Objective To investigate the value of imaging-pathology fusion guided targeted cryoablation for localized prostate cancer.Methods Between June 2014 and February 2017,64 patients undergoing targeted cryoablation for localized prostate cancer were retrospectively collected and analyzed.The average age was 77.8 years old,ranging 45-87 years old.The preoperative valne of PSA ranged from 5.1 to 19.8ng/ml,with mean of 15.3 ng/ml,including 6 case of cT1c,35 cases of cT2a,and 23 cases of cT2b,and 35 cases of Gleason score 6,8 cases of 3 + 4 and 21 cases of 4 + 3.All patients had good continence and 11 cases had good erectile function before operation.All the patients received MRI or contrast-enhanced ultrasonography examinations before biopsies,and the sites and range of cryoablation were determined by MRI or contrast-enhanced ultrasonography and biopsy pathological results.Results All the patients underwent the surgery successfully.The average postoperative hospital stay was 1.6 days,ranging 1 to 3 days,including 22 cases discharged within 24 h after surgery.The operative duration ranged from 85 to 152 min,with mean of 99.6 min.The satisfaction rate of the patients was 100％.Seven patients had Clavien Ⅰ or Ⅱ postoperative complications,and recovered after symptomatic treatment.The follow-up duration ranged from 0.5 to 32.2 months,with median of 11.8 months.All patients were alive without new metastasis.Eight patients developed biochemical recurrence,5 of those underwent intermittent endocrine therapy,resulting in stable PSA levels.Conclusion Imaging-pathology fusion guided targeted cryoablation was safe and effective for localized prostate cancer with the advantages of few complications,high satisfaction rate and quick recovery.

Objective: To study difference of the immune response between oral administration and intraperitoneal injection of total polysaccharide of Sijunzi decoction (SJTP) in mice. Methods: The immunosuppressed mice model was established by intraperitoneal injection of cyclophosphamide (CY). The effects of SJTP on the weight of immune organs,hemolysin response and delayed type hypersensitivity (DTH) were observed,and the influences on normal mouse spleen lymphocytic proliferation of mice were also studied. Results:SJTP can remarkably counteract the immunosuppression induced by CY, decrease the weight loss immune organs,increase the hemolysin response and DTH,and promote the proliferation of lymphocytes.The effect of oral administration is superior to intrapertoneal injection.Conclusion:SJTP can improve the humoral and cellalar immunity of mice.The immune activities resulting from oral administration of SJTP have some special characteristics,and its possible mechanism is also discussed.

OBJECTIVETo establish a SPE-HPLC method for analyzing astilbin in rats serum and explore the effects of Yinxieling (YXL) prescription and Smilacis Glabrae Rhizoma on the pharmacokinetic characteristics of effective components.

METHODMale Sprague-dawley rats were administrated YXL and Smilacis Glabrae Rhizoma respectively. At different time points, serum concentration of astilbin was extracted by Solid Phase Extraction (SPE) and determined using HPLC method. Chromatographic separation was achieved on a reversed-phase Phenomenex C18 column with the mobile phase of methanol-acetonitrile-formic acid water solution (0.05% formic acid) and gradient elution, temperature of bar was 24 degrees C, flow rate was 0.8 mL x min(-1).

RESULTThe method showed excellent linearity over the concentration range 0.266-53.1 mg x L(-1) of astilbin (r = 0.996). The extract recoveries were from 79.0% to 89.1%. Significant diffenerce in pharmacokinetic parameter of astilbin including t1/2, Cmax, AUC(0-t), AUC(0-infinity) and MRT were obtained through non-compartment model after oral administration of YXL prescription comparing with Smilacis Glabrae Rhizoma.

CONCLUSIONThe method was applied to a pharmacokinetic study of astilbin. It indicated that the bioavailability of astilbin in YXL enhanced in rats and one of the reasons may be that components of prescription affect the pharmacokinetics of astilbin in vivo.

