Osteoarthritis (OA) is a chronic degenerative joint disease whose main characteristic is the destruction of articular cartilage, causing pain and disability in patients and seriously affecting their quality of life. OA can be induced by a variety of causes, and pathological changes in articular cartilage are considered to be one of the key driving factors for the occurrence of OA. High mobility group box-1 protein (HMGB1), as a non-histone protein in eukaryotic cells, can participate in regulating the inflammation and apoptosis process of OA chondrocytes, thus leading to the occurrence of OA. This article reviews the research on the mechanism of HMGB1 in OA chondrocytes, with a view to providing new ideas for the clinical prevention and treatment of OA.

Objective To investigate the effects of calcitriol intervention on PI3K/AKT signaling pathway and wound healing in rats with diabetic foot ulcer(DFU).Methods Thirty-two male SD rats were divided into normal control(Con)group,DFU group,calcitriol low dose(L)group and calcitriol high dose(H)group.A circular wound of 5 mm in diameter and deep to the fascia was made on the dorsum of the left foot of rats in each group.HE staining was used to evaluate the histopathological changes of the wounds.Immunohistochemical method was selected to compare the distribution of CD34-positive cells and the expression of p-PI3K and p-AKT in traumatic tissues of each group.ELISA was adopted in the detection of serum IL-6,IFN-γ,TNF-α and IL-7.RT-PCR was used to detect the mRNA expression of PI3K and AKT in each group,and western blot was used to detect the protein expression of PI3K,p-PI3K,AKT,p-AKT and VEGF.Results Compared with Con group,the expressions of IL-6,IFN-γ,TNF-α,IL-7,CD34,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K,p-AKT/AKT increased,while PI3K protein expression decreased in DFU,L and H groups(P<0.05),VEGF and AKT protein expression decreased in DFV and L groups(P<0.05).Compared with DFU group,the expressions of VEGF,AKT and PI3K protein increased(P<0.05),while the expressions of p-PI3K/PI3K,p-AKT/AKT decreased in L and H groups(P<0.05),IL-6 decreased in L group(P<0.05),and CD34 expression increased in H group(P<0.05),while IL-6,IFN-γ,TNF-α and IL-7,PI3K mRNA,AKT mRNA,p-AKT protein and p-PI3K protein expression decreased(P<0.05).Compared with L group,the expressions of CD34,VEGF,AKT and PI3K protein increased(P<0.05),while IL-6,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K and p-AKT/AKT decreased in H group(P<0.05).Conclusions Calcitriol intervention may reduce the activity of the PI3K/AKT signaling pathway,inhibit inflammation,promote neovascularization,and facilitate wound healing in rats with DFU.

Objective:To investigate the immunoregulatory effects of Glycyrrhiza uralensis ethanol extract(GUEE) on the maturation of dendritic cells (DCs) and the adjuvant effect of GUEE on OVA in na?ve BALB/c mice and an ovalbumin (OVA)-induced asthma mouse model. Methods:GUEE was prepared, and the effects of different concentrations of GUEE on the maturation of DCs and the secreted cytokines as well as the effects of GUEE on bacterial lipopolysaccharide (LPS)-induced DC maturation were examined in vitro. The effect of GUEE on the morphology of mouse bone marrow derived DCs was observed using microscopy. Molecular expression levels on the surface of DCs were detected using flow cytometry. The levels of interleukin-1β (IL-1β), IL-6, IL-12, and tumor necrosis factor-α (TNF-α) in the supernatant of DCs cultures were measured by enzyme-linked immunosorbent assay (ELISA). The maturation status of DCs was detected by flow cytometry by injecting different concentrations of GUEE into the paws of mice and isolating the draining lymph nodes 24 h later. The naive BALB/c mice were co-immunized with OVA, and the changes in regulatory T cells (Treg) were detected by flow cytometry. An OVA-protein-induced mouse asthma model was established to investigate whether GUEE as a tolerogenic adjuvant has an antigen-specific therapeutic effect on asthmatic mice. Pulmonary pathological changes were analyzed by hematoxylin-eosin staining (HE) and PAS staining. OVA-specific antibodies in serum and the frequencies of Tregs, CD4 + IFN-γ + and CD4 + IL-4 + T cells in the spleen were detected by ELISA and flow cytometry, respectively. Results:GUEE suppressed DCs maturation induced by LPS both in vitro and in vivo (all P<0.05), and reduced proinflammatory cytokine production, including IL-1β, IL-6, IL-12 and TNF-α in the absence or presence of LPS (all P<0.05). Moreover, co-immunization with OVA and GUEE increased the amount of Tregs in na?ve BALB/c mice ( P<0.05). In OVA-induced asthmatic mice, OVA and GUEE co-immunization and GUEE alone treatment substantially ameliorated the inflammation of lung tissues, decreased the levels of IgG 1 and the amount of CD4 + IL-4 + T cells, and increased the amount of Tregs (all P<0.05). Conclusions:GUEE alone or as the tolerogenic adjuvant can ameliorate allergic diseases through inhibition of DC maturation and type 2 helper T cell responses and induction of Tregs.

