Objective:To investigate the regulatory effects of ring finger protein 43 (RNF43) on CD8 + T cell-mediated anti-tumor immune reaction in melanoma. Methods:RNF43 gene was over-expressed and knockdown in mouse melanoma cells line B16-OVA by lentivirus infection; In vivo proliferation of mouse melanoma cells line B16-OVA in the Lv-Ctrl-OE, Lv-RNF43-OE, Lv-Ctrl-KD and Lv-RNF43-KD groups was detected by subcutaneous tumorigenesis assay in mice, and the expression levels of CD8 + T cells perforin and interferon γ (IFN-γ) in tumor immune microenvironment of melanoma were detected by flow cytometry; The expression levels of β-catenin and programmed death-ligand 1 (PD-L1) mRNA in cells were detected by quantitative real-time PCR assay; The effect of RNF43 on the transcriptional regulation of PD-L1 was detected by dual-luciferase reporter gene assay. Results:Stable RNF43 over-expressing and RNF43 knockdown mouse melanoma cells lines Lv-RNF43-OE and Lv-RNF43-KD were successfully constructed. The results of subcutaneous tumorigenesis experiment in mice showed that the tumor mass of the Lv-RNF43-OE group was (0.08±0.06) g, which was significantly smaller than that of the Lv-Ctrl-OE group [ (1.04±0.52) g], with a statistically significant difference ( t=3.71, P=0.032) ; The tumor mass of Lv-RNF43-KD group was (1.94±0.29) g, with no statistically significant difference ( t=-1.70, P=0.164) compared with that of the Lv-Ctrl-KD group (1.15±0.74) g. The flow cytometry results showed that the fluorescence intensity of CD8 + T cell perforin in the Lv-RNF43-OE group was 9 034 ± 2 628, which was significantly higher than that in the Lv-Ctrl-OE group (3 847 ±1 637), with a statistically significant difference ( t=-3.35, P=0.015) ; The fluorescence intensity of CD8 + T cell perforin in the Lv-RNF43-KD group was 966±247, which was significantly lower than that in the Lv-Ctrl-KD group (2 226±646), with a statistically significant difference ( t=3.16, P=0.034) ; The fluorescence intensity of IFN-γ of CD8 + T cell in the Lv-RNF43-OE group was 2 422±429, which was significantly higher than that of 1 688±324 in the Lv-Ctrl-OE group, with a statistically significant difference ( t=-2.73, P=0.034) ; The fluorescence intensity of IFN-γ of CD8 + T cell in the Lv-RNF43-KD group was 614 (454, 863), with a statistically significant difference ( Z=-1.96, P=0.050) compared with 1 159 (1 152, 2 068) in the Lv-Ctrl-KD group. The results of quantitative real-time PCR showed that the relative expression level of β-catenin mRNA in the Lv-RNF43-OE group was 0.67±0.16, which was significantly lower than that of 1.00±0.11 in the Lv-Ctrl-OE group, with a statistically significant difference ( t=2.98, P=0.041) ; The relative expression level of PD-L1 mRNA in the Lv-RNF43-OE group was 0.32±0.09, which was significantly lower than that of 1.00±0.09 in the Lv-Ctrl-OE group, with a statistically significant difference ( t=9.13, P=0.001). The results of the dual-luciferase reporter gene assay showed that the PD-L1 promoter luciferase activity in the pCMV6-NC, RNF43, RNF43+β-catenin and β-catenin groups were 1.00±0.00, 0.84±0.00, 1.49±0.00 and 1.57±0.03 ( F=2 218.33, P<0.001). Further pairwise comparison showed that compared with the pCMV6-NC group, PD-L1 promoter luciferase activity was significantly lower in the RNF43 group ( P<0.001) and significantly higher in the RNF43+β-catenin and β-catenin groups ( P<0.001; P=0.003) ; compared with the RNF43 group, PD-L1 promoter luciferase activity was significantly higher in the RNF43+β-catenin group ( P<0.001) . Conclusion:RNF43 may reduce the expression of PD-L1 mRNA in melanoma by inhibiting the expression of β-catenin and promote CD8 + T cell-mediated anti-tumor immune reaction.

