestation of a systemic metabolic disease in liver. However, limitations in the definition and diagnostic criteria of NAFLD could not fully and accurately describe the metabolic disorder. A consensus statement proposed renaming NAFLD to metabolic associated fatty liver disease (MAFLD). Compared with NAFLD, MAFLD links fatty liver disease with metabolic factors such as overweight or obesity and diabetes, and the diagnosis of the disease no longer excludes the presence of metabolic abnormalities in patients with alcohol consumption or other chronic liver diseases. The authors focus on definition changes of fatty liver disease, discuss the epidemiological changes from NAFLD to MAFLD and the relationship of MAFLD with liver fibrosis and extrahepatic diseases, and also the significance of MAFLD for public health.

Yuebawei refers to 8 kinds of genuine medicinal materials in south China area，namely Citri Grandis Exocarpium， Citrus reticulata， Amomum villosum， Pogostemon cablin， Morinda officinalis， Aquilaria sinensis， Citrus medica and Polygonum multiflorum. The results of this review show that， the pharmacological effects of Yuebawei are very extensive. It has significant effects in relieving cough and phlegm， anti-bacterial and anti-inflammatory， enhancing immunity， anti-oxidation， antidepressant， immune regulation and regulating gastrointestinal function. Its development and application prospects are broad， but most of the existing pharmacological studies stay on pharmacodynamic studies. In the aspect of the safety research of Yuebawei， there are few studies on the safety of other medicinal materials， except for the liver toxicity of P. multiflorum； at the same time， there are few comparative studies on the therapeutic advantages of Yuebawei and other local medicinal materials in clinical application. It is necessary to strengthen the research on the material basis of pharmacological action mechanism， and safety and efficacy observation of clinical medication for Yuebawei， so as to provide scientific basis for the development of new drugs and clinical promotion and application of Yuebawei.

Objective:To compare and analyze the clinical characteristics between acute fatty liver of pregnancy (AFLP) and the hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome.Methods:This is a retrospective cohort study. The clinical data of 13 cases with AFLP and 34 cases with HELLP syndrome were collected from three tertiary referral centers in Yunnan (the First Affiliated Hospital of Kunming Medical University, the Second Affiliated Hospital of Kunming Medical University, and Yan'an Hospital of Kunming City) from January 2016 to December 2021. The patients were diagnosed to AFLP and HELLP syndrome according to the Swansea criteria and the Tennessee classification system. The general characteristics, clinical features, laboratory results within 24 hours after admission, complications, maternal and neonatal outcomes were compared to analysis the differences between the two groups.Results:① Maternal characteristics: compared with HELLP syndrome group, AFLP group had lower body mass index (BMI) and blood pressure at admission (both P < 0.01). ②Clinical features: the most common symptoms in AFLP patients were skin jaundice, abdominal pain, nausea and vomiting, edema. The main manifestations of patients with HELLP syndrome were albuminuria, hypertension, edema, headache. Some patients had multiple symptoms concurrently. ③ Laboratory results: compared with HELLP syndrome group, the levels of platelet count (PLT), total bilirubin (TBil), direct bilirubin (DBil), γ-glutamyl transferase (γ-GGT), alkaline phosphatase (ALP), total bile acid (TBA), serum creatinine (SCr) and international standardized ratio (INR) in AFLP group were significantly increased within 24 hours after admission [PLT (×10 9/L): 107.69±51.13 vs.76.71±43.25, TBil (μmol/L): 121.60 (83.20, 170.00) vs.15.25 (7.22, 29.05), DBil (μmol/L): 86.50 (58.60, 104.00) vs. 4.30 (2.22, 10.10), γ-GGT (U/L): 87.00 (37.00, 127.00) vs. 41.00 (19.00, 64.42), ALP (U/L): 199.10 (109.00, 349.20) vs. 125.50 (90.50, 155.25), TBA (μmol/L): 51.50 (16.20, 117.40) vs. 4.15 (2.02, 6.95), SCr (μmol/L): 155.80 (129.00, 237.00) vs. 79.00 (65.43, 113.70), INR: 1.28 (1.17, 1.63) vs. 0.94 (0.88, 1.08), all P < 0.05], prothrombin time (PT) was significantly prolonged [seconds: 16.10 (14.50, 19.20) vs. 12.40 (11.43, 13.40), P < 0.05]. The level of blood glucose (GLU), fibrinogen (FIB) and the activity of antithrombin Ⅲ (ATⅢ) decreased significantly [GLU (mmol/L): 5.18±1.33 vs. 6.33±1.19, FIB (g/L): 1.96±1.46 vs. 3.81±1.58, ATⅢ (%): 40.61±25.84 vs. 66.39±24.11, all P < 0.05]; ④ Complications: compared with HELLP syndrome group, the incidence of patients with hypoglycemia [30.77% (4/13) vs. 0% (0/34)], acute liver failure [53.85% (7/13) vs. 5.88% (2/34)], acute renal insufficiency [69.23% (9/13) vs. 8.82% (3/34)], coagulopathy [76.92% (10/13) vs. 38.24% (13/34)], disseminated intravascular coagulation (DIC) [53.85% (7/13) vs. 5.88% (2/34)], and multiple organ dysfunction syndrome (MODS) [53.85% (7/13) vs. 5.88% (2/34)] were significantly higher in AFLP group (all P < 0.05). ⑤ Maternal and neonatal outcome: all patients delivered after admission. The total length of hospital and intensive care unit stay were significantly longer in the AFLP group than in the HELLP syndrome group [days: 17.00 (11.00, 25.00) vs. 9.00 (7.00, 12.00), 12.00 (4.00, 22.00) vs. 3.91 (0, 7.00), both P < 0.01]. Two AFLP patients died, including one due to intracranial venous thrombosis and one due to multiple organ failure and cardiopulmonary arrest. There were no deaths in the HELLP syndrome group. Conclusions:There are significant differences in maternal characteristics, laboratory results and complications between AFLP and HELLP syndrome. TBil, γ-GGT, SCr, FIB, INR and ATⅢ activity may help to distinguish the two diseases.

