Objective: To explore the relationship between the changes of plasma levels of resistin with the contemporary body weigh changes in the same population. Methods: The community based epidemiological surveys were carried out in the same population in Shijingshan district of Beijing at the year of 2005 and year of 2010. A total of 943 subjects with the entire information of cardiovascular related risk factors were enrolled including 316 male with the mean age of (58.2 ± 8.5) years and 627 female with the mean age of (59.3 ± 7.5) years. Plasma levels of resistin in both year of 2005 and year of 2010 in all subjects were recorded, and the subjects were divided into 4 groups based on the quartile levels of resistin. Group①, the subjects with plasma level of resistin ≤ (-0.66) mmol/L,n=239, Group②, resistin level (from -0.67 to 0.25) mmol/L,n=233, Group③, resistin level (0.26-1.24) mmol/L, n=235 and Group④, resistin level ≥1.25 mmol/L,n=236. Pearson correlation study with uni- and multi- regression analysis were conducted to investigate the relationship between the changes of plasma levels of resistin with the contemporary body weight changes in the same population.Results: The uni-variate analysis showed that in female subjects, plasma levels of resistin were obviously related to the percentage (%) of body weight changes (correlation coefifcient: 0.1173), body weight index (kg/m2) changes (0.1521), the% of body weight index changes (0.1412), the waist circumference (cm) changes (0.1228) and the % of waist circumference changes (0.1057) respectively, allP<0.05; while the above changes in male subjects were not signiifcant, allP>0.05. Multi-regression analysis indicated that with adjusted baseline variables, in female subjects, the plasma levels of resistin were obviously related to body weight (kg) changes and the % of body weight changes (regression coefifcient: 0.0261 and 0.2916), body weight index (kg/m2) changes and % of body weight index changes (0.2157 and 0.3072), the waist circumference (cm) changes and the% of waist circumference changes (0.0532 and 0.2738) respectively, allP<0.05; while the above changes in male subjects were not signiifcant, allP>0.05. Conclusion: The changes of plasma levels of resistin are signiifcantly related to contemporary body weight changes in female subjects, but not in male subjects.

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.

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 compare the efficacy and safety of radium-223 in the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients with and without homologous recombination repair (HRR) gene mutation.Methods:The clinical data of 27 patients with mCRPC bone metastases who received radium-223 therapy from April 2021 to November 2022 in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine were retrospectively analyzed. Among the 27 mCRPC patients, 18 patients carrying HRR gene mutations belonged to the HRD(+ ) group, and 9 patients without HRR gene mutation belonged to the HRD(-) group. The age of patients in HRD(+ ) group was 69.5 (63.8, 77.0) years old, alkaline phosphatase (ALP) was 243.0 (82.8, 301.3) U/L, prostate specific antigen (PSA) was 71.6 (7.3, 329.8) ng/ml, pain score was 3.0 (1.0, 5.0) points. Eastern Cooperative Oncology Group (ECOG) score ranged from 0 to 1 points in 7 cases, and 2 points in 11 cases. In the HRD(-) group, the median age was 72.0 (64.5, 76.5) years old, ALP was 88.0 (67.5, 260.6) U/L, PSA was 19.1 (1.1, 117.8) ng/ml, and pain score was 2.0 (0, 4.5) points. The ECOG score ranged from 0 to 1 in 4 cases, and 2 in 5 cases in the HRD(-) group. There was no significant difference in the above general data between the two groups ( P>0.05). All patients received radium-223 treatment every 4 weeks, no more than 6 times. The changes of ALP, PSA, pain score and hematological adverse reactions were compared between the two groups. Results:In the HRD(+ ) group, the median number of radium-223 treatment was 4.5 (3.0, 5.3) couses, 4 patients (22.2%) completed 6 courses, and 6 patients died of prostate cancer during follow-up. In the HRD(-) group, the median number of radium treatment was 4.0 (2.5, 6.0) couses, 3 patients (33.3%) completed 6 courses, and 1 patient died of prostate cancer during follow-up. There was no significant difference in the number of radium treatment courses between the two groups ( P=0.320). ALP in HRD(+ ) group was 101.8 (61.3, 147.0) U/L after radium-223 treatment, which was significantly lower than that before treatment ( P=0.002). ALP in HRD(-) group was 73.0 (64.0, 113.5) U/L after radium-223 treatment, and it was not significantly different from that before treatment ( P=0.327). The rate of ALP response (ALP decrease >10%) in HRD(+ ) group was significantly higher than that in HRD(-) group [83.3% (15/18) vs. 44.4% (4/9), P=0.037]. PSA was 105.9(5.2, 798.4) ng/ml in HRD (+ ) group after radium-223 treatment, and was 25.6(0.8, 1 031.0) ng/ml in HRD(-) group, and they were not significantly different from that before treatment ( P=0.145, P=0.386). There were no significant differences in the rate of PSA response (PSA decrease>10%) between HRD(+ ) group and HRD(-) group [38.9% (7/18) vs. 22.2% (2/9), P=0.386]. The median pain score of HRD(+ ) group was 3.0 (0, 4.0) points after treatment, which was significantly lower than that before treatment ( P=0.028). The pain score of HRD(-) group was 1.0(0, 3.0) points after treatment, and it was not significantly different from that before treatment ( P=0.129). There was no significant difference in pain relief rate between HRD(+ ) group and HRD(-) group [66.7% (12/18) vs. 44.4% (4/9), P=0.411]. The incidence of at least one hematological adverse event during radium-223 treatment in the HRD(+ ) group was higher than that in the HRD(-) group [77.8% (14/18) vs. 33.3% (3/9), P=0.039]. There was no significant difference in the incidence of grade 1-2 hematological adverse events between the two groups [72.2%(13/18) vs. 33.3%(3/9), P=0.097]. Only 1 patient in the HRD(+ ) group experienced grade 3 anemia during treatment which was recovered after blood transfusion. Conclusions:Compared to mCRPC patients without HRR gene mutation, patients with HRR gene mutations had better ALP response and bone pain relief after radium-223 treatment. The overall incidence of adverse events in the HRD(+ ) group is higher than that in HRD(-) group, and there was no significant difference in grade 1-2 hematological adverse events between the two goups. It is necessary to expand the sample size to further verify the conclusion.

