Objective:Rheumatoid arthritis(RA) is a systemic autoimmune disease,but its etiology is unclear.Therefore,it is urgent to search antigens which is relate to induce this disease,however,there are few reports about the new self-antigens at home and abroad.In this study,we investigate new autoantigen through cloning.Methods: We used antigens in synovium of patients with rheumatoid arthritis as probe,extracted mRNA from synoviocyte,performed cDNA library immunological screening and sequence,and analyzed the conformation and performed Northern blotting.Results: We found that new autoantigen had 36.5% homology with retinoblastoma binding protein 1(RBP1)and it was found that these special protein structure such as AT-rich interaction domain,chromo domain,A+T-hook and TAF homology domain.Therefore,it will be named RBP1-like Protein(Rbik).Rbik RNA is not only expressed in the synovial membrane,but also in the heart,small intestine,muscle and other organs.Conclusion: We report that the discovery of the new autoantibodies to RBP1-like Protein(Rbik)may provide a new possible index and target in diagnosis and therapy.

Tumor-specific promoters can induce high-efficiency and specific expression of exogenous genes in tumor cells. At present, commonly used promoters include alpha-fetoprotein promoter, carcinoembryonic antigen promoter,prostate specific antigen promoter,human telomerase reverse transcriptase promoter and multidrug resistance gene promoter and etc. Dual promoters, enhancer, regulatory element and other physical or chem-ical factors could be used to reconstruct or modify promoters to increase the expression and location of exogenous genes in tumor cells. Tumor-specific promoters play an important role in cancer gene targeted therapy by cou-pling with suicide gene, anti- oncogene, antiseuse nucleic acid, apoptosis gene and RNA interference.

Objective:To clarify whether IL-10 enhanced the M2 phenotype induced by IL-4.Methods:M-CSF induced bone marrow-derived macrophages ( BMDMs) were generated from C57BL/6J mice bone marrow cells.The RNA transcriptional profile was e-valuated using the Mouse Whole Genome.We performed in vitro eosinophil migration assay and in vivo macrophage transfer.Results:The results showed that IL-10 enhanced gene expression of M2a markers induced by IL-4 in M-CSF-induced BMDMs.Moreover,IL-4 and IL-10 synergistically induced CCL24 ( Eotaxin-2) production.Enhanced CCL24 expression was also observed in GM-CSF-induced BMDMs and zymosan-elicited,thioglycolate-elicited and naive peritoneal macrophages.CCL24 was a CCR3 agonist and an eosinophil chemoattractant.In vitro,IL-4+IL-10-stimulated macrophages produced a large amount of CCL24 and increased eosinophil migration, which was inhibited by anti-CCL24 antibody.IL-4+IL-10-stimulated ( but not IL-4 or IL-10 alone) macrophages transferred into the peritoneumof C57BL/6J mice increased eosinophil infiltration into the peritoneal cavity.Conclusion:These results demonstrate that IL-4+IL-10-simulated macrophages have enhanced M2a macrophage-related gene expression,CCL24 production and eosinophil infiltration-inducing activity,thereby suggesting theircontribution to eosinophil-related diseases.

Diabetic kidney disease(DKD)is a chronic kidney disease caused by diabetes,influenced by genetic and environmental factors and their interaction.It is the primary cause of chronic kidney disease and end-stage renal disease.Recent studies have found,as a natural isoquinoline alkaloid,berberine(BBR)has hypoglycemic,hypolipidemic,antiox-idant,anti-inflammatory and anti-fibrotic properties,thus protects against kidney injury in DKD.The mechanisms of action of BBR may involve improving glucolipid metabolism,reducing oxidative stress,alleviating inflammatory responses,mitigat-ing renal fibrosis,regulating DNA methylation,promoting mitochondrial function and modulating the gut microbiota to enhance gut metabolism and clearance.This article systematically reviews the current status of research on the mechanisms of BBR in the treatment of DKD and provides reference for future clinical application of BBR in the treatment of DKD.

