OBJECTIVE To establish a method for determining the content of 11 antioxidants and their degradation products in recombinant Exendin-4-FC fusion protein injection by HPLC. METHODS The protein was precipitated with saturated ammonium sulfate. After centrifugation, the supernatant was transferred to a C18 solid phase extraction cartridge activated by methanol. Then the cartridge was eluted with 4 mL of methanol and 5 mL of ethyl acetate respectively, and the eluent was diluted with methanol-ethyl acetate(2∶3) mixed solvent and passed through a 0.22 µm PTFE hydrophobic filter. It was analyzed by HPLC and quantified by external standard method. Chromatographic conditions: Kinetex® XB-C18 100Å (100 mm×4.6 mm, 2.6 µm)column, the detection wavelength was 230 nm, the column oven was 30 ℃, the injection volume was 5 µL and the flow rate was 0.4 mL·min–1, mobile phase was 0.1% formic acid-methanol(A)-0.1% formic acid aqueous solution(B), the running time was 45 min. RESULTS The 11 target substances showed a good linear relationship in the range of 2.5−35 μg·mL–1 with R2 ≥0.99. At three different concentration(25, 10, 5 μg·mL–1) of spiked samples, the average recovery rates of 11 antioxidants ranged from 88.1% to 106.5%, with RSDs in the range of 0.10%–9.05%. The RSDs of 6 repeatable samples was 2.01%–4.77%, which of 12 intermediate precision samples was 2.58%–9.75%. The positive/inverted samples of three batches of recombinant Exendin-4-FC fusion protein injection were detected at 0 month, 3 months and 6 months(25 ℃), and the results showed that there was no antioxidant and its degradation leaching in all batches of samples at different detection points. CONCLUSION The method has good specificity, high accuracy and precision, good solution stability, high durability and can be used for the content detection of antioxidants in drugs.

Objective:To investigate the effect of local anesthesia in patients with a PI-RADS score of 5 and ECOG score ≥2 for prostate puncture.Methods:Retrospective analysis of case data of 33 patients admitted to the Subei People's Hospital for prostate puncture from April 2020 to April 2022. Age (82.5±3.6) years. There were 18 cases with hypertensive disease, 8 cases with diabetes mellitus, and 6 cases with both diabetes mellitus and hypertensive disease. Body mass index (25.2±3.5) kg/m 2. prostate-specific antigen (PSA)(131.5±69.7) ng/ml. prostate volume (38.5±21.4) ml. all patients had a PI-RADS score of 5 on multiparametric magnetic resonance (mpMRI) and an Eastern Cooperative Oncology Group (ECOG) score ≥2. All 33 cases in this group underwent trans-perineal targeted prostate puncture using local anesthesia at the tip of the prostate. The visual analog score (VAS) and visual numeric score (VNS) were applied by the same surgeon to assess the patient's pain level and satisfaction at the time of puncture (VAS-1 and VNS-1) and 30 min after puncture (VAS-2 and VNS-2), and to record the duration of the procedure and the occurrence of postoperative complications. Results:In this group of 33 cases, the VAS-1 score was (1.9±0.3) and the VAS-2 score was (0.1±0.2); the VNS-1 score was (2.9±0.2) and the VNS-2 score was (3.9±0.1). Postoperative pathological results indicated that one of the 33 patients had a negative puncture result (pathology report indicating interstitial inflammation), while the rest of the patients had a positive puncture pathology report (puncture pathology report indicating prostate cancer), with a positive rate of 97%. One case of postoperative carnal haematuria occurred, which gradually improved after the patient was advised to drink water and take alpha-blockers. No perineal hematoma occurred, and all patients did not suffer complications such as urinary tract infection, urinary retention, azoospermia, vagal reaction, and infectious shock.Conclusion:In patients with a PI-RADS score of 5 and ECOG score ≥2, the use of single-hole local anesthesia for performing trans-perineal targeted puncture biopsy has the advantages of good paroxysmal pain and high safety.