Objective:To investigate the relationship between the positive surgical margin and clinical factors such as neoadjuvant hormonal therapy after robot-assisted laparoscopic radical prostatectomy (RARP) in high-risk patients with prostate cancer.Methods:The clinical data of 164 patients with high-risk prostate cancer being performed RARP by one surgeon were analyzed retrospectively in our hospital from January 2016 to January 2022. The mean patient’s age was (65.3±6.2) years old, mean body mass index (BMI) was (25.6±3.0) kg/m 2, the median value of total prostate specific antigen (tPSA) before operation was 18.6(11.3, 31.3)ng/ml, the median value of Gleason score before operation was 7 (7, 8), the median value of prostate volume was 29.3 (22.4, 40.2) ml, and the clinical stage was T 2aN 0M 0-T 4N 0M 0. 80 patients with prostate cancer were treated with neoadjuvant endocrine therapy. All of them were treated with complete androgen blockade with a median course of 3 months. Univariate analysis was used to analyze the correlation between age, BMI, prostate volume, neoadjuvant hormonal therapy, preoperative tPSA, clinical stage, Gleason score before operation and positive surgical margin. Then multivariate logistic regression was used to further analyze the independent risk factor of positive surgical margin after RARP. Results:The postoperative pathological diagnosis included pT 2 stage in 111 cases (67.7%), pT 3a stage in 15 cases (9.1%), pT 3b stage in 25 cases (15.2%), pT 4 stage in 13 cases (7.9%). No lymph node metastasis was noticed in all patients. The Gleason scores included 6 in 11 cases (6.7%), 3+ 4 in 26 cases (15.9%), 4+ 3 in 36 cases (22.0%), 8 in 17 cases (10.4%), 9-10 in 24 cases (14.6%), un-evaluation due to endocrine therapy in 50 (30.5%). The positive surgical margin of high-risk patients with prostate cancer was 44.5% (73/164). Univariate analysis showed that the neoadjuvant hormonal therapy, tPSA and clinical stage were correlated with positive surgical margin ( P<0.05). Multivariate logistic regression analysis showed that non-neoadjuvant hormonal therapy, preoperative tPSA>20ng/ml and clinical stage>T 2b were independent risk factors for positive surgical margin of high-risk patients with prostate cancer. Stratified analysis showed that when the preoperative tPSA was 10-20 ng/ml(21.1% vs.55.9%, P=0.014), the clinical stage was T 2c(29.6% vs.49.1%, P=0.040), the Gleason score before operation was 7(19.4% vs.54.1%, P=0.003), the positive surgical margin of high-risk patients in the neoadjuvant hormonal therapy group was significantly lower than that in the non-neoadjuvant hormonal therapy group ( P<0.05). Conclusions:Non-neoadjuvant hormonal therapy, preoperative tPSA>20 ng/ml and clinical stage>T 2b were independent risk factors for positive surgical margin of RARP in the high-risk patients with prostate cancer. For high-risk patients with preoperative tPSA of 10-20 ng/ml, clinical stage of T 2c and Gleason score before operation of 7, neoadjuvant hormonal therapy has important clinical significance in reducing the positive surgical margin of RARP.

