A 38-year-old male patient with ankylosing spondylitis received subcutaneous injection of adalimumab 40 mg once every 2 weeks. After 21 months of medication, the patient developed fever, fatigue, swelling, and pain in the right neck lymph node and throat. Laboratory tests showed that the tuberculin test was strong positive, mycobacterium tuberculosis γ-interferon release test was 1 911.98 ng/L, and erythrocyte sedimentation rate was 27 mm/1 h. The biopsy of right neck lymph node showed granulomatous inflammation of the lymph node. The patient was diagnosed with cervical lymph node tuberculosis, which was considered to be related to adalimumab. The drug was stopped and anti-tuberculosis treatments were given. The next day, the patient′s temperature returned to normal. After 5 days, the swelling and pain of cervical lymph nodes and throat, and the fatigue were relieved gradually. After 45 days, the above symptoms in the patient disappeared.

A 38-year-old male patient with ankylosing spondylitis received subcutaneous injection of adalimumab 40 mg once every 2 weeks. After 21 months of medication, the patient developed fever, fatigue, swelling, and pain in the right neck lymph node and throat. Laboratory tests showed that the tuberculin test was strong positive, mycobacterium tuberculosis γ-interferon release test was 1 911.98 ng/L, and erythrocyte sedimentation rate was 27 mm/1 h. The biopsy of right neck lymph node showed granulomatous inflammation of the lymph node. The patient was diagnosed with cervical lymph node tuberculosis, which was considered to be related to adalimumab. The drug was stopped and anti-tuberculosis treatments were given. The next day, the patient′s temperature returned to normal. After 5 days, the swelling and pain of cervical lymph nodes and throat, and the fatigue were relieved gradually. After 45 days, the above symptoms in the patient disappeared.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective To analyze the clinicopathological features,treatment and prognosis of patients with proliferative glomerulonephritis with monoclonal immunoglobulin deposition.Methods The clinical data,renal pathology,treatment and prognosis of patients with PGNMID diagnosed by renal biopsy in Xijing Hospital from January 2018 to January 2024 were retrospectively analyzed and summarized.Results A total of 28 patients were enrolled in this study,with a male to female ratio of 4:3.The clinical manifestations were proteinuria(100%),hematuria(82.1%),renal insufficiency(28.6%),and low complement C3 or C4 emia(32.1%).One patient(3.6%)had serum monoclonal immunoglobulin,and 5 patients(17.9%)had abnormal serum free light chain ratio.The deposition of immunoglobulin in the kidney was IgG3 in 24 cases,IgG1 in 4 cases,and IgG3κwas the most common type(17 cases).Then there are 24 cases(85.7%)of MPGN,3 cases(10.7%)characterized by EPGN,1 case(3.6%)of MGN.Under electron microscope,most of the electron-dense deposits were found in the mesangial area and subendothelium,and a few were accompanied by subepithelial deposits.The follow-up time ranged from 3 to 56 months.Until the last follow-up,a total of 5 patients entered ESRD,of which 2 patients died,1 patient underwent peritoneal dialysis,1 patient underwent hemodialysis,and 1 patient underwent preparation for renal replacement therapy.Follow-up of 1 year,2 years,3 years renal total response rate of 32.1%,57.1%and 64.2%respectively.According to the situation of kidney ease into remission group(n=16)and non-remission group(n=12).The average age of the remission group was 44±17.35 years,including 8 males(50%);The average age of the non-remission group was 59.83±18.09 years,including 8 males(66.7%).The age,nT-proBNP,troponin I and urea nitrogen of the non-remission group were higher than those of the remission group,and the differences were statistically significant(P＜0.05).Among the 5 patients with renal complete remission,2 were treated with BD(bortezomib combined with dexamethasone),1 was treated with Dara,and the remaining 2 were treated with steroids combined with immunosuppressants.Conclusions The clinical manifestations of PGNMID are proteinuria,hematuria and renal insufficiency.Under light microscope,MPGN was the main manifestation,and IgG3κwas the most common subtype.Based on bortezomib treatment can obtain good hematology and kidney remission rate.Dara may be a safe and effective drug for the treatment of PGNMID,the best treatment needs further exploration.

