BACKGROUND:Rheumatoid arthritis is a chronic autoimmune disease.Early diagnosis is crucial for preventing disease progression and for effective treatment.Therefore,it is of significance to investigate the diagnostic characteristics and immune cell infiltration of rheumatoid arthritis. OBJECTIVE:Based on the Gene Expression Omnibus(GEO)database,to screen potential diagnostic markers of rheumatoid arthritis using machine learning algorithms and to investigate the relationship between the diagnostic characteristics of rheumatoid arthritis and immune cell infiltration in this pathology. METHODS:The gene expression datasets of synovial tissues related to rheumatoid arthritis were obtained from the GEO database.The data sets were merged using a batch effect removal method.Differential expression analysis and functional correlation analysis of genes were performed using R software.Bioinformatics analysis and three machine learning algorithms were used for the extraction of disease signature genes,and key genes related to rheumatoid arthritis were screened.Furthermore,we analyzed immune cell infiltration on all differentially expressed genes to examine the inflammatory state of rheumatoid arthritis and investigate the correlation between their diagnostic characteristics and infiltrating immune cells. RESULTS AND CONCLUSION:In both rheumatoid arthritis and normal synovial tissues,we identified 179 differentially expressed genes,with 124 genes up-regulated and 55 genes down-regulated.Enrichment analysis revealed a significant correlation between rheumatoid arthritis and immune response.Three machine learning algorithms identified LRRC15 and MICB as potential biomarkers of rheumatoid arthritis.LRRC15(area under the curve=0.964,95%confidence interval:0.924-0.992)and MICB(area under the curve=0.961,95%confidence interval:0.923-0.990)demonstrated strong diagnostic performance on the validation dataset.The infiltration of 13 types of immune cells was altered,with macrophages being the most affected.In rheumatoid arthritis,the majority of proinflammatory pathways in immune cell function were activated.Immunocorrelation analysis revealed that LRRC15 and MICB had the strongest correlation with M1 macrophages.To conclude,this study identified LRRC15 and MICB as potential diagnostic markers for rheumatoid arthritis,with strong diagnostic performance and significant correlation with immune cell infiltration.Machine learning and bioinformatics analysis deepened the understanding of immune infiltration in rheumatoid arthritis and provided new ideas for the diagnosis and treatment of rheumatoid arthritis.

The liver has diverse functions such as metabolism， detoxification， and immune defense， and the maintenance of hepatic microenvironment homeostasis is crucial for overall bodily health. The hepatic microenvironment consists of the components such as parenchymal cells， non-parenchymal cells， and non-cellular components. Chronic inflammatory responses induced by various etiological factors may promote the formation and progression of liver fibrosis. During the dynamic progression of liver fibrosis， from the early to advanced stages， various components within the hepatic microenvironment undergo a series of changes， which can promote the malignant progression of liver fibrosis. An in-depth exploration of the mechanisms underlying such changes in each component of the liver fibrosis microenvironment is of great significance for understanding the pathogenesis of liver fibrosis and discovering potential treatment strategies.