Objective To explore the correlation between contrast sensitivity and binocular visual function in indi-viduals with high myopia,aiming to understand how binocular visual function impacts contrast sensitivity in this popula-tion.Methods In this cross-sectional study,a total of 33 patients(66 eyes)with high myopia attending the Optometric Center of Tianjin Eye Hospital from March to December 2020 were included.They were measured for oculomotor parame-ters as well as binocular contrast sensitivity in photopic and scotopic conditions.According to the type of functional indica-tors to which the oculomotor parameters belong,they were divided into two groups:accommodation and vergence.The oculomotor parameters of accommodation include accommodative amplitude(AMP),monocular accommodative facility(MAF)and binocular accommodative facility(BAF);the oculomotor parameters of vergence include distance lateral pho-ria(DLP),near lateral phoria(NLP),positive fusional vergence(PFV),negative fusional vergence(NFV),and vergence facility(VF),among them,PFV includes the near and distance PFV breaking points and recovery points,and NFV includes the near and distance NFV breaking points and recovery points.Pearson bivariate correlation analysis was used to analyze the bivariate correlations between binocular contrast sensitivity and the oculomotor parameters of accommodation and ver-gence.In addition,canonical correlation analysis was used to analyze the associations between binocular contrast sensitivi-ty and accommodation and vergence indicators in patients with high myopia.Results The spherical equivalent refraction of the participants was(-9.51±2.71)D in the left eye and(-10.00±2.88)D in the right eye.The bivariate correlation analysis showed that among the oculomotor parameters of accommodation,the AMP of the left eye was negatively correla-ted with the contrast sensitivity at 18 c·d-1 under scotopic conditions(r=-0.406,P=0.019);among the oculomotor pa-rameters of vergence,the near PFV breaking point was positively correlated with the contrast sensitivity at 1.5 c·d-1(r=0.458)and3.0 c·d-1(r=0.441)under scotopic conditions(both P＜0.05),the near PFV recovery point was positively correlated with the contrast sensitivity at 3.0 c·d-1(r=0.351)and 6.0 c·d-1(r=0.396)under photopic conditions(both P＜0.05)and positively correlated with contrast sensitivity at 1.5 c·d-1(r=0.449),3.0 c·d-1(r=0.537)and 12.0 c·d-1(r=0.375)under scotopic conditions(all P＜0.05),and VF was positively correlated with contrast sensitivity at 1.5 c·d-1(r=0.358)under photopic conditions and 3.0 c·d-1(r=0.458)under scotopic conditions(both P＜0.05).Except for the above indicators,other oculomotor parameters of accommodation and vergence were not correlated with contrast sensitivity(all P＞0.05).Canonical correlation analysis showed that only the oculomotor parameters of vergence were correlated with the first pair of canonical correlation coefficients of contrast sensitivity under scotopic conditions(P=0.008)and the canonical correlation coefficient was 0.912.The oculomotor parameters of convergence U1 were mainly de-termined by NLP,near NFV recovery point,near PFV breaking point,and near PFV recovery point.Contrast sensitivity V,under scotopic conditions was mainly determined by contrast sensitivity at 1.5 c·d-1 and 6.0 c·d-1under scotopic condi-tions.The typical structural analysis showed that there was a strong positive correlation of U1 with near PFV breaking point and contrast sensitivity at 1.5 c·d-1 under scotopic conditions;there was a strong positive correlation of V1 with near PFV breaking point and contrast sensitivity at 1.5 c·d-1 under scotopic conditions.Conclusion There is an association be-tween vergence and contrast sensitivity under scotopic conditions among high myopia patients.Improving binocular visual function may enhance contrast sensitivity and overall visual quality in high myopia patients.

Objective: To investigate the prevalence of autonomic dysfunction and its influencing factors in the elderly in Jizhou community of Tianjin. Methods: By using a cross-sectional study, a questionnaire survey was conducted in the elderly in order to investigate the prevalence of autonomic dysfunction and its influencing factors. Results: A total of 1 292 elderly patients were enrolled.Of them, 196 cases had autonomic dysfunction(15.2%, 196/1 292). The main symptoms of autonomic dysfunction were frequent urination, urination urgency, urination incontinence(19.7%, 255/1 292)and constipation(15.9%, 205/1 292). Multivariate Logistic regression analysis showed that women(OR=1.808, 95%CI: 1.253~2.607), 75-85 years of age(OR=1.573, 95%CI: 1.109~2.232), general anesthesia history(OR=1.552, 95%CI: 1.044~2.307), sleep disorders(OR=2.906, 95%CI: 1.506~2.916), diabetes(OR=1.791, 95%CI: 1.197~2.678)and headache(OR=2.589, 95%CI: 1.482~4.520)were risk factors for autonomic dysfunction. Conclusions The prevalence of autonomic dysfunction is high in the elderly in Jizhou community of Tianjin city.It is necessary to pay great attention to potential risk factors of autonomic dysfunction in the elderly.And the autonomic dysfunction symptoms should be diagnosed and treated as early as possible.