Objective To study the genotoxicities of raceanisodamine hydrochloride injection. Methods Bacterial reverse mutation test, in vitro Chromosomal aberration test and in vivo Micronucleus test were performed to investigate the genotoxicities of raceanisodamine hydrochloride injection. Results The Ames test showed that raceanisodamine hydrochloride injection did not increase mutagenicity for TA1535, TA102, TA100, TA98 and TA97 strains at the dosage of 0.5, 5, 50, 500, 5000 μg per plate under two parallel system conditions (±S9). Results of CA test indicated that there was no statistical difference between raceanisodamine hydrochloride injection groups (doses of 58.75,117.5 and 235.0 μg/ml) and the solvent control group under two parallel system conditions (±S9). In MNT test, with doses of 7.5, 15.0 and 30.0 mg/kg respectively, the micronucleus induction rate of bone marrow of ICR mice was not statistically significant (P>0.05) when compared with that of vehicle control group in all dose groups. Conclusion Under the conditions of these study, the results indicated that raceanisodamine hydrochloride injection had no mutagenicity to Salmonella typhimurium, had no aberration effect on the chromosome of mammalian cultured cells, and had no effect on inducing micronucleus of bone marrow polychromatic erythrocytes in ICR mouse. All test results showed that raceanisodamine hydrochloride injection had no potential carcinogenicities and genetic toxicities under the test conditions.

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 effects of aflatoxin B1 (AFB1) on the biophysical properties and cytoskeleton structure of human hepatocellular carcinoma cells (HCCs) . Methods: HepG2 cells were respectively treated with 0 , 0. 01 , 0. 1 , 1 , 5 , 10 μmol/L AFB1 for 24 h and 48 h , and the cell viability was measured by CCK⁃8 kit.Based on this result , the influences of 10 μmol/L AFB1 on the osmotic fragility , membrane fluidity , electrophoretic mobility (EPM) and F ⁃actin structure of cells were analyzed. Subsequently , total RNAs were extracted and the PCR. Results: The increased viability of HepG2 cells was induced by AFB1 in a dose⁃dependent manner after 48h treatment. After treated with 10 μmol/L AFB1 , the anti⁃hypotonic ability and EPM of HepG2 cells were en⁃hanced. The content of F ⁃actin in HepG2 cells increased obviously , while the mRNA expression levels of the main cytoskeleton binding proteins were altered. Conclusion AFB1 can affect the biophysical properties , cytoskeleton structure and its binding proteins of HepG2 cells , which may be directly related to its toxic action.

Objective To evaluate the in vitro synergistic antifungal activity of HDAC inhibitors in combination with azole drugs against azoles-resistant Candida strains. Methods The checkerboard microdilution method was used to evaluate the antifungal activity of the HDAC inhibitors in combination with azole drugs against clinically drug-resistant strains. The fungistatic activity and toxicity of Rocilinostat was determined through time-growth curve assay and cytotoxicity assay. Results The compound Rocilinostat combined with azole drugs showed excellent synergistic antifungal activity against a variety of azoles-resistant Candida albicans and Candida glabrata. The combination of high concentration Rocilinostat with FLC exhibited fungistatic effects. Very low toxicity was detected with Rocilinostat towards normal cells. Rocilinostat showed better HDAC inhibitory activity than SAHA. Conclusion As a fungi HDAC inhibitor, Rocilinostat has excellent in vitro synergistic antifungal activity and no severe toxicity to normal human cells.

The proteolysis targeting chimeras (PROTACs) technology has been rapidly developed since its birth in 2001, attracting rapidly growing attention of scientific institutes and pharmaceutical companies. At present, a variety of small molecule PROTACs have entered the clinical trial. However, as small molecule PROTACs flourish, non-small molecule PROTACs (NSM-PROTACs) such as peptide PROTACs, nucleic acid PROTACs and antibody PROTACs have also advanced considerably over recent years, exhibiting the unique characters beyond the small molecule PROTACs. Here, we briefly introduce the types of NSM-PROTACs, describe the advantages of NSM-PROTACs, and summarize the development of NSM-PROTACs so far in detail. We hope this article could not only provide useful insights into NSM-PROTACs, but also expand the research interest of NSM-PROTACs.

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.

