Objective To explore the safety and efficacy of neoadjuvant chemotherapy(NAC)combined with immunotherapy before radical cystectomy plus pelvic lymph nodes dissection(RC-PLND)for muscle-invasive bladder cancer(MIBC).Methods The clinical data of 101 patients with MIBC who underwent neoadjuvant therapy followed by RC-PLND in the Department of Urology,the First Affiliated Hospital of Xi'an Jiaotong University during Jan.2019 and Dec.2023 were retrospectively analyzed,including 71 patients(70.3％)who received NAC(NAC group)and 30(29.7％)who received NAC combined with immunotherapy(NAC combine immunotherapy group).The clinical and pathological data and adverse events during neoadjuvant therapy were compared.Logistic regression analysis was used to explore the independent predictors of pathological complete response(pCR)and pathological partial response(pPR).Results There were no significant differences in the baseline data between the two groups(P＞0.05).However,the proportion of multiple tumors in patients receiving NAC before surgery was significantly higher than that in the NAC combined immunotherapy group(69.0％vs.46.7％,P=0.034).Compared with NAC group,NAC combined with immunotherapy group had significantly improved rate of pathological downstaging and pPR(60.6％vs.83.3％,P=0.026;45.1％vs.70.0％,P=0.022).Furthermore,the rate of pCR in patients undergoing NAC combined immunotherapy was higher than those undergoing NAC,but the difference was not significant(53.3％vs.33.8％,P=0.067).Logistic regression analysis revealed that clinical T-stage and tumor diameter were independent predictors of pCR and pPR(P＜0.05).In addition,the most common adverse events during neoadjuvant therapy were anemia,decreased white blood cells,nausea,and vomiting,but most of them were grade 1-2 and could be relieved through symptomatic treatment.Conclusion NAC combined with immunotherapy is safe and effective,which can improve the rate of pathological downstaging,pPR and pCR,without increasing the incidence of adverse reactions.

【Objective】 To explore the expressions of PBRM1 and PD-L1 in renal cell carcinoma (RCC), and the molecular mechanism of PBRM1 regulating PD-L1, in order to provide experimental results for clinical immunotherapy. 【Methods】 The protein expressions of PBRM1 and PD-L1 were detected with immunohistochemistry, and their mRNA expressions were determined by analyzing TCGA database. Meanwhile, the relationship between overall survival and mRNA expressions of PBRM1 and PD-L1 were analyzed in TCGA database. The exosomes were extracted with exoEasy Maxi Kit. Expressions of exosomal biomarkers CD63 and CD9 were detected with Western blotting, and their morphology was observed with transmission electron microscope. PD-L1 expression after IFN-γ, IL-6 and TNF-α treatment was detected with Western blotting. 【Results】 The expression of PBRM1 was significantly lower in canver tissue than in paracancerous tissue (P<0.001). The loss rate of PBRM1 was up to 76.4%. PBRM1 expression was not correlated with PD-L1 expression. PBRM1 deletion activated TNF-α/exosome signaling pathway, leading to increase of PD-L1 secretion in exosomes, which was then transported to the outside of cells. 【Conclusion】 There is no relationship between PBRM1 and PD-L1 protein expressions in RCC. However, PBRM1 mutation can lead to inflammatory signaling pathway activation, inducing PD-L1 secretion, which is encapsulated in exosomes and transported to the outside of cells, and affects the response of immunotherapy.

【Objective】 To investigate the effects of 450 nm diode blue laser on the morphological changes and thermal damage of renal pelvis under different conditions. 【Methods】 An ex vivo study was conducted on a fresh porcine pelvis model (7 cm×5 cm×3 cm). The laser fiber was fixed on the mechanical arm perpendicular to the renal pelvis tissue, and the distance between them was 1-2 mm. The renal pelvis tissue was incised at a speed of 1-2 mm/s and power of 5-30 W. After the incised tissue was fixed in formalin (4%), the morphology, depth, width and coagulation thickness were observed with naked eyes and a microscope. 【Results】 The different powers had different vaporization and incision effects. When the operating distance was 2 mm, the speed was 2 mm/s and power was 5 W, the vaporization depth, width and coagulation thickness were approximately 0 9 mm, 0.25 mm and 0.35 mm, respectively. With the increase of power, the vaporization width and depth increased, and the coagulation thickness was 0.35-0.50 mm. When the power was more than 10 W, the renal pelvis tissue was easily penetrated. When the laser power was 20 W, the section of the renal pelvis showed an irregular shape of vaporization. When the operating distance was 1 mm, the whole renal pelvis tissue was easily vaporized. When it was 2 mm, a wide and safe energy treatment window was produced. 【Conclusion】 The 450 nm diode blue laser can vaporize and incise renal pelvis tissue safely and effectively, with high precision and little thermal damage. It is expected to be a new surgical tool in the treatment of renal pelvis lesions.