Objective To investigate the pharmacological effects of"Yajieshaba"on mice with alcohol-induced liver injury and to investigate the mechanism of the impact of"Yajieshaba"on the regulation of intestinal flora by 16S rDNA technology.Methods Healthy male KM mice were randomly divided into control,model,"Yajieshaba"low,medium,and high dose(0.39,1.17 and 3.51 g·kg-1)groups and Bifendatatum(2.93 mg·kg-1)groups,with eight mice in each group.After one week of pre-administration of"Yajieshaba",a mouse model of acute alcoholic liver injury was established by a single instillation of 56%alcohol,and the levels of AST and ALT in the serum of mice were measured,and the morphological changes of liver histology were observed by HE staining;secondly,faecal DNA was extracted from each group under aseptic operation,and 16S rDNA sequencing and differential analysis by alpha diversity and species composition at the phylum and genus levels were performed.Results The results showed that the biochemical indexes of liver function(ALT and AST)were significantly improved by"Yajieshaba",and the degree of liver damage was significantly reduced by HE staining.At the phylum level,it significantly decreased the abundance of Aspergillus and increased the quantity of Bacteroides;at the genus level,it significantly up-regulated the plenty of Bacteroides and Prevotella and downregulated a lot of Prevotella and Helicobacter.At the genus level,"Yajieshaba"significantly up-regulated the abundance of Bacillus spp.and Prevotella spp.and down-regulated the abundance of Prevotella spp.and Helicobacter spp.Conclusion"Yajieshaba"may play an anti-acute alcoholic liver injury effect by regulating the intestinal flora and metabolites.

Objective To analyze the clinicopathological features,treatment and prognosis of patients with proliferative glomerulonephritis with monoclonal immunoglobulin deposition.Methods The clinical data,renal pathology,treatment and prognosis of patients with PGNMID diagnosed by renal biopsy in Xijing Hospital from January 2018 to January 2024 were retrospectively analyzed and summarized.Results A total of 28 patients were enrolled in this study,with a male to female ratio of 4:3.The clinical manifestations were proteinuria(100%),hematuria(82.1%),renal insufficiency(28.6%),and low complement C3 or C4 emia(32.1%).One patient(3.6%)had serum monoclonal immunoglobulin,and 5 patients(17.9%)had abnormal serum free light chain ratio.The deposition of immunoglobulin in the kidney was IgG3 in 24 cases,IgG1 in 4 cases,and IgG3κwas the most common type(17 cases).Then there are 24 cases(85.7%)of MPGN,3 cases(10.7%)characterized by EPGN,1 case(3.6%)of MGN.Under electron microscope,most of the electron-dense deposits were found in the mesangial area and subendothelium,and a few were accompanied by subepithelial deposits.The follow-up time ranged from 3 to 56 months.Until the last follow-up,a total of 5 patients entered ESRD,of which 2 patients died,1 patient underwent peritoneal dialysis,1 patient underwent hemodialysis,and 1 patient underwent preparation for renal replacement therapy.Follow-up of 1 year,2 years,3 years renal total response rate of 32.1%,57.1%and 64.2%respectively.According to the situation of kidney ease into remission group(n=16)and non-remission group(n=12).The average age of the remission group was 44±17.35 years,including 8 males(50%);The average age of the non-remission group was 59.83±18.09 years,including 8 males(66.7%).The age,nT-proBNP,troponin I and urea nitrogen of the non-remission group were higher than those of the remission group,and the differences were statistically significant(P＜0.05).Among the 5 patients with renal complete remission,2 were treated with BD(bortezomib combined with dexamethasone),1 was treated with Dara,and the remaining 2 were treated with steroids combined with immunosuppressants.Conclusions The clinical manifestations of PGNMID are proteinuria,hematuria and renal insufficiency.Under light microscope,MPGN was the main manifestation,and IgG3κwas the most common subtype.Based on bortezomib treatment can obtain good hematology and kidney remission rate.Dara may be a safe and effective drug for the treatment of PGNMID,the best treatment needs further exploration.

