Objective To investigate the prognostic differences among pure urothelial carcinoma,squamous-differentiated urothelial carcinoma,and pure squamous cell carcinoma,so as to provide reference for postoperative risk stratification.Methods The clinical data of bladder cancer patients who visited the Department of Urology,Peking University First Hospital and underwent radical cystectomy during Jan.2005 and Jun.2024 were retrospectively analyzed.Patients were categorized into the pure urothelial carcinoma group(n=725),squamous-differentiated urothelial carcinoma group(n=189),and pure squamous cell carcinoma group(n=36).General characteristics,surgical approaches,pathological staging,muscle invasion status,and lymph node positivity were compared among the three groups.Kaplan-Meier survival curves were plotted,and prognostic differences among the groups were compared after 1∶1 propensity score matching between each pair.Independent risk factors of prognosis were identified with Cox multivariable regression.Results The pure squamous cell carcinoma group had a higher proportion of female patients(50.00％vs.25.24％vs.22.75％,P=0.002 4).Compared with the pure urothelial carcinoma group,the other two groups demonstrated higher proportions of stage Ⅲ+Ⅳ,higher rates of muscle invasion,and higher lymph node positivity,with the pure squamous cell carcinoma group showing the highest overall staging(69.45％vs.58.20％vs.29.38％,P＜0.000 1).Kaplan-Meier analysis showed that squamous-differentiated urothelial carcinoma group and pure squamous cell carcinoma group had significantly worse survival than the pure urothelial carcinoma group(P＜0.05),while the former two groups exhibited similar outcomes(P=0.85).After propensity score matching,postoperative survival curves among the three groups were not significantly different(all P＞0.05).In multivariable Cox proportional hazards models adjusting for confounders,prognosis was primarily associated with age,muscle invasion,and lymph-node positivity(P＜0.05);pathological subtype was not an independent predictor of postoperative survival.Conclusion In a cohort of non-metastatic patients undergoing radical cystectomy,pure squamous cell carcinoma and squamous-differentiated urothelial carcinoma presented with higher clinical and pathological staging and poorer unadjusted prognosis compared with pure urothelial carcinoma.However,postoperative survival did not differ significantly among the three groups in the same clinicopathological conditions.

Objective:To investigate the relationship between oxygen consumption (VO 2), carbon dioxide production (VCO 2), and Oxygen Consumption/lactate (VO 2/Lac) with risk of death in patients with severe ARDS. Methods:A retrospective cohort study method was used, and the study subjects were hospitalized for >5 days adult patients with severe ARDS in the central intensive care unit of Henan Provincial People's Hospital from 1 March 2020 to 30 June 2023. The following patients were excluded: IC test was not completed on the 4th day of ICU admission, IC test results were unreliable, mechanical ventilation duration had exceeded 48 h at the time of ICU transfer or admission, palliative care patients and pregnant and parturient women. Using indirect calorimetry to determine VO 2 and VCO 2 values on the 4th day of admission, reviewing medical records to obtain general condition, disease information, blood gas analysis (including lactate value), diagnostic and therapeutic measures, and following up deaths by telephone and time of death. The primary outcome measure was death at 90 days, and the secondary outcome measure was death at 28 days, length of stay in ICU, total length of stay, and total hospitalization cost. Cox regression analysis and linear regression analysis were used to investigate the relationship between VO 2, VCO 2, VO 2/Lac and primary and secondary outcome indexes. Results:A total of 216 patients were enrolled, 78 patients (36.1%) died and 138 patients (63.9%) survived at 90 days. After correction for confounders, the results of multifactorial Cox regression analysis suggested that compared with the Q4 group, HR (95% CI) for 90-day risk of death in the VO 2 Q1 and Q2 groups was 3.21 (1.38, 7.49) and 3.24 (1.42, 7.38), and HR (95% CI) for 90-day risk of death in the VCO 2 Q1, Q2 and Q3 groups was 5.88 (2.33, 14.84), 4.26 (1. 60, 11.34) and 3.54 (1.34, 9.35), respectively, and the HR (95% CI) for 90-day risk of death in the VO 2/Lac Q1, Q2 and Q3 groups were 8.72 (3.01, 25.25), 8.43 (2.91, 24.47) and 4.04 (1.34, 12.17) respectively. P-trends were all <0.05, indicating that VO 2, VCO 2 and VO 2/Lac were linearly and negatively associated with the risk of 90-day mortality. In addition, VO 2, VCO 2, and VO 2/Lac were negatively associated with 28-day risk of death and higher VO 2/Lac was negatively associated with length of ICU stay. Conclusions:VO 2, VCO 2 and VO 2/Lac were negatively associated with 90-day mortality risk and 28-day mortality risk in patients with severe ARDS and may be independent risk factors predicting mortality risk of such patients.