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

Objective:To investigate the characteristics of bacterial community in upper gastrointestinal tumors.Methods:The study population was patients with upper gastrointestinal tumors (esophageal cancer and gastric cancer). Gastroscopy was performed on the enrolled patients ( n=17), and the specimens were taken from the tumor sites. At the same time, non-tumor tissues more than 4 cm away from the tumor tissues were taken as the control. After total DNA was extracted and purified, high-throughput 16S DNA gene sequencing was used to detect the microbiota in tumor tissues and control tissues. Bioinformatics analysis was carried out and the differences between groups were compared. Results:16S DNA PCR showed that there was no significant difference in bacterial load between tumor tissues and control tissues. The α-diversity and β-diversity indexes showed that the community composition of the two groups was similar; the samples were discrete and the colony composition was different, but there was no significant difference between the two groups. The results of Venn diagram showed that there were more operational taxonomic units (OTUs) in non-tumor tissues than in tumor tissues (2 068 vs 1 358), indicating that the bacterial species in normal tissues were more abundant than those in tumor tissues. Compared with the control tissues, the percentages of Prevotellaceae ( Prevotella), Lactobacaceae ( Lactobacillus) and Fusobacteriaceae ( Fusobacterium) in tumor tissues were relatively higher (the average percentage was more than twice that of the control). Further paired comparison of the top ten bacteria in the family and genus abundance of the two groups of samples showed that Pseudomonas decreased significantly in tumor tissues at the family ( P=0.041) and genus ( P=0.041) levels, while Prevotella was significantly enriched in tumor tissues at the family ( P=0.031) and genus ( P=0.007) levels. Conclusions:The bacterial community in the tumor microenvironment of the upper gastrointestinal tumor changed, and the species enriched in the tumor site were mainly oral common anaerobic bacteria, such as Prevotellaceae ( Prevotella), Lactobacaceae ( Lactobacillus) and Fusobacteriaceae ( Fusobacterium), especially Prevotellaceae ( Prevotella).

Objective:To investigate the risk factors for Gleason score upgrading after radical prostatectomy in clinical low-risk prostate cancer patients aged≥65 years.Methods:A total of 485 clinical low-risk prostate cancer patients aged≥65 years at five centers of the national multi-center PC-follow database from January 2015 to March 2019 were retrospectively analyzed.Data including age at diagnosis, prostate-specific antigen(PSA), MRI prostate imaging, puncture Gleason score, operation method, puncture method, positive incision margin and capsule penetration were collected.Differences in Gleason scores before and after operation were compared, and the risk factors for Gleason score upgrading after radical resection were evaluated by univariate and multivariate Logistic regression analysis.Results:Of 485 patients with a puncture Gleason score of 3+ 3=6, 261(53.8%)cases had postoperative pathological upgrading, in whom 228(87.4%)cases had Gleason score upgrading of 7, 22(8.4%)had Gleason score upgrading of 8, and 11(4.2%)had Gleason score upgrading of 9 or more.The rate of Gleason score upgrading was elevated with increased preoperative PSA levels, positive pelvic MRI, and higher positive rates of puncture biopsy.The incidences of postoperative capsule penetration(27.2% vs.12.5%, P<0.001)and positive incision margin(25.2% vs.17.4%, P=0.036)had statistically significant differences between the pathologically upgraded group and the pathologically non-upgraded group.Multivariate analysis showed that preoperative PSA level, percentage of positive puncture biopsies, biopsy Gleason score and pelvic MRI were independent predictors of prostate cancer. Conclusions:For clinical low-risk prostate cancer patients aged≥65 years with high risk factors for Gleason score upgrading, repeated biopsies should be carried out when necessary and the treatment plan should be adjusted accordingly.