Objective:To explore the clinical effectiveness of a self-designed robot reduction system for femoral intertrochanteric fractures.Methods:A retrospective study was conducted to analyze the 57 patients with intertrochanteric fracture who had been treated at Department of Orthopedics, The Fourth Affiliated Central Hospital of Tianjin Medical University from June 2022 to February 2023. The patients were divided into a robot group (using the self-designed robot reduction system to assist intramedullary nailing) and a traction bed group (using a traction bed to assist intramedullary nailing) based on their fracture reduction method. The robot group: 31 patients, 11 males and 20 females, with an age of (78.7±9.3) years; 16 left and 15 right sides; 17 cases of type 31-A1, 12 cases of type 31-A2 and 2 cases of type 31-A3 by the AO/OTA classification. The traction bed group: 26 patients, 12 males and 14 females, with an age of (78.7±7.7) years; 13 left and 13 right sides; 16 cases of type 31-A1, 9 cases of type 31-A2 and 1 cases of type 31-A3 by the AO/OTA classification. The 2 groups were compared in terms of reduction and operation time, intraoperative blood loss, fluoroscopy frequency, reduction quality, and VAS and Harris score at preoperation, 1 week and 6 months postoperation.Results:The 2 groups were comparable due to insignificant differences in their preoperative general data ( P>0.05). The robot group was significantly better than the traction bed group in reduction time [(4.4±2.2) min versus (9.4±3.2) min], operation time [(29.0±13.5) min versus (49.3±13.3) min], intraoperative blood loss [(76.5±30.5) mL versus (115.0±38.4) mL], fluoroscopy frequency [(10.2±2.6) times versus (14.8±3.2) times], and good/excellent rate of reduction [80.6% (25/31) versus 50.0% (13/26)] ( P<0.05). All patients were followed up for (6.8±0.3) months. Respectively, the VAS scores at preoperation and 6 months postoperation was (6.2±1.3) and (2.4±0.8) points for the robot group, and (6.3±1.3) and (2.7±0.8) points for the traction bed group, showing no statistically significant differences between the 2 groups ( P>0.05). However, the VAS score was (3.3±1.2) points for the robotic group and (4.8±1.5) points for the traction bed group at 1 week postoperation, showing a statistically significant difference between the 2 groups ( P<0.001). Respectively, the Harris scores at preoperation and 6 months postoperation were (35.3±3.0) and (88.7±3.4) points for the robot group, and (35.6±2.9) and (87.2±3.5) points for the traction bed group, showing no statistically significant differences between the 2 groups ( P>0.05). However, the Harris score was (57.3±3.7) points for the robotic group and (46.7±2.8) points for the traction bed group at 1 week postoperation, showing a statistically significant difference between the 2 groups ( P<0.05). The patient satisfaction rates in the robot and traction bed groups were 96.8% (30/31) and 92.3% (24/26), respectively, showing no statistically significant difference ( P>0.05). Conclusion:Our self-designed robot reduction for femoral intertrochanteric fractures can effectively shorten reduction and operation time, reduce bleeding and fluoroscopy frequency, and enhance anatomical reduction.

Artemsia argyi Levl.et Vant is a commonly used Chinese herbal medicine and moxibustion raw material plant,so far has more than two thousand years of medicinal history,as one of the most commonly used Chinese medicinal materials.The incopat patent database was used to search the worldwide patent data of the last 20 years,and a total of 25279 argyi related patents were retrieved.The pattern of argyi patents was analyzed from the perspectives of global application trend,main technical fields,national economy composition,applicant ranking,patent value and other aspects by means of graph combination.The analysis shows that the innovation and development of argyi is in the stage of rapid development;The medical,Chinese patent medicine,cosmetics and physiotherapy of argyi are the hot research and development of current technology;There are a large number of patents related to argyi in the world,but they are mainly distributed in China and South Korea.Among them,the number of patents related to argyi in China reaches 20381,far higher than that in other countries,but the number of high-value patents is not very large,and the value and quality of patents are still insufficient compared with other countries.From the perspective of the current development trend of argyi,with the deepening of clinical application recognition and scientific research of argyi,there is a large patent space in the field of argyi.Patent applicants can formulate corresponding patent application strategies according to the global development opportunities,technological development status and existing weaknesses.

Renal tubular secretion mediated by organic anion transporters(OATs)and the multidrug resistance-associated protein 4(MRP4)is an important means of drug and toxin excretion.Unfortunately,there are no biomarkers to evaluate their function.The aim of this study was to identify and characterize an endogenous biomarker of the renal tubular OATs-MRP4 channel.Twenty-six uremic toxins were selected as candidate compounds,of which kynurenic acid was identified as a potential biomarker by assessing the protein-binding ratio and the uptake in OAT1-,OAT3-,and MRP4-overexpressing cell lines.OAT1/3 and MRP4 mediated the transcellular vectorial transport of kynurenic acid in vitro.Serum kynurenic acid concentration was dramatically increased in rats treated with a rat OAT1/3(rOAT1/3)inhibitor and in rOAT1/3 double knockout(rOAT1/3-/-)rats,and the renal concentrations were markedly elevated by the rat MRP4(rMRP4)inhibitor.Kynurenic acid was not filtered at the glomerulus(99％of albumin binding),and was specifically secreted in renal tubules through the OAT1/3-MRP4 channel with an appropriate affinity(Km)(496.7 μM and 382.2 μM for OAT1 and OAT3,respectively)and renal clearance half-life(ti/2)in vivo(3.7±0.7 h).There is a strong correlation in area under the plasma drug concentration-time curve(AUC0-t)between cefmetazole and kynurenic acid,but not with creatinine,after inhibition of rOATs.In addition,the phase of increased kynurenic acid level is earlier than that of creatinine in acute kidney injury process.These results suggest that albumin-bound kynurenic acid is an appropriate endogenous biomarker for adjusting the dosage of drugs secreted by this channel or predicting kidney injury.

