Objective To assess whether the T~ -786 →C mutation of endothelial nitric oxide synthase (eNOS) gene is associated with endothelial dysfunction in type 2 diabetes. Methods A total of 162 type 2 diabetic men without angiopathy were studied. PCR/alleles-specific oligonucleotide (ASO) probes were used to analyse the T~ -786 →C mutation of eNOS gene, and high resolution ultrasound was used to measure endothelium-dependent arterial dilation (EDD). Results The EDD among subjects with T/C or C/C was 3.73%?0.50%, which was significantly lower than that in subjects with T/T(4.15%?0.49%)(P

Objective To review the experience in diagnosis and treatment of pheochromocytoma in a single center. Methods A total number of 142/145 pheochromocytoma cases treated surgically in our institute from August 2002 to February 2010 were retrospectively reviewed. The mean diameter of tumor was 5.9 cm (1.3- 18. 0 cm). The majority of the tumors (92.9%) were adrenal pheochromocytomas. Ninety-eight patients (69.0 % ) presented initially with hypertension, whereas 44 patients (31%)presented with adrenal incidentaloma. A specific anti-hypertensive pre-surgery preparation with phenoxybenzamine or doxazosine mesylate was started over 1 week before the operation.Of the 142 patients, 91 accepted open surgery, 54 accepted laparoscopic surgery, of which, 5 converted from laparoscopic surgery to open surgery. Results Histopathological results showed that all the cases were pheochromocytoma, while 83 cases were benign, 23 cases were malignant and 37 cases were suspected malignant. Sudden rising of blood pressure during operation was related to the preoperative serum level of catecholamine. Eighty-seven of 98 patients with preoperative hypertension had normal postoperative blood pressure; the remaining 11 patients reduced the dosage of anti-hypertension medication postoperatively. During the follow-up of 3-96 months (median 46 months), 10 of 91patients had a recurrence or metastasis. Six patients died of recurrences or metastasis within 5 years.Conclusions The procedures of qualitative and locative diagnosis of phechromocytoma include clinical manifestations, biochemical tests and imaging investigation. Surgical excision is the fundamental treatment for cure. Patients with high serum level of catecholamine tend to have a sudden rising of blood pressure during operation. Preoperative management is extremely important for the safety of the patient. Intensive follow up is necessary.

Objective: To investigate the impact of temperature changes between neighboring days (TCN) on the mortality risk of respiratory diseases, so as to provide the evidence for the study of deaths from respiratory diseases caused by climate change. Methods: The monitoring data of deaths from respiratory diseases in Zibo City from 2015 to 2019 were collected from Shandong Provincial Management Information System for Chronic Diseases and Cause of Death Surveillance. The meteorological and air pollutant data of the same period were collected from China Meteorological Data Website and ChinaHighAirPollutants dataset. The effect of TCN on the risk of deaths from respiratory diseases was examined using a generalized additive model combined with a distributed lag non-linear model, and subgroup analyses for gender and age were conducted. The disease burden attributed to TCN at different intervals was assessed by calculating attributable fraction. Results: Totally 11 767 deaths from respiratory diseases were reported in Zibo City from 2015 to 2019, including 6 648 males (56.50%) and 5 119 females (43.50%). There were 1 307 deaths aged <65 years (11.11%), and 10 460 deaths aged 65 years and older (88.89%). A monotonically increasing exposure-response relationship was observed between TCN and deaths from respiratory diseases in the general population, females, and the population aged 65 years and older. The 95th percentile of TCN (P95, 3.84 ℃) reached the peak at a cumulative lagged of day 11 (RR=2.063, 95%CI: 1.261-3.376). The results of subgroup analyses showed greater impacts on females and the population aged 65 years and older, with cumulative lagged effects peaking at day 12 (RR=3.119, 95%CI: 1.476-6.589) and day 11 (RR=2.107, 95%CI: 1.260-3.523). The results of attributional risk analysis showed that next-day warming might increase the attributable risk of deaths from respiratory diseases, and next-day cooling might decrease the attributable risk. Conclusion Next-day warming may increase the mortality risk of respiratory diseases, and has greater impacts on females and the population aged 65 years and older.