Objective To determine the influence of abiraterone acetate (AA) on neuroendocrine differentiation (NED) in metastatic castration-resistant prostate cancer (mCRPC) and the prognostic predicting value of the serum NED markers in mCRPC patients treated with AA.Methods We conducted an analysis in 115 chemotherapy-naive mCRPC patients who were treated with chemotherapy in Renji hospital from 2013 to 2017.The median age was 70,ranged from 65 to 76 years old.The median CgA,NSE and PSA levels were 101.1 ng/ml (78.5-150.0 ng/ml),13.4 ng/ml (10.5-17.6 ng/ml) and 38.8 ng/ml (11.2-123.2 ng/ml),respectively.Among them,48 cases were classified as the group without AA treatment.The other 67 cases were classified as group after AA failure.In group without AA treatment,the median CgA,NSE and PSA levels were 109.1 ng/ml(80-151.5 ng/ml);13.8 ng/ml(10.8-18.2 ng/ml) and 39.2 ng/ml (8.6-200 ng/ml),respectively.In group after AA failure,the median CgA,NSE and PSA levels were 105.4 ng/ml(78.8-175.5 ng/ml),13.8 ng/ml(10.8-17.6 ng/ml) and 39.0 ng/ml(8.4-219.8 ng/ml),respectively.In the group with serial evaluation of NED markers during AA treatment,the median serum CgA,NSE levels at baseline were 115.9 ng/ml(90.1-201.5 ng/ml),13.3 ng/ml (10.4-18.1 ng/ml),respectively.The endpoints were PSA PFS(progression-free survival) and radiographic PFS (rPFS).Results In 34 patients with serial evaluation,serum NED markers level in 19 patients increased after the failure of AA treatment.Median serum CgA and NSE levels were 115.9 ng/ml(90.1-201.5 ng/ml)and 13.25 ng/ml (10.37-18.14 ng/ml) at baseline.Median serum CgA and NSE levels were 129.6ng/ml (75.5-230.5 ng/ml) and 14.7 ng/ml (11.8-19.1 ng/ml) after 6 months treatment,respectively.The median serum CgA and NSE levels were 130.4 ng/ml (95.7-205.7 ng/ml) and 15.2 ng/ml(12.4-18.7 ng/ml) at the time of failure of AA treatment,respectively.There was no significant difference of NED markers between baseline and failure of AA treatment (P =0.243).In logistic univariate analysis,AA treatment and its duration were not independent factors influencing NED(P =0.30;P =0.52).Compared with the NED markers elevation group in the first 6 months of AA treatment and baseline supranormal NED markers group,the NED markers decline group(PSA PFS(17.1 vs.10.4 months,P ＜ 0.001) and rPFS (17.0 vs.10.4 months,P =0.003)) and baseline normal NED markers group(PSA PFS(14.1 vs.9.5 months,P =0.001) and rPFS(16.4 vs.10.5 months,P ＜ 0.001)) has a longer median PSA PFS and rPFS respectively.In multivariate Cox analysis,baseline NED markers level and NED markers variation during the first 6 months of AA treatment remained significant predictors of rPFS(P ＜ 0.05),and PSA-PFS (P ＜ 0.05).Conclusions We found there was heterogeneity in changes of NED markers in different mCRPC patients during AA treatment,and AA might not significantly lead to progression of NED of mCRPC in general.Serial CgA and NSE evaluation might help clinicians guide clinical treatment of mCRPC patients.Serum NED markers elevation during the first 6 months of AA treatment and elevated baseline NED markers levels indicated poor prognosis in mCRPC treated with AA.