Administration, Oral ; Animals ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Flavonols ; blood ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results

Objective· To evaluate the safety of neoadjuvant therapy which was constituted by docetaxel based systemic chemotherapy and maximal androgen blockage for patients with locally advanced prostate cancer and to summarize the related adverse events and clinical managements.Methods· From June 2015 to February 2017,the clinical data of 55 patients undergoing neoadjuvant chemotherapy combined with complete androgen deprivation were retrospectively reviewed.The patients were given docetaxel and prednisone as DP regimen every 3 weeks and LHRH analogues with bicalutamide as maximal androgen deprivation for a total of 4 cycles.All treatment-related adverse events were observed and then recorded.Results· Two cases with liver function impairment after 2 cycles of treatment were withdrawn from the study.No severe allergic reactions occurred during neoadjuvant therapy.The most common adverse events were hematologic toxicity,while 23.6％ of patients had grade Ⅲ-Ⅳ neutropenia,and about 12.7％ had anemia.Due to a relatively short course of treatment,the skin or mucous damage,peripheral neurotoxicity and fluid retention were rare.However,hot flash,male breast development as well as erectile dysfunction were very frequently observed due to maximal androgen deprivation.The majority of these adverse events were relieved by symptomatic and supportive treatment.Conclusion · After strict selection,4 cycles of neoadjuvant chemotherapy combined with total androgen blockade could be well tolerated by the patients with high-risk locally advanced prostate cancer.Even though the adverse events were controllable,they still need to be closely monitored during treatment in order to reduce the incidence.In addition,the very low testosterone level associated endocrinal metabolic disorders caused by complete androgen deprivation were also of great concern.

Mammalian reproduction is closely related to their metabolic status. The hypothalamus-pituitary-gonad axis ( HPG axis) is regulated by various metabolic factors. Glucagon-like peptide-1 ( GLP-1) is one of various metabolic factors that not only affect glycemic and metabolic control, but also with many other effects, including affecting HPA axis. The function of GLP-1 is related to the location of glucagon-like peptide-1 receptor ( GLP-1R) distribution. It has been confirmed that GLP-1R is widely distributed in HPG axis. The effects of GLP-1 and GLP-1R agonists on the HPG axis have also attracted much attention. The positive effects of GLP-1 and GLP-1R agonists on the HPG axis indicated it could be the new target for the new treatment for gonadal diseases. The role of GLP-1 and GLP-1R agonists in the central nervous system is reviewed.

Patients with spinal cord injury is associated with seriously affected gastrointestinal function and imbalance of intestinal flora, leading to increased inflammation of spinal cord nerves. With the proposal of the theory of gut microbiota-gut-brain axis in recent years, the regulatory role of gut microbiota in the central nervous system and gastrointestinal system has gradually attracted attention. Although a considerable number of studies have focused on the effects of intestinal flora characteristics on spinal cord nerve function repair in patients with spinal cord injury from different perspectives, there are numerous research models for treating spinal cord injury with intestinal flora as intervention targets and remains a lack of unified and effective clinical treatment methods. In this paper, the authors review the research progress in characteristics of intestinal microflora and intestinal microflora-targeted therapeutic methods in patients with spinal cord injury, hoping to provide a reference for the clinical treatment and basic research of spinal cord injury.

Purpose: In non-metastatic prostate cancer (nmPCa) setting, it is important to early identify the patients at risk of biochemical recurrence (BCR) for immediate postoperative intervention. Our study aimed to evaluate the potential clinical utility of circulating tumor DNA (ctDNA) for predicting disease recurrence. Materials and Methods: This real-world observational study evaluated 161 cases of nmPCa undergoing next-generation sequencing at our institution. A total of 139 ctDNA samples and 31 biopsied tumor tissue underwent genomic profiling. The study endpoint was BCR after radical prostatectomy. Relationships between the ctDNA status and the biochemical progression-free survival (bPFS) were analyzed by log-rank test and multivariate Cox regression. Results: Of 161 enrolled patients, 19 (11.8%) harbored deleterious alterations in NCOR2, followed by BRCA2 (3.7%), ATR (2.5%), and CDK12 (2.5%). Of available pre-operative blood samples (n=139), ctDNA was detectable in 91 (65.5%). Until last follow-up, 56 of 68 patients (85.3%) with detectable ctDNA had achieved BCR, whereas only eight of 39 patients (20.5%) with undetectable ctDNA had achieved BCR. Patients who had undetectable ctDNA experienced significantly longer bPFS compared with those who had detectable ctDNA (not available vs. 8.2 months; hazard ratio, 0.14; p < 0.01). Pre-operative ctDNA status was a significant prognostic factor of disease recurrence. Conclusion Pre-operative ctDNA detection could identify patients at high risk of recurrence and has the potential to inform immediate postoperative interventions, but these approaches remain to be validated in prospective studies. ctDNA studies can provide insights into accurate monitoring and precise treatment rather than simply following routine clinical care.