Objective:To investigate the efficacy and safety of hemodiafiltration (HDF) in treating CAR-T related grade 3-4 cytokine release syndrome after ineffective treatment with IL-6 receptor inhibitors.Methods:Between July 2015 and July 2021, retrospective analysis of hemodiafiltration for the treatment of 3 patients, including 2 cases of acute B-lymphoblastic leukemia and 1 case of diffuse large B-cell lymphoma, with grade 3-4 CRS after CAR-T cell therapy and ineffective treatment with IL-6 receptor inhibitor was carried out.Results:The patient's clinical symptoms, including body temperature, blood pressure, and blood oxygen, were relieved within 12 hours of all treatments, and the cytokines (IL-6, IL-10, TNF-α, INF-γ) and C-reactive protein (CRP) levels decreased significantly. No adverse side effects were observed during the follow-up period of 3 months.Conclusion:HDF can be a safe and feasible method to treat CAR-T related grade 3- 4 CRS after ineffective treatment with IL-6 receptor inhibitors.

Objective:To investigate the prognostic value of 18F-fluorodeoxygen-D-glucose-positron emission tomography /computerized tomography ( 18F-FDG-PET-CT) in Hodgkin′s lymphoma (HL) at the end of first-line treatment (PET-end), by comparing the ratio of maximum standardized uptake value (SUV max) of lesion and liver SUV (rLL), SUV max reduction between baseline PET (PET-0) and PET-end (ΔSUV max), and Deauville 5-point scale (5-PS). Methods:Patients with HL newly treated in our hospital from August 2006 to December 2015 were retrospectively analyzed. All the patients enrolled in the study underwent post-treatment FDG PET-CT. The rLL and ΔSUV max were calculated, and all the cases were scored using Deauville 5-PS. The receiver operating characteristic (ROC) approach was applied to identify the optimal cut-point value, and survival curves according to different PET-CT assessment methods were estimated using the Kaplan-Meier analysis. The prognostic efficacy of different PET-CT assessment methods was compared, and DeLong test was used to verify it. Kaplan-Meier method and multivariate analysis using the Cox proportional hazards model were performed to analyze the potential independent risk factors. Results:There were 5 patients progressed within a 3-year follow-up. In the three PET-CT assessment methods, the predictive value of rLL and Deauville 5-PS were significant effective. ROC analysis for rLL as a progression predictor showed an optimal cut-point of 1.29. Deauville 5-PS=4 and rLL=1.29 showed the best prognostic accuracy. The sensitivity of rLL and Deauville 5-PS were both 80.0%, and the specificity of each was 98.0% and 93.7%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of rLL were 66.7% and 98.7%, while the PPV and NPV of 5-PS were 44.4% and 98.7%. The 3-years progression-free survival (PFS) rates of rLL≥1.29 group and rLL<1.29 group were 33.3% and 98.7%, with significant difference ( P<0.001). The 3-years PFS rates of post-treatment Deauville 5-PS<4 group and Deauville 5-PS≥4 group were 98.7% and 55.6%, with significant difference ( P<0.001). The prognostic evaluation efficacy of rLL was positively correlated with that of Deauville 5-PS ( r=0.75, P<0.05). Area under curves (AUC) of rLL and Deauville 5-PS were 0.93 (95% CI: 0.825-1.000) and 0.91 (95% CI: 0.757-1.000), respectively. DeLong test showed the significant difference between the two methods ( P<0.05). The univariate analysis results showed that clinical baseline stage, post-treatment rLL and Deauville 5-PS were associated with the prognoses of HL patients ( P<0.05). The multivariate analysis results showed that post-treatment rLL and Deauville 5-PS were independent prognostic factors of HL ( P<0.05). Conclusions:The rLL and Deauville 5-PS are potential prognostic factors for HL response assessment. The new semi-quantitative method rLL has methodological advantages over visual analysis, and it is a good supplement for Deauville 5-PS. rLL can improve prognostic evaluation accuracy of PET-CT and is useful to early identify patients with HL at a high risk of relapsing after first-line treatment.