Objective:To investigate the factors affecting the effect of periprostatic nerve block (PNB), establish a prediction model of pain degree, and verify the prediction efficiency.Methods:The clinical data of 314 patients who underwent transperineal prostate biopsy in our hospital from June 2022 to January 2023 were retrospectively analyzed. The median age was 71 (65, 76) years, the median prostate-specific antigen (PSA) was 14.6 (10.70, 24.65) ng/ml, and the median puncture needle number was 21 (19, 23) needles, median prostate volume 45.86 (31.52, 67.96) ml, median body mass index (BMI)24.02(22.97, 25.33)kg/m 2, including 109 patients with a history of diabetes, 90 patients with a history of surgery, and 57 patients with a history of severe trauma. The patients were divided into mild pain group (1-3 points), moderate pain group (4-6 points) and severe pain group (7-10 points) according to the intraoperative visual analogue scale (VAS). According to the clinical characteristics, the factors affecting the effect of PNB were analyzed by univariate analysis and multiple ordered logistic regression method. R language was used to construct a nomogram model for predicting PNB effect, receiver operating characteristic (ROC) curve and calibration curve were drawn, and Hosmer-Lemeshow test was carried out to verify the prediction efficiency of the model. Results:The results of univariate analysis showed that 171 patients in the mild pain group had a median age of 71 (65, 75) years, a median PSA14.5 (9.6, 24.6) ng/ml, a median number of puncture needles of 20 (18, 22), and a median prostate volume of 34.94 (26.36, 45.12) ml, median BMI24.17(23.14, 25.79)kg/m 2, including 74 patients with a history of diabetes, 51 patients with a history of surgery, and 40 patients with a history of severe trauma; There were 110 patients in the moderate pain group, the median age was 71 (65, 76) years, the median PSA14.8 (11.03, 24.27) ng/ml, the median number of puncture needles was 23 (20, 24) needles, median prostatic volume 63.24 (49.14, 78.72) ml, median BMI23.91(22.58, 24.88)kg/m 2, including 26 patients with a history of diabetes, 29 patients with a history of surgery, and 10 patients with a history of severe trauma; In the severe pain group, 33 patients had a median age of 73 (67, 78) years, a median PSA14.6 (10.85, 34.80) ng/ml, and a median puncture needle number of 23 (22.5, 24) needles, median prostate volume 70.64 (61.50, 104.51) ml, median BMI24.32(23.00, 26.06)kg/m 2, including 9 patients with a history of diabetes, 10 patients with a history of surgery, and 7 patients with a history of severe trauma. The results of univariate analysis showed that the number of puncture needles ( P<0.01), prostate volume ( P<0.01), history of diabetes ( P=0.002) and history of major trauma ( P= 0.009) were the factors affecting the effect of PNB. Multiple logistic regression analysis showed that puncture needle number ( P=0.009), prostate volume ( P<0.01) and diabetes history ( P=0.041) were independent risk factors for PNB effect. The area under ROC curve (AUC) of the moderate and above pain prediction model was 0.872, P<0.01; the area under ROC curve of the severe pain prediction model was 0.817, P<0.01; the result of Hosmer-Lemeshow test of the moderate and above pain prediction model was χ2=5.001, P=0.757. The results of the severe pain prediction model were χ2=4.452 and P=0.814. The calibration curve was established, which showed that the prediction probability of pain degree was in good agreement with the actual risk. Conclusions:The number of puncture needles, prostate volume and history of diabetes are the risk factors affecting the effect of PNB. The prediction model of PNB effect based on this model can be used to predict the pain degree of patients undergoing prostate biopsy after PNB.