Objective To investigate the efficacy and safety of docetaxel chemotherapy combined with androgen-deprivation therapy (ADT) for patients with metastatic hormone-sensitive prostate cancer.Methods One hundred and ninety-two cases of metastatic hormone-sensitive prostate cancer in Renji Hospital between January 2015 and July 2016 were analyzed retrospectively.Patients' age was 39 to 90,the median age was 71 years.The median prostate-specific antigen (PSA) at diagnosis was 90.6ng/ml (4.1-2 556.0 ng/ml).One hundred and eighty were with bone metastasis and 12 were with distant lymphatic metastasis.Sixty-one of them received docetaxel chemotherapy plus ADT for 3 weeks,131 received hormonal treatment alone.The median age of combination therapy group was 67 years (39-80 years),that of single treatment group was 75 years (50-93 years) (P ＜ 0.001).The median PSA baseline of the two groups were 91.6 ng/ml (35.5-157.5ng/ml) and 89.1 ng/ml (59.6-191.0 ng/ml) (P =0.324).Gleason score of combination therapy group showed that 3 cases (4.9％) was 6,23 cases (37.7％) 7,35 cases (57.4％) ≥8.That of single treatment group showed that 17 cases (13.0％) 6,51 cases (38.9％) 7,63 cases (48.1％) ≥8.There was no statistic difference between the two groups (P =0.122).But there was statistic difference in the rate of T3 or T4 clinical stage in primary lesion,that of combination therapy group was 50.7％ (37/61) and 34.4％ (21/61),and that of single treatment group was 60.3％ (79/131) and 21.4％ (28/131) (P =0.011).Imaging showed local lymph node metastasis in the two groups (80.3％ vs.67.9％,P =0.005).As to physical condition,the combination therapy group showed a lower ECOG score than the single treatment group (P ＜ 0.001).All the patients' survival condition,PSA response rate and adverse events were analyzed.Results One hundred and ninety-two patients were regularly followedup.The median follow-up time was 23.3 (14.4-33.4) months.Median progression free survival time of combination therapy group and single treatment group were respectively 24.4 (7.5-31.3) months vs.17.5(3.0-30.7) months (P ＜ 0.001).There were 1 and 16 cases died in the two groups due to disease progression.During the treatment,the rate of PSA level less than 0.2 ng/ml was 29.5％ (18/61) vs.13.7％ (18/131) in combination therapy group and single treatment group.Regarding the tolerance of combination therapy group,the incidence rate of grade 3-4 neutropenia was 27.9％ (17/61).Skin and mucous membrane damaged in 24.6％ (15/61) patients,transaminase rised in 13.1％ (8/61) patients,and peripheral nerve toxicity occurred in 9.8％ (6/61) patients.There was no significant difference between the 2 groups in relevant events caused by ADT,gynecomastia (14.8％ vs.16.3％) and erectile dysfunction (100％ vs.100％).Most of them could be relieved by symptomatic treatment.Conclusions For metastatic hormone-sensitive prostate cancer,docetaxel combined with hormonal treatment showed longer progression free survival than ADT alone with adverse reactions acceptable.