Objective:This study aimed to observe the dynamic changes of NUP98::NSD1 expression before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Moreover, the clinical value of measurable residual disease (MRD) was analyzed.Methods:Sixteen AML patients who were diagnosed with the NUP98::NSD1 fusion gene and received allo-HSCT at Peking University People’s Hospital were included. The NUP98::NSD1 fusion gene and leukemia-associated immunophenotype (LAIP) were monitored before and after transplantation to evaluate their MRD status.Results:The median follow-up time for all patients was 526 days (139-1136 days) , with four patients (25.0%) experiencing hematological recurrence at a median of 474 days (283-607 days) after transplantation. Three patients (18.8%) died, two of whom (12.5%) died of leukemia recurrence. The median expression level of NUP98::NSD1 in newly diagnosed patients with complete data was 78.5% (18.9%-184.4%) at the time of initial diagnosis. The recurrence rate was higher in NUP98::NSD1-positive patients after transplantation, with 44.4% of patients experiencing recurrence, whereas no recurrence occurred in NUP98::NSD1-negative patients after transplantation. The area under the receiver operating characteristic curve predicted by the NUP98::NSD1 level after transplantation was 1.000 (95% confidence interval: 1.000-1.000, P=0.003) . Among the four patients with recurrence, NUP98::NSD1 was more sensitive than flow cytometry residual (FCM) and Wilms’ tumor gene 1 (WT1) . Conclusions:The NUP98::NSD1 fusion gene can be used to evaluate the MRD status of allo-HSCT. NUP98::NSD1-positive patients after transplantation have a high relapse rate and poor prognosis. NUP98::NSD1 was more sensitive than FCM and WT1 in predicting posttransplant relapse.

ObjectiveTo observe the effects of Fuzitang （FZT） on the proliferation of MH7A cells， the human rheumatoid arthritis synovial fibroblasts， and the expression of miR-155 and explore its anti-rheumatoid arthritis mechanism. MethodMH7A cells were cultured in vitro and divided into a blank group， high- （25 g·L^-1） and low-dose （12.5 g·L^-1） FZT groups， and a positive drug group （hydroxychloroquine， 0.006 25 g·L^-1）. The cell proliferation was detected by cell counting kit-8（CCK-8） method， and the change in the MH7A cell cycle was detected by flow cytometry. The mRNA expression of miR-155 and its downstream genes， including SH2 domain-containing inositol 5-phosphatase-1（SHIP-1）， protein kinase B 3（Akt3）， and mammalian target of rapamycin（mTOR）， was detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression of phosphatidylinositol 3-kinase （PI3K）， Akt3， and mTOR was detected by Western blot. ResultFZT in vitro in a concentration of 6.25 g·L^-1 above could inhibit the proliferation of MH7A cells in the significant dose- and time-effect manner. Compared with the blank group， the FZT groups showed increased proportions of cells in the G₂/M phase （P<0.05）， and the high-dose FZT group showed a decreased proportion of cells in the G₀/G₁ phase （P<0.05）. The arresting effect of FZT on the cell cycle was in a significant dose-effect manner. Compared with the blank group， the FZT groups showed down-regulated miR-155 and mTOR mRNA expression （P<0.05）， and the high-dose FZT group showed up-regulated SHIP1 mRNA expression and down-regulated Akt3 mRNA expression （P<0.05）. Compared with the blank group， the FZT groups showed reduced protein expression of PI3K， Akt3， and mTOR （P<0.05）. ConclusionFZT can significantly inhibit the proliferation of MH7A cells， and the mechanism is related to the promotion of the expression of SHIP-1 and down-regulation of the gene expression of the PI3K/Akt3/mTOR signaling pathway by down-regulating the expression of miR-155.

