Anti-phospholipase A2 receptor antibody levels at diagnosis predicts outcome of TAC-based treatment for idiopathic membranous nephropathy patients.

BACKGROUND: Idiopathic membranous nephropathy (iMN) is recognized as an organ-specific autoimmune disease, mainly caused by anti-PLA2R antibody. This study aimed to study between anti-PLA2R antibody level at diagnosis and the response to tacrolimus (TAC)-based treatment in iMN patients. METHODS: This was a retrospective cohort study including 94 kidney biopsy-proven MN patients with positive anti-PLA2R antibody at diagnosis from May 2017 to September 2021 in our center. All iMN patients received the TAC regimen as the initial immunosuppressive therapy. All patients were divided into two groups according to anti-PLA2R antibody titer at diagnosis: high-level group (> 150 RU/ml; n = 42) and low-level group (≤ 150 RU/ml; n = 52). The association between anti-PLA2R antibody levels and clinical outcomes was assessed using the Kaplan-Meier method. RESULTS: The low density lipoprotein in the high-level group was significantly higher than low-level group at diagnosis, otherwise, serum albumin was significantly lower than low-level group; however, there was no significant difference in creatinine levels between two groups. The remission rates were significantly higher in the low-level group than high-level group after treatment with TAC for 12, 18, or 24 months (all P < 0.05). After 12 months of treatment with TAC, 82.7% of the patients in the low-level group achieved complete remission (CR) or partial remission (PR) (mean, 6.52 ± 0.53 months). However, 38.1% of the patients in high-level group achieved CR or PR (mean, 9.86 ± 0.51 months). Moreover, CR rate at 12 months in the high-level group was only 4.7% (mean, 11.88 ± 0.63 months). The infection frequency in the high-level group (35.6%) was higher than the low-level group (20%) during the TAC treatment, although there was no significant difference (P = 0.065). There were 19% patients who had end-stage kidney disease (ESKD), and 7.1% of patients died of ESKD in the high-level group during the follow-up period. CONCLUSION: Anti-PLA2R antibody level above 150 RU/ml at diagnosis can predict a poor treatment response and outcome of TAC treatment in iMN patients, who may not benefit from TAC or other calcineurin inhibitor regimens as the initial treatment.

Changes in the spectrum of kidney diseases: a survey of 2803 patients from 2010 to 2018 at a single center in southeastern China.

Primary glomerular disease was the leading cause of chronic kidney disease (CKD) in China; however, changes in the economy and environment introduce variations in the spectrum of kidney diseases. This study aimed to analyze renal biopsy data to inform disease prevention and public health interventions. In this retrospective cohort study, data from 2,803 consecutive renal biopsies conducted at our center between January 2010 and December 2018 were analyzed. The sample was disaggregated by age and the date of biopsy to facilitate analysis. Primary glomerulonephritis (PGN) is the most frequent (81.84%) finding, followed by secondary glomerulonephritis (SGN; 15.38%), tubulointerstitial nephritis (15.38%), and others (1.57%). IgA nephropathy (IgAN), idiopathic membranous nephropathy (iMN), and minimal change disease were the primary causes of PGN. Among PGN cases, the incidence of iMN arose, especially among those aged ≥ 60 years old, during the observation period. Contrary to the case of iMN, the proportion of IgAN in PGN trended downward, continuously, and at length. Moreover, IgAN mainly affected those aged 25-44 years old and less so those aged ≥ 60 years old. Lupus nephritis, Henoch-Schönlein purpura nephritis, and diabetic nephropathy (DN) were key causes of SGN. A ratio reversal between infectious disease and chronic disease dramatically changed SGN patterns. In the past year, the incidence of hepatitis B-related nephritis has constantly declined; however, the proportion of DN among SGN had steadily increased. The incidence of iMN significantly increased during these years. Among SGN cases, the proportion of DN has increased.

A novel missense mutation in complement factor I predisposes patients to atypical hemolytic uremic syndrome: a case report.