Objective:To investigate the diagnostic and prognostic value of D-dimer level in patients with hepatitis B-related acute-on-chronic liver failure (HBV-ACLF).Methods:A total of 142 cases diagnosed with ACLF were randomly selected as research objects in the open cohort using the Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH-ACLF). Plasma D-dimer levels were compared between patients with ACLF and non-ACLF and patients with different ACLF grades. Survival and death group D-dimer levels were compared with the end points of 28 days and 90 days, respectively. The correlation between D-dimer and other laboratory indicators and prognostic scores were investigated. Area under receiver operating characteristic curve (AUROC) was used to evaluate the D-dimer value for predicting the prognosis of ACLF patients. 125 external ACLF cases were used for validation. A Student t test or Mann-Whitney U test was used to compare continuous measurement data between two groups. Kruskal-Wallis test was used to compare continuous measurement data between multiple groups.Results:Plasma D-dimer levels in the ACLF [2 588.5 (1 142.8, 5 472.8) μg/L] ] and non-ACLF group [1 385.5 (612.0, 3 840.3) μg/L] had a significant difference ( P<0.001). ACLF-3 patients had significantly higher D-dimer levels than ACLF-1/2 patients (ACLF-3 vs. ACLF-1, P<0.001; ACLF-3 vs. ACLF-2, P<0.05). Patients who died at 28/90 days had significantly higher D-dimer levels than those whom survived ( P<0.001). There was a significant positive correlation between D-dimer level with prothrombin time (PT), international normalized ratio (INR), high-density lipoprotein C, as well as various prognostic scores (COSSH-ACLFs, CLIF-C ACLFs, CLIF-OFs, MELDs). AUROC of D-dimer in predicting the prognosis of ACLF patients at 28 days and 90 days was 0.751 (95% CI: 0.649-0.852) and 0.787 (95% CI: 0.695-0.878), respectively, which did not differ significantly compared with the predictive ability of other scores ( P<0.05), and similar results were confirmed by an external validation group of 125 cases. Conclusion:D-dimer level is significantly higher in patients with ACLF, so it is an independent predictor of prognosis at 28 and 90 days.

Objective:To investigate the clinical characteristics, response, and prognosis of splenic diffuse red pulp small B-cell lymphoma (SDRPL) .Methods:Eight cases of SDRPL were diagnosed and treated at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, between May 2017 and April 2022. Data on the clinical features, laboratory results, bone marrow and spleen biopsy results, response, and prognosis were collected and analyzed.Results:The median age at diagnosis was 54 (42-69) years. Splenomegaly and lymphocytosis were present in all cases, and PET/CT revealed normal to slightly elevated splenic FDG uptake. All cases were in stage Ⅳ, with spleen, peripheral blood, and bone marrow but no proximal lymph nodes involved. The cytoplasm of neoplastic villous cells was abundant, and splenic pathology showed that small homogenous lymphocytes permeated the splenic sinus and splenic cord, and the white pulp atrophied. Immunohistochemistry was not typical, and B-cell markers including CD19, CD20 and CD79α were positive. After a median follow up of 35.5 (4-60) months, 7 cases were alive after splenectomy with or without chemoimmunotherapy. The patient with CCND3 P284A and MYC S146L mutation developed to B-cell prolymphocytic leukemia (B-PLL) 1 month after splenectomy and died at 16 months of follow-up.Conclusion:A rare indolent B-cell lymphoma that primarily affects the elderly, SDRPL. Most patients achieved long-term survival, but the prognosis of patients who progress to B-PLL was poor.