Objective:To analyze the impact of different surgical methods on perioperative complication rate after radical cystectomy in patients over 75 years of age.Methods:A retrospective study reviewed 1 432 patients who received radical cystectomy from January 2003 to January 2015.A total of 239 pa-tients were ≥75 years (median age:78 years),of whom,74 patients (31.0%)suffered one or more perioperative complications.According to the different operation methods,patients could be divided into ileal conduit group and cutaneous ureterostomy group.The ileal conduit group included laparoscopic and open radical cystectomy with ileal conduit.The cutaneous ureterostomy group included transperitoneal laparoscopic,transperitoneal and extraperitoneal open radical cystectomy with cutaneous ureterostomy. Results:Perioperative complications were significantly associated with the patient’s age (P =0.012), American Society of Anesthesiologists (ASA)score (P =0.001),node staging (P =0.043),and dif-ferent surgical methods.Perioperative complications caused a prolonged hospital stay and delayed recovery (34 d vs.21 d,P =0.002).For different surgical methods,the perioperative complication rate of ileal conduit was higher than cutaneous ureterostomy (P =0.013).However,there were no significant differences between transperitoneal laparoscopic and open radical cystectomy with ileal conduit in perioperative complication rate (P =0.836).The perioperative complication rate was statistically signifi-cant among transperitoneal laparoscopic,transperitoneal and extraperitoneal open radical cystectomy with cutaneous ureterostomy (P =0.022).On multivariate analysis,age (hazard ratio =4.856,95% CI:1.465 -16.103,P =0.010),ASA score (P =0.008),and different surgical methods (P =0.016) were significantly associated with the perioperative complication rate.Conclusion:The perioperative complication rate after radical cystectomy in elderly patients was associated with the patients’age,ASA score,and different surgical methods.Patients who received extraperitoneal open radical cystectomy with cutaneous ureterostomy suffered fewer perioperative complications,which was an appropriate choice for elderly patients.

Objective To evaluate the efficacy and safety of sunitinib in the treatment of metastatic renal cell carcinoma (RCC). Methods A total of 37 patients with metastatic RCC were treated with between June 2008 and April 2010, including 28 males and 9 females. The median age was 52 (17-74) years. All patients received a pathologic diagnosis of RCC, which consisted of 1 papillary cell carcinoma and 36 clear cell carcinomas, 4 of which accompanied with partial sarcoma differentiation. Thirty cases were treated with first line therapy and 7 cases showed progression on first-line cytokine or sorafinib therapy. Sunitinib monotherapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off in 34 patients, while another 3 patients received 37. 5 mg Qd continuously until disease progression or unacceptable toxicities occurred. Overall response rate and safety were evaluated. Results The median follow up was 12 months (8 cycles),range 1.5-19. 5 months (1-13 cycles). 26.5% (9/34) patients achieved partial responses, 70.6%(24/34) patients demonstrated stable disease over≥3 months and 1 (2. 9%) patient developed progressive disease. The objective response rate was 26.5%, and the disease control rate was 97. 1%.The 12 months' overall survival rate was 95.8% (23/24), and 12 months' progression-free survival rate was 62.5 % (15/24). The most common treatment-related adverse events were thrombocytopenia (30 cases, 81.1%), thyroid dysfunction (18/22, 81.8%) ,hand-foot syndrome (27 cases, 73.0%),neutropenia (23 cases, 62.2%) and hypertension (18 cases, 48.6%). The major grade 3 adverse events included thrombocytopenia (8 cases, 21.6%), hand-foot syndrome (4 cases, 10.8%) and diarrhea (2 cases, 5. 4%). Most adverse events were ameliorated by treatment interruption. Ten (27.0%) patients had dose decrement or drug discontinuation and 1 patient quit the treatment for intolerable fatigue. Conclusion The efficacy and manageable adverse event profile of sunitinib as a single agent in first- or second-line therapy for patients with metastatic RCC.

Objective To evaluate the efficacy of dexmedetomidine mixed with sufentanil for patient-controlled intravenous analgesia (PCIA) in the patients undergoing transcatheter hepatic arterial chemoembolization (TACE).Methods One hundred and twenty patients of both sexes,aged 40-65 yr,weighing 45-80 kg,of American Society of Anesthesiologists physical status Ⅰ-Ⅲ,scheduled for elective TACE under monitored anesthesia care,were divided into 2 groups (n =60 each) using a random number table:sufentanil group (S group) and dexmedetomidine mixed with sufentanil group (DS group).At 15 min prior to surgery,0.1 μg/kg sufentanil and 5 mg tropisetron were intravenously injected in both groups.In addition,dexmedetomidine 0.6 μg/kg was intravenously infused for 15 min in DS group,while the equal volume of normal saline was given instead in S group.PCIA solution contained sufentanil 2 μg/kg and tropisetron 5 mg in 100 ml of normal saline in S group.PCIA solution contained sufentanil 2 μg/kg,dexmedetomidine 2.μg/kg and tropisetron 5 ng in 100 ml of normal saline in DS group.The PCIA pump was programmed to deliver a 0.5 ml bolus dose with a lockout interval of 15 min and background infusion of 2 ml/h.Observer's Assessment of Alertness/Sedation Scale scores and scores for patient's satisfaction with analgesia were recorded at 30 min and 2,6,12,24 and 48 h after surgery.The pressing times of PCIA,total consumption of sufentanil and requirenent for morphine as rescue analgesics were recorded.The development of requirement for antiemetics,nausea and vomiting,bradycardia,respiratory depression and agitation was also recorded during analgesia.Results Compared with S group,the pressing times of PCIA,total consumption of sufentanil and requirement for morphine were significantly reduced,scores for satisfaction with analgesia were increased,and Observer's Assessment of Alertness/Sedation Scale scores were decreased (P＜0.05),and no significant change was found in the incidence of nausea and vomiting,additional requirement for antiemetics,bradycardia,respiratory depression or agitation in DS group (P＞0.05).Conclusion Dexmedetomidine mixed with sufentanil produces better efficacy than sufentanil alone when used for PCIA in the patients undergoing TACE.