BACKGROUND: Atypical hemolytic uremic syndrome, also called the nondiarrheal form of hemolytic uremic syndrome, is a rare disease characterized by the triad of thrombocytopenia, Coomb's test-negative microangiopathic hemolytic anemia, and acute renal failure. Approximately 60% of cases of atypical hemolytic uremic syndrome are associated with deficiencies of the complement regulatory protein, including mutations in complement factor H, complement factor I, or the membrane co-factor protein. CASE PRESENTATION: We report the case of a 26-year-old Asian man who presented with pulmonary infection, elevated blood pressure, microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Renal biopsy revealed diffuse capillary fibrin deposition, endothelial swelling, and arteriole narrowing like "onion skinning" consistent with thrombotic microangiopathy. Bidirectional sequencing of CFH, CFHR5, CFHR1, CFI, DGKE, CFB, and MCP confirmed that the patient was heterozygous for a novel missense mutation, p.Cys67Phe, in CFI. This patient had rapid evolution to end-stage renal disease and needed renal replacement therapy. Plasma exchange seemed inefficacious in this patient. CONCLUSIONS: This report confirms the importance of screening patients with atypical hemolytic uremic syndrome for mutations in genes involved in complement system to clarify the diagnosis and demonstrates the challenges in the management of these patients.

Clinical retrospective study on the expression of the PD-L1 molecule in sporadic colorectal cancer and its correlation with K-ras gene mutations in Chinese patients.

OBJECTIVE: To detect the expression of PD-L1 and K-ras gene status in colorectal cancer tissues and analyze the relationship between PD-L1 expression and the clinicopathological features and K-ras gene status in colorectal cancer. METHODS: Two hundred fifty colorectal cancer tissues were collected from the First Affiliated Hospital of Nanchang University. The normal intestinal mucosal tissues of 20 patients were randomly selected for inclusion in the control group. PD-L1 expression was detected by immunohistochemistry. K-ras gene mutation in colorectal cancer tissues was detected by sequencing. The clinical significance of PD-L1 expression and relationship between PD-L1 expression and K-ras gene mutation were analyzed. RESULTS: The immunohistochemistry assay showed that PD-L1 was highly expressed in colorectal cancer. The positive expression of PD-L1 was increased with lymph node metastasis and high TNM stage. The 5-year survival rate of PD-L1-positive patients was significantly lower than that of PD-L1-negative patients. The K-ras gene mutation rate was 35.6%, and the main mutation site was in codon 12. The positive PD-L1 expression rate in patients with K-ras gene mutations was significantly higher than that in patients with wild-type K-ras gene mutations. CONCLUSION: PD-L1 is highly expressed in colorectal cancer, and its expression is related to metastasis and tumor stage. PD-L1 expression is closely related to K-ras gene mutation, and the K-ras gene status may affect PD-L1 expression. TRIAL REGISTRATION: retrospectively registered.

Using Machine Learning Modeling to Explore New Immune-Related Prognostic Markers in Non-Small Cell Lung Cancer.

OBJECTIVE: To find new immune-related prognostic markers for non-small cell lung cancer (NSCLC). METHODS: We found GSE14814 is related to NSCLC in GEO database. The non-small cell lung cancer observation (NSCLC-OBS) group was evaluated for immunity and divided into high and low groups for differential gene screening according to the score of immune evaluation. A single factor COX regression analysis was performed to select the genes related to prognosis. A prognostic model was constructed by machine learning, and test whether the model has a test efficacy for prognosis. A chip-in-chip non-small cell lung cancer chemotherapy (NSCLC-ACT) sample was used as a validation dataset for the same validation and prognostic analysis of the model. The coexpression genes of hub genes were obtained by pearson analysis and gene enrichment, function enrichment and protein interaction analysis. The tumor samples of patients with different clinical stages were detected by immunohistochemistry and the expression difference of prognostic genes in tumor tissues of patients with different stages was compared. RESULTS: By screening, we found that LYN, C3, COPG2IT1, HLA.DQA1, and TNFRSF17 is closely related to prognosis. After machine learning, we constructed the immune prognosis model from these 5 genes, and the model AUC values were greater than 0.9 at three time periods of 1, 3, and 5 years; the total survival period of the low-risk group was significantly better than that of the high-risk group. The results of prognosis analysis in ACT samples were consistent with OBS groups. The coexpression genes are mainly involved B cell receptor signaling pathway and are mainly enriched in apoptotic cell clearance. Prognostic key genes are highly correlated with PDCD1, PDCD1LG2, LAG3, and CTLA4 immune checkpoints. The immunohistochemical results showed that the expression of COPG2IT1 and HLA.DQA1 in stage III increased significantly and the expression of LYN, C3, and TNFRSF17 in stage III decreased significantly compared with that of stage I. The experimental results are consistent with the previous analysis. CONCLUSION: LYN, C3, COPG2IT1, LA.DQA1, and NFRSF17 may be new immune markers to judge the prognosis of patients with non-small cell lung cancer.