Objective:To investigate the prognostic value of 18F-fluorodeoxygen-D-glucose-positron emission tomography /computerized tomography ( 18F-FDG-PET-CT) in Hodgkin′s lymphoma (HL) at the end of first-line treatment (PET-end), by comparing the ratio of maximum standardized uptake value (SUV max) of lesion and liver SUV (rLL), SUV max reduction between baseline PET (PET-0) and PET-end (ΔSUV max), and Deauville 5-point scale (5-PS). Methods:Patients with HL newly treated in our hospital from August 2006 to December 2015 were retrospectively analyzed. All the patients enrolled in the study underwent post-treatment FDG PET-CT. The rLL and ΔSUV max were calculated, and all the cases were scored using Deauville 5-PS. The receiver operating characteristic (ROC) approach was applied to identify the optimal cut-point value, and survival curves according to different PET-CT assessment methods were estimated using the Kaplan-Meier analysis. The prognostic efficacy of different PET-CT assessment methods was compared, and DeLong test was used to verify it. Kaplan-Meier method and multivariate analysis using the Cox proportional hazards model were performed to analyze the potential independent risk factors. Results:There were 5 patients progressed within a 3-year follow-up. In the three PET-CT assessment methods, the predictive value of rLL and Deauville 5-PS were significant effective. ROC analysis for rLL as a progression predictor showed an optimal cut-point of 1.29. Deauville 5-PS=4 and rLL=1.29 showed the best prognostic accuracy. The sensitivity of rLL and Deauville 5-PS were both 80.0%, and the specificity of each was 98.0% and 93.7%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of rLL were 66.7% and 98.7%, while the PPV and NPV of 5-PS were 44.4% and 98.7%. The 3-years progression-free survival (PFS) rates of rLL≥1.29 group and rLL<1.29 group were 33.3% and 98.7%, with significant difference ( P<0.001). The 3-years PFS rates of post-treatment Deauville 5-PS<4 group and Deauville 5-PS≥4 group were 98.7% and 55.6%, with significant difference ( P<0.001). The prognostic evaluation efficacy of rLL was positively correlated with that of Deauville 5-PS ( r=0.75, P<0.05). Area under curves (AUC) of rLL and Deauville 5-PS were 0.93 (95% CI: 0.825-1.000) and 0.91 (95% CI: 0.757-1.000), respectively. DeLong test showed the significant difference between the two methods ( P<0.05). The univariate analysis results showed that clinical baseline stage, post-treatment rLL and Deauville 5-PS were associated with the prognoses of HL patients ( P<0.05). The multivariate analysis results showed that post-treatment rLL and Deauville 5-PS were independent prognostic factors of HL ( P<0.05). Conclusions:The rLL and Deauville 5-PS are potential prognostic factors for HL response assessment. The new semi-quantitative method rLL has methodological advantages over visual analysis, and it is a good supplement for Deauville 5-PS. rLL can improve prognostic evaluation accuracy of PET-CT and is useful to early identify patients with HL at a high risk of relapsing after first-line treatment.