Objective:To explore the effect of upper limb function exercise based on knowledge, attitude and practice (KAP) in cancer chemotherapy patients with peripherally inserted central catheter (PICC) .Methods:From January to July 2021, convenience sampling was used to select 90 cancer chemotherapy patients with PICC in the Oncology Department of the Yancheng First People's Hospital as the research object. According to the random number table method, the patients were divided into the intervention group and the control group, 45 cases in each. The control group received routine nursing, and the intervention group carried out the upper limb function exercise based on KAP on the basis of the control group. PICC-related complications and self-management ability were compared between the two groups.Results:After 14, 21, and 28 days of catheterization, the incidence of upper limb venous thrombosis was lower than that in the control group, and the difference was statistically significant ( P<0.05) . There was no significant difference in the incidence of catheter-related complications between the intervention group and the control group ( P>0.05) . The self-management ability score of the intervention group was higher than that of the control group, and the difference was statistically significant ( P<0.05) . Conclusions:KAP-based upper limb exercise can prolong APTT and PT in cancer patients with PICC, which is beneficial to improve the axillary vein blood flow rate and average blood flow rate in cancer patients with PICC, reduce the incidence of venous thrombosis and the self-management ability of patients.

[Abstract] Objective: Elevated levels of soluble PD-L1 (sPD-L1) are associated with worse prognosis of renal cell carcinoma and multiple myeloma. However, the regulatory roles and functions of sPD-L1 in advanced melanoma are not fully understood. This study was designed to evaluate the association between circulating sPD-L1 concentrations and prognosis of patients with advanced acral or mucosal melanoma. Methods: A total of 102 untreated patients with advanced acral and mucosal melanoma admitted to Peking University Cancer Hospital between January 2012 and December 2015 were enrolled in this study. In the meanwhile, peripheral blood samples were obtained from 40 healthy donors. Circulating sPD-L1 concentrations were determined using an enzyme-linked immunosorbent assay. Results: The advanced melanoma cohort included 58 acral melanoma patients and 44 mucosal melanoma patients. The pre-treatment concentration of sPD-L1 (2.91±2.23 ng/ml) in plasma of patients group was elevated as compared with that in healthy donors (0.59 ng/ml). The concentration of sPD-L1 in serum was significantly upregulated in 39/102 (38.2%) patients and significantly associated with increased LDH level (P=0.021) and number of Tregs (P=0.017). The overall survival rates of patients with high or low concentrations of sPD-L1 were statistically different (8.5 months [high level] vs 11.6 months [low level], P=0.022). Conclusion: sPD-L1 concentration is elevated in patients with advanced acral or mucosal melanoma, which may play an important role in predicting prognosis.

[Abstract] Objective: To explore the expression patterns of melanoma lineage antigens and nuclear antigen Ki-67 and their correlations with survival in melanoma patients. Methods: A retrospective analysis was conducted to analyze the pathological data of melanoma patients treated at the Department of Melanoma, Peking University Cancer Hospital from February 2008 to August 2020, mainly including the expression patterns of melanoma lineage antigens (S-100, HMB-45, Melan-A) and Ki-67, demographics, clinical features and survival. The correlation between expression patterns of melanoma lineage antigens, Ki-67 and melanoma-specific survival (MSS) was analyzed. Results: In total, 603 patients were included in this study. The median follow-up time was 47.4 months. The positive rates of S-100, HMB, and Melan-A were 92.8%, 92.1% and 90.0%, respectively. The percentages of patients with melanoma lineage antigen scores (S-100, HMB-45 and Melan-A was scored each, as 1 when positive and 0 when negative) of 0, 1, 2, and 3 were 0.5%, 5.0%, 15.6%, and 78.8%, respectively. The percentages of patients with Ki-67 scores of 0, 1, 2, and 3 were 43.0%, 36.3%, 16.3%, and 4.5%, respectively. Ki-67 was highly expressed in mucosal and progressive melanomas. In a multivariate analysis, Ki-67 expression was an independent prognostic factor for poorer MSS (HR=1.506, 95%CI: 1.248-1.818, P<0.001) as the incidence of MSS event increased by 50% per 25% increase in Ki-67 expression, whereas there was no statistical correlation between melanoma lineage antigen expression and MSS (HR=0.991, 95%CI: 0.759-1.293, P=0.94). Conclusion: High expressions melanoma lineage antigens are ubiquitous in melanoma tissues, and Ki-67 is an independent prognostic factor for MSS.