ObjectiveTo explore the effect and mechanism of Sishenjian on synovial lesions induced by monosodium iodoacetate （MIA） in rats with knee osteoarthritis （KOA）. MethodSixty female Sprague-Dawley （SD） rats were randomly divided into the following six groups： normal group， model group， celecoxib group， and high-， medium-， and low-dose Sishenjian group. The KOA rat model was established by intra-articular injection of MIA. Celecoxib （18 mg·kg^-1） and Sishenjian （14.4， 7.2， 3.6 g·kg^-1） were administered by gavage according to the groups. All rats were euthanized after four weeks of continuous administration. The transverse diameter of the bilateral knee joints of rats was measured， and gross observation of the knee joint was performed. Pathological changes in knee joint synovial tissue were observed by hematoxylin-eosin （HE） staining and picrosirius red staining. Immunohistochemistry （IHC） was used to detect the expression of vascular endothelial growth factor A （VEGFA） in synovial tissue. The levels of inflammatory cytokines in the joint synovial fluid were detected by enzyme-linked immunosorbent assay （ELISA）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the expression of mRNA and proteins related to the transforming growth factor-β₁ （TGF-β₁）/Smad2/3 pathway in knee joint synovium. ResultCompared with the normal group， the transverse diameter of the knee joint in the model group significantly increased （P<0.01）. Compared with the model group， the transverse diameter of the knee joint in rats of each Sishenjian group significantly decreased （P<0.01）. Compared with the normal group， the expression levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the knee joint synovial fluid of model group significantly increased （P<0.01）. Compared with the model group， the expression levels of IL-1β and TNF-α in the knee joint synovial fluid of rats in each Sishenjian group significantly decreased （P<0.01）. Compared with the normal group， the expression levels of TGF-β₁， Smad2/3， phosphorylation（p）-Smad2/3， type Ⅰ collagen α1 （ColⅠ_α1）， type Ⅲ collagen α1 （ColⅢ_α1）， VEGFA proteins and TGF-β₁， Smad2/3， ColⅠ_α1， ColⅢ_α1 mRNA in knee joint synovium of model group significantly increased （P<0.01）. Compared with the model group， the expression levels of TGF-β₁， Smad2/3， phosphorylation （p）-Smad2/3， ColⅠ_α1， ColⅢ_α1， VEGFA proteins and TGF-β₁， Smad2/3， ColⅠ_α1， ColⅢ_α1 mRNA in knee joint synovium of rats in each Sishenjian group significantly decreased （P<0.05， P<0.01）. ConclusionSishenjian can inhibit synovial inflammation and angiogenesis， and may become a potential drug for treating synovial lesions in KOA by regulating the TGF-β₁/Smad2/3 pathway.

Objective:To evaluate the value of serum protein electrophoresis in the diagnosis of periprosthetic joint infection (PJI) after hip and knee arthroplasty.Methods:The data of 171 patients who underwent one side hip or knee revision surgery in the affiliated Hospital of Qingdao University from August 2013 to June 2019 were analyzed retrospectively. According to the reasons for revision, 55 patients in PJI group, 29 males and 26 females, aged 67.38±9.60 years, 26 hips and 29 knees, were classified as Tsukayama type IV; Aseptic loosening (AL) group consisted of 116 patients, 67 males and 49 females, aged 69.69±9.20 years, 97 hips and 19 knees .The ratios of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), D-dimer, fibrinogen, serum total protein, serum albumin, serum globulin and serum protein electrophoresis bands in the two groups were statistically analyzed. The sensitivity and specificity of each index were calculated according to the receiver operating characteristic (ROC) curve, and the diagnostic value was compared according to the area under the curve (AUC).Results:There was no significant difference in age, sex or body mass index (BMI) between PJI group and AL group ( P>0.05), but there was significant difference in joint type with 26 hips and 29 knees in PJI group, 97 hips and 19 knees in AL group (χ 2=24.41, P<0.001). The proportion of α1 globulin band was 6.40% (5.30%, 8.10%) in PJI group, which increased significantly compared to 4.20% (3.90%, 4.80%) in AL group ( H=453.50, P<0.001). Albumin band was 49.00% (44.00%, 52.20%) in PJI group, which decreased significantly compared to 54.35% (51.25%, 56.70%) in AL group ( H=4 954.00, P<0.001). The AUC of CRP, ESR, D-dimer, fibrinogen, albumin band and α1 globulin band were 0.87[95% CI (0.80, 0.93)], 0.88[95% CI (0.82, 0.94)], 0.67[95% CI (0.58, 0.76)], 0.87[95% CI (0.82, 0.93)], 0.78[95% CI (0.70, 0.85)] and 0.87[95% CI (0.81, 0.93)], respectively. Conclusion:Albumin bands and α1 globulin bands in serum protein electrophoresis had high diagnostic value for PJI, and the accuracy of α1 globulin bands was as good as that of routine inflammatory markers such as CRP and ESR.