Acute kidney injury associated with minimal change disease in systemic lupus erythematosus: a case report.

INTRODUCTION: In systemic lupus erythematosus, acute kidney injury is usually associated with severe lupus nephritis and rarely associated with other glomerular diseases. CASE PRESENTATION: We recently encountered a patient with acute kidney injury that was associated with minimal change disease in systemic lupus erythematosus. A 26-year-old Chinese woman who had a history of systemic lupus erythematosus presented with nephrotic syndrome and acute kidney injury. She fulfilled four of the American College of Rheumatology criteria for the classification of systemic lupus erythematosus. However, a renal biopsy revealed that there were no glomerular abnormalities or deposition of immune complex. Her generalized edema disappeared, and her high serum creatinine level decreased to normal after prednisolone therapy. CONCLUSION: Though the relationship between lupus and minimal change disease is still not defined, the possibility of systemic lupus erythematosus combined with minimal change disease must be differentiated in patients with lupus and severe proteinuria.

Gastric ulcer patients are more susceptible to developing gastric cancer compared with concomitant gastric and duodenal ulcer patients.

Intestinal metaplasia (IM) and dysplasia are precancerous lesions of gastric cancer (GC); however, the prevalence of IM and dysplasia in patients exhibiting single gastric ulcer (GU) and concomitant gastric and duodenal ulcer (CGDU) varies. In the present study consecutive patients who had undergone esophagogastroduodenal endoscopy were retrospectively screened, and those presenting with GU or CGDU were further evaluated for IM and dysplasia. Patients diagnosed with GC or lymphoma and patients with a history of anti-Helicobacter pylori, non-steroidal anti-inflammatory medicine (NSAIM), H2-receptor antagonist or proton pump inhibitor therapy, were excluded from the present study. Of the 204,073 consecutively screened cases, 8,855 (4.3%) and 2,397 (1.2%) were diagnosed with GU and CGDU, respectively. A total of 1,722 GU and 233 CGDU patients were excluded; thus, 7,133 and 2,164 cases of GU and CGDU, respectively (n=9,297), were included in the present study. IM and dysplasia were observed in 1,348 (14.5%) and 210 (2.3%) patients, respectively. IM was more frequently identified in GU patients compared with CGDU patients (16.4 vs. 8.3%; odds ratio [OR], 2.158; 95% confidence interval [CI], 1.830-2.545; χ2=86.932; P<0.001); furthermore, GU patients exhibited significantly more frequent IM compared with CGDU patients at the gastric antrum (14.2 vs. 5.5%; OR, 2.818; 95% CI, 2.199-3.610; χ2=72.299; P<0.001), gastric incisura (24.0 vs. 14.1%; OR, 1.922; 95% CI, 1.502-2.432; χ2=30.402; P<0.001) and gastric corpus (12.6 vs. 3.3%; OR, 4.259; 95% CI, 1.030-17.609; χ2=4.736; P=0.026). Dysplasia was significantly more frequently identified in GU patients compared with CGDU patients (2.7 vs. 0.7%; OR, 4.027; 95% CI, 2.376-6.823; χ2=31.315; P<0.001), with GU patients exhibiting significantly more severe dysplasia at the gastric antrum (2.4 vs. 0.7%; OR, 3.339; 95% CI, 1.735-6.425; χ2=14.652; P<0.001) and the gastric incisura (2.9 vs. 0.7%; OR, 4.255; 95% CI, 1.694-10.689; χ2=11.229; P<0.001). Additionally, mild IM was more frequently identified in GU patients compared with CGDU patients (15.2 vs. 7.1%; OR, 2.353; 95% CI, 1.972-2.807; χ2=94.798; P<0.001) and dysplasia of a mild (1.7 vs. 0.6%; OR, 2.807; 95% CI, 1.580-4.987; χ2=13.519; P<0.001) or moderate/severe grade (1.1 vs. 0.09%; OR, 11.642; 95% CI, 2.857-47.439; χ2=18.896; P<0.001) was more frequent in GU patients compared with CGDU patients. IM and dysplasia were more frequently observed in GU compared with CGDU patients in the present study, which may be associated with an increased probability of developing GC.

