[Objective] To explore the expression of Nectin-4 in invasive bladder urothelial carcinoma (BUC) tissue and its clinical significance, so as to provide reference for clinical diagnosis and treatment of BUC. [Methods] Nectin-4 expression in 60 cases of invasive BUC and 40 cases of chronic inflammation of bladder mucosa was detected with immunohistochemical staining (IHC) and RNAscope.The results of the two methods were analyzed and compared, and the relationship between the two methods and the clinicopathological characteristics of invasive BUC was discussed.The correlation between the protein expression of Nectin-4 in BUC tissues, human epidermal growth factor receptor 2 (Her-2) and programmed death factor ligand 1 (PD-L1) was analyzed. [Results] The positive protein expression rates of Nectin-4 detected by IHC were 78.33%(47/60) and 17.50% (7/40) in the invasive BUC group and inflammatory group, respectively, while the positive mRNA expression rates of Nectin-4 detected by RNAscope were 83.33% (50/60) and 12.50% (5/40), respectively.The Kappa values of Nectin-4 in the invasive BUC group and inflammatory group were 0.732 and 0.610, respectively, with general consistency.The protein expression of Nectin-4 in invasive BUC was correlated with muscular invasion, histological grade, vascular thrombus, lymph node metastasis and clinical stage (P<0.05). The mRNA expression of Nectin-4 in invasive BUC was correlated with max tumor diameter, muscular invasion, histological grade, vascular thrombus, lymph node metastasis and clinical stage (P<0.05). The high expression of Nectin-4 in invasive BUC was positively correlated with the expression of Her-2 (P=0.002), but not with the expression of PD-L1 (P>0.05). [Conclusion] Nectin-4 is highly expressed in invasive BUC, and is usually associated with the pathological parameters of poor prognosis.Detection of Nectin-4 expression will help to guide clinical diagnosis and treatment.

Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.

AIM:From the perspective of regulating mitochondrial complex I activity by DJ-1 protein,this study aims to explore the mechanism of DJ-1-mediated resveratrol(RES)preconditioning in protecting against oxidative stress injury induced by myocardial ischemia-reperfusion(I/R)in rats.METHODS:After intramyocardial injection of lentivirus carrying DJ-1 shRNA(sh-DJ-1)or negative control(NC)shRNA,the myocardial I/R model was constructed by ligating the left anterior descending branch of the rat coronary artery.Sprague-Dawley(SD)rats were randomly divided in-to 6 groups:sham group,I/R group,RES+I/R group,NC+RES+I/R group,sh-DJ-1+RES+I/R group,and IACS-010759(mitochondrial complex I inhibitor)+RES+I/R group,with 10 rats in each group.The rats in RES treatment groups were given RES(20 mg/kg)via gavage for 7 d prior to the myocardial I/R modeling,once daily.Moreover,the rats in sham and I/R groups received an equivalent volume of normal saline via gavage.Myocardial infarction area and cardiac function were assessed by TTC staining and echocardiography,respectively.The MitoSOX fluorescent probe was used to detect levels of mitochondrial reactive oxygen species(ROS)in the myocardium.The levels of malondialdehyde(MDA),superoxide dis-mutase(SOD)and lactate dehydrogenase(LDH)in the serum were detected using kits.Western blot and co-immunopre-cipitation assays were used to observe the interaction between DJ-1 and the two subunits,ND-1 and NDUFA4,of the mito-chondrial complex I.RESULTS:Compared with I/R group,RES pretreatment significantly reduced the myocardial in-farction area,mitochondrial ROS levels,serum LDH activity,and serum MDA content(P＜0.01).It also elevated left ventricular ejection fraction,left ventricular fractional shortening and serum SOD activity(P＜0.01).Pretreatment with RES increased the expression and mitochondrial translocation of DJ-1(P＜0.01),promoted the interaction between DJ-1 and ND-1/NDUFA4,which in turn protected the activity of mitochondrial complex I(P＜0.01).However,when the ex-pression of DJ-1 was suppressed,the protective effects of RES against myocardial I/R injury were significantly inhibited compared with RES+I/R group(P＜0.05 or P＜0.01).CONCLUSION:Pretreatment with RES increases the expression and mitochondrial translocation of DJ-1,and facilitates the interaction of DJ-1 with ND1 and NDUFA4 subunits of mito-chondrial complex I,thus preserving the activity of mitochondrial complex I and attenuating myocardial I/R-induced oxida-tive stress damage.