【Objective】 To explore the characteristics of white matter degeneration in amyotrophic lateral sclerosis (ALS) patients with different onset and spreading patterns by using diffusion tensor imaging (DTI). 【Methods】 We enrolled 86 ALS patients and 44 healthy controls. The patients were divided into bulbar- and spinal-onset subgroups according to their onset site, as well as horizon, vertical, interpose/skip, and caudal-rostral subgroups based on the spreading direction of the involved regions. The white matter fiber tracts corresponding to the motor network were set as the region of interest. We used tract-based spatial statistics to evaluate differences between the above groups and the normal controls, with family-wise error (FWE) correction and P<0.05 as statistical significance. 【Results】 The white matter degeneration of ALS patients with bulbar onset was mainly limited to the corona radiation part of the corticospinal tract, while those with spinal onset showed extensive degeneration of corticospinal tract and corpus callosum Ⅲ area (FWE correction, P<0.05). In patients with horizontal and vertical dissemination, decreased integrity of the entire corticospinal tract was found, with patients in the latter group showed extra degeneration in the Ⅲ part of the corpus callosum. Restricted degeneration of the corticospinal tract within bilateral corona radiata was detected in patients with caudal-rostral and interposed/skip spreading pattens (FWE correction, P<0.05). 【Conclusion】 Different onset and disease spread patterns of ALS patients correspond to divergent brain degeneration patterns. The diagnosis, treatment, and management of ALS should fully consider the heterogeneity of the disease.

【Objective】 To investigate cortical thickness changes in the face-head region of the primary motor cortex (PMC) and its effect on survival in amyotrophy lateral sclerosis (ALS) patients. 【Methods】 A retrospective analysis was performed on 105 ALS patients who underwent head MRI scan at the same time. The A4hf (face-head) region of PMC was used as the region of interest (ROI). According to clinical symptoms, patients were divided into two groups: bulbar involvement and non-bulbar involvement. The differences of clinical features and cortical thickness in ROI were analyzed. According to the symptoms of bulbar palsy, physical examination of nervous system and EMG of tongue muscle, the patients with bulbar palsy were divided into lower motor neuron (LMN), upper motor neuron (UMN) and LMN+UMN groups. The differences of bulbar subgroup score and ROI of cortical thickness were analyzed. Age at onset, body mass index, delayed time of diagnosis, bulbar subgroup score, and ROI cortical thickness were included in survival analysis. 【Results】 ① The ROI cortical thickness was significantly lower in bulbar involvement group than non-bulbar involvement group (-0.198±0.87 vs. 0.235±0.95, P=0.017). ② There were no significant differences in the bulbar subgroup scores or cortical thickness of ROI between LMN, UMN and LMN+UMN groups (P>0.05). ③ Survival analysis showed age of onset (HR=3.296, 95% CI:1.63-6.664, P=0.001), delayed time of diagnosis (HR=0.361, 95% CI:0.184-0.705, P=0.003), bulbar subgroup score (HR 0.389, 95% CI:0.174-0.868, P=0.021), and ZRE_ROI cortical thickness (HR=2.309, 95% CI:1.046-5.096, P=0.038) were independent influencing factors of ALS survival. 【Conclusion】 Cortical thickness in A4hf (face-head) region can more objectively reflect UMN signs of region bulbar. In addition to age of onset and delayed time of diagnosis, bulbar subgroup score and cortical thickness of face-head region are also independent influencing factors, and cortical thinning in face-head region is a protective factor for survival of ALS patients.