Objective:To explore the feasibility and safety of the clinical application of the diagnosis and treatment mode combining rapid frozen pathological examination of prostate biopsy tissue with radical prostatectomy.Methods:Suspected prostate cancer patients with PSA>10 ng/ml and PI-RADS score ≥4 in, Northern Jiangsu People's Hospital from April to September 2021 were collected. The included patients underwent mpMRI/TRUS image fusion-guided transperineal prostate targeted biopsy with 16G biopsy needle, 2-3 needles for biopsy, and rapid frozen pathological examination. Robot-assisted laparoscopic radical prostatectomy (RALP) was performed immediately for patients with prostate cancer with rapid freezing pathology. For undiagnosed prostate cancer, 18G biopsy needle for prostate targeted + systematic biopsy were used, 18-22 needles for systematic biopsy, and routine pathological examination. The baseline data, frozen pathological results, perioperative conditions, pathological results and follow-up data of all patients were collected.Results:Eleven patients were included in the study, the mean age of the patients was 69.9(66-73) years, the mean BMI was 22.8(19-26) kg/m 2, the mean PSA was 23.2(14.25-32.00), the mean prostate volume was 45(32-52) ml, mean PSAD 0.54(0.33-0.75). PI-RADS score was 4 in 3 cases and 5 in 8 cases; digital rectal examination was positive in 5 cases. All 11 cases underwent rapid freezing and the pathological results showed that: 9 cases were prostate adenocarcinoma, and RALP was performed immediately. The operation time was 111.5(96-126) min, the intraoperative blood loss was 78.9(55-105) ml, and the postoperative extubation time was 4.3(3.5-5.0) days, postoperative hospital stay 5.8(5.0-6.5) days. Postoperative pathology showed that Gleason score 3+ 4=7 in 1 case, 4+ 3=7 in 3 cases, 8 points in 4 cases, and 10 points in 1 case; 3 cases had positive resection margins, and 1 case had seminal vesicle invasion, the average number of dissected lymph nodes was 10.9 (8.5-14.0), and there was no tumor metastasis. Pathological T staging included 2 cases of T 2b stage, 5 cases of T 2c stage, 1 case of T 3a stage, and 1 case of T 3b stage. Two patients were undiagnosed by rapid freezing pathology, of which one was prostate adenocarcinoma with a Gleason score of 4+ 3=7, and then received RALP; the other one was prostate inflammation. 11 patients were followed up; the postoperative follow-up time was 3-7 months, with an average of 5.2 months. Among the 10 patients who underwent RALP, 8 patients recovered urinary continence 2 weeks after surgery, and all recovered within 2 months after surgery. Three patients with positive surgical margins were given regular androgen deprivation therapy in the second week after surgery. PSA did not drop below 0.1 ng/ml in patients with positive margins and seminal vesicle invasion 3 months after surgery. No complications of Clavien grade Ⅰ or higher occurred after operation and during follow-up. Conclusions:For patients with high suspicion of prostate cancer, rapid frozen pathological examination of prostate biopsy tissue is performed. RALP is performed immediately for patients with prostate cancer. The results show that this diagnosis and treatment model could be safe and feasible.

The present study retrospectively analyzed the clinical data of 137 patients who underwent prostate in North Jiangsu People's Hospital from June 2020 to May 2021. All patients underwent peripheral prostatic nerve block anesthesia (PPNB). The observation group received 1% ropivacaine 32 ml local, and the control group received the same dose of lidocaine. There was no significant difference in general data before puncture between the two groups ( P>0.05). All 137 cases were performed by the same surgeon. The number of puncture needles in the observation group and the control group was (20.2±2.8) and (20.2±2.9), respectively, and the difference was not statistically significant ( P>0.05). The visual analogue scores (VAS-1) of pain during puncture in the observation group and the control group were (2.62±0.74) and (2.48±0.79) points, respectively. The visual numeric score (VNS-1) was (3.03±0.88) points and (3.15±0.80) points, respectively, and there was no significant difference ( P>0.05). 30 min after puncture, VAS-2 was (0.48±0.53) points and (0.30±0.47) points, VNS-2 was (3.31±0.48) points and (3.55±0.71) points, respectively.The differences were statistically significant ( P<0.05). There was no significant difference in overall complication rate between the two groups ( P=0.661).

