1.Risk factors for local recurrence after radical resection of rectal cancer
Shengping SONG ; Xiaosheng HE ; Yufeng CHEN ; Jianping WANG ; Ping LAN ; Xiaojian WU
Chinese Journal of Digestive Surgery 2013;(6):431-434
Objective To investigate the risk factors for locally recurrent rectal cancer after radical resection.Methods The clinical data of 50 locally recurrent rectal cancer patients (recurrent group) and 100 matched controls (control group) who received radical resection at the Sixth Affiliated Hospital of Sun Yat-Sen university from January 2000 to March 2009 were retrospectively analyzed.Factors including tumor location,postoperative chemotherapy,tumor differentiation,vascular or neural invasion,T stage,tumor diameter,number of lymph nodes dissected and number of positive lymph nodes of the 2 groups were analysed by univariate analysis,and factors correlated with tumor recurrence were screened out.All data were analyzed using the chi-square test,t test,Wilcoxon test or Logistic regression analysis.Results All the patients were followed up till January 2013,and the median time of follow-up was 52 months.Twenty-two patients in the recurrent group and 32 patients in the control group died during the follow-up.The results of univariate analysis showed that there were significant differences in tumor location and T stage between the 2 groups (x2 =6.407,9.652,P < 0.05).There were no significant differences in postoperative chemotherapy,tumor differentiation,vascular and neural invasion,tumor diameter,number of lymph nodes dissected and number of positive lymph nodes between the 2 groups (x2 =1.349,0.342,0.656,Z =7142.5,8214.5,7241.5,P > 0.05).The results of multivariate analysis showed that tumor location and T stage were the factors correlated with the tumor recurrence after radical resection (Wald =3.954,5.615,P < 0.05).Compared with upper rectal cancer,the local recurrence rate was not significantly different in the middle rectal cancer (OR =1.893,P > 0.05),whereas the lower rectal cancer had a higher local recurrence rate (OR =3.201,P <0.05).Compared with patients in T2 stage,the local recurrence rate was not significantly different in patients in T3 stage (OR =4.913,P >0.05),while patients in T4 stage had a higher local recurrence rate (OR =16.103,P < 0.05).Conclusion Locally recurrent rectal cancer is closely related to tumor location and T stage,which indicates that factors reflecting the extent of surgical resection (such as circumferential margin) are of great importance in assessing the prognosis and making subsequent treatment schedule.
2.Prognostic impact of GSTA1 polymorphisms on breast cancer patients treated with cyclophosphamide-based adjuvant chemotherapy
Lihua LI ; Zijian GUO ; Xiaosheng HANG ; Xike ZHOU ; Jie HE ; Mingxu SONG ; Zhihui LIU
Chinese Journal of Laboratory Medicine 2011;34(4):309-314
Objective To investigate the association between the genetic polymorphisms in GSTA1 and the clinical outcome of breast cancer patients treated with cyclophosphamide-based adjuvant chemotherapy. Methods A total of 137 breast cancer patients receiving cyclophosphamide-based adjuvant chemotherapy were recruited ( 124 cases with infiltrative ductal carcinoma, 5 cases with infiltrative lobular carcinoma and 8 cases with other histological types). PCR-LDR method was used to detect the genotypes of GSTA1. Survival curves were generated by the Kaplan-Meier method, and verified by the log-rank test. Cox proportional hazards regression analysis was used to estimate the prognostic factors in multivariate analysis. Results Of the 137 breast cancer patients, the genotypic frequencies of the GSTA1 * A/* A,* A/* B and * B/* B were 67.2% ( 92/137 ), 31.4% ( 43/137 ) and 1.5% ( 2/137 ), respectively. No significant differences were found between the genotypic frequencies and groups categorization according to age, stage, lymph node metastasis, ER or PR status (x2 = 0. 722,1. 967, 3. 303, 0. 226 and 0. 709, all P >0. 05 ) ;through Fisher exact test, also no significant differences were found between the genotypic frequencies and group categorization according to tumor size, histological types and grading ( all P > 0. 05 ) . The recurrence rates in patients with GSTA1 * A/* A and * A/* B or * B/* B genotypes were 47. 8% (44/92) and 31.1% ( 14/45 ), respectively, and the mortality rates were 22. 8% ( 21/92 ) and 17. 8% ( 8/45 ),respectively. Patients with GSTA1 * A/* B and * B/* B genotypes were significantly associated with reduced hazard of relapse (x2 =18.723, P<0. 01)and mortality (x2 =7.352, P<0.01), compared to cases with the common * A/* A genotypes, according to Kaplan-Meier survival analysis and log-rank test. Moreover,Cox multivariate analysis showed that GSTA1 polymorphisms appeared to be an independent risk factor for recurrence-free survival ( OR =0. 222, 95% CI:0. 108-0. 458, P <0. 01 ) and overall survival ( OR =0. 362,95% CI:0. 145-0. 902, P < 0. 05 ). Conclusion These data indicate that GSTA1 polymorphism may be a potential prognostic factor for recurrence-free survival and overall survival in breast cancer patients treated with cyclophosphamide-based adjuvant chemotherapy.
3.Clinicopathological factors on the prognosis of patients with stage lⅡ colorectal cancer
Yufeng CHEN ; Yang ZENG ; Xiaosheng HE ; Xianrui WU ; Ruixue YUAN ; Shengping SONG ; Ping LAN ; Xiaojian WU
Chinese Journal of Digestive Surgery 2