【Objective】 To investigate changes in thalamus structure and function and their associations with cognitive impairment in patients with amyotrophic lateral sclerosis (ALS). 【Methods】 3D high-resolution structural imaging and resting-state fMRI were applied in 78 ALS patients and 49 healthy volunteers. The shape of the thalamus was assessed using a vortex analysis and functional connectivity between the thalamus subregion and cortex was evaluated by a seed-based correlation analysis. Partial correlation analysis was used to evaluate the correlation between focal thalamus alterations and clinical assessments. 【Results】 Compared with the control group, vertex analysis showed significant atrophy in the prefrontal and temporal subregions of bilateral thalamus in the ALS group. Patients exhibited increased functional connectivity of motor-sensory ROI with the right motor cortex, of temporal ROI with the bilateral lateral occipital cortex, precuneus and right temporal subregion. In contrast, decreased function connectivity was found mainly between temporal ROI and paracingulate gyrus, left dorsomedial prefrontal lobe and left caudate. Partial correlation analysis showed that the functional connectivity of the precuneus, paracingulate cortex, left caudate nucleus and left prefrontal lobe was correlated with multiple cognitive performances. 【Conclusion】 Selective damage of thalamic structure and function in ALS plays an important role in cognitive and behavioral disorders.

【Objective】 The involvement of upper motor neuron (UMN) degeneration is crucial to the diagnosis of amyotrophic lateral sclerosis (ALS). This study aimed to determine objective and sensitive UMN degeneration markers for an accurate and early diagnosis. 【Methods】 A total of 108 ALS patients and 90 age- and gender-matched control subjects were recruited from ALS Clinic of The First Affiliated Hospital of Xi’an Jiaotong University. The motor homunculus cortex thickness data in MRI were collected from all the participants. The clinical characteristics and UMN clinical examination of bulbar, cervical, thoracic and lumbosacral regions were collected from the ALS patients. 【Results】 Cortical thickness was significantly thinner in the ALS group than in the control group in bilateral head-face-bulbar and upper-limb areas (P<0.05). The cortical thickness of the global UMN positive group was significantly thinner than that of control groups in bilateral head-face-bulbar and upper-limb areas (P<0.05). The cortical thickness of the UMN positive group in the corresponding region was significantly thinner than that of control groups in bilateral head-face-bulbar and upper-limb areas (P<0.05). 【Conclusion】 The thinning of the motor homunculus cortex can be used as an objective marker of UMN involvement in ALS patients in clinical practice.

Hepatocellular carcinoma (HCC) has an insidious onset, and most patients are in the advanced stage when attending the hospital and thus lose the opportunity for radical surgical resection, which results in the poor prognosis of patients. With the development of clinical treatment, the treatment of advanced HCC has gradually transitioned from the relatively single and limited treatment options in the past to the new model of comprehensive treatment. In recent years, immunotherapy, represented by immune checkpoint inhibitors (ICIs), has become widely used in clinical practice. At present, a number of clinical studies have been conducted for immunotherapy combined with local and targeted antitumor therapy, and in particular, ICIs combined with targeted therapy have become a research hotspot in the field of HCC treatment. This article reviews the research advances in immunotherapy for the treatment of HCC.