Laparoscopic cholecystectomy (LC) is the first preferred treatment of benign gallbladder diseases such as gallbladder stones and gallbladder polyps, however bile duct injury is a serious complication of LC. Although bile duct injury is a rare complication, improper treatments will seriously affect the quality of life or even threaten life. Therefore, the prevention and correct treatments of bile duct injury in LC are crucial. Based on domestic and overseas researches, the authors investigate risk factors for bile duct injury in LC, share experiences of timely detection, diagnosis and treatment, so as to provide references for hepatic and biliary surgeons.

Biliary tract cancer is found in the middle and advanced stages mostly and patients will deprive surgical indications. Conversion therapy can make the stage of some patients down and thus make radical resection feasible. Biliary tract cancer is highly heterogeneous in clinical features, cell origin, histology, molecular biology and other aspects, resulting in a lack of specific and effective conversion therapy strategies. Currently, it is the important development direction to evaluate and classify different individual conditions and select individualized conversion therapy regimens. With the deepening of the research on the pathogenesis and the improvement of treatment protocols, the future conversion therapy will undoubtedly develop towards the direction of individualization and precision.

Objective:Proximal femur tumor resection often leads to hip joint instability and functional loss.Various methods have been clinically applied to repair hip joint soft tissue function,but deficiencies remain.This study aims to evaluate the advantages and disadvantages of the ligament advanced reinforcement system(LARS)tumor tube in assisting soft tissue function reconstruction in patients undergoing tumor type artificial hip replacement surgery. Methods:This study included 85 patients(41 males,44 females)with proximal femoral tumors treated at the Xiangya Bone Tumor Treatment Center from January 2012 to January 2022,aged 10 to 79(38.5±18.2)years.Among them,13 cases had benign aggressive tumors,45 had primary malignant bone tumors,and 27 had bone metastases.Clinical data,imaging data,and intraoperative photos were collected.Patients were followed up and postoperative functional evaluations were conducted using the Musculoskeletal Tumor Society(MSTS)scoring system and Harris hip joint scoring system to assess limb function and hip joint function. Results:Preoperative pathological fractures were present in 37 cases(43.5％),with a lesion length of(9.4±2.9)cm.Among non-metastatic tumor patients,7 experienced postoperative recurrence,including 6 cases of osteosarcoma and 1 case of fibrosarcoma.Pulmonary metastases occurred in 9 osteosarcoma patients.Five patients required reoperation due to postoperative complications,including 3 cases of deep vein thrombosis,1 case of giant cell granuloma,and 1 case of prosthesis infection.Postoperatively,5 patients exhibited Trendelenburg gait,and 6 had leg length discrepancies.The postoperative MSTS score was 26.7±1.4,and the Harris score was 89.6±5.3. Conclusion:The LARS tumor tube can effectively assist in reconstructing the soft tissue function of the hip joint and greatly reduce postoperative complications,making it an effective technical improvement in joint function reconstruction in tumor type artificial hip replacement surgery.

Biliary tract cancer is found in the middle and advanced stages mostly and patients will deprive surgical indications. Conversion therapy can make the stage of some patients down and thus make radical resection feasible. Biliary tract cancer is highly heterogeneous in clinical features, cell origin, histology, molecular biology and other aspects, resulting in a lack of specific and effective conversion therapy strategies. Currently, it is the important development direction to evaluate and classify different individual conditions and select individualized conversion therapy regimens. With the deepening of the research on the pathogenesis and the improvement of treatment protocols, the future conversion therapy will undoubtedly develop towards the direction of individualization and precision.