Objective:To establish a nomogram model for predicting positive resection margins after prostate cancer surgery, and to perform the corresponding verification, in order to predict the risk of positive resection margins after surgery.Methods:A total of 2 215 prostate cancer patients from The First Affiliated Hospital of Naval Medical University, Hospital, Peking University First Hospital, Peking University Third Hospital, Peking University, and First Affiliated Hospital of Xi′an Jiaotong University were included in the PC-follow database from 2015 to 2018, and a simple random sampling method was used. They were divided into 1 770 patients in the modeling group and 445 patients in the verification group. In the modeling group, the age (<60 years, 60 to 70 years, >70 years), PSA (<4 ng/ml, 4-10 ng/ml, 11-20 ng/ml, >20 ng/ml), pelvic MRI (negative, suspicious, positive), clinical stage of the tumor (T 1-T 2, ≥T 3), percentage of positive needles (≤33%, 34%-66%, >66%), Gleason score of biopsy pathology (≤6 points, 7 points, ≥8 points). Univariate and multivariate logistic analysis were performed to screen meaningful indicators to construct a nomogram model. The model was used for validation in the validation group. Results:The results of multivariate analysis showed that preoperative PSA level ( OR=2.046, 95% CI 1.022 to 4.251, P=0.009), percentage of puncture positive needles ( OR=1.502, 95% CI 1.136 to 1.978, P=0.002), Gleason score of puncture pathology ( OR=1.568, 95% CI 1.063 to 2.313, P=0.028), pelvic MRI were correlated ( OR=1.525, 95% CI 1.160 to 2.005, P=0.033). Establish a nomogram model for independent predictors of positive margin of prostate cancer. The area under the receiver operating characteristic (ROC) curve of the validation group is 0.776. The area under the ROC curve of the preoperative PSA level, percentage of puncture positive needles, puncture pathology Gleason score, pelvic MRI, postoperative pathology Gleason score were 0.554, 0.615, 0.556, 0.522, and 0.560, respectively. The difference between the nomogram model and other indicators was statistically significant ( P<0.05). Conclusions:The constructed nomogram model has higher diagnostic value than the preoperative PSA level, percentage of puncture positive needles, Gleason score of puncturing pathology, pelvic MRI, and postoperative pathological Gleason score in predicting positive margin.

Objective To investigate the characteristics of pulmonary function and pathological changes in rats with acute lung injury (ALI) and provide experimental basis for further study on the mechanism of ALI.Methods Twenty five male SD rats were randomly divided into the control group (n =5) and acute lung injury (ALI) group (n =20).Lipopolysaccharide (LPS) (4.5 mg/kg) were injected into the ALI group rats to establish the ALI rat model.The rats in control group were given 150 μl isotonic saline.At 12,24,48,and 72 hours after injury,lung function of the rats were tested by Buxco small animal lung function test system,including the dynamic lung compliance (Cdyn),forced vital capacity (FVC),functional residual gas (FRC),quasi static compliance (Cchord),100th millisecond expiratory volume (FEV100),and airway resistance (RI).In addition,the bronchoalveolar lavage fluid (BALF) was collected for detection of protein level and tumor necrosis factor (TNF-alpha)concentration.At the same time,the changes of lung tissues were recorded,and the pathological changes were observed by HE staining.Results Compared with the control group,Cdyn,FVC,FRC,and FEV100 in ALI group were significantly decreased at each time point after injury (P ＜0.05 or ＜0.01),while the airway resistance (R1) in ALI group was significantly increased at 24 and 48 hours after injury (P ＜ 0.01).There was no significant difference in quasi static compliance (Cchord) between two groups (P ＞ 0.05).The protein level and TNF-alpha concentration of BALF in ALI group were increased significantly (P ＜0.05 or ＜0.01) 12-72 hours after injury (P ＜ 0.01).Compared with the control group,the whole lung was dark red in ALI group 12 hours after injury,and the most serious bleeding occurred in the pulmonary hilum area with single or multiple hemorrhagic foci of different sizes.Multiple punctate and focal bleeding of different sizes were seen on the lung surface,which were radially distributed around the pulmonary hilum.The color of lung tissue was gradually restored to normal at 72 hours after injury.Under the light microscope,pulmonary interstitial edema,inflammatory cell infiltration,pulmonary vascular congestion and focal pulmonary hemorrhage were observed 12 h after injury,showing typical ALl pathological changes.The pathological changes were the most significant at 24 hours and reduced obviously at 72 hours.Conclusions A single intratracheal injection of LPS can induce typical ALI pathological changes.There is a similar trend between the pulmonary function indexes,lung pathology characteristics,and the protein level of BALF and proinflammatory cytokine level,suggesting that the pulmonary function test parameters can provide reference for evaluation of ALI.