Objective:To evaluate the accuracy of the domestic "Skywalker" surgical robot in implementing personalized lower limb alignment reconstruction scheme in total knee arthroplasty (TKA) and the short-term clinical outcome of robotic assisted TKA.Methods:From September 2020 to January 2021, the data of patients who received surgical robot assisted TKA in 5 clinical centers in China (Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Southwest Hospital affiliated to Third Military Medical University, The Affiliated Hospital of Qingdao University, The First Affiliated Hospital of Chongqing Medical University and Yantai Yuhuangding Hospital, and Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine was the group leader) were prospectively collected and retrospectively analyzed. There were 24 males and 82 females with an average age of 67.6±7.3 years, (range 45-80 years); Average body mass index 26.42±4.31 kg/m 2, all the operation were performed by "Skywalker" surgical robot system according to preoperative design based on CT. The operation time, intraoperative blood loss, hospitalization days and postoperative complications were recorded, and the imaging indexes including hip-knee-ankle (HKA), lateral distal angle of femur (LDFA) and medial proximal angle of tibia (MPTA) measured before and after the operation, implant model indexes (preoperative planning implant model and postoperative implant model) and short-term clinical efficacy indexes [Western Ontario and McMaster Universities (WOMAC) osteoarthritis index] pain score, stiffness score, joint function score, total score and SF-12 score before and 3 months after the operation) were compared. Results:The average follow-up period was 109.60±9.80 d, (range 95-143 d). The average operation time of 106 patients was 105.30±23.22 min; The average intraoperative blood loss was 141.70±58.33 ml; The average length of hospitalization was 5.82±2.80 d. One patient had ischemic stroke after operation, and one patient had abnormal liver function after operation. According to the judgment of the investigator, all of them were not related to the operation. The actual angle error is the difference between the preoperative planning angle and the postoperative measurement angle. The absolute error of 99.1% (105/106) of the HKA angle was within 3°, 90.8% (69/76) of LDFA, 98.7% (75/76) of the MPTA. In 45 patients in one center where data were available, the actual implant models used in all patients were consistent with the preoperative planning size, and there were only differences in version selection such as Asian condyle. WOMAC pain score, joint function score, total score was improved from 7.34±2.85, 25.10±9.85, 34.75±13.02 to 3.34±2.66, 14.68±9.64, 18.66±13.49 before and after operation, respectively, which were statistically significant ( P<0.001) and SF-12 physiological score and psychological score were improved form 27.24±6.42, 30.68±8.26 to 38.83±5.74, 39.36±7.85 before and after operation, respectively, which were statistically significant ( t=7.33, P<0.001; t=4.53, P=0.043). Conclusion:Domestic surgical robot system "Skywalker" can assist the surgeon to achieve accurate and personalized reconstruction of lower limb alignment and achieve satisfactory short-term clinical outcomes. The long-term clinical outcomes of personalized reconstruction and survival rate of implant still need to be further studied.

Objective To investigate the effect of different concentrations of Echinococcus multilocularis secretion antigen (Em-sAg) on the phenotype and function of mouse bone marrow-derived dendritic cells (BMDCs) induced by lipopolysaccharide (LPS). Methods The bone marrow precursor cells isolated from the mouse bone marrow cavity were stimulated by mouse recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) to form BMDCs, and then cell morphology was observed under an inverted microscope. After the purity of BMDCs was identified by flow cytometry, BMDCs were divided into control group, positive control group (LPS 1 μg/ml), LPS+3 mg/ml Em-sAg group, LPS+1.5 mg/ml Em-sAg group, LPS+0.75 mg/ml Em-sAg group, and LPS+0.375 mg/ml Em-sAg group. Flow cytometry was used to measure the expression of BMDC surface molecules (CD80, CD86, and MHC-Ⅱ molecules) in each group, and ELISA was used to measure the expression level of the cytokine IL-12p70. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Observation under an inverted microscope showed that after 8-10 days of culture, the cells had burr-like protrusions and were in a state of complete suspension. Flow cytometry showed that the positive rate of CD11c was above 70% and most of the cultured cells were identified as BMDCs based on this. Flow cytometry further showed that compared with the control group, the LPS group had significant increases in the cell molecules CD80, CD86, and MHC-Ⅱ on surface (all P < 0.05); compared with the LPS group, the LPS+3 mg/ml Em-sAg group, the LPS+1.5 mg/ml Em-sAg group, the LPS+0.75 mg/ml Em-sAg group, and the LPS+0.375 mg/ml Em-sAg group had a significant reduction in CD80 ( F =34.870, P < 0.001), while there were no significant reductions in CD86 and MHC-Ⅱ( P > 0.05). ELISA showed that there was a significant difference in the level of IL-12 p70 between groups ( F =73.140, P < 0.05); compared with the control group, the LPS group had a significant increase in the expression level of IL-12p70 after stimulation ( P < 0.05); compared with the positive control group, the LPS+3 mg/ml Em-sAg group, the LPS+1.5 mg/ml Em-sAg group, the LPS+0.75 mg/ml Em-sAg group, and the LPS+0.375 mg/ml Em-sAg group had a significant reduction in the expression level of IL-12p70 ( P < 0.05), and the degree of reduction in the pro-inflammatory factor IL-12p70 increased with the increase in the concentration of Em-sAg. Conclusion Different concentrations of Em-sAg can inhibit LPS-induced maturity of BMDCs and the expression of the pro-inflammatory cytokine IL-12p70.