Objective:To analyze the risk of missed diagnosis in patients with PI-RADS score>3 and negative prostate initial biopsy and to explore its risk factors.Methods:The clinical data of 268 patients with negative prostate biopsy in Northern Jiangsu People's Hospital from May 2013 to December 2018 were retrospectively analyzed. The patients were divided into observation group (PI-RADS score>3) and control group (PI-RADS score≤ 3) according to different PI-RADS scores. There were insignificant differences in age [(67.4(60.0, 74.0)years and 65.6(66.5, 72.0)years], prostate volume of initial biopsy [62.4(40.0, 72.0)ml and 60.8(38.0, 77.0)ml], biopsy cores [ 20.6(18.0, 22.0)cores and 20.4(18.0, 22.0)cores] between the observation group (n=124) and the control group(n=144)(all P>0.05). But there were significant differences in PSA [17.5(6.5, 23.0)ng/ml and 11.5(6.3, 12.0)ng/ml], PSAD[0.316(0.128, 0.363)ng/ml 2 and 0.211(0.106, 0.256)ng/ml 2], prostate inflammation of the initial biopsy [70 (56.5%) and 32 (22.2%)] between the observation group and the control group(all P<0.05). According to the follow-up results after the initial biopsy, the two groups of repeated biopsy were compared.Furthermore, Logistic regression was used to conduct univariate and multivariate analysis to explore the risk factors of patients with PI-RADS>3 for positive repeated biopsy. At the same time, the receiver operating characteristic curve (ROC curve) was used to analyze the accuracy of the risk factors. Results:There were significant differences in repeated biopsy rate [ 27.4%(34/124)and 14.6%(21/144)], CsPCa detection rate[ 41.4%(14/34) and 4.8%(1/21)]between the observation group and the control group(all P<0.05). The positive rate of repeated biopsy in the observation group (41.1%) was higher than that in the control group (23.8%), but there was no statistical difference ( P=0.248). The risk of positive repeated biopsies in the observation group was 2.24 times than that in the control group. Univariate analysis found repeated biopsy PSA ( P =0.02, OR=1.438, 95% CI 1.161-1.896), PSA ratio (repeated biopsy PSA/initial biopsy PSA) ( P=0.011, OR=10.087, 95% CI 1.714-59.36) were risk factors for positive of repeated biopsy in patients with PI-RADS score >3. Multivariate analysis also found that repeated biopsy PSA ( P=0.017, OR=1.15, 95% CI 1.076-2.123), PSA ratio ( P=0.032, OR=10.2, 95% CI 0.883-116.168) were risk factors for positive repeated biopsy. ROC curve analysis, the accuracy of repeated biopsy PSA (AUC=0.971, P<0.001, 95% CI 0.926-1.000), PSA ratio (AUC=0.839, P=0.001, 95% CI0.707-0.971) to predict positive of repeated biopsy were high. The cut-off values were 21.3 ng/ml and 1.4, respectively. The accuracy was higher when combines repeated biopsy PSA with PSA ratio (AUC=0.993, P<0.001, 95% CI 0.974-1.000). Conclusions:Patients with negative PI-RADS score > 3 have a higher risk of missed diagnosis of CsPCa than those with PI-RADS score≤3. When PSA>21.3 ng/ml and PSA ratio>1.4 during follow-up, the possibility of missed diagnosis in the initial biopsy is high.

Objectives To evaluate the effectiveness and safety of peramivir trihydrate in patients with influenza.Methods This was a randomized,double-blind,double-dummy,placebo and positive control,multicenter clinical trial,comparing peramivir trihydrate with oseltamivir and placebo.The inclusive criteria were 15-70 years old,onset within 48 h,positive rapid influenza antigen test,and febrile(＞38℃) accompanied with at least two associated symptoms.The severe cases complicated with chronic pulmonary and cardiac diseases,malignancies,organ transplantation,hemodialysis,uncontrolled diabetes,immunocompromised status,pregnancy and coexistence of bacterium infections were excluded.All patients were randomized 2:2:1 to receive peramivir,oseltamivir and placebo respectively.The primary endpoint was the disease duration,the secondary endpoints included time to normal axillary temperature and normal living activities,viral response,and adverse effects.Results Following informed consent,133 patients were included in this study.Four patients were exclude due to missing medical records,not fitting inclusion or exclusion criteria and poor compliance.A total of 129 patients were finally analyzed,including 49 cases,54 cases and 26 cases in peramivir group,oseltamivir group and placebo group.The median disease duration were 96 (76,120)hours,105(90,124) hours,and 124 (104,172)hours in three groups respectively(P＞0.05).The time to normal axillary temperature,normal living activities and viral response were not significantly different in three groups(P＞0.05).Conclusion The value of antiviral therapy in patients with mild influenza needs to be further determined.