【Objective】 To evaluate the predictive value of isoform [-2] proprostate-specific antigen, p2 PSA (p2PSA) and its derived indexes for prostate cancer in a Chinese cohort with PSA 4-20 ng/mL. 【Methods】 A total of 139 males scheduled for biopsy were enrolled in the prospective study from Nov.2021 to Jun.2022. The total PSA (tPSA), free PSA (fPSA), fPSA/tPSA (f/t) and p2PSA were collected, and the percentage of p2PSA(%p2PSA) and prostate health index(PHI) were calculated. The predictive value of p2PSA and its derived indexes were compared with traditional indexes with receiver operating characteristic (ROC) curve and Logistic analysis. 【Results】 Prostate cancer was found in 54 cases (38.8%). There were significant statistical differences in tPSA(10.68 vs.8.14, P=0.021), f/t(0.13 vs.0.16, P=0.006), p2PSA(30.25 vs.19.81, P<0.001), %p2PSA(21.52 vs.13.15, P<0.001) and PHI(64.3vs.38.2, P<0.001) between prostate cancer patients and non-prostate cancer patients. The area under the ROC curve (AUC) of tPSA, fPSA, %fPSA, p2PSA, %p2PSA and PHI were 0.63, 0.51, 0.63, 0.71, 0.73, and 0.80, respectively. The inclusion of %p2PSA and PHI significantly increased the prediction efficiency of the basic prediction model (AUCbase+PHI=0.81, AUCbase+%p2PSA=0.78, AUCbase=0.67). With 35 as the recommended cut-off value of PHI, the incidence of meaningless puncture was reduced by 25.8%(36/139). 【Conclusion】 The application of p2PSA and its derived indexes have good predictive value for patients with PSA 4-20 ng/mL. The combined detection of %p2PSA and PHI can significantly increase the detection efficiency of prostate cancer and reduce the incidence of meaningless prostate puncture by 25.8%.

Objective:To establish a simple and efficient clinical prediction model of moderate and severe obstructive sleep apnea hypopnea (OSAHS) in snoring patients based on the clinical data and morphological measurement data in order to increase the early diagnosis and then early intervention of OSAHS. The prediction model is evaluated by external validation.Methods:A total of 299 subjects from January 2015 to December 2018 were selected to perform polysomngraphy (PSG) in Yangpu Hospital, Tongji University School of Medicine. According to the PSG results, they were divided into moderate and severe OSAHS groups (143 cases) and control groups (156 cases). Clinical complications data and morphological measurement data were collected. The regression equation and ROC curve were established according to the Logistic regression method. Then, another 110 subjects from January 2019 to October 2019 were chosen as verified data group, and used to verify the accuracy of the prediction model. The data of 110 subjects were put into the equation according to risk factors and assignment. The ROC curve was drawn and the area under the curve was calculated. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value were calculated.Results:The predicted equation was: y = -10.707 86+0.589 60 × sex+ 0.141 61 × BMI+ 1.281 62 × tonsil size degree+ 1.807 43 × modified Mallampati degree′tongue position. The AUC of the ROC curve of prediction model in training set was 0.851(95% CI 0.807-0.895), the sensitivity was 83.9%, the specificity was 79.5%, and the cut-off value was 0.634.The AUC of the ROC curve in validation set was 0.827(95% CI 0.751-0.904) with a sensitivity of 73.3% and a specificity of 86.0%, and an accuracy of 79.1%. Its positive predictive value was 5.238, and negative predictive value was 0.310. Conclusions:The predictive model constructed by the combination of clinically accessible data (sex) and morphological measurement (BMI, tonsil size degree, modifiedMallampatidegree) has a relatively high predictive efficiency for screening snoring patients with moderate and severe OSAHS. The predictive model is proved with good forecast accuracy by the external verification method.

