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.

Objective To assess the safety,efficacy and reliability of IUPU(Abbreviation of Institute of Urology,Peking University)technique in setting up the retroperitoneal cavity for retroperitoneoscopy. Methods From February 1996 to March 2006,more than 1100 retroperitoneoscopic procedures were performed with the IUPU technique in setting up the retroperitoneal cavity,First,at the cross point of the line 2 cm above the iliac crest and the longitudirml line close to the anterior auxiliary line,a 1 cm skin incision was made and the Veress needle was penetrated into the retroperitoneal space(RPS)with a 0°-30° angle to the perpendicular line.The CO2 gas was pumped into the RPS till the pressure increases to 14mmHg and the first port was inserted into the RPS.The laparoscope was then inserted into the RPS through the first port and kept swinging right and left with its tip and trunk tO set up the retroperitoneal cavity.Other 2 ports were put into the RPS at cross points of the sub-costal line and anterior and posterior auxiliary lines under monitor observation.Then other appliances are introduced into the RPS to expand the cavity.More than 1100 procedures had been done with the IUPU technique,including 54 cases of simple nephrectomy (loss of function due to tuberculosis,hydronephrosis and atrophy), 188 radical nephrectomy, 154 ureteronephrectomy, 344 adrenalectomy, 302 renal cyst decortications, 35 partial nephrectomy, 37 pyeloplasty. Results The average time for the IUPU technique was (5.4±2.8)min (range 4. 5 to 14. 5 min) to set up the RPS. Complications included converting to open surgery due to bleeding in 8 cases(8/1114,0. 72%) when the first port was inserted into the RPS and entered into the peritoneal cavity for the first port penetration in 32 cases (32/1114,2. 87%),although the retroperitoneal cavity could be set up successfully by adjusting the laparoscope into the RPS.There was no injury to other viscera. Conclusions The IUPU technique is safe, efficient and reliable in setting up the RPS and no other special instrument is needed. It can be finished within 5 min on skilled hands and is valuable as a routine method to set up the retroperitoneal cavity.

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.

ObjectiveTo analyze the clinicopathological characteristics and survival time of penile cancer after surgery.MethodsThe clinicopathological data of 93 cases of penile cancers patients treated from January 2002 to December 2010 were collected retrospectively.The Kaplan-Meier method was used to draw the survival function and calculate the survival rate.Log-rank test was further used to compare survival difference.ResultsThe median age of the 93 patients was 51 years ( range,23 to 82).Squamous carcinoma was most common with 87 eases (93.5％) in our group.Sixty-one patients were successfully followed up and the median follow up duration was 28 months(range,2 to 89 months).All 3 cases of verrucous carcinoma had progression free survive after surgery after follow up of 12,19,and 67 months.In the 55 patients with penile invasive squamous carcinoma,11 patients died of metastatic disease with a median survival time of 10 months ( range,2 to 24 months).Two years cumulative survival rate was 75.7％ (95％ CI 63.0％ to 88.4％ ).Six cases of 12 patients with lymph node metastasis died of penile cancer while only 5 cases of 43 patients without lymphnode metastasis died.The survival difference was significant (log rank,P =0.000).ConclusionsSquamous carcinoma is the most common type,and patients with lymphnode metastasis have poor prognosis.Verrucous carcinoma has good prognosis.

Objective To evaluate the safety and efficacy of the anatomical retroperitoneoscopic nephrectomy(RSN)and standardize the procedure of RSN. Methods The retrospective analysis was performed on 405 consecutive patients underwent anatomical RSN in Our institute from January 2002 to June 2008.There were 232 male and 173 female patients with the average age of(57.2±14.2)years,among whom there were 228 renal cell carcinoma patients accepted RSU,96 and 49 renal pelvic carcinoma and ureteral carcinoma cases accepted retroperitoneoscopic ureteronephrectomy (RSUN) and 32 cases accepted simple RSN due to loss of renal function caused by benign renal discsses.The tadical RSN was performed by dissecting outside Gerota's fascia and in the latent cavities between this fascia and lateral conal fascia in the dorsal side and between this fascia and prerenal fusion fascia in the ventral side,whereas the simple RSN was done inside Gerota's fascia by making direct incision on it and dissecting between this fascia and perirenal adipose tissue.Kidneys and perirenal adipose tissue were completely removed by dissection along several avascular planes around the kidney under the amplified view of laparoscopy. The software SPSS 12.0 was used for the statistical analysis of all data. Results The mean operative time was (132±48)min for radical and simple RSN and (245 ± 62)min for radical RSUN, which included the time for position change and second skin preparation. The medium estimated blood loss was 100 ml(10-2500 ml) and the average drainage volume was 150 ml (0-1152 ml) postoperatively. 15 cases (3. 70%) required blood transfusion with the median volume of 400ml (400-1650 ml). Four cases (0. 99%) were converted to open surgery due to severe adhesion (2 cases), difficult exposure of renal helium (1 case) and severe bleeding (1 case).The mean drainage time was (3. 9±1.8)d, the mean time to first oral intake was (2.7±1.2)d and the mean postoperative hospital stay was (8.6±3. 8)d. Conclusion The anatomical RSN is safe and effective and should be the standard surgical procedure for laparoscopic nephrectomy.

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 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.

BACKGROUNDThe advent of targeted therapy has proved a milestone in the history of metastatic renal cell carcinoma treatment, and several guidelines now recommend sunitinib as first- or second-line treatment. But little is known about its efficacy in Asian patients. The aim of this article was to evaluate the efficacy of sunitinib monotherapy in patients with metastatic renal cell carcinoma treated at two Chinese centers.

METHODSOne hundred and forty-one patients with metastatic renal cell carcinoma were included in the study. Of them, 119 patients received single-agent sunitinib as first-line therapy and the remaining 22 patients received it as second-line therapy. One hundred and twenty patients received sunitinib in a dosage of 50 mg orally once daily on a 4-2 schedule (4 weeks on treatment, 2 weeks off), while 21 patients received 37.5 mg/day continuously until either disease progression or unacceptable toxicity occurred. The overall response rate, survival outcomes, and safety were evaluated.

RESULTSOver a median follow-up time of 23 months (16 cycles; range 2-45 months), complete responses, partial responses, and stable disease lasting two cycles or longer were achieved in 2.8%, 24.1%, and 60.3% of patients respectively (objective response rate 26.9%; overall benefit 87.2%). The median progression-free survival was 14.2 months (range 3-39 months). During the study, 53 patients died and the median survival time was 13.5 months (range 7-25 months). Dose modification or treatment interruption due to adverse events was required in 36.9% of the patients. The most common adverse events were hand-foot syndrome (71.4%), thrombocytopenia (68.8%), hypertension (47.1%), and fatigue (46.3%).

CONCLUSIONSunitinib had a favorable efficacy/tolerability profile in Chinese patients with metastatic renal cell carcinoma.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Renal Cell ; drug therapy ; Female ; Humans ; Indoles ; therapeutic use ; Kidney Neoplasms ; drug therapy ; Male ; Middle Aged ; Pyrroles ; therapeutic use ; Retrospective Studies ; Young Adult