Objective To investigate the value of muhiple inflammatory cells and clinical score in early diagnosis and prognosis assessment of trauma sepsis risks.Methods This retrospective control study enrolled 209 severe trauma patients admitted from January 2010 and May 2016.White blood cell count,lymphocyte count and percentage,monocyte count and percentage,neutrophil count and percentage,ratio of neutrophil to lymphocyte count (N/L),acute physiology and chronic health evaluation (APACHE) Ⅱ score,sequential organ failure assessment (SOFA),improved early warning score (MEWS),Glasgow coma score (GCS),multiple organ dysfunction syndrome (MODS) score and lactic acid (LAC) were collected on the day of admission and 3,5,7 days after trauma.These data were applied to construct weighted and biological score models for early diagnosis and prognosis of traumatic sepsis.Receiver operating characteristic curve (ROC) was performed and area under the curve (AUC) was calculated to measure the value of the two models in early diagnosis and prognosis of sepsis.Results AUC of the weighted model combined by APACHE Ⅱ score,SOFA score and MEWS was 0.729 on the day of admission.AUC of the weighted model combined by inflammatory cells was 0.680 and AUC of the biological score model was 0.800 3 days after trauma (P ＜ 0.05).AUC of the weighted models combined by inflammatory cells was 0.798 and AUC of the biological score model was 0.812 5 days after trauma (P ＜ 0.05).AUC of the weighted models combined by inflammatory cells was 0.706 and AUC of the biological score model was 0.713 7 days after trauma (P ＞ 0.05).AUC of the biological score model had significant difference 3 days and 5 days after trauma (P ＜ 0.05).Of the weighted model combined by APACHE Ⅱ score,MODS score,GCS and LAC to evaluate the prognosis of sepsis,the AUC showed significant difference on the day of admission (0.838),3 days after trauma (0.878),5 days after trauma (0.947) and 7 days after trauma (0.936) (P ＜ 0.05).Conclusions Biological score possesses better effect on early diagnosis of sepsis 3 days after trauma.Weighted model combined by APACHE Ⅱ score,MODS score,GCS and LAC can effectively predict the prognosis of sepsis 5 days after trauma.

BACKGROUNDOveractive bladder (OAB) is a series of symptoms with high prevalence in elderly people. This study was conducted using the overactive bladder symptom score (OABSS) to evaluate the efficacy of solifenacin succinate for the treatment of OAB.

METHODSThis was a prospective, multicenter, single-arm, 12-week study that enrolled 241 OAB patients. The patients received 5-10 mg/day solifenacin. Changes in OABSS, symptoms from voiding diary, perception of bladder condition (PPBC) score, international prostate symptom score (IPSS) and quality of life (QOL) were evaluated at weeks 0, 4, and 12. The relationship between OABSS and PPBC score or parameters of voiding diary was also evaluated.

RESULTSAt baseline, the mean OABSS for all patients was 9.41 ± 2.40, and was reduced significantly at week 12 (-3.76 points; 61.21%, P < 0.0001). The OABSS subscore, PPBC score, IPSS, and QOL were also significantly reduced during the study (P < 0.0001). The overall incidence of adverse events was 19.91% (44 cases). The gastrointestinal system was the most commonly affected (11.31%). Around 5.88% of the cases had adverse events related to the genitourinary system. There was a strong correlation between OABSS and urinary symptoms that was recorded in the 3-day voiding dairy.

CONCLUSIONSWe showed that solifenacin was clinically effective for relieving OAB symptoms, considering the balance between efficacy, patients' well-being, and tolerability. OABSS integrates four OAB symptoms into a single score and can be a useful tool for research and clinical practice.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Muscarinic Antagonists ; therapeutic use ; Prospective Studies ; Quality of Life ; Quinuclidines ; therapeutic use ; Solifenacin Succinate ; Tetrahydroisoquinolines ; therapeutic use ; Treatment Outcome ; Urinary Bladder, Overactive ; drug therapy