Objective To summarize the characteristics of clinical manifestation of bone flare after the treatment with new endocrine therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) in order to evaluate the curative effect of patients properly and determine the reasonable treatment strategy.Methods We retrospectively analyzed the clinical data of two patients with mCRPC performed "bone flare" defined as PSA decline and bone metastases progression in the initial treatment with new endocrine therapy in Urology Department of Peking University First Hospital,and analyzed the clinical characteristics and treatment methods with the relative literature.Case 1,a 79-year-old man,presented with frequent urination and prostate-specific antigen (PSA) was 115.900 ng/ml,was diagnosed as prostate cancer (cT3N0M1) with bone metastasis.After androgen deprivation therapy of 24 months,PSA elevated and multiple bone metastases progressed.The patient was diagnosed with mCRPC and then began the treatment of enzalutamide.Case 2,a 62-year-old man,complained about emaciation and frequent urination,was diagnosed with prostate cancer(cT4N1M1)with bone and lymph metastases.After androgen deprivation therapy of 22 months,PSA elevated and multiple bone metastases progressed.The patient was diagnosed with mCRPC and then began the treatment of abiraterone.Results Case 1 was treated with enzalutamide and 2 months later PSA decreased from 133.400 ng/ml to 5.530 ng/ml,while bone scan showed multiple bone metastases,part of which was newly metastatic lesions.6 months later,the number of metastatic lesions kept stable,and part of lesions presented metabolism decrease.8 months later,the number of metastatic lesions began to decrease.1 year later,the patient started to receive chemical therapy because of the progression of the disease.After 5 cycles of chemotherapy,PSA progression occurred and chemotherapy was stopped.Liver failure and disseminated intravascular coagulation caused death in June 2016.Case 2 was treated with abiraterone and 2 months later PSA decreased from 54.820 ng/ml to 3.580 ng/ml,while bone scan showed multiple bone metastases,part of which was newly metastatic lesions.6 months later,the number of metastatic lesions began to decline.10 months later,the number of metastatic lesions kept stable.The treatment of abiraterone was continued so far and the patient was in a stable condition.Conclusions Enzalutamide and abiraterone,two new endocrine therapy,are determined as preferred methods for the treatment of mCRPC.The bone scanning is required to evaluate the possibility of "bone flare" which is defined as PSA decline and bone metastases progression in the initial treatment.These patients should be evaluated to make appropriate clinical decision.

Objective: To evaluate the safety and efficiency of patient-controlled intravenous analgesia (PCIA) using hydromorphone supplement with dexmedetomidine on patients undergoing transcatheter arterial chemoembolization. Methods: One hundred and eighty patients, age ranged from 40 to 65 years, body mass index from 18 to 25 kg/m^2, ASA physical status Ⅱ-Ⅲ, who were scheduled for transcatheter arterial chemoembolization (TACE) under monitor anesthesia care (MAC) were randomly divided into 3 groups: hydromorphone group (H group), hydromorphone supplement with dexmedetomidine 1 μg/kg group (D1 group), hydromorphone supplement with dexmedetomidine 2 μg/kg group (D2 group), 60 patients in every group. All the groups of patients received PCIA pump, in the H group, the PCIA reagent was composed of 120 μg/kg hydromorphone and 5 mg tropisetron in 100 ml of normal saline. In comparison, PCIA regiment was composed of 120 μg/kg hydromorphone, 1 μg/kg dexmedetomidine and 5 mg tropisetron in 100 ml of normal saline in the D1 group, while 120 μg/kg hydromorphone, 2 μg/kg dexmedetomidine and 5 mg tropisetron in 100 ml of normal saline in the D2 group. The visual analogue scale (VAS) score, the observer′s assessment of alertness/sedation scale (OAA/S) score, patients′ satisfaction index, consumption of hydromorphone, the additional dose of morphine, the effective pressing times of PCIA and adverse reactions were recorded in detail at 0, 0.5, 1, 4, 12 and 24 hours after the patients underwent TACE. Results: The total consumptions of hydromorphone were (4.3±0.1), (4.1±0.1), and (3.8±0.1) mg in group H, D1, and D2, respectively, and the effective pressing times were 13±3, 6±2 and 2±1, the additional doses of morphine were (30±5), (15±3), and (3±1) mg, and adverse reaction rates were 45.0%, 28.3%, and 10.0%, respectively. The manifestations mentioned above in D2 group were significantly lower than those in group H and group D1 (P<0.05). Immediately and 5 min after embolization, at the end of surgery and 0.5, 1, 4, 12 and 24 h after surgery, the VAS scores in the D2 group were 1.9±0.2, 2.1±0.3, 1.8±0.4, 1.8±0.3, 1.7±0.3, 1.6±0.3, 1.3±0.2, 1.3±0.3, respectively, lower than those in group H and group D1 (P<0.05); The satisfaction index in D2 group at these times were 8.7±1.1, 8.9±0.8, 9.2±0.9, 9.0±0.7, 9.1±0.8, 9.0±0.6, 9.1±0.7, 9.2±0.9, respectively, higher than those in group H and group D1 (P<0.05). No breath depression happened in these three groups. Conclusion The formula of hydromorphone combined with dexmedetomidine to patients undergoing TACE is greatly safe and efficient, with advantages in alleviating pain, reducing hydromorphone consumption and the incidence of adverse reaction of hydromorphone, and without breath depression.