Objective To investigate the prognostic differences among pure urothelial carcinoma,squamous-differentiated urothelial carcinoma,and pure squamous cell carcinoma,so as to provide reference for postoperative risk stratification.Methods The clinical data of bladder cancer patients who visited the Department of Urology,Peking University First Hospital and underwent radical cystectomy during Jan.2005 and Jun.2024 were retrospectively analyzed.Patients were categorized into the pure urothelial carcinoma group(n=725),squamous-differentiated urothelial carcinoma group(n=189),and pure squamous cell carcinoma group(n=36).General characteristics,surgical approaches,pathological staging,muscle invasion status,and lymph node positivity were compared among the three groups.Kaplan-Meier survival curves were plotted,and prognostic differences among the groups were compared after 1∶1 propensity score matching between each pair.Independent risk factors of prognosis were identified with Cox multivariable regression.Results The pure squamous cell carcinoma group had a higher proportion of female patients(50.00％vs.25.24％vs.22.75％,P=0.002 4).Compared with the pure urothelial carcinoma group,the other two groups demonstrated higher proportions of stage Ⅲ+Ⅳ,higher rates of muscle invasion,and higher lymph node positivity,with the pure squamous cell carcinoma group showing the highest overall staging(69.45％vs.58.20％vs.29.38％,P＜0.000 1).Kaplan-Meier analysis showed that squamous-differentiated urothelial carcinoma group and pure squamous cell carcinoma group had significantly worse survival than the pure urothelial carcinoma group(P＜0.05),while the former two groups exhibited similar outcomes(P=0.85).After propensity score matching,postoperative survival curves among the three groups were not significantly different(all P＞0.05).In multivariable Cox proportional hazards models adjusting for confounders,prognosis was primarily associated with age,muscle invasion,and lymph-node positivity(P＜0.05);pathological subtype was not an independent predictor of postoperative survival.Conclusion In a cohort of non-metastatic patients undergoing radical cystectomy,pure squamous cell carcinoma and squamous-differentiated urothelial carcinoma presented with higher clinical and pathological staging and poorer unadjusted prognosis compared with pure urothelial carcinoma.However,postoperative survival did not differ significantly among the three groups in the same clinicopathological conditions.

Muscle-invasive bladder cancer (MIBC) is the predominant type of muscle-invasive urothelial carcinoma (MIUC). MIBC features an unfavorable prognosis with limited treatment approaches. The backbone of treatment strategy was neoadjuvant chemotherapy followed by radical cystectomy before 2021. Immunotherapy represented by nivolumab has gained breakthrough results in adjuvant setting, demonstrating significant improvement in disease free survival in high-risk MIUC population, and become a standard of care for MIUC adjuvant therapy since 2021. Immunotherapy has both efficacy and safety advantages compared to adjuvant chemotherapy. Predictors for adjuvant therapy response in MIUC have yet not been identified. The most evaluated predictive biomarkers to date for immune checkpoint inhibitor treatment response are programmed death ligand 1 (PD-L1) expression and circulating tumour DNA (ctDNA), etc. Further research is crucial to assess the value of the biomarkers. Studies of perioperative immunotherapy combined with chemotherapy or antibody-drug conjugate are ongoing. Combined immunotherapy as part of bladder-sparing treatment regimen for MIUC is limited to small scale studies and has shown promising early outcomes. Further phase 3 clinical trials are underway to add mature data to bladder-sparing strategies incorporating immune checkpoint inhibitors in adjuvant setting.

Muscle-invasive bladder cancer (MIBC) is the predominant type of muscle-invasive urothelial carcinoma (MIUC). MIBC features an unfavorable prognosis with limited treatment approaches. The backbone of treatment strategy was neoadjuvant chemotherapy followed by radical cystectomy before 2021. Immunotherapy represented by nivolumab has gained breakthrough results in adjuvant setting, demonstrating significant improvement in disease free survival in high-risk MIUC population, and become a standard of care for MIUC adjuvant therapy since 2021. Immunotherapy has both efficacy and safety advantages compared to adjuvant chemotherapy. Predictors for adjuvant therapy response in MIUC have yet not been identified. The most evaluated predictive biomarkers to date for immune checkpoint inhibitor treatment response are programmed death ligand 1 (PD-L1) expression and circulating tumour DNA (ctDNA), etc. Further research is crucial to assess the value of the biomarkers. Studies of perioperative immunotherapy combined with chemotherapy or antibody-drug conjugate are ongoing. Combined immunotherapy as part of bladder-sparing treatment regimen for MIUC is limited to small scale studies and has shown promising early outcomes. Further phase 3 clinical trials are underway to add mature data to bladder-sparing strategies incorporating immune checkpoint inhibitors in adjuvant setting.