Over-expression of eukaryotic translation initiation factor 4 gamma 1 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma.

BACKGROUND: The aim of the present study was to analyze the expression of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) in nasopharyngeal carcinoma (NPC) and its correlation with clinicopathologic features, including patients' survival time. METHODS: Using real-time PCR, we detected the expression of EIF4G1 in normal nasopharyngeal tissues, immortalized nasopharyngeal epithelial cell lines NP69, NPC tissues and cell lines. EIF4G1 protein expression in NPC tissues was examined using immunohistochemistry. Survival analysis was performed using Kaplan-Meier method. The effect of EIF4G1 on cell invasion and tumorigenesis were investigated. RESULTS: The expression levels of EIF4G1 mRNA were significantly greater in NPC tissues and cell lines than those in the normal nasopharyngeal tissues and NP69 cells (P < 0.001). Immunohistochemical analysis revealed that the expression of EIF4G1 protein was higher in NPC tissues than that in the nasopharyngeal tissues (P < 0.001). In addition, the levels of EIF4G1 protein in tumors were positively correlated with tumor T classification (P = 0.039), lymph node involvement (N classification, P = 0.008), and the clinical stages (P = 0.003) of NPC patients. Patients with higher EIF4G1 expression had shorter overall survival time (P = 0.019). Multivariate analysis showed that EIF4G1 expression was an independent prognostic indicator for the overall survival of NPC patients. Using shRNA to knock down the expression of EIF4G1 not only markedly inhibited cell cycle progression, proliferation, migration, invasion, and colony formation, but also dramatically suppressed in vivo xenograft tumor growth. CONCLUSION: Our data suggest that EIF4G1 can serve as a biomarker for the prognosis of NPC patients.

[Establishment of a stable nasopharyngeal carcinoma cell line with lentivirus-mediated RNA interference for EIF4G1 gene silencing].

OBJECTIVE: To establish a nasopharyngeal carcinoma (NPC) cell line with stable EIF4G1 gene silencing induced by small interfering RNA (siRNA). METHODS: The EIF4G1 mRNA levels in 8 NPC cell lines including 5-8F, 6-10B, C666-1, CNE1, CNE2, HNE1, HONE1, and SUNE1 were detected by fluorescence quantitative RT-PCR (QRT-PCR). The recombinant lentivirus shRNA expression plasmid targeting EIF4G1 gene was packaged into mature lentivirus by 293FT cells and used to infect 5-8F cells. After blasticidin selection of NPC cells with constant expression of the EIF4G1-siRNA, the efficiency of EIF4G1 mRNA expression interference was determined using QRT-PCR. RESULTS: The 8 NPC cell lines showed differential expression of EIF4G1 mRNA, among which 5-8F cells had the highest EIF4G1 expression. The recombinant lentivirus plasmid pLenti6/BLOCK-iT-DEST/EIF4G1-shRNA was successfully constructed and verified by PCR and sequencing. The EIF4G1 mRNA level of 5-8F cells infected with shRNA-EIF4G1 lentivirus was significantly reduced as compared with the negative control and the blank control cells. CONCLUSION: The recombinant lentivirus vector pLenti6/BLOCK- iT-DEST/EIF4G1-shRNA we constructed results in marked downregulation of EIF4G1 mRNA expression and constant expression of EIF4G1-siRNA after infection of 5-8F cells.