Objective To investigate the efficacy of pretreatment systemic inflammation response index (SIRI) in predicting the prognostic of prostate cancer (PCa) patients treated with maximal androgen blockade (MAB).Methods The data of 351 PCa patients who had undergone MAB as first-line therapy between January 2010 and June 2015,were retrospectively analyzed.The age of patients in our cohort ranged from 51 to 89 years old,mean 76 years old.The median value of PSA was 91.60ng/ml,ranging 0.11-1 000.00 ng/ml.39 cases had a Gleason score of 6,47 cases had a score of 3 + 4,89 cases had a score of 4 +3,107 cases had a score of 8,and 69 cases had a score of 9-10.158 cases had bone metastasis.Patients were categorized in two groups using a cut-off point of 1.2 as calculated by the receiver-operating curve analysis.Correlations between SIRI and clinical characteristics were analyzed.Meanwhile,univariate and multivariate cox regression analyses were performed to determine the associations of SIRI with progression-free survival (PFS),cancer-specific survival (CSS) and overall survival (OS).Results The median follow-up duration was 43.0 months,ranging 9-75 months.The disease progression occurred in 162 patients,91 patients died,including 75 who died because of PCa at the end of the last follow-up.The differences of age,Gleason score and incidence of metastasis between low SIRI group (＜ 1.2) and high SIRI group (≥1.2) were not significant (P ＞0.05).But the patients in high SIRI group had higher PSA (P =0.046).Multivariate analyses identified SIRI,Gleason score and metastasis as independent prognostic factors for PFS,CSS and OS.Conclusions Pretreatment SIRI ≥ 1.2 was an independent predictor for poor prognosis in PCa patients treated with MAB.

Objective:To investigate the clinical efficacy of neoadjuvant chemo-hormonal therapy(NCHT)followed by radical prostatectomy(RP) plus extended pelvic lymphadenectomy for very-high-risk locally advanced prostate cancer.Methods:The data of 327 cases of very-high-risk locally advanced prostate cancer treated in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, The Second Hospital of Tianjin Medical University, and The Third Affiliated Hospital of Sun Yat-sen University from December 2014 to July 2019 were retrospectively analyzed. Patients were divided into two groups according to treatment regimens: the RP group (direct RP + extended pelvic lymphadenectomy 4-6 weeks after the biopsy of prostate) and the NCHT group (4-6 cycles of NCHT prior to RP). There were 171 cases in RP group and 156 cases in NCHT group, respectively. In the RP group, the median age was 67 (ranging 44-83)years. The median PSA at diagnosis was 27.24 (ranging 4.55-207.00) ng/ml. Patients’numbers of clinical T 2, T 3a, T 3b, T 4 stage were 13, 85, 57, 16, respectively, and clinical N 1, N 0 stage were 33 and 138, respectively. Patients’numbers of ISUP grade groups of 1, 2, 3, 4, 5 were 5, 35, 41, 51, 39, respectively. In the NCHT group, The median age was 67 years, ranging 46-78 years. The median PSA at diagnosis was 72.09(ranging 4.08-722.95)ng/ml. Patients’ numbers of clinical T 2, T 3a, T 3b, T 4 stage were 11, 47, 58, 40, respectively, and clinical N 1, N 0stage were 76 and 80, respectively. Patients’numbers of ISUP grade groups of 1, 2, 3, 4, 5 were 1, 11, 33, 43, 68, respectively. At baseline, the NCHT group showed higher PSA, higher ISUP grade, and more advanced clinical stage at diagnosis( P<0.05). The PSA, pathological down-staging rate, and positive surgical margin rate as well as the biochemical recurrence free survival(bRFS)were compared between the two groups. Results:After radical prostatectomy, compared with the RP group, the NCHT group had a higher proportion of patients achieving PSA<0.2 ng/ml at 6-week postoperative follow-up ( P<0.001), a higher pathologic tumor stage down-staging rate ( P<0.001), a higher ISUP down-grading rate ( P<0.001), and a lower positive surgical margins rate ( P<0.001). In addition, 10.9% of the NCHT group achieved pT 0 or minimal residual disease in postoperative pathology exams. Eighty-three patients (48.5%) in the RP group and 125 patients (80.1%) in the NCHT group achieved undetectable PSA after surgery and entered further analysis for bRFS, which showed NCHT group had significantly longer bRFS (19.46 months vs. 6.35 months). NCHT significantly reduced the risk for biochemical recurrence in locally advanced prostate cancer patients( HR=0.278, 95% CI 0.198-0.390, P<0.001). Such a reduce in risk for biochemical recurrence was seen in all subgroups( P<0.001). Conclusions:NCHT might improve surgical outcomes as well as bRFS in very-high-risk locally advanced prostate cancer patients.