Objective:To explore the therapeutic effect of intra-articular injection of triptolide nanomaterials on rabbit antigen-induced knee arthritis.Methods:Twenty-seven New Zealand white rabbits were randomly divided into 4 groups. After antigen-induced arthritis (AIA) model were induced, the knee joints of triptolide nanomaterials (TPNA) group, triptolide (TP) group and betamethasone (BS) group were injected intra-articularly under ultrasound guidance with triptolide nanomaterials, triptolide and betamethasone respectively, 7 rabbits in each group. And the other 6 rabbits were punctured but not injected with any drugs as the control group. The pathological changes of joint swelling, synovitis and bone erosion were examined. Student's test, repeated measure data of analysis of variance (ANOVA), Mann-Whitney U test and Kruskal- Wallis test were used for statistical analysis. Results:① Before treatment, the knee joint diameters of the TPNA group, TP group, BS group and control group were (2.02±0.08) cm, (2.08±0.06) cm, (2.10±0.06) cm and (2.18±0.07) cm, respectively. After one week of administration, the knee joint diameters of the above groups were (1.85±0.06) cm, (1.89±0.07) cm, (1.93±0.08) cm and (2.15±0.08) cm, respectively. Knee joint swelling was significantly reduced in each treated group after a week of intra-articular injection. With the extension of treatment, the diameter of rabbit knee joints in each experimental group gradually decreased gradually ( F=58.83, P<0.01; F=53.78, P<0.01; F=68.24, P<0.01), and the diameter of rabbit knee joints in the TP group, TPNA group and BS group was significantly smaller than that of the control group ( F=63.83, P<0.01; F=71.94, P<0.01; F=140.79, P<0.01). ② The synovitis score of TP group was lower than that of the control group ( Z=-2.082, P<0.05), which was mainly mild synovitis. While the synovitis scores of TPNA group and BS group were lower than that of TP group ( Z=-2.082, P<0.05; Z=-2.687, P<0.05), most of which were free from synovitis. There was no statistical significant difference between BS group and TPNA group ( Z=-1.000, P>0.05). ③ The pathological scores of bone destruction in the TPNA group, TP group and BS group were all reduced compared with the control group ( Z=-2.505, P<0.05; Z=-2.216, P<0.05; Z=-2.505, P<0.05). There was no statistical significant difference between the TPNA group, TP group and BS group ( χ2=0.588, P>0.05). Conclusion:Intra-articular injection of triptolide nanomaterials can relieve joint swelling, reduce synovitis, and delay bone erosion. Its effect is similiar to glucocorticoid, better than simple triptolide. Triptolide nanomaterials have the potential to be an effective drug for arthritis by intra-articular injection.