Objective To observe the effect of berberine on the expression of GLUT4 and PGC-1α in mice with insulin resistance,and to explore the molecular mechanism of berberine in improving insulin resistance.Methods Mice models with insulin resistance were established,and berberine was used by intragastric administration to detect blood glucose,insulin and insulin sensitivity.RT-PCR was used to detect the expression level of GLUT4 and mRNA of PGC-1α in skeletal muscle.Results Berberine significantly reduced blood sugar,increased insulin sensitivity,and promoted the expression of GLUT4 and PGC-1α in skeletal muscle.Conclusion Berberine can improve the expression of PGC-lo,promote the expression of GLUT4 and improve insulin resistance.

Objective To observe the effect of berberine on the expression of GLUT4 and PGC-1α in mice with insulin resistance,and to explore the molecular mechanism of berberine in improving insulin resistance.Methods Mice models with insulin resistance were established,and berberine was used by intragastric administration to detect blood glucose,insulin and insulin sensitivity.RT-PCR was used to detect the expression level of GLUT4 and mRNA of PGC-1α in skeletal muscle.Results Berberine significantly reduced blood sugar,increased insulin sensitivity,and promoted the expression of GLUT4 and PGC-1α in skeletal muscle.Conclusion Berberine can improve the expression of PGC-lo,promote the expression of GLUT4 and improve insulin resistance.

BACKGROUND:For pediatric patients with aplastic anemia in China, it is difficult to find human leucocyte antigen-matched sibling donors that are mostly replaced by parental donors.
OBJECTIVE:To retrospectively analyze the clinical efficacy and safety of parental haploidentical peripheral blood hematopoietic stem cel transplantation in children with relapsed and refractory severe aplastic anemia.
METHODS:Seventeen children with relapsed and refractory severe aplastic anemia who had no matched sibling or unrelated donor and failed to respond to immunosuppressive therapy were subjected to parental haploidentical peripheral blood hematopoietic stem cel transplantation. A conditioning regimen of fludarabine+cyclophosphamide+rabbit anti-human thymocyte immunoglobulin antibody and the triple therapy of methotrexate, cyclosporine A and mycophenolate mofetil were applied to prevent graft-versus-host disease.
RESULTS AND CONCLUSION: (1) Of the 17 children, 16 cases (94%) reached hematopoietic reconstitution, and the median time of neutrophils≥ 0.5×109/L and platelets≥ 20×109/L was 13 (11-15) days and 17 (12-28) days, respectively. (2) Incidence of acute graft-versus-host disease was 47% (8 of 17 cases), including 29% (5/17) of grades I-II and 18% (3/17) of grades III-IV. Incidence of chronic graft-versus-host disease was 41% (7/17). (3) With a median folow-up duration of 268 (43-753) days, the overal survival rate was 70.6% (12/17). Five dead cases (29%) belonged to transplantation-related death, including one case of fungal skin infections, one case of graft-versus-host disease, three cases of severe lung infection. No relapse case was reported. These findings indicate that if there are no matched sibling or unrelated donors and the immunosuppression effect is poor, parental haploidentical peripheral blood hematopoietic stem cel transplantation is a safe and effective salvage treatment for children with relapsed and refractory severe aplastic anemia.