Objective:To investigate the clinical efficacy of 3D printed metal augment or tibial prosthesis for reconstruction of large bone defects in total knee arthroplasty (TKA) and knee revision surgery.Methods:A total of 7 patients (7 knees) with TKA or knee revision who were admitted to the Department of Orthopaedics of the Second Affiliated Hospital of Zhejiang University School of Medicine with large bone defects from July 2018 to December 2023 were retrospectively analyzed, including 4 patients with TKA and 3 patients with knee revision. There were 3 males and 4 females, aged 58.7±7.6 years (range, 54-68 years), 3 patients with left knee and 4 patients with right knee. All the patients had bone defects in the knee joint (AORI type III), 2 cases had bone defects only in the femur, 4 cases had bone defects only in the tibia, and 1 case had bone defects in both the tibia and femur, which were treated with personalized reconstruction using 3D printing. Hip-knee-ankle angles, American Knee Society score (KSS) before and after surgery were compared, and postoperative complications were observed.Results:All patients successfully completed the operation, and the operation time was 189.3±35.5 min (range, 125-240 min). Complex TKA was performed in 4 cases with surgical times of 175, 195, 210, and 240 min, and revision surgery was performed in 3 cases with surgical times of 125, 180, and 200 min, respectively. Intraoperative blood loss was 114±24.4 ml (range, 100-150 ml). Five cases used 3D printed metal augment, and two used 3D printed one-piece tibial components. All patients were followed up for 2, 2, 5, 6, 7, 20, 57 months, respectively. The KSS of the five patients at 3 months postoperatively were 56, 61, 66, 56, and 56 points, respectively, greater than the preoperative scores of 35, 44, 36, 27, and 41 points. The KSS functional scores of the five patients at 3 months postoperatively were 45, 45, 45, 30, and 45 points, respectively, which were greater than the preoperative scores of 30, 30, 15, 20, and 20 points. The hip-knee-ankle angle was 181.8°±3.4° (range, 177.9° to 188.0°) at the final follow-up and 175.8°±12.4° (range, 153.3° to 192.1°) before surgery, with no significant difference ( t=-1.230, P=0.242). At the final follow-up, the 3D printed component was well integrated with the bone surface, the prosthesis was securely positioned, and the force lines of the lower limbs were normal. There were no postoperative complications such as poor wound healing, infection, fat liquefaction, nerve injury, deep vein thrombosis of lower limbs, knee joint stiffness, periprosthesis infection and loosening. Conclusion:Using 3D printed metal augment or tibial prosthesis to reconstruct the huge bone defect in TKA and revision has a satisfactory early clinical effect, satisfactory joint function and good surgical safety.

BACKGROUND:Stem cell transplantation is a new way to prevent and cure intervertebral disc degeneration.However,whether the transplanted stem cells can survive,proliferate,differentiate,and restore the function of nucleus pulposus cells after transplantation,is the key and difficult point to overcome. OBJECTIVE:To explore the effects of Bushenhuoxue decoction on survival,proliferation,and nucleus pulposus-like differentiation of adipose-derived stem cells. METHODS:A Transwell chamber was used to construct a co-culture model of human adipose-derived stem cells and human degenerative nucleus pulposus cells.The experiment was divided into control group,model group,drug-containing serum group,and drug-free serum group.Except for the control group,the co-culture system of other groups was treated with 50 μmol/L tert-butyl hydrogen peroxide for 24 hours.The drug-containing serum group and drug-free serum group were treated with DMEM low-glucose complete culture medium containing drug-containing serum of Bushenhuoxue decoction or drug-free serum with 20％volume fraction for 48 hours.The sublayer adipose-derived stem cells were taken.Toluidine blue staining was used to detect proteoglycan synthesis levels.Real-time PCR method was used to detect mRNA expression of type Ⅱ collagen,proteoglycan and SRY-box transcription factor 9.The protein expression of SOX9 was detected by western blot assay.Lactate dehydrogenase assay was used to detect cytotoxicity.Flow cytometry was used to detect reactive oxygen species,and β-galactosidase staining was used to detect cell senescence. RESULTS AND CONCLUSION:(1)Compared with the control group,the proportion of necrotic cells in the model group increased;toluidine blue staining became lighter,and the expression levels of type Ⅱ collagen,proteoglycan,SOX9 mRNA and SOX9 protein decreased(P<0.05).Compared with the model group,the drug-containing serum of Bushenhuoxue decoction could significantly reduce cell injury and promote the expression of type Ⅱ collagen,proteoglycan,SOX9 mRNA,and SOX9 protein(P<0.05),but the improvement in the drug-free serum group was not significant(P>0.05).(2)Compared with the control group,the contents of cytotoxicity,reactive oxygen species,and cell senescence in the model group were significantly increased.Compared with the model group,the microenvironment of the coculture system was significantly improved by drug-containing serum of Bushenhuoxue decoction(P<0.05),while drug-free serum had no significant effect on the microenvironment of the co-culture system(P>0.05).(3)The results show that Bushenhuoxue decoction can promote the survival,proliferation,and nucleus pulposus-like differentiation of adipose-derived stem cells.