Objective:To study the value of urine-based multi-dimensional bioinformatics evaluation model (utLIFE model) in early diagnosis and postoperative monitoring of upper urinary tract urothelial carcinoma (UTUC).Methods:Morning urine samples of patients clinically diagnosed with UTUC without bladder cancer from Peking University First Hospital from August 2022 to October 2022 were collected. Urine samples were collected before and after surgery, and DNA was extracted for gene sequencing. The utLIFE model previously constructed by our center was used to calculate the score, based on 155 gene mutation sites and copy number variation, and the score ≥60 was defined as utLIFE positive. The sensitivity of utLIFE model in diagnosis of UTUC was analyzed with postoperative pathology as the gold standard. The utLIFE scores before and after operation were also compared.Results:A total of 53 patients were included in this study, all of whom were confirmed as UTUC by postoperative pathology. The median age of patients was 66 (59, 72) years. Twenty-four cases (45.3%) of UTUC tumors were located in the renal pelvis, 26 cases (49.1%) were located in the ureter, and 2 cases (5.7%)involved both ureter and renal pelvis. There were 27 patients (50.9%) at T 1stage and 26 patients (49.1%) at ≥T 2 stage. Preoperative utLIFE score of 53 patients was 79 (70, 84). The sensitivity of preoperative utLIFE diagnosis of UTUC was 96.2% (51/53). utLIFE showed similar high sensitivity in T 1 stage and ≥T 2 stage [100.0% (27/27) vs. 92.3% (24/26), P=0.236], in N 0 and ≥N 1 stage [ 95.0% (38/40) vs. 100.0% (5/5), P=1.000]. In addition, the sensitivity of preoperative utLIFE was higher than that of urine cytology [ 95.2% (20/21) vs. 23.8% (5/21). P<0.001], fluorescence in situ hybridization (FISH) [ 92.6% (25/27) vs. 55.5% (15/27), P=0.004] and ureteroscopy [ 86.7% (13/15) vs. 60.0% (9/15), P=1.000]. A total of 45 patients postoperative utLIFE samples were collected, and the postoperative utLIFE score was significantly lower than that of preoperative [ 36 (18, 61) vs. 79 (70, 84), P<0.001]. Conclusions:utLIFE, as a non-invasive urine DNA bioinformatics assessment model, is significantly superior to cytology and FISH in early detection and has high sensitivity in diagnosis of UTUC, and can reflect perioperative minimal residual disease levels.