Objective:To investigate the radiation field and dose selection of patients with isolated chest wall recurrence (ICWR) after modified radical mastectomy, and analyze the prognostic factors related to subsequent chest wall recurrence.Methods:Clinical data of 201 patients with ICWR after mastectomy admitted to the Fifth Medical Center, Chinese PLA General Hospital from 1998 to 2018 were retrospectively analyzed. None of the patients received postoperative adjuvant radiotherapy. After ICWR, 48 patients (73.6%) underwent surgery and 155 patients (77.1%) received radiotherapy. Kaplan-Meier method was used to calculate the post-recurrence progression-free survival (PFS) rates and the difference was compared by log-rank test. Multivariate analysis was performed using Cox regression model. Competing risk model was adopted to estimate the subsequent local recurrence (sLR) rates after ICWR and the difference was compared with Gray test. Multivariate analysis was conducted using F&G analysis. Results:With a median follow up of 92.8 months after ICWR, the 5-year PFS rate was 23.2%, and the 5-year sLR rate was 35.7%. Multivariate analysis showed that patients with surgery plus radiotherapy and recurrence interval o F>12 months had a lower sLR rate. Patients with recurrence interval o F>48 months, local plus systemic treatment and surgery plus radiotherapy had a higher PFS rate. Among the 155 patients who received chest wall radiotherapy after ICWR, total chest wall irradiation plus local boost could improve the 5-year PFS rate compared with total chest wall irradiation alone (34.0% vs. 15.4%, P=0.004). Chest wall radiation dose (≤60 Gy vs.>60 Gy) exerted no significant effect upon the sLR and PFS rates (both P>0.05). In the 53 patients without surgery, the 5-year PFS rates were 9.1% and 20.5%( P=0.061) with tumor bed dose ≤60 Gy and>60 Gy, respectively. Conclusions:Local radiotherapy is recommended for patients with ICWR after modified radical mastectomy of breast cancer, including total chest wall radiation plus local boost. The radiation dose for recurrence should be increased to 60 Gy, and it should be above 60 Gy for those who have not undergone surgical resection. In addition, patients with ICWR still have a high risk of sLR, and more effective treatments need to be explored.

Objective:To analyze the prognosis of patients with isolated regional recurrence (RR) after mastectomy, and evaluate the efficacy of radiotherapy and identify the optimal radiation target volumes.Methods:Clinical data of 144 patients with first isolated RR after mastectomy between 2001 and 2018 were retrospectively analyzed. All patients had not received post-mastectomy radiotherapy. The primary endpoints consisted of the subsequent locoregional recurrence (sLRR), distant metastasis (DM), progression-free survival (PFS) and overall survival (OS).Results:With a median follow-up of 82.5 months after RR, the 5-year sLRR, DM, PFS and OS rates for the entire group were 42.1%, 71.9%, 22.9% and 62.6%, respectively. Local plus systemic therapy was an independent favorable prognostic factor for sLRR ( P<0.001) and PFS ( P=0.013). The sLRR rate in the surgery plus radiotherapy group was the lowest ( P<0.001). Surgery plus radiotherapy significantly reduced the 5-year risk of recurrence within the initially involved nodal regions ( P<0.001). Patients with chest wall irradiation obtained the 5-year subsequent chest wall recurrence rate of 12.1% compared to 14.8%( P=0.873) for those without chest wall irradiation. The subsequent supraclavicular recurrence rate was lower in patients with prophylactic supraclavicular irradiation than that without prophylactic supraclavicular irradiation (9.9% vs. 23.8%, P=0.206). The incidence rates of initially uninvolved axillary and internal mammary nodal recurrence were below 10% regardless of prophylactic irradiation or not. Conclusions:Patients with RR alone have an optimistic 5-year OS in the contemporary era. Comprehensive locoregional treatment including surgery and radiotherapy combined with systemic therapy is recommended. The chest wall, axillary and internal mammary nodal prophylactic irradiation should not be routinely performed for all patients with RR. The value of supraclavicular prophylactic irradiation remains to be evaluated.