A 34-year-old male patient received a subcutaneous injection of 300 mg of secukinumab once a week for 5 times, subsequently 300 mg once every 4 weeks for 3 times because of psoriasis. Then the patient developed bloody purulent stool. Electronic colonoscopy revealed diffuse mucosal congestion and edema in the sigmoid colon at a distance of 25 cm from the anus. The pathological examination results of tissue biopsy showed severe chronic inflammation, erosion, and shallow ulcer formationin the sigmoid colon. Inflammatory bowel disease caused by secukinumab was considered. Then the drug was stopped, and mesalazine enema solution 60 g once daily was given. After half a month of treatment, the patient′s bloody purulent stool was improved significantly, and after 2 months, it disappeared. Electronic colonoscopy showed that the mucosa of the sigmoid colon was rough, granular, and scattered with small patches of bleeding at a distance of 20 cm to 25 cm from the anus, which was diagnosed as having ulcerative colitis (in remission). Mesalazine enema was discontinued and changed to mesalazine suppository 0.5 g once daily.

A 34-year-old male patient received a subcutaneous injection of 300 mg of secukinumab once a week for 5 times, subsequently 300 mg once every 4 weeks for 3 times because of psoriasis. Then the patient developed bloody purulent stool. Electronic colonoscopy revealed diffuse mucosal congestion and edema in the sigmoid colon at a distance of 25 cm from the anus. The pathological examination results of tissue biopsy showed severe chronic inflammation, erosion, and shallow ulcer formationin the sigmoid colon. Inflammatory bowel disease caused by secukinumab was considered. Then the drug was stopped, and mesalazine enema solution 60 g once daily was given. After half a month of treatment, the patient′s bloody purulent stool was improved significantly, and after 2 months, it disappeared. Electronic colonoscopy showed that the mucosa of the sigmoid colon was rough, granular, and scattered with small patches of bleeding at a distance of 20 cm to 25 cm from the anus, which was diagnosed as having ulcerative colitis (in remission). Mesalazine enema was discontinued and changed to mesalazine suppository 0.5 g once daily.

Objective:To screening differentially expressed genes (DEGs) in proliferative diabetic retinopathy (DR) patients to provide new biological therapeutic targets for proliferative DR (PDR) therapy.Methods:A basic research. A total of 3 PDR patients (group PDR) and 3 non-diabetic patients (control group) were enrolled in the study in Tianjin Medical University Eye Hospital in October 2020. In addition, 40 cases of PDR and non-diabetic patients were selected and divided into PDR validation group and control validation group. Peripheral blood validation test was performed in PDR validation group and control validation group; RNA sequencing was performed in PDR group and control group. Transcriptomics (RNAseq) sequencing technology was used to screen DEG in PDR group and control group. The selected DEGs were analyzed by gene ontology (GO) function enrichment analysis, signal pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction network (PPI). The gene expression database was used to find the high-throughput data related to PDR, and multi queue comparison analysis was carried out. The target genes of differentially expressed miRNAs were predicted through targetscan platform, so as to clearly screen the correlation between DEG and PDR. Reverse transcription polymerase chain reaction and Western blot were used to verify the expression of DEG mRNA and protein related to PDR. The relative expression of PDR related DEG mRNA and protein between PDR validation group and control validation group were compared by paired t-test. Results:A total of 1 337 DEGs were screened by RNAseq sequencing in the peripheral blood of patients with PDR, of which 419 genes were up-regulated and 918 down-regulated. Among them, direct inhibitor of apoptosis protein-binding protein with low isoelectric point ( DIABLO), zinc finger and BTB domain containing 10 ( ZBTB10), polo-like kinases 3 ( PLK3), regulatory subunit 1 ( PIK3R1) and B cell translocation gene 3 (BTG3) were differentially expressed in PDR patients. The function of GO was enriched from the analysis of molecular function, biological process and cellular composition. The results showed that DIABLO, ZBTB10, PLK3, PIK3R1, BTG3 were involved in the pathological process related to PDR. KEGG enrichment analysis showed that glucose metabolic pathways such as extracellular matrix receptors, cytokine regulatory pathway, p53 signal pathway and galactose metabolism may be involved in the process of differential genes. The analysis of PPI protein interaction network showed that the larger the DEG-associated protein node, the greater the number of associated nodes. Among them, DIABLO, ZBTB10, PLK3, PIK3R1 and BTG3 played significant roles in the formation of the action network. By comparing and analyzing the existing high-throughput data related to diabetic retinopathy in Gene Expression Omnibus database and predicting by Targetscan platform, it was found that some significant differences in miRNA reported in aqueous humor, vitreous fluid and plasma of DR patients can be regulated by the differential genes found in this study. Compared with the control verification group, the relative expressions of DIABLO, ZBTB10, PLK3, PIK3R1 mRNA and protein in peripheral blood of the PDR verification group were up-regulated, and the relative expression of BTG3 mRNA and protein was down-regulated. Conclusion:DIABLO, ZBTB10, PLK3, PIK3R1 and BTG3 are DEGs in patients with PDR, and they can participate in the disease process by regulating the biological processes of cell proliferation, fibrosis and oxidative stress.