Objective:To investigate the efficacy and safety of AcoStream peripheral thrombus aspiration system combined with catheter-directed thrombolysis in the treatment of lower extremity deep vein thrombosis.Methods:The clinical data of 16 lower extremity deep vein thrombosis cases treated with AcoStream peripheral thrombus aspiration system combined with catheter-directed thrombolysis, admitted to the authors′ hospital from May 2022 to November 2022, were retrospectively analyzed. The differences in circumferential diameter between the affected limb and the healthy side, venous patency score, thrombus clearance grade and intraoperative blood loss were observed and compared. The Villalta score was used during the follow up. Paired sample t-test and Wilcoxon rank sum test were used to compare the changes in the observed indicators before and after treatment to evaluate the efficacy. Results:Treatment were successfully performed in all patients. Before treatment, the circumference differences between the affected and unaffected thighs and calves were (3.69±0.97) and (3.34±0.75)cm, respectively, the venous patency score of the affected side was 8(7.25,9) points. After treatment, the circumference differences between the affected and unaffected thighs and calves were (0.81±0.68) and (0.84±0.70)cm, respectively. The venous patency score of the affected side was 1(0,1)points, with statistically significant differences ( P<0.001). Grade Ⅲ thrombus clearance was achieved in 7 patients, grade Ⅱ thrombus clearance was achieved in 9 patients. The average blood loss during thrombus aspiration was (133.1±12.0) ml. Following up for 6 months, the Villalta score was 0(0,1.75) points. Conclusion:Acostream peripheral thrombus aspiration system combined with catheter-directed thrombolysis is safe and effective for the treatment of lower extremity deep venous thrombosis, with satisfactory short-term efficacy and high clinical application value.

Objective To evaluate the efficacy and safety of a domestic arterial thrombus aspiration catheter in treating acute arterial ischemic events in the experimental dogs,and to compare this catheter with Penumbra suction catheter.Methods Acute ischemic embolism model was established in the external carotid and renal arteries of experimental dogs,and the experimental dogs were randomly assigned to the study group and control group.The embolized blood vessels were treated with thrombectomy.Results A total of 12 experimental dogs were enrolled in this study,with 6 dogs in each group.All of the 12 experimental dogs were successfully modeled.In the study group and the control group,the cumulative success rates of thrombectomy were 92.9％and 66.7％respectively(P＞0.05),the incidences of intraoperative vascular dissection were 0％and 8.3％respectively(P＞0.05),and the incidences of vasospasm were 35.7％and 0.75％respectively(P＞0.05).Conclusion In treating thrombus-embolized blood vessels with mechanical thrombectomy in experimental dogs,no statistically significant differences in the efficacy and safety exist between using domestic arterial thrombus aspiration catheter and using Penumbra suction catheter.(J Intervent Radiol,2023,32:1207-1210)