Objective: To evaluate the effect of multimodal analgesia using periprostatic nerve block anesthesia (PNB) combined with flurbiprofen in patients undergoing transperineal template-guided prostate biopsy (TTPB). Methods: Totally 166 patients (aged (68.2±9.1) years, range: 47 to 81 years) who received TTPB from October 2017 to June 2018 at Department of Urology, Northern Jiangsu People′s Hospital Affiliated to Yangzhou University were enrolled prospectively. All the patients were randomly divided into 2 groups. The observation group (n=79) was given flurbiprofen axetil 1 mg/kg intravenously for half an hour before operation and lidocaine was used for PNB before the biopsy. The control group (n=87) was given normal saline combined with PNB. A visual analog scale (VAS) and visual numeric scale (VNS) were used to assess the patients′ pain and quantify their satisfaction at two time points: VAS-1 and VNS-1: during biopsy procedure, VAS-2 and VNS-2: 30 min after the procedure. The date were compared by t test, χ² test, Fisher exact test and two-way repeated measures anova analysis between the 2 groups. Results: The age, total prostate volume, serum prostate-specific antigen and the number of cores were comparable among the 2 groups (P>0.05). The VAS-1 scores of the control group and the observation group were 2.8±1.7, 1.9±1.2, respectively, and the VNS-1 were 3.1±0.7, 3.4±0.3, respectively. The VAS-1 were significantly lower in observation group than in control group (F=3.904, P=0.000). Conversely, the VNS-1 were higher in observation group (F=3.526, P=0.000). At 30-minute postoperative, the VAS-2 and VNS-2 were 0.7±0.4 and 3.7±0.2 in the control group, respectively. The VAS-2 and VNS-2 were 0.6±0.5 and 3.8±0.1 in the observation group, respectively. There were no significant differences in the pain scores or the satisfaction scores between the 2 groups (F=1.429, 2.825; P=0.136, 0.083). The incidence of overall complications was 26.4% (23/87) in the control group and 25.3% (20/79) in the observation group, with no statistical difference between the 2 groups (χ²=0.027, P=0.869). And the complications had no statistically significant difference among the 2 groups including hematuria, urinary retention, infection, hematospermia, vascular and neurological reactions, nausea, vomiting, dizziness, headache, and respiratory depression (P>0.05). Conclusion The multimodal analgesia induced by PNB and flurbiprofen could effectively relieve the pain for patients who received TTPB.

Objective To investigate the influence factors of periprostatic nerve block (PNB) anaesthesia.Methods A total of 375 patients who underwent prostate biopsy under PNB were analyzed retrospectively from July 2014 to February 2018.It was evaluated the correlation of the anesthetic efficacy of PNB with age,prostate volume,PSA,body mass index,spouse,degree of education,occupation,diabetes history,operation time,number of cores and clinical stage.A visual analog scale (VAS) were used to assess pain of the patients.Univariate analysis was performed for each factor.Factors found to be significantly different that were further analyzed using multiple linear regression analysis.Results The average VAS score of all patients was 2.5 ± 1.4.Univariate analysis showed that the following factors were associated with the anesthetic efficacy of PNB:age (F =2.262,P =0.029),prostate volume (F =2.529,P =0.011),occupation (F =2.203,P =0.042),operation time (F =2.233,P =0.033),number of cores (F =2.401,P =0.016) and diabetes history (F =2.271,P =0.027).Multiple linear regression analysis showed that prostate volume (t =3.742,P ＜ 0.001),number of cores (t =4.252,P ＜ 0.001) and diabetes history (t =-2.242,P =0.032) were independent factors.The VAS score of patients with large volume prostate was higher than that of small volume prostate.The number of cores was high,and the VAS score was higher.However,diabetic patients had lower VAS score.Conclusions The anesthetic efficacy of PNB was poor in patients with larger prostate volume and more number of cores.However,patients with chronic diabetes had better pain tolerance.

Objective To evaluate the clinical efficacy of brachytherapy with 125I seeds implantation in patients with castration resistant prostate cancer (CRPC).Methods Twenty-eight patients with CRPC from February 2010 to December 2015 in Northern Jiangsu People's Hospital were analyzed retrospectively.Patients were divided into 2 groups according to different treatment methods.Control group (n =13) received endocrine therapy,and study group (n =15) underwent brachytherapy combined with endocrine therapy.The progression was defined as posttreatment prostate specific antigen (PSA) ≥ 125％ PSA of baseline level.PSA-progression-free survival (PFS),overall survival (OS) and quality of life (physical functioning,social functioning,general health,general physical discomfort,urinary symptoms and treatment-related symptoms) of 2 groups were compared using Kaplan-Meier analysis and log-rank test.Results The median PSA-PFS and OS of study group were 29(24,37) months and 37(32,50) months respectively,both of them were longer than those of control group (13(7,21) months,19(14,23) months;x2 =13.300,19.362,both P＜0.01).Comparing with control group,the physical functioning,social functioning,general health and general physical discomfort of study group were improved.Conclusion Brachytherapy can effectively prolong the survival of CRPC patients and improve the patients' life quality.