Objective:To analyze the distribution of solute carrier organic anion transporter family member 1b1 ( SLCO1B1) and apolipoprotein E ( ApoE) genes in a population from southern Yunnan. Methods:The data of 104 patients who received treatment in Southern Central Hospital of Yunnan Province (The First People's Hospital of Honghe State) between May 2019 and June 2020 were collected. The distribution of SLCO1B1 and ApoE genes and their relationship with nationality, sex, and age were analyzed and compared between different regions. Results:The percentage of patients carrying *1a/*1a, *1a/*1b, *1b/*1b, *1a/*15, *1b/*15, five phenotypes of SLCO1B1 gene, in the population from southern Yunnan was 4.81%, 32.69%, 42.31%, 12.50% and 7.69% respectively. Phenotypes *1a/*5, *5/*5, *5/*15 and *15/*15 were not detected. Normal metabolic phenotype of SLCO1B1 accounted for 79.81%, and intermediate metabolic phenotype of SLCO1B1 accounted for 20.19%. Weak metabolic phenotype was not detected. The percentage of patients carrying E2/E2, E2/E3, E3/E3, E3/E4, E4/E4, five phenotypes of ApoE gene in the population from southern Yunnan was 0.96%, 16.35%, 70.19%, 11.54% and 0.96% respectively. E2/E4 phenotype was not detected. The percentage of patients with ApoE protective phenotype, ApoE normal phenotype, and ApoE risk phenotype was 17.31%, 70.19% and 12.50% respectively. The observed polymorphism mutation frequency of SLCO1B1 and ApoE genes was consistent with the Hardy-Weinberg equilibrium ( P > 0.05), suggesting constancy and a population representation. The Fisher test showed that SLCO1B1 gene distribution differed significantly between ethnic minorities and Han nationality in southern Yunnan ( P = 0.013). There was no significant difference in SLCO1B1 gene distribution between different sexes and between different ages (all P > 0.05). There was no significant difference in ApoE gene distribution between ethnic minorities and Han nationality, between different sexes, and between different ages in the population from southern Yunnan (all P > 0.05). Conclusion:SLCO1B1 gene distribution is related to nationality in the population from southern Yunnan, but it is unrelated to sex and age. ApoE gene distribution is unrelated to nationality, sex and age.

Objective:To study the expression of forkhead box P1 (FOXP1) in intrahepatic cholangiocarcinoma (ICC), and its clinicopathological and prognostic significance.Methods:The clinical data of ICC patients treated with radical resection at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 1, 2013 to December 12, 2019 were retrospectively analysed. Of 48 ICC patients, there were 24 males and 24 females, with age of (59.1±10.1) years old (range 42 to 83 years old). Their clinicopathological data, including age, gender, tumor size, degree of differentiation, and staging were recorded. Immunohistochemical method was used to detect the expression of FOXP1 protein in ICC cancer tissues and the corresponding adjacent normal tissues. Kaplan-Meier method was used to calculate survival rates and to construct survival curves of patients. Cox regression model was used to analyze factors affecting prognosis of patients.Results:Forty-eight ICC cancer tissues and 40 corresponding paracancerous tissues were collected. The positive rates of FOXP1 proteins in ICC were significantly lower than the adjacent normal tissues [54.2%(26/48) vs. 92.5%(37/40), χ 2=15.76, P<0.05]. The degrees of tumor differentiation, lymph node metastasis, organ invasion and TNM staging were related to expression of FOXP1 ( P<0.05). Forty-two patients were followed-up with a median follow-up time of 11.5 (7.75, 19.25) months. Cox multivariate analysis revealed that invasion to adjacent organs, lymph node metastasis, high TNM staging (stage Ⅲ) and negative expression of FOXP1 were independent risk factors affecting overall survival of ICC patients. The overall survival and recurrence-free survival of FOXP1-positive ICC patients were 17.5 months and 15.5 months, which were significantly higher than the 14.0 months and 11.1 months, respectively, in FOXP1-negative patients. Conclusion:Negative FOXP1 expression was closely correlated with aggressive biological behavior and poor prognosis of ICC. FOXP1 may be used as new diagnostic and therapeutic targets.