Objective:To observe the effect of escitalopram combined with repetitive transcranial magnetic stimulation (rTMS) on efficacy and attention function in patients with first-episode unipolar depression.Methods:Fifty-two first-episode initial-naive unipolar depression patients were enrolled in Department of Neurology of Guangzhou First People's Hospital from March 2022 to April 2023 were chosen. They were randomly allocated to active stimulation group ( n=27) and sham stimulation group ( n=25); both were treated with escitalopram, and active treatment or sham treatment in the left dorsolateral prefrontal cortex (DLPFC) were given for 4 weeks (5 d per week, 20 d totally). Before treatment and 2 and 4 weeks after treatment, Hamilton Depression Rating Scale (HAMD)-24 was used to evaluate depressive symptoms, and Birmingham Cognitive Screening Scale-Chinese (BCoS-C) was used to evaluate the attention function. Results:(1) In terms of depressive symptoms: HAMD-24 scores of the active stimulation group 2 and 4 weeks after treatment (20.63±2.73, 15.85±2.43) were significantly lower than those before treatment (25.74±2.68, P<0.05); HAMD-24 scores of sham stimulation group 4 weeks after treatment were also significantly lower than those before treatment ([20.48±2.33] vs. [25.80±2.57], P<0.05); HAMD-24 scores of the active stimulation group 2 and 4 weeks after treatment were significantly lower than those of sham stimulation group ( P<0.05). (2) In terms of auditory attention indicators: total correct number (selective attention) in active stimulation group 4 weeks after treatment was significantly larger than that before treatment (51.74±1.38 vs. 47.48±1.60), and the sustained index (sustained attention) was significantly lower than that before treatment (0.74±0.71 vs. 4.37±1.15, P<0.05); total correct number in active stimulation group 4 weeks after treatment was significantly larger than that in sham stimulation group (48.00±1.66), and the sustained index was significantly lower than that in sham stimulation group (3.72±1.28, P<0.05). Conclusion:Combined with escitalopram, rTMS can more effectively mitigate the depressive symptoms in first-episode unipolar depression patients, and depressive symptoms improve more quickly than attentional function.

Objective:To explore the Epstein-Barr virus (EBV) latent infection membrane protein (LMP) 1 or LMP2 specific T cell immune response and clinical significance in stage III-IVa nasopharyngeal carcinoma (NPC), aiming to provide ideas and evidence for immunotherapy in NPC.Methods:Fifty-nine NPC patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University from February 2018 to October 2020 for primary treatment were collected. Peripheral blood monocytes (PBMCs) were stimulated by LMP antigen. Intracellular cytokine staining and flow cytometry were applied to study the expression levels of IL-2, IL-13, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) from CD4 + T and CD8 + T cells, and then analyzed in conjunction with clinical factors. Results:The positive rates of total PBMCs to LMP1 and LMP2 in NPC patients were different. The positive rate of LMP1 specific CD4 + T cells was statistically higher in stage T 3-T 4 NPC than that in stage T 1-T 2 (51.0% vs. 10.0%, P=0.042). There were also differences in the expression of cytokines between LMP1 and LMP2, CD4 +T cells and CD8 +T cells. Survival analysis showed the 2-year and 3-year overall survival (OS) rates were 91.5% and 88.2%, and the 2-year and 3-year progression-free survival (PFS) rates were 83.3% and 75.3%. Univariate analysis suggested that smoking history, male and LMP1 stimulated IL-13 positive expression in CD4 + T cells affected the disease progression ( P=0.026, 0.045 and 0.006); multivariate analysis showed LMP1 stimulated IL-13 positive expression in CD4 + T cells and smoking history were the independent prognostic factors affecting PFS ( P=0.017, 0.019). Conclusions:LMP1 and LMP2 generate specific T-cell immune response in PBMCs of NPC patients, with differential expression in two T-cell subsets. LMP1 and LMP2 specific T cell immune response is associated with primary tumor size and metastatic lymph node volume. LMP1 stimulated IL-13 positive expression in CD4 + T cells and smoking history affects the disease progression.

BCG vaccine is one of the most widely used vaccines in human history, with tens of billions of doses administered annually over the past century as an important means of preventing tuberculosis. However, BCG is also used for non-traditional purposes of prevention and treatment, such as bladder cancer immunotherapy. In addition to cancer immunotherapy, BCG is increasingly found to be helpful for a variety of immune diseases, including multiple sclerosis, typeⅠdiabetes, and some atopic diseases. It also can protect against non-tuberculous mycobacterium infections, viral infections and even COVID-19. This allogenic protective effect lies in the BCG vaccine's ability to alter immune set points through allogenic T cell immunity, as well as in the epigenetic and immunological effects of metabolomic changes in innate immune cells, a process known as ^“training immunity^”. This paper summarizes the anti-TB effect of BCG and focuses on its heterologous protection and related mechanism.