Objective To explore the characteristic of early evaluation of patients with amplitude-integrated electroencephalogram (aEEG) on brain function prognosis after cardiopulmonary cerebral resuscitation (CPCR). Methods A retrospective analysis of the clinical data of patients with adult CPCR in intensive care unit (ICU) of Henan Provincial People's Hospital from March 2016 to March 2017 was performed. The length of stay, recovery time, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, aEEG and Glasgow coma scale (GCS) within 72 hours were recorded. The main clinical outcome was the prognosis of brain function (Glasgow-Pittsburgh cerebral performance category, CPC) in patients with CPCR after 3 months. Relationship between aEEG and GCS and their correlation with brain function prognosis was analyzed by Spearman rank correlation analysis. The effects of aEEG and GCS on prognosis of brain function were evaluated by Logistic regression analysis. The predictive ability of aEEG and GCS for brain function prognosis was evaluated by receiver operating characteristic (ROC) curve.Results A total of 31 patients with CPCR were enrolled, with 18 males and 13 females; mean age was (41.84±16.96) years old; recovery time average was (19.42±10.79) minutes; the length of stay was (14.84±10.86) days; APACHE Ⅱ score 19.29±6.42; aEEG grade Ⅰ(normal amplitude) in 7 cases, grade Ⅱ (mild to moderate abnormal amplitude) in 13 cases, grade Ⅲ (severe abnormal amplitude) in 11 cases; GCS grade Ⅰ (9-14 scores) in 7 cases, grade Ⅱ (4-8 scores) in 14 cases, grade Ⅲ (3 scores) in 10 cases; 19 survivals, 12 deaths; the prognosis of brain function was good (CPC 1-2) in 8 cases, and the prognosis of brain function was poor (CPC 3-5) in 23 cases. There was no significant difference in age, gender, recovery time, length of stay and APACHE Ⅱ score between two groups with different brain function prognosis, while aEEG grade and GCS grade were significantly different. Cochran-Armitage trend test showed that the higher the grade of aEEG and GCS, the worse the prognosis of CPCR patients (bothP-trend < 0.01). With the increase in GCS classification, the classification of aEEG was also increasing (r = 0.6206,P = 0.0003). Both aEEG and GCS were positively correlated with the prognosis of brain function (r1 = 0.7796,P1 < 0.0001;r2 = 0.7021,P2 < 0.0001). Univariate Logistic regression analysis showed that aEEG and GCS had significant effect on early brain function prognosis [aEEG: odds ratio (OR) = 37.234, 95％confidence interval (95％CI) = 3.168-437.652,P = 0.004, GCS:OR = 12.333, 95％CI = 1.992-76.352,P = 0.007]; after adjusting for aEEG and GCS, only aEEG had significant effect on the early prognosis of brain function (OR = 26.932, 95％CI = 1.729-419.471,P = 0.019). The ROC curve analysis showed that in the evaluation of the prognosis of CPCR patients with brain function, the area under ROC curve (AUC) of aEEG was 0.913, when the cut-off value of aEEG was 1.5, the sensitivity was 95.7％ and the specificity was 75.0％. The AUC of GCS was 0.851, the best cut-off value was 1.5, the sensitivity was 91.3％ and the specificity was 62.5％.Conclusion aEEG and GCS scores have a good correlation in the evaluation of brain function prognosis in patients with CPCR, the accuracy of aEEG in the early evaluation of the prognosis of patients with CPCR is higher than the GCS score.

Objective To investigate the protective effect of hesperidin on severe acute pancreatitis (SAP) in rats and its related mechanism.Methods Sixty male Sprague-Dawley (SD) rats were randomly divided into five groups (n = 12 in each group): sham group, SAP model group, dexamethasone group (5 mg/kg), low and high dose of hesperidin groups (10 mg/kg and 20 mg/kg). SAP rats were administered a retrograde infusion of 3.5％ sodium taurocholate solution into the biliopancreatic duct after laparotomy. Sham rats were administered with equivalent saline. The treatment was intravenously injected 5 minutes after operation through femoral vein. After 24 hours, the survival of animals was observed, the level of serum amylase, the volume of ascites and the relative specific gravity of the pancreas were measured; the pathological changes of pancreatic tissue were observed by Hematoxylin-eosin (HE) staining; the levels of serum and pancreatic tissue interleukin (IL-1β, IL-6) and tumor necrosis factor-α (TNF-α) were detected by enzyme linked immunosorbent assay (ELISA); the expression of Toll-like receptor 4 (TLR4), the phosphorylation of IL-1 receptor associated kinase (IRAK1) and nuclear factor-κB (NF-κB) were detected by Western Blot.Results Compared with SAP model group, the 24-hour survival rate were increased in low and high dose of hesperidin groups (83.3％, 100％ vs. 58.3％), the volume of ascites were reduced (mL: 7.36±0.91, 6.10±1.02 vs. 13.82±2.06), the levels of serum amylase were reduced (U/L: 1081.48±78.23, 1048.58±49.97 vs. 1990.37±127.27), the relative specific gravity of the pancreas were reduced [(7.52±1.02)％, (5.59±0.96)％ vs. (11.22±0.96)％], and the pathological damage of pancreatic tissue were reduced; the levels of serum and pancreatic tissue inflammatory factors were reduced in high dose hesperidin group [serum IL-1β (ng/L): 68.08±10.49 vs. 130.30±23.35, IL-6 (ng/L): 63.88±10.47 vs. 158.41±21.38, TNF-α(ng/L): 10.42±1.49 vs. 18.16±2.01; pancreas IL-1β (pg/μg): 13.87±1.84 vs. 20.08±1.66, IL-6 (pg/μg): 21.90±3.12vs. 38.13±3.57, TNF-α (pg/μg): 1.88±0.20 vs. 4.26±0.58]; the expression of TLR4, and the phosphorylation levels of IRAK1 and NF-κB were decreased in low and high dose of hesperidin groups (the sham operation group was 100, TLR4/β-actin: 91.9±15.6, 83.7±11.2 vs. 168.5±9.0, p-IRAK1/IRAK1: 117.4±7.6, 104.7±11.5 vs. 173.5±15.8, p-NF-κB p65/NF-κB p65: 119.9±9.3, 105.8±12.6 vs. 174.1±13.0), with statistically significant differences (allP < 0.05). The effects of dexamethasone were similar to that of high dose of hesperidin.Conclusions Hesperidin could significantly protect SAP rats, and this protection was related to the inhibition of TLR4/IRAK1/NF-κB signaling pathway, and to the reduction of pro-inflammatory cytokine expressions. The effect of high dose hesperidin (20 mg/kg) was more significant.