Objective:To evaluate changes of large-scale motor and cognition related networks′ function in patients with amyotrophic lateral sclerosis (ALS) and their relationship with corresponding clinical symptoms using independent component analysis combined with dual regression.Methods:Forty-six ALS patients (ALS group) who were treated in the First Affiliated Hospital of Xi′an Jiaotong University from January 2014 to June 2016 were prospectively collected, and 40 gender- and age-matched normal controls (control group) were recruited. All the participants completed the motor and multi-dimensional cognitive function evaluation[including Mini-mental State Examination (MMSE), Montreal Cognitive Assessment (MoCa), Semantic Fluency (SVF), Phonological Fluency (PVF), Digital Span Forward (DS_F), Digital Span backward (DS_B), frontal assessment battery (FAB), Wisconsin Card Sorting Test (WCST) for classification accuracy, classification error, persistent response classification, persistent error response classification, non-persistent error classification and Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA)]. The resting-state MRI data of all subjects were collected, and independent component analysis was carried out with multivariate interpretation linear optimization independent component decomposition. Dual regression analysis was performed to compare network differences between groups based on voxel level in sensorimotor network (SMN), default mode network (DMN) and frontal-parietal control network (FPCN). Multivariate covariance analysis was used to evaluate the differences of different cognitive function indexes between ALS group and normal control group, the comparison of brain network differences between the two groups was performed by nonparametric permutation test, corrected by family-wise error (FWE), P<0.008 as the statistical threshold; partial correlation and multiple linear regression were used to evaluate the relationship between changes in functional connectivity of different brain regions and cognitive functions. Results:The scores of MMSE, MoCa, SVF, PVF, DS_B, and classification accuracy were lower, while the number of error classifications, the non-persistent error classifications, HAMD and HAMA scores were higher in patients with ALS group than those in control group ( P<0.05). After adjusting for gender and age, there was no significant difference in the SMN between ALS group and control group (FWE correction, P>0.008). Compared with control group, patients with ALS showed increased functional connectivity in the left ventromedial prefrontal cortex (vmPFC) of the DMN, and decreased functional connectivity in the right anterior cingulate gyrus (ACC), the right posterior cingulate gyrus, the left inferior parietal lobule and the left inferior temporal gyrus of the FPCN (FWE correction, P<0.008). Increased functional connectivity of the vmPFC in ALS patients was negatively correlated with MoCa score ( r=-0.565, P<0.001), FAB score ( r=-0.373, P=0.015) and the classification accuracy of WCST ( r=-0.478, P=0.002), SVF ( r=-0.458, P=0.002) scores, and was positively correlated with the number of error classifications and HAMA scores ( r=0.416, P=0.007; r=0.388, P=0.011). Decreased functional connectivity were detected in multiple brain regions of FPCN, and the functional connectivity of the ACC was positively correlated with the DS_F ( r=0.341, P=0.027) and MMSE ( r=0.351, P=0.023). The effect of increased vmPFC functional connectivity accounted for 49.6% changes on MoCa score; 35.2% and 34.2% for FAB and HAMA respectively. While the impact of increased functional connectivity in the vmPFC was less than 30% on classification accuracy, classification error of WCST and SVF. The reduced functional connectivity in the ACC accounted for 37.7% impact on the DS_F score. Conclusions:Large-scale brain network changes are dominated by the frontotemporal core brain regions in ALS patients. DMN and FPCN network changes are closely related to the clinical cognitive performance of ALS patients.