Objective: To investigate the clinicopathological characteristics and diagnosis of ovarian Brenner tumors. Methods: Forty-seven cases of ovarian Brenner tumors were enrolled from January 2012 to May 2018 at Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Clinical data, imaging examination, histopathological characteristics and immunohistochemical phenotype were analyzed. Results: The age of the patients ranged from 30-73 years and the mean age was 55 years. Thirty-nine patients (83.0%) were postmenopausal. Forty cases (85.1%) of the Brenner tumors were benign, five (10.6%) borderline and two (4.3%) malignant. Usual tumor markers of ovarian carcinoma, including CA199 and CA125 were normal or mild elevated in the 47 cases. Imaging before surgery was not specific to Brenner tumors. Microscopically, benign Brenner tumors were composed of nests of bland, transitional-type cells within a fibromatous stroma. In our 5 cases of borderline Brenner tumors, mildly atypical transitional-type cells were projected into the cyst lumens and lack of stromal invasion. In 2 cases of malignant Brenner tumors, different degrees of nuclear atypial transitional-type cells exhibited stromal invasion. Immunohistochemical stains for CK7, GATA3, p63 and CK5/6 were positive in all cases. Ki-67 was less than 5% in Brenner tumors, and up to 20%-30% in malignant Brenner tumors. Conclusion Brenner tumors are mostly seen in postmenopausal patients and are usually benign. Imaging examination and usual ovarian tumor markers do not provide diagnostic value. Diagnosis and classification of Brenner tumors depend on histopathological evaluation.

Objective: To investigate the clinical value of modified transperineal template-guided prostate biopsy (mTTPB) in the detection of prostate cancer. Methods: A total of 217 patients were enrolled in this study. All the patients were randomly divided into 2 groups. The control group (n=112) underwent transperineal template-guided prostate biopsy (TTPB) which was traditional transperineal template-guided 11-region biopsy. On the basis of the control group, the apex of prostate was divided into four areas for biopsy in the observation group (mTTPB). The positive rate of apex and the incidence of complications were analyzed. The prostatic specimens from the radical prostatectomy underwent whole mount sections examination. The prostate biopsy results were compared with the postoperative pathological results. Results: The average age of the control group and the observation group were (68.5±7.9) years and (67.3±8.5) years, PSA were (31.2±18.9) ng/ml and (29.7±19.5) ng/ml, prostate volume were (44.6±15.2) ml and (41.3±17.3) ml, respectively. In the control group, the positive rates of prostate cancer in 1-10 region were 24.1% (27/112), 27.7%(31/112), 23.2% (26/112), 28.6% (32/112), 26.8% (30/112), 25.0% (28/112), 26.8% (30/112), 19.6% (22/112), 25.9% (29/112), 25.0% (28/112), respectively, with an average of 25.3%. In the observation group, the positive rates in 1-10 region were 27.6% (29/105), 28.6% (30/105), 22.9% (24/105), 26.7% (28/105), 25.7% (27/105), 24.8% (26/105), 27.6% (29/105), 21.9% (23/105), 27.6% (29/105), 26.7% (28/105), respectively, with an average of 26.0%. There was no statistical difference between the two groups (P=0.904). The positive rate of apical prostate cancer in the control group and observation group was 37.5% (42/112) and 44.8% (47/105), respectively, and there was no statistical difference between the two groups (P=0.277). Patients were grouped according to PSA>20 ng/ml and PSA≤20 ng/ml. When PSA>20 ng/ml, the positive rate of apex was 58.6% (34/58) and 56.6% (30/53) respectively in the control group and the observation group, and there was no statistical difference between the two groups (P=0.830). When PSA≤20 ng/ml, the positive rate of apex was 14.8% (8/54) in the control group and 32.7% (17/52) in the observation group, with statistically significant differences (P=0.030). Before radical prostatectomy, 12 cases (57.1%) in the control group and 19 cases (73.1%) in the observation group showed apical invasion by biopsy. Results of whole mount sections examination in the control group showed that there were 19 cases (90.5%) with apical invasion, which was statistically different from that before surgery (P=0.035). The results of whole mount sections examination in the observation group showed that there were 23 cases (88.5%) with apex invasion, which had no statistical difference compared with that before surgery (P=0.291). There were no significant differences in the incidence of hematuria, fever, urinary retention and perineal discomfort between the observation group and the control group (all P>0.05). Conclusions mTTPB can significantly improve the detection rate of apical prostate cancer without increasing the incidence of complications, especially for patients with PSA≤20 ng/ml. Hence is safe and efficacious.