Objective:To analyze the prognostic factors of breast cancer patients with isolated chest wall recurrence (ICWR) after mastectomy, and investigate the optimal treatment.Methods:A total of 201 breast cancer patients with ICWR after mastectomy who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and the Fifth Medical Center Chinese PLA General Hospital from October 1998 to April 2018 were retrospectively analyzed. The median follow-up was 92.8 months and survival data were obtained.Results:Among 201 patients with ICWR, 103 patients developed subsequent locoregional recurrence (sLRR) and 5-year cumulative sLRR rate was 49.1%; 134 patients developed distant metastasis (DM) and 5-year DM rate was 64.4%; 103 patients died, the median progression-free survival (PFS) was 17.4 months and the 5-year PFS rate was 23.2%; the median overall survival (OS) was 62.5 months and the 5-year OS rate was 52.1%. Multivariate analysis showed that the recurrence interval ( HR=2.17, 95% CI: 1.26-3.73) and the locoregional treatment ( HR=1.59, 95% CI: 1.05-2.40) were the independent prognostic factors for sLRR. The initial HER2 status ( HR=1.60, 95% CI: 1.03-2.48) was the independent prognostic factor for DM. The recurrence interval ( HR=1.99, 95% CI: 1.30-3.04), the locoregional treatment ( HR=1.99, 95% CI: 1.43-2.76) and the treatment modalities after recurrence ( HR=1.70, 95% CI: 1.18-2.46) were the independent prognostic factors for PFS. The initial HER2 status ( HR=1.69, 95% CI: 1.02-2.81), the recurrence interval ( HR=1.85, 95% CI: 1.15-2.98) and the treatment modalities after recurrence ( HR=2.48, 95% CI: 1.56-3.96) were the independent prognostic factors for OS. Conclusions:Breast cancer patients after ICWR have an optimistic OS until now, but the risk of sLRR and DM is high. Comprehensive treatment modalities including surgery, radiotherapy and systemic therapy improve the outcome of breast cancer patients with ICWR after mastectomy.

Objective:To analyze the prognostic factors of breast cancer patients with isolated chest wall recurrence (ICWR) after mastectomy, and investigate the optimal treatment.Methods:A total of 201 breast cancer patients with ICWR after mastectomy who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and the Fifth Medical Center Chinese PLA General Hospital from October 1998 to April 2018 were retrospectively analyzed. The median follow-up was 92.8 months and survival data were obtained.Results:Among 201 patients with ICWR, 103 patients developed subsequent locoregional recurrence (sLRR) and 5-year cumulative sLRR rate was 49.1%; 134 patients developed distant metastasis (DM) and 5-year DM rate was 64.4%; 103 patients died, the median progression-free survival (PFS) was 17.4 months and the 5-year PFS rate was 23.2%; the median overall survival (OS) was 62.5 months and the 5-year OS rate was 52.1%. Multivariate analysis showed that the recurrence interval ( HR=2.17, 95% CI: 1.26-3.73) and the locoregional treatment ( HR=1.59, 95% CI: 1.05-2.40) were the independent prognostic factors for sLRR. The initial HER2 status ( HR=1.60, 95% CI: 1.03-2.48) was the independent prognostic factor for DM. The recurrence interval ( HR=1.99, 95% CI: 1.30-3.04), the locoregional treatment ( HR=1.99, 95% CI: 1.43-2.76) and the treatment modalities after recurrence ( HR=1.70, 95% CI: 1.18-2.46) were the independent prognostic factors for PFS. The initial HER2 status ( HR=1.69, 95% CI: 1.02-2.81), the recurrence interval ( HR=1.85, 95% CI: 1.15-2.98) and the treatment modalities after recurrence ( HR=2.48, 95% CI: 1.56-3.96) were the independent prognostic factors for OS. Conclusions:Breast cancer patients after ICWR have an optimistic OS until now, but the risk of sLRR and DM is high. Comprehensive treatment modalities including surgery, radiotherapy and systemic therapy improve the outcome of breast cancer patients with ICWR after mastectomy.

Objective To explore the effect of prognosis of consolidation radiotherapy for patients after R0 resection of local recurrence after radical mastectomy. Methods Totally 110 breast cancer patients with local recurrence receiving R0 resection were admitted and treated in our hospital from January 1st, 2003 to November 30th, 2015 were retrospectively analyzed. Results The median local progression time of 74 patients receiving consolidation radiotherapy ( 67.3％) was remarkably better than that of those without radiotherapy(36 patients, 32.7％), and the difference was statistically significant (χ2 =8. 526, P<0.05). Meanwhile, there was no statistically significant difference (P>0.05) of distance disease-free survival and overall survival between the radiotherapy group and the non-radiotherapy group. Multifactor analysis indicated that pseudo-adjuvant endocrine therapy (χ2 =7.541,95％CI:27.1％ -80.4％, P <0.05), DDFS(≥2 years vs. <2 years,χ2 =4.068,95％CI:101.4％ -267％,P<0. 05) and pseudo-adjuvant radiotherapy(χ2 =14.126, 95％CI:21.7％ -80.4％, P <0. 05 ) were the independent risk factors affecting the OS of patients with local recurrence after R0 resection. Conclusions For the patients with local recurrence after R0 resection of local recurrence, it is recommended that consolidation radiotherapy should be done and the radiation field should include the same side of the chest wall and clavicle area lymphatic drainage area.