Objective:To evaluate the risk factors of clinical cure and biochemical recurrence (BCR) after radical prostatectomy (RP).Methods:The clinical data of 896 patients who underwent RP at Peking University First Hospital from April 2001 to December 2020 were retrospectively analyzed. Average age was (65.90±6.3) years, median preoperative prostate specific antigen (PSA) was 10.75 (0.36-264.20) ng/ml, median prostate volume was 40.0 (12.0-220.9) ml, median PSA density (PSAD) was 0.27 (0.02-3.42) ng/(ml·g). Clinical staging: 432 cases in T 1c stage, 333 cases in T 2a/bstage, 76 cases in T 2c stage, and 55 cases in ≥T 3 stage. Preoperative Gleason score of biopsy: 193 cases in 3+ 3, 315 cases in 3+ 4, 162 cases in 4+ 3, 226 cases in ≥8. The RP surgery was operated by open or laparoscopic or robot-assisted approach. Clinical cure and BCR were used as the end points for analysis. Clinical cure was defined as a decrease in serum PSA level below 0.03 ng/ml 6 weeks after surgery. BCR was defined as the 2 consecutive serum PSA >0.2ng/ml during the follow-up after RP. Multivariate logistic regression was used to analyze the independent risk factors of clinical cure. The Kaplan-Meier method was used to draw the biochemical recurrence-free survival curve, the log-rank method was used for univariate analysis of BCR, and the Cox regression analysis was used for multivariate analysis. Results:All 896 patients were followed-up for 58 (5-241) months, 678 cases (75.7%) achieved clinical cure. Based on univariate analysis and multivariate analysis, among the preoperative indicators, whether the proportion of positive biopsy needles ≥33% ( P=0.007) and preoperative Gleason score of biopsy ( P=0.041) were independent risk factors of clinical cure. A total of 890 cases were included in the analysis of risk factors of BCR, of whom 172 cases (19.3%) had BCR. The 1-, 5-, and 10-year biochemical recurrence-free survival(BFS)rates were 98.1%, 83.1% and 68.4% respectively. The median BFS has not been reached, and the average BFS was 181 months (95% CI 172-189). The results of univariate and multivariate analysis showed that whether achieved clinical cure ( P=0.001) and postoperative pathological staging ( P<0.001) were independent risk factors of BCR. Conclusions:Whether the proportion of positive biopsy needles≥33% and preoperative Gleason score of biopsy were independent risk factors of clinical cure. Postoperative pathological staging and whether achieved clinical cure may be independent risk factors of BCR.

Hepatocellular carcinoma （HCC） is a major cause of cancer-related death， and surgical resection remains an important method for radical treatment， but it is urgently needed to solve the problem of high postoperative recurrence rate. Neoadjuvant therapy can reduce the high recurrence rate after surgery， and there are little benefits from neoadjuvant therapy for HCC due to a lack of effective treatment methods in the past. At present， combination therapy based on immune checkpoint inhibitors has a relatively high response rate and has thus changed the treatment landscape for patients with advanced HCC. This urges investigators to reexamine the neoadjuvant treatment strategies for HCC， and it is expected that neoadjuvant therapy can provide new opportunities， reduce the postoperative recurrence rate， and improve the survival rate after treatment. This article discusses the current status and prospects of neoadjuvant therapy for HCC and related hot topics， so as to provide more ideas for exploring neoadjuvant therapy for HCC.