Objective:To compare the clinical efficacy of transperitoneal robot assisted laparoscopic radical prostatectomy (RARP) versus extraperitoneal single port RARP.Methods:A retrospective analysis was perfoumed on 142 cases of RARP from July 2019 to June 2020 in Robotic Minimally Invasive Center of Sichuan Provincial People's Hospital, including 82 cases(Group A) , aged 70.0(65.6-78.0), undergoing transperitoneal RARP and 60 cases(Group B), aged 68.2 years old(60.1-79.2), undergoing extraperitoneal single port RARP. For group A, PSA was 12.9(5.6-64.0) ng/ml, with 26 cases of less than 10 ng/ml(31.7%), 40 cases of 10-20 ng/ml(48.8%), and 16 cases of more than 20 ng/ml(19.5%), the Gleason score was 7.2(6.0-10.0), with 14 cases(17.1%) of ≤6, 56 cases(68.3%) of 7, and 12 cases(14.6%) of ≥8, and the prostate volume was 61.3(29.0-112.0) ml. There were 49 cases with BMI≤25 kg/m 2, accounting for 59.8%, and 33 cases with BMI>25 kg/m 2, accounting for 40.2%. There were 17 cases(20.7%) of T 1, 44 cases(53.7%) of T 2 and 21 cases(25.6%) of T 3. The proportion of lymph node dissection was 17.1%, and 4 cases(4.9%)had a history of operation. For group B, the PSA was 12.2(1.0-42.6)ng/ml, with 20 cases (33.3%) of <10 ng/ml, 31 cases(51.7%)of 10-20 ng/ml, and 9 cases (15%) of >20 ng/ml. Gleason score was 7.1(6.0-9.0), with 12 cases (20.0%) of ≤6, 42 cases (70.0%) of 7, and 6 cases (10.0%)of ≥8. Prostate volume was 42.4(31.2-72.8)ml on average. There were 37 cases (61.7%) with BMI≤25 kg/m 2, and 23 cases (38.3%)with BMI >25 kg/m 2 . There were 17 cases(28.3%)of T 1, 32 cases(53.3%)of T 2 and 11 cases(18.3%)of T 3.The proportion of lymph node dissection was 11.7% and 4 cases (6.7%) had a history of operation.There was no statistically significant difference in term of age, PSA level, Gleason score, BMI, clinical stage, proportion of lymph node dissection or history of operation between the two groups( P>0.05), but there was statistically significant difference for prostate volume( P<0.05). All operations were performed by the same operator. Four different ways of bladder neck and urethral dissociation was selected according to the intraoperative conditions in Group A, include VIP style, T-shape incision style, VIP plus T-shape incision style or the style along the lateral side of the bladder neck. Small and single anterograde incision stripping of bladder neck was routinely performed in the Group B. Postoperative follow-up was performed to compare the operation time, intraoperative blood loss, bladder neck and urethral anastomosis time, postoperative hospital stay, postoperative exhaust time, postoperative complications, positive rate of surgical margin, indwelling time of urinary catheter, urinary continence satisfaction rate of immediately after operation, 3 months and 6 months after operation, wound healing and aesthetics. Results:All of the operations were successfully completed under robot-assisted laparoscopy, and there was no conversion to open surgery. The operation time was 56.0(45.0-112.0) min in the Group A and 65.4(55.5-96.8) min in the Group B, and there was no statistically significant difference( P>0.05). The intraoperative blood loss was 76.2(30.0-120.5) ml and 55.6(45.5-114.6) ml, respectively, and the difference was not statistically significant( P>0.05). The time of bladder neck urethral anastomosis was 18.9(12.6-25.6) min and 16.2(10.7-19.3) min, respectively, and the difference was not statistically significant( P>0.05). The postoperative hospital stay days were 9.3(8.0-16.0) d and 8.4(7.0-13.0) d, respectively, and the difference was not statistically significant( P>0.05). The postoperative exhaust time was 1.3(0.7-3.0) d and 3.4(2.0-7.0) d, respectively, and the difference was statistically significant( P<0.05). There was 1 case of anastomotic fistula with ureteral injury in Group A, and no serious complication in Group B, and the difference was not statistically significant( P>0.05). The number of positive surgical margin in the two groups was 13(15.9%)and 9(15.0%)respectively, and the difference was not statistically significant( P>0.05). The indwelling time of urinary catheter after operation was 9(7-21) d and 6(4-8) d, respectively, and the difference was statistically significant( P<0.05). The number of patients with satisfactory urinary continence immediately after surgery, 3 months and 6 months after surgery in the two groups were 8(9.8%), 51(62.2%), 62(75.6%) and 17(28.3%), 43(71.7%) and 54(90.0%), respectively. The differences were statistically significant( P<0.05). The total incision lengths in the two groups were 12.1(10.4-13.4) cm and 5.6(5.0-6.0) cm, respectively, and the difference was statistically significant( P<0.05). Conclusions:The extraperitoneal single port RARP is safe and feasible, and the postoperative effect is similar to that of transperitoneal RARP. It has the advantages of shorter recovery time, higher urinary continence satisfaction rate, neater and more beautiful incision. The long-term therapeutic effect needs further confirming by prospective study.