Objective To investigate the influence of simvastatin treatment on Toll-like receptor 4 (TLR4) in monocytes of peripheral blood in patients with sepsis and severe sepsis and its significance. Methods A prospective randomized controlled trial was conducted. 106 patients with sepsis and 92 patients with severe sepsis admitted to Department of Critical Care Medicine of Henan Provincial People's Hospital from August 2013 to June 2015 were enrolled. These two groups of patients were randomized into conventional treatment group and simvastatin group. All patients received treatment according to the 2012 International Sepsis Treatment Guidelines, including anti-infection drugs, nutritional support, and palliative treatment, and the patients with severe sepsis were given early goal-directed therapy (EGDT). The patients in simvastatin group received simvastatin 40 mg daily orally for at least 15 days. The peripheral blood was collected and the monocytes were isolated at 1, 5, 10, 15 days after intensive care unit (ICU) admission. TLR4 expression on the surface of TLR4/CD14+ double positive monocytes was determined by flow cytometry, and adverse reaction was observed during treatment. Results TLR4 expression on the surface of monocytes showed a tendency of decreasing with prolongation of simvastatin treatment in the simvastatin group in patients with sepsis (n = 59) or severe sepsis (n = 54). However, in patients with sepsis, TLR4 level was significantly decreased from 10 days in simvastatin group as compared with that of conventional therapy group (n = 47), and it was decreased up to 15 days [mean fluorescence intensity (MFI): 21 (19, 28) vs. 27 (25, 33) at 10 days, Z = 2.198, P = 0.021; 16 (15, 21) vs. 26 (23, 34) at 15 days, Z = 4.611, P = 0.002]. In patients with severe sepsis, there was no significant difference in TLR4 level at different time points between simvastatin group and conventional treatment group (n = 38) [MFI: 55 (52, 63) vs. 56 (48, 65) at 1 day, Z = 0.313, P = 0.692; 47 (42, 56) vs. 49 (41, 58) at 5 days, Z = 0.827, P = 0.533; 40 (35, 42) vs. 42 (37, 45) at 10 days, Z = 1.012, P = 0.301; 33 (30, 38) vs. 38 (35, 41) at 15 days, Z = 0.539, P = 0.571]. No adverse reaction related with simvastatin was found during treatment in patients with sepsis or severe sepsis. Conclusions Statins could significantly down-regulate the TLR4 expression on peripheral blood monocytes in septic patients, while it showed no significant influence on TLR4 expression in patients with severe sepsis. A different effect of statins on TLR4 expression and the downstream inflammation process in sepsis and severe sepsis patients might partially explain the discrepancy in previous reports about the therapeutic effect of statins therapy in sepsis and severe sepsis patients.

Background and objective hTe abnormal expression of human long chain non encoding RNA gene is related to many kinds of tumors. hTe aim of this study is to investigate the expression of long non-coding RNA maternally expressed gene 3 (SPRY4-IT1) in lung cancer (A549) cells, and to observe the effect of SPRY4-IT1 on the invasion and migra-tion of A549 cells.Methods hTe levels of SPRY4-IT1 in A549 was detected by Real-time PCR. hTe effects of SPRY4-IT1 on the invasion and migration of A549 cell were analyzed by MTT and Transwell assay. hTe expression of matrix metalloproteinase (MMP) family proteins was determined by Western blot.Results hTe invasion and migration of A549 cells were increased atfer SPRY4-IT1 over-expression. hTe cell spaces were narrower atfer SPRY4-IT1 over expression in the wound healing assay. Tran-swell assays showed that the numbers of transmembrane A549 cells were signiifcantly higher in SPRY4-IT1 over expression group than that in control group (P<0.05). Meanwhile, over expression of SPRY4-IT1 reduced the expression of MMP-2 and MMP-9.Conclusion Over expression of SPRY4-IT1 enhanced the invasion and migration of A549 cells. MMP-2 and MMP-9 might play an important role in this regulation.