Objective:To evaluate the safety and clinical efficacy of AngioJet pharmacomechanical thrombectomy (APMT) in rescue treatment for patients with acute massive pulmonary embolism (AMPE) after unsuccessful thrombolysis with urokinase (UK).Methods:From June 2016 to June 2018, the clinical data of 16 AMPE patients underwent APMT after unsuccessful thrombolysis with UK were collected. For these patients, the therapy was discontinued and replaced with APMT adjunctive low-dose thrombolysis with UK. Heart rate (HR), systolic blood pressure (SBP), arterial partial pressure of oxygen (PaO 2), pulmonary artery pressure (PAP), CT obstruction index (CTOI) and therapy replacement safety were evaluated. The pared-samples t-test was used to analyze quantitative data before and after treatment. Results:All 16 patients completed APMT procedure. PAP posterior was lower than prior treatment ( P<0.05). The average adjunctive thrombolysis duration of UK was (3.25±1.78) d, HR, SPB, PaO 2 after APMT were significantly improved ( P<0.01). CTOI before and after APMT were (26.81±14.86)% and (11.56±3.26)%, respectively, and the difference was statistically significant ( t=3.435, P<0.01). Symptoms and signs of pulmonary embolism were significantly improved after treatment. The complications associated with APMT occurred in 2 patients with bradyarrhythmia, 2 patients with chest discomfort and 2 patients with hemoglobinuria. There were no statistically significant difference between the biochemistry indexes before and after APMT treatment ( P>0.05). Moreover, no major bleeding occurred during thrombolysis procedure, and minor bleeding complications occurred only in two cases. Conclusions:APMT adjunctive low-dose UK thrombolysis for rescue treatment of AMPE patients after unsuccessful thrombolysis with UK is relatively safe and effective. It can remove pulmonary artery thrombus rapidly, and improve clinical symptoms and signs of PE.

Objective: To investigate the safety and clinical efficacy of comprehensive endovascular treatment for acute deep vein thrombosis(DVT)in elderly patients. Methods: Clinical data of 94 elderly patients who underwent endovascular treatment from June 2013 to June 2016 were retrospectively analyzed.All patients underwent inferior vena cava filter implantation(IVCF). Of them, 57 patients initially underwent thrombectomy and subsequently received the adjunctive catheter-directed thrombolysis(CDT)(Group A)and 37 cases underwent CDT(Group B). Clinical efficacy and safety of treatments in the two groups were examined. Results: Among the 94 patients, 88 cases had retrievable IVCF, and the retrieval rate was 94.3%(83/88). There were significant differences in total infusion time(73.92±31.68 h vs.156.2±30.2 h)and total doses of infused thrombolytic agents(180.71±44.83 million unit vs.355.0±96.0 million unit)between Groups A and B(P<0.05). There was a significant difference in average hospitalized time between Groups A and B(9.4±2.4 d vs.12.8±4.3 d, t=-4.99, P<0.01). There was no significant difference in clinical efficacy between Groups A and B(χ²=1.263, P>0.05). Fifty-six patients were treated with angioplasty(PTA), 34 of them were combined with stent implantation, and there was no difference between the two groups(χ²=1.128, P>0.05). Neither of the two groups saw serious complications.The incidence of minor hemorrhage was 9.6%(9/94), including 2 cases and 7 cases in Group A and Group B respectively, and the difference was statistically significant(χ²=4.503, P=0.034). The average follow-up time was 16.7±8.3 months in the 94 patients, and the stent patency rate was 91.2%(31/34). Doppler ultrasonography results at the last follow-up showed that the reverse flow rate of the valve was 20.2%(19/94), the occurrence rates of post-thrombotic syndrome(PTS)were 24.6%(14/57)and 29.7%(11/37)in Group A and Group B respectively, and the difference was not statistically significant(χ²=0.307, P=0.580). Patients in the mild, moderate and severe stages assessed by Villata scoring were 9 vs.6, 4 vs.5, 0 vs.1 in Group A and Group B respectively, and the differences were not statistically significant(χ²=0.007 and 0.205, P>0.05). Conclusions It is safe and effective for elderly patients with DVT when timely and appropriate the treatment strategies are chosen and comprehensive approaches including IVCF, anticoagulation, endovascular CDT, thrombectomy, PTA and stent implantation are used.

Compared with age-matched controls,mild cognitive impairment (MCI) populations are at a higher risk of developing Alzheimer's disease (AD).There is no consensus that any pharmacological treatment can improve MCI,thus it is plausible to turn attention to cognitive interventions.This paper reviewed the prior researches on cognitive stimulation,cognitive training,and cognitive rehabilitation for MCI based on the categories defined by Clare and Woods in order to clarify the effect of these interventions on improving cognitive function in MCI individuals.The results indicate that cognitive interventions may improve multiple cognitive domains including memory performance,executive functions,processing speed,attention,and social functions in adults with MCI,while the mechanism remains unclear.It suggested that further studies should examine the mechanism of cognitive intervention by applying neuroscience technology and strengthening the control of heterogeneity of the etiologies and symptoms of MCI,and improve the clinical effect by combining cognitive stimulation,cognitive training,and cognitive rehabilitation.