Regarding radioactive iodine-refractory failure or advanced differentiated thyroid cancer,multiple multikinase inhibitors including sorafenib and lenvatinib,which target platelet derived growth factor receptor,vascular endothelial growth factor pathway,and rearranged during transfection (RET) pathway were proved to have obvious antitumor activity.Moreover,selective BRAF inhibitor,promoting drug uptake of radioactive iodine also showed a certain therapeutic effect.These molecular targets which are relevant with differentiated thyroid cancer occurrence,development,invasion and metastasis have become of its moment,and,selective inhibitors and re-differentiation agents were shown to be promising.In the future,individual genetic testing would provide more specific information in directing individualized molecular-targeted therapy.

Objective To investigate the effect of estrogen on the expression of matrix metallopro-teinase protein 9 and 2(MMP-9,MMP-2)and tight junction protein Occludin in mouse brain mi-crovascular endothelium cell line bEnd.3 injured by homocysteine(Hcy),and explore the protec-tive effects and underlying mechanisms of estrogen on small cerebral vascular diseases.Methods bEnd.3 cells were treated with Hcy andβ-estradiol respectively,and the optimal concentration was determined for cell proliferation and toxicity with enhanced cell counting kit-8.The cells were divided into control group,Hcy group(200 μmol/L),E2β group(200 nmol/L)and combined treatment group(200 nmol/L E2β treatment for 30 min followed by 200 μmol/L Hcy).After 6 h corresponding treatment,Western blotting was used to detect the protein levels of MMP-9,MMP-2 and Occludin in each group of cells.Results There were no significant differences in the protein levels of MMP-9,MMP-2 and Occludin in above groups after treatment for 24 and 48 h(P＞0.05).Compared with the control group,the expression levels of MMP-9 and MMP-2 was signifi-cantly increased in the Hcy Group after treatment of 72 h(1.45±0.14 vs 1.00±0.00,1.35±0.15 vs 1.00±0.00,P＜0.05),while the level of Occludin was obviously decreased(0.64±0.05 vs 1.00±0.00,P＜0.05).Compared in the Hcy Group,the MMP-9 and MMP-2 levels were obviously decreased(0.84±0.19 vs 1.45±0.14,1.01±0.78 vs 1.35±0.15,P＜0.05),and that of Occludin was notably elevated in the combined treatment group(0.91±0.10 vs 0.64±0.05,P＜0.05).Con-clusion E2β can ameliorate blood-brain barrier damage in Hcy-treated bEnd.3 cells,resulting in decreased MMP-9 and MMP-2 expressions and increased Occludin expression.