Objective:To observe the effect of bone morphogenetic protein 4 (BMP4) on the proliferation and migration of human retinal microvascular endothelial cells (hRMEC) under oxidative stress.Methods:The hRMEC cultured in vitro were divided into control group, 4-hydroxynonenal (HNE) treatment group (4-HNE group), 4-HNE+BMP4 group (BMP4 group). Cell culture medium of 4-HNE treatment group was added with 10 μmmol/L 4-HNE; cell culture of BMP4 group was cultured with 10 μmmol/L 4-HNE, and after stimulation for 6 h, 100 ng/ml recombinant human BMP4 was added. The effects of 4-HNE and BMP4 on hRMEC viability was detected by thiazole blue colorimetric method. The effects of 4-HNE and BMP4 on cell migration was determined by cell scratch test. The relative expression of BMP4 mRNA in the cells of the control group and 4-HNE treatment group and the mRNA expression of the control group, the fibronectin (FN) of BMP4 group, laminin (Laminin), α-smooth muscle contractile protein (α-SMA), and collagen type Ⅰ (Collagen Ⅰ), vascular endothelial growth factor (VEGF), and connective tissue growth factor (CTGF) were detected by real-time quantitative polymerase chain reaction (qRT-PCR). Western blot was used to detect the relative expression of BMP4 protein in the control group and 4-HNE group. The control group and 4-HNE group were compared by t test. Results:Compared with the control group, cell viability ( t=12.73, 16.26, P=0.000 2, <0.000 1), cell migration rate ( t=28.17, 37.48, P<0.000 1, <0.000 1) in 4-HNE group and BMP4 group were significantly increased, and the difference was statistically significant; the relative expression of BMP4 mRNA and protein in the 4-HNE group was significantly increased, and the difference was statistically significant ( t=16.36, 69.35, P=0.000 1, <0.000 1). The qRT-PCR test results showed that compared with the control group, the relative expression of VEGF, FN, Laminin, α-SMA, Collagen Ⅰ, and CTGF mRNA in the cells of the BMP4 group was significantly increased, and the difference was statistically significant ( t=10.61, 17.00, 14.85, 7.78, 12.02, 10.61, P=0.0004, <0.000 1, 0.000 1, 0.001 5, 0.000 1, 0.000 4). Conclusion:BMP4 can induce the proliferation and migration of hRMEC; it can also regulate the expression of angiogenesis factors and fibrosis-related factors in hRMEC.