Unrestrained inflammation is harmful to tissue repair and regeneration. Immune cell membrane-camouflaged nanoparticles have been proven to show promise as inflammation targets and multitargeted inflammation controls in the treatment of severe inflammation. Prevention and early intervention of inflammation can reduce the risk of irreversible tissue damage and loss of function, but no cell membrane-camouflaged nanotechnology has been reported to achieve stage-specific treatment in these conditions. In this study, we investigated the prophylactic and therapeutic efficacy of fibroblast membrane-camouflaged nanoparticles for topical treatment of early inflammation (early pulpitis as the model) with the help of in-depth bioinformatics and molecular biology investigations in vitro and in vivo. Nanoparticles have been proven to act as sentinels to detect and competitively neutralize invasive Escherichia coli lipopolysaccharide (E. coli LPS) with resident fibroblasts to effectively inhibit the activation of intricate signaling pathways. Moreover, nanoparticles can alleviate the secretion of multiple inflammatory cytokines to achieve multitargeted anti-inflammatory effects, attenuating inflammatory conditions in the early stage. Our work verified the feasibility of fibroblast membrane-camouflaged nanoparticles for inflammation treatment in the early stage, which widens the potential cell types for inflammation regulation.
Escherichia coli ; Fibroblasts ; Humans ; Inflammation/drug therapy* ; Nanoparticles

OBJECTIVES: The measurement of diabetic foot ulcers is important for the success in diabetic foot ulcer management. At present, it lacks the accurate and convenient measurement tools in clinical. In recent years, artificial intelligence technology has demonstrated the potential application value in the field of image segmentation and recognition. This study aims to construct an intelligent measurement model of diabetic foot ulcers based on the deep learning method, and to conduct preliminary verification. METHODS: The data of 1 042 diabetic foot ulcers clinical samples were collected. The ulcers and color areas were manually labeled, of which 782 were used as the training data set and 260 as the test data set. The Mask RCNN ulcer tissue color semantic segmentation and RetinaNet scale digital scale target detection were used to build a model. The training data set was input into the model and iterated. The test data set was used to verify the intelligent measurement model. RESULTS: This study established an intelligent measurement model of diabetic foot ulcers based on deep learning. The mean average precision@.5 intersection over union (mAP@.5IOU) of the color region segmentation in the training set and the test set were 87.9% and 63.9%, respectively; the mAP@.5IOU of the ruler scale digital detection in the training set and the test set were 96.5% and 83.4%, respectively. Compared with the manual measurement result of the test sample, the average error of the intelligent measurement result was about 3 mm. CONCLUSIONS The intelligent measurement model has good accuracy and robustness in measuring the diabetic foot ulcers. Future research can further optimize the model with larger-scale data samples.
Artificial Intelligence ; Diabetes Mellitus ; Diabetic Foot ; Humans

Objective:To analysis the status of the mental health and related factors of fire fighters in Tianjin Binhai New District, and to provide suggestions for their psychological health protection.Methods:399 fire fighters in Tianjin Binhai New District were selected as study subjects in Jan to April 2019. Depression symptoms were measured by the depression module of the Patient Health Questionnaire (PHQ-9) . The Chinese version of Efrort Reword Imbalance (ERI) Questionnnaire were used to investigate and evaluate their occupational stress. Chi-Square test was used to analysis Categorical data. Binary logistic regression model was used to analysis the ralated factors of depression.Results:Among the 399 fire fighters, 71.1% (280/394) were found high level of depression symptom. The detection rates of depression symptoms in the related influceing factors ERI、station、disease、life pressure、eating habits and sleep disorder occupational stress were difierent ( P<0.05) . Sleep disorder, life pressure and ERI occupational stress were risk factors for depressive symptoms ( OR=1.921, 95% CI=1.002-3.682; OR=2.852, 95% CI=1.561-5.212; OR=2.367, 95% CI=1.163-4.818, P<0.05) . Conclusion:The rate of depression of fire fighters is relatively higher. Government should pay attention to and take measures to improve the psychological condition of fire fighters.