Objective:To investigate the correlation between serum anti-phospholipase A2 receptor antibody (SAb) combined with glomerular complement C3 (GC3) deposition and clinicopathologic features and prognosis in patients with idiopathic membranous nephropathy (IMN).Methods:It was a retrospective cohort study. The patients diagnosed with IMN in Affiliated Hospital of Qingdao University from July 1, 2019 to April 30, 2022 were enrolled, and the clinical and pathological data were collected and analyzed. The patients were divided into negative SAb and negative GC3 (SAb -/GC3 -) group, negative SAb and positive GC3 (SAb -/GC3 +) group, positive SAb and negative GC3 (SAb +/GC3 -) group and positive SAb and positive GC3 (SAb +/GC3 +) group according to the status of SAb titer and GC3 deposition. Clinical and pathological characteristics among the groups were compared. Kaplan-Meier survival curve was used to compare the cumulative renal remission rates of different groups. Cox regression analysis model was used to analyze the related factors of renal remission. Results:A total of 143 IMN patients aged (53.35±12.34) years old were included in the study, including 94 males (65.7%). There were 17 patients (11.9%) in the SAb -/GC3 - group, 30 patients (21.0%) in the SAb -/GC3 + group, 19 patients (13.3%) in the SAb +/GC3 - group, and 77 patients (53.8%) in the SAb +/GC3 + group. Compared with SAb -/GC3 - group, the level of serum albumin was lower in the SAb +/GC3 + group, and the level of 24 h urine protein, SAb titer, and the proportions of glomerular anti-phospholipase A2 receptor antigen and renal tubule atrophy were higher in the SAb +/GC3 + group (all P<0.05). After 26.0 (19.0, 36.0) months of follow-up, a total of 96 patients (67.1%) attained remission. The proportion of patients receiving immunosuppressive therapy in the SAb +/GC3 + group was higher than that in the SAb -/GC3 - group [93.5% (72/77) vs. 70.6% (12/17), fisher value=8.974, P=0.016] and the proportion of renal remission rate in the SAb +/GC3 + group was lower than that in the SAb -/GC3 - group [49.4% (38/77) vs. 100% (17/17), χ2=25.438, P<0.001]. Kaplan-Meier survival curve result showed that the cumulative renal remission rate in the SAb +/GC3 + group was significantly lower than that in the SAb -/GC3 - group (Log-rank χ2=31.538, P<0.01). Multivariate Cox regression analysis result showed that 24 h urine protein level ( HR=0.891, 95% CI 0.803-0.988, P=0.029), SAb titer ( HR=0.996, 95% CI 0.992-1.000, P=0.042) and SAb +/GC3 + (with SAb -/GC3 - group as reference, HR=0.414, 95% CI 0.204-0.827, P=0.013) were independent related factors for renal remission in patients with IMN. Conclusions:IMN patients with positive SAb and GC3 deposition have more severe clinical and pathological changes, lower renal cumulative remission rates, and are more likely to have poor prognosis. The combined assessment of SAb and GC3 deposition may be helpful for evaluating prognosis and guiding treatment in IMN patients.

Objective This study aims to explore the clinical characteristics of common mutation sites in the SOD1 gene and provide assistance for the early identification, diagnosis, and course evaluation of amyotrophic lateral sclerosis (ALS). Methods The clinical data and genetic testing results of a patient with ALS caused by the c.131A>G:p.H44R mutation in the second exon of the SOD1 gene were retrospectively analyzed and discussed in conjunction with the literature. Results The patient presented with pain and weakness in the right lower limb accompanied by muscle atrophy. No positive signs were observed in the sensory system. The electromyogram revealed subclinical neurogenic changes in the unaffected limbs. Whole-exome sequencing identified a rare mutation in exon c.131A>G:p.H44R of the SOD1 gene. Conclusion Early diagnosis of ALS is challenging, and the clinical manifestations vary depending on the gene site mutations. Genetic testing can assist in diagnosis and has significant identification value in the early stages of the disease.

Objective:To investigate the differences in the expression of microRNA (miR)-216a and its target gene SerpinB5 at the tissue level, and the effects of miR-216a on the proliferation of different liver cancer cells by regulating the expression of SerpinB5.Methods:Through bioinformatics prediction and selection of miR-216a that regulated SerpinB5. the expressions in liver cancer and normal tissues were detected by real time polymerase chain reaction (PCR). The miR-216a simulacrum and inhibitor, si-Serpinb5 and pcdna3.1-Serpinb5 to HepG2 and MHCC97H (97H) were transfected with liposomes, respectively. Real time PCR and Wester-Blot were used to detect the expression of miR-216a and SerpinB5 before and after transfection, and CCK8 was used to detect the influence of both on the proliferation of liver cancer cells.Results:The expression of miR-216a in human liver cancer tissues was higher than that in adjacent tissues, and the difference was statistically significant ( P < 0.01). The expression of SerpinB5 in human liver cancer tissues was lower than that adjacent tissues, and the difference was statistically significant ( P < 0.01). In HepG2 and 97H, miR-216a inhibitor and SerpinB5 overexpression group showed down-regulated miR-216a expression, which was statistically different from the control group ( P < 0.01). The proliferation of miR-216a inhibitor and pcdna3.1-serpinb5 group was lower than the control group, with statistically significant differences ( P < 0.01). Conclusions:The high expression of SerpinB5 can inhibit the proliferation of liver cancer cells, suggesting that SerpinB5 may have an anti-oncogene effect. MiR-216a may negatively regulate the expression of SerpinB5 and affect the proliferation of HCC cells.