A patient aged 68 years old presented urinary frequency, urgency, and gross hematuria for 1 month, with initial PSA of 72.72 ng/ml and alkaline phosphatase (ALP)of 114 U/L. Prostate biopsy pathology showed small cell neuroendocrine carcinoma of prostate. The patient was immediately administered 6 cycle of chemotherapy including etoposide and cisplatin combined with medical castration. The CDK4 gene was detected 1.99 times amplification by peripheral blood free DNA (cfDNA)gene analysis. The chemotherapy was followed by parbosini therapy. The number and density of bone metastases continued to decrease significantly by bone scan at 3 and 6 months after treatment, with a continuous decline of ALP and PSA. After 1 year of follow-up, pelvic MRI and bone systemic imaging indicated stable lesions, with PSA of 0.05 ng/ml and ALP of 59 U/L.

OBJECTIVE： To study the mechanism of analgesic effect of 8-O-acetyl-safalinoside （8-OaS） on chronic inflammatory pain model rats. METHODS ：Totally 30 male SD rats were divided into sham operation group （normal saline ）， model group （normal saline ），8-OaS low-dose ，medium-dose and high-dose groups （3，10，30 μg/kg），with 6 rats in each group. Except for sham operation group ，other groups were given planter injection of Freund ’s complete adjuvant to induce chronic inflammatory pain model. After successful modeling ，the rats in each group were given corresponding drugs intrathecally ，once a day，for 7 consecutive days. Then Von-Frey filaments were used to detect the planter pain threshold of the rats in each group ；the area under the planter pain threshold curve of each group and the half effective dose （ED50）of 8-OaS were calculated. Another 36 male SD rats were divided into sham operation group （normal saline ），model group （normal saline ）and 8-OaS group （dose of ED50），and the modeling method and administration route were the same as above. Immunofluorescence histochemical staining was used to observe the positive expression of ionized calcium binding adapter molecule 1（Iba-1）and signal molecule phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）；Western blotting assay was used to determine the expression of Iba- 1，p-p38 MAPK，IL-1β，IL-6 and TNF-α in spinal dorsal horn of rats. RESULTS：Compared with sham operation group ，plantar pain threshold and area under the curve in model group were reduced significantly （P＜0.01）. Compared with model group ，plantar pain threshold increased significantly after 5，6，7 days of administration in 8-OaS low-dose group （P＜0.05），plantar pain threshold and area under the curve in 8-OaS medium-dose and high-dose groups were increased significantly （P＜0.05 or P＜0.01）. Most of above indexes in each dose group of 8-OaS were signifficantly different ，and ED 50 of 8-OaS was 18.87 μ g/kg. Results of immunohistochemistry staining and Western blotting showed that p-p 38 MAPK was mainly expressed in Iba- 1 positive cells. Compared with sham operation group ，the fluorescence density of Iba- 1 and p-p 38 MAPK in spinal dorsal horn ，the expression of Iba-1，p-p38 MAPK，IL-6，IL-1β and TNF-α were significantly increased in model group（P＜0.05 or P＜0.01）. Compared with model group ，the fluorescence density of Iba- 1 and p-p 38 MAPK in spinal dorsal horn ，the expression of Iba- 1，p-p38 MAPK， IL-6，IL-1β and TNF-α were decreased significantly in 8-OaS group （P＜0.05）. CONCLUSIONS ：Intrathecal administration of 8-OaS can effectively alleviate chronic inflammatory pain in rats. The mechanism may be related to the inhibition of the phosphorylation of p 38 MAPK and the expression of IL- 6，IL-1β and TNF-α.

OBJECTIVE： To study the effects of 8-O-acetyl-shanzhiside methylester （8-OaS） on the expression of histone deacetylase 1-5 （HDAC1-5） in the spinal dorsal horn of chronic inflammatory pain model rats， and its relationship with Janus-activated kinase 2-signal transductions and activators of transcription 3 （JAK2-STAT3） signaling pathway. METHODS： SD rats were randomly divided into normal control group， sham operation group （normal saline）， complete Freund’s adjuvant （CFA） group （normal saline）， 8-OaS low-dose， medium-dose and high-dose groups （2， 20， 200 μg/kg）， with 6 rats in each group. Except for normal control group and sham operation group， chronic inflammatory pain model was induced by subcutaneous injection of CFA into the left hind toe of rats in other groups； after modeling， those groups were given relevant medicine intraperitoneally， once a day， for consecutive 7 d. Thermal radiation method was used to detect the latency of paw withdraw in rats on the 1st， 2nd， 3rd， 4th， 5th， 6th， 7th， 8th， 11th and 15th day of administration. Rats were grouped and given medicine according to the above method of the latter 5 groups. The protein expression of HDAC 1-5， phosphorylated JAK2 （pJAK2） and phosphorylated STAT3 （pSTAT3） in the spinal dorsal horn of lumbar enlargement segment in rats were detected by Western blot method after last medication. Rats were randomly divided into sham operation group （normal saline）， CFA group （normal saline）， 8-OaS group （20 μg/kg） and JAK2-STAT3 inhibtor AG490 group （8 mg/kg）， with 6 rats in each group； IP model was established by same method as above and then were given relevant medicine intraperitoneally， once a day， for consecutive 7 d. The expression of HDAC5 and glial fibrillary acidic protein （GFAP） in spinal dorsal horn of rats were detected by immunofluorescence histochemical staining. RESULTS： Compared with normal control group and sham operation group， the latency of paw withdraw was shortened significantly in other groups （P＜0.05）. Compared with CFA group， the latency of paw withdraw was prolonged significantly in 8-OaS low-dose， medium-dose and high-dose groups （P＜0.05）， in dose-dependent manner. Compared with sham operation group， the protein expression of HDAC 1-5， pJAK2 and pSTAT3 in spinal dorsal horn of rats were increased significantly in CFA group （P＜0.05）. Compared with CFA group， the protein expression of HDAC5， pJAK2 and pSTAT3 in spinal dorsal horn of rats were decreased significantly in 8-OaS low-dose， medium-dose and high-dose groups （P＜0.05）， but there was no statistical significance in the protein expression of HDAC 1-4 （P＞0.05）. HDAC5 was expressed on astrocytes in the spinal dorsal horn； compared with sham operation group， the expression of GFAP and HDAC 5 were increased significantly in spinal dorsal horn of rats in CFA group （P＜0.05）. Compared with CFA group， the expression of GFAP and HDAC5 in spinal dorsal horn of rats were decreased significantly in 8-OaS group and AG490 group （P＜0.05）. CONCLUSIONS： 8-OaS can effectively relieve CFA-induced chronic inflammatory pain， the mechanism of which may be associated with the down-regulation of HDAC5 expression and the phosphorylation levels of JAK2 and STAT3.

OBJECTIVETo examine the incidence of obesity and its modifiable risk factors in Chinese adults aged 35-74 years.

METHODSA total of 27 020 participants aged 35 to 74 years from two prospective cohort studies in China were followed up in the years of 2007 and 2008. Obesity and overweight were defined as body mass index ≥ 28.0, and 24.0-27.9 kg/m(2), respectively. Relative risks of obesity for risk factors were computed by using logistic regression.

RESULTSThe annual incidence rates of obesity and overweight were 6.97 ‰ and 24.83 ‰ in Chinese adults aged 35-74 years, respectively. Women had a higher incidence of obesity than men (7.74 ‰ vs. 6.10 ‰). Participants in northern China had a higher incidence than those in southern (9.29 ‰ vs. 5.10 ‰) part of the country. Adults in rural had a higher incidence than those in urban (7.28 ‰ vs. 6.52 ‰). After adjusting for the baseline variables, such as gender, age, geographic region, degree of urbanization, the relative risk for obesity was 0.82 (95% CI:0.68-0.99) for participants with ≥ 12 years' education, compared with those <12 years. Participants with middle income, less physical activity at work/housework or being retirees, consuming more red meat and scented tea etc, had higher risk of incidence of obesity. Participants who consumed milk and moderate amount of fruits, would show a lower risk of obesity.

CONCLUSIONThe incidence of obesity was 6.97 ‰ in Chinese middle and older adults. Our results underscored that the promotion of healthy lifestyle which include issues as increasing physical activity, consuming moderate amount of fruits and milk but less red meat, drinking less scented tea etc, could play key roles in obesity prevention and control among the Chinese adults, especially among people with low education level or with middle income.

Adult ; Aged ; China ; epidemiology ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Middle Aged ; Obesity ; epidemiology ; Prospective Studies ; Risk Factors