Background and purpose:Human epidermal growth factor receptor 2(HER2)is closely associated with drug efficacy and prognosis in urothelial carcinoma(UC).HER2 is a significant biomarker and therapeutic target in various tumors.In recent years,anti-HER2 antibody-drug conjugates have shown significant clinical efficacy in UC patients with HER2 overexpression.Therefore,an in-depth understanding of HER2 expression and its characteristics in Chinese UC patients is crucial to guide treatment decision-making,optimize treatment strategies and achieve personalized therapy.This study aimed to thoroughly investigate correlation of HER2 expression and clinicopathological characteristics in Chinese patients with UC.Methods:This study was a multicenter study that retrospectively included UC patients from urology departments of 8 tertiary hospitals in 5 geographical regions of China(North China,East China,South China,Central China and Northwest)whose tissue samples were collected from January 2023 to March 2024.Inclusion criteria:① age above 18 years;② UC diagnosed by histopathological or cytological examination;③ complete results of HER2 expression detection using immunohistochemistry(IHC)in the primary tumor site were required.Exclusion criteria:① diagnosed patients with tumors in other parts of the body;② physicians evaluated other situations that were not suitable for inclusion in this study.IHC results for HER2 expression and clinicopathological data were collected.HER2 expression was determined according to the criteria outlined in"Clinical pathological expert consensus on HER2 testing in urothelial carcinoma in China",with HER2 2+and 3+defined as HER2 overexpression.The HER2 expression and clinicopathological features were analyzed.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethical number:2301268-12)and was registered at China Clinical Trial Registry(registration number:ChiCTR2300069746).Results:A total of 1054 patients with UC were included.Most of the tumors were bladder UC(n=807,76.6%).The mean age of patients was(66.8±10.5)years,and the majority were male(78.5%).The HER2 overexpression rate was 58.4%(n=616),with an additional 23%of patients having HER2 1+expression(n=242),and a small proportion exhibiting negative HER2 expression(n=196,18.6%).HER2 expression was significantly associated with various clinical and pathological characteristics such as Eastern Cooperative Oncology Group(ECOG)performance status,history of cardiovascular disease,history of metabolic disorders,smoking,UC disease location,differentiation grade,pathological type,and tumor stage.Conclusion:Retrospective analysis of multi-center data shows that HER2 expression is frequently observed in Chinese UC patients,with an overexpression rate of up to 58.4%.Furthermore,HER2 expression is closely associated with various clinical and pathological features of UC patients.This study underscores the critical importance of accurately assessing HER2 expression in UC patient to guide personalized therapies.

Objective To investigate the effects of pretreatment with Xuebijing injection on renal tubular injury in rats with contrast-induced acute kidney injury(CI-AKI).Methods Twenty-four Sprague-Dawley(SD)rats were selected and divided into normal group,model group,control group,and treatment group according to the random number table method,with 6 rats in each group.The animal model of CI-AKI was prepared by adopting iohexol,and the normal group was not subjected to any treatment.The rats in the treatment group were injected with Xuebijing injection via the tail vein 15 hours before modeling until 24 hours after modeling.The injection volume was 10 mL/kg for every 6 hours.The control group was injected with normal saline at the same time point.After 24 hours of modeling,the urine of rats in each group was collected to determine the levels of blood urea nitrogen(BUN)and urine N-acetyl-β-D-gluco-aminidase(uNAG),and the blood was collected to determine the levels of serum creatinine(SCr).Then the rats were killed and the kidney tissues were extracted,and then stained with hematoxylin-eosin(HE),and the pathological changes of the kidney tissues were observed under the light microscope.Results BUN,SCr and uNAG were significantly higher in the model group than those in the normal group[BUN(μmol/L):37.29±6.18 vs.6.37±1.19,SCr(mmol/L):30.43±4.44 vs.14.90±1.61,uNAG(U/L):47.77±4.71 vs.11.32±3.62,all P<0.01];BUN,SCr and uNAG levels were obviously decreased in the treatment group compared to the model group[BUN(μmol/L):9.45±3.04 vs.37.29±6.18,SCr(mmol/L):19.83±2.16 vs.30.43±4.44,uNAG(U/L):21.70±6.21 vs.47.77±4.71,all P<0.05],however,BUN and uNAG in the treatment group were still significantly higher than those in the normal group[BUN(μmol/L):9.45±3.04 vs.6.37±1.19,uNAG(U/L):21.70±6.21 vs.11.32±3.62,P<0.05 or P<0.01];SCr in the treatment group was not statistically significant compared to the normal group(μmol/L:19.83±2.16 vs.14.90±1.61,P>0.05).Under the light microscope,the renal tubular epithelial cells at the junction of cortex and dermatomedulla in the kidneys of the model group were obviously vacuolated,accompanied by cell detachment and necrosis,and the tubules were dilated,with no obvious lesions in the glomeruli.The degree of damage in the control group and the treatment group was reduced compared with that in the model group.The degree of renal tubular damage in the model group was higher than that in the normal group;while the degree of renal tubular damage in the control group was significantly lower than that in the model group;and the degree of renal tubular damage in the treatment group was lower than that in the model group.There was no statistically significant difference in the degree of renal tubular damage between the treatment group and the control group.Conclusion Xuebijing injection may exert a protective effect on renal function in rats with CI-AKI by attenuating renal tubular injury.

Objective　To explore the application of time series models based on meteorological factors in the population density of Aedes albopictus in Hainan Province, and to provide a scientific basis for the prevention and control of dengue fever in Hainan Province. Methods　The density of Aedes albopictus in different habitats in 18 cities and counties of Hainan Province from 2017 to 2022 was monitored monthly using the double-mosquito net trapping index and the Breteau index. Mann-Kendall trend test was used to analyze the temporal trends of the two density indices; Spearman's correlation analysis was employed to assess the correlation strength between each meteorological factor and the two indexes, eliminating unrelated variables, and further selecting the final variables through the full-subset regression method. Three time-series models were constructed for the two density indices, with root mean square error (RMSE), mean absolute error (MAE), and other accuracy metrics used to determine the optimal model; predictions for the density indices for 2023-2024 were made. All statistical analyses were performed in R (4.3.1). Results　The net trapping and Breteau indices showed an overall decrease over the years (Z-values of Mann-Kendall trend test were -6.15 and -4.03, respectively, and P<0.05). The meteorological factor most strongly associated with the trap index was the monthly average minimum temperature; monthly mean minimum temperature and monthly mean relative humidity were strongly correlated with the Breteau index. Based on various evaluation indicators, the multivariate time series model demonstrated the highest accuracy. The study predicts one to two peaks in both the trap index and Breteau Index for the years 2023 and 2024, with peak periods occurring between June to September and May to September, respectively. The predicted value for 2023 aligns with the measured value, demonstrating outstanding predictive accuracy. Conclusions　This study has introduced meteorological factors into the seasonal time series model, allowing for more accurate predictions of the density of Aedes albopictus in Hainan Province from 2023 to 2024, providing a model framework for the prevention and control of dengue fever in Hainan Province.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid decline of renal function in a short period of time. In recent years, the incidence of AKI has been increasing gradually. Once the AKI occurs in a patient whose mortality in hospital may be increased significantly, the length of stay in hospital will be prolonged and the hospitalization costs increased in a short term, the long-term consequences include AKI recurrence, development into chronic kidney disease (CKD) or end-stage kidney disease (ESRD), cardiovascular events and death, etc. Ischemia/reperfusion (I/R) injury and contrast agents are common causes of AKI. The nephropathy induced by I/R and contrast agent is associated with intracellular calcium overload caused by Na+-Ca2+ exchanger (NCX). In this article, a systematic review of the relationship between NCX and AKI was conducted, aiming to provide a reference for further recognizing the prevention, treatment and prognosis of AKI.

Objective: To explore the predictive value of circulating tumor cells (CTCs) characterization for time to castration resistance of newly diagnosed high volume metastatic castration sensitive prostate cancer (mCSPC) patients. Methods: Newly diagnosed high volume mCSPC patients were prospectively enrolled in this study from September 2015 to February 2017. The inclusion criteria include that the patients' age should be between 18 to 85 years old. The Prostate cancer should be diagnosed by biopsy or cytopathology. No endocrinological therapy, radiative therapy or chemotherapy was used before the study. High-volume metastatic lesion was confirmed by imaging. Those patients who accepted previous endocrinological therapy, radiative therapy or chemotherapy were excluded in this study. Those patients combined with concomitant tumor were also excluded. The health males were enrolled in the control group. All patients received androgen deprivation therapy (ADT) with goserelin plus bicalutamide (goserelin 3.6 mg subcutaneous injection, once a month plus bicalutamide 50mg orally, once a day). CanPatrol system was used to count CTCs in peripheral blood of patients and characterize CTCs based on expressions of epithelial markers(EpCAM and CK8/18/19) and mesenchymal markers(vimentin and twist). Primary endpoint was time to castration resistance. Survival analysis was conducted using Kaplan-Meier method and log-rank test was used to assess the difference of survival between groups, and univariate and multivariate analyses of prognostic factors were conducted using the Cox proportional hazards model. Results: A total of 108 newly diagnosed high volume mCSPC patients were enrolled in this study. The median age of enrolled patients was 68 years old (ranging 51-85 years old), and median PSA was 196.2 ng/ml(ranging 5.8-5 011.9 ng/ml). The median level of hemoglobin was 32 g/L(ranging 9-172 g/L). The median level of LDH was 179 U/L(ranging 49-630 U/L). The ECOG scores was 0-1 score in 94 cases(87.0%), 2 scores in 14 cases (13.0%). The Gleason scores was 6-7 in 20 cases (18.5%) and more than 8 in 88 cases (81.5%). All patients had bone metastatic lesions, among which 41 (38.0%) patients had more than 10 metastatic lesions and 6 (5.6%) patients with visceral metastasis, 30(27.8%) patients with limb bone metastasis. The median CTCs count was four, and ranging 0-35. Mesenchymal CTCs positive and negative (negative included CTCs negative, epithelial CTCs positive and biophenotypic CTCs positive) patients were 58(53.7%) and 50, respectively. There was no correlation between CTCs characterization with age, baseline PSA, Gleason score, ALP and other clinical parameters (P>0.05). In control group, the mean age was 26 years old (ranging 20-31 years old). No CTCs were detected among those people. After a median follow-up of 24 months (ranging 18-32 months), 90 patients (83.3%) progressed to castration resistant prostate cancer (CRPC). The median time to CRPC for patients of mesenchymal CTCs positive and negative was (10.5±1.4) and (14.0±3.4) months, respectively(P<0.001). Univariate analysis revealed CTCs characterization(HR=1.647, P=0.003), the number of metastatic lesions (HR=1.624, P=0.025)and limb bone metastasis(HR=1.706, P=0.019) were prognostic factors of time to CRPC; further multivariate analysis showed that only baseline mesenchymal CTCs positive (HR=1.562, P=0.008) was independent prognostic factors of unfavorable time to CRPC. Conclusions CTCs characterization can predict time to CRPC of newly diagnosed high volume mCSPC patients receiving ADT, and patients of baseline mesenchymal CTCs positive are more likely to progress to CRPC.

Objective To evaluate the effects of autophagy on contrast-induced acute kidney injury (CI-AKI) in rat models.Methods Eighteen male rats were divided into control group (Con),CI-AKI group (CI-AKI) and rapamycin-pretreated group (Rapa).In the CI-AKI group,CI-AKI was induced by intraperitoneal injection of iohexol (12.25 g/kg I).In the Rapa group,rapamycin was given by intraperitoneal injection with a dose of 5 mg/(kg ·d) for consecutive 7 days,and then injected with iohexol (12.25 g/kg I).Rats in the Con group were injected by the same dose of saline.The renal function,renal histopathology,and the levels of LC3 Ⅱ / Ⅰ and Beclin-1 as well as catalase (CAT) in the kidneys of rats were evaluated one day after the injection.Results Compared with the Con group,serum creatinine in the CI-AKI group was significantly increased ((239.93±27.00)μmol/L) vs (51.70±10.59) μmol/L,P＜0.05),and the content of CAT was significantly decreased ((14.86 ± 0.32) U/mg vs (18.72±1.46) U/mg,P＜0.05).In the CI-AKI group,renal tubules were severely injured,and the expression of autophagy-related proteins LC3 Ⅲ / Ⅰ and Beclin-1 in renal tissue was increased.Compared with the CI-AKI group,the pretreatment of rapamycin (Rapa group) increased the expression of LC3 Ⅱ / Ⅰ and Beclin-1 as well as the content of CAT in renal tissue ((17.62±1.86) U/mg vs (14.86±0.32) U/mg,P＜0.05),and inhibited the increase of contrast-induced serum creatinine ((187.62± 47.76) μmol/L vs (239.93±27.00) μmol/L,P＜0.05) and renal tubule injury.Conclusions The results showed that contrast administration can induce autophagy activation in kidneys,while enhancing autophagy can attenuate contrast-induced oxidative stress injury and related renal injury.

OBJECTIVETo analyze the risk factors to impact biochemical recurrence after radical prostatectomy.

METHODSA total of 1 090 patients who received radical prostatectomy from May 2002 to December 2013 in Department of Urology of Fudan University Shanghai Cancer Center were recruited. The average age of the patients was 67.9 years (ranged from 41 to 84 years) and the average preoperative prostate specific antigen (PSA) level was 32.7 (ranged from 3.2 to 256.3) µg/L. The distribution of patients with respect to clinical stage was: 20.09% (219/1 090) had T1, 50.09% (546/1 090) had T2 and 29.82% (325/1 090) had T3. The biochemical-free-survival curve was drawn by Kaplan-Meier method and the univariate and multivariate Cox regression models were used to evaluate the clinical and pathological variables for the development of biochemical recurrence.

RESULTSOf all the 1 090 patients, the biochemical recurrence free survival was 95.99%, 81.90% and 70.89% at 1, 3 and 5 years. PSA level at diagnosis (P=0.000), neo-adjuvant hormonal therapy (P=0.001), pre-operative Gleason score (P=0.000), clinical stage (P=0.010), surgical margin status (P=0.028), post-operative Gleason score (P=0.000), pathological stages (P=0.000) and pelvic lymph-node metastasis (P=0.000) were associated with biochemical recurrence in the univariate analysis. However, in the multivariate analysis, only PSA level at diagnosis (P=0.000), pre-operative Gleason score (P=0.020), pathological stages (P=0.014) and pelvic lymph-node metastasis (P=0.017) were independent prognostic factors.

CONCLUSIONFor the patients who received radical prostatectomy, PSA level at diagnosis, pre-operative Gleason score, pathological stages and pelvic lymph-node metastasis status are independent prognostic factors for biochemical recurrence.

Adult ; Aged ; Aged, 80 and over ; China ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Pelvis ; pathology ; Postoperative Period ; Proportional Hazards Models ; Prostate-Specific Antigen ; blood ; Prostatectomy ; Prostatic Neoplasms ; pathology ; surgery ; Risk Factors

Objective To determine the effect of moderate hypothermia on coagulation in patients with severe traumatic brain injury (sTBI) and investigate the clinical significance of thrombelastogram (TEG) monitoring.Methods Seventy-five patients with sTBI were randomly assigned to hypothermia group (conventional treatment + moderate hypothermia within 24 hours posttrauma,n =38) and control group (conventional treatment alone,n =38).TEG aided in monitoring coagulation function by measuring clot reaction time (R),clot formation time (K),clotting rate (α),maximal amplitude (MA),and percent fibrinolysis at 30 minutes after MA (LY30).Meantime,the intracranial pressure,vital signs,blood gas values,and blood electrolytes were also measured.Outcome was evaluated by using Glasgow outcome scale (GOS).Results The two groups were similar on admission with respect to R,K,α,MA,and LY30 (P ＞ 0.05),but the coagulation index in hypothermia group was significantly different from that in control group at days 1,2,3 and 7 posttreatment (P ＜ 0.05).Moreover,moderate hypothermia therapy demonstrated decrease of intraeranial pressure (P ＜ 0.01),with no severe complications,low mortality and improved outcome in comparison with control group.Conclusion Moderate hypothermia improves the hypercoagulability in patients with sTBI without increasing the risk of hyperfibrinolysis and protects brain tissue by decreasing intracranial pressure.

Objective To evaluate the effects of autophagy on oxidative stress induced by contrast media in podocytes.Methods The differentiated mouse podocytes were exposed to contrast media (Iopromide,50 mg/L)、rapamycin (Rap,autophagy enhancer,1 ng/L),3-methyladenine (3-MA,autophagy inhibitor,2 mmol/L) for 2 hours.The expression of autophagy protein LC3-Ⅱ and Beclin-1 as well as oxidative stress-related proteins Catalase,MnSOD were detected by Western blot.The formations of autophagy were observed by MDC staining,and the levels of reactive oxygen species (ROS) by CM-H2DCFDA staining.Cell activity was evaluated by CCK8 assay.Results Both the levels of oxidative stress and autophagy in podocytes increased when stimulated by contrast media,the expression of LC3-Ⅱ and Beclin-1 were enhanced,Catalase and MnSOD were inhibited (all P ＜ 0.05).Rapamycin increased the expression of Catalase,MnSOD and cell activity of podocytes,reduced the generation of ROS (all P ＜ 0.05),but in Rap group,cell activity showed no significant difference (P ＞ 0.05).3-MA decreased the expression of Catalase 、MnSOD and inhibited the cell activity of podocyte,increased the generation of ROS (all P ＜ 0.05).Conclusion Autophagy protects podocyte from contrast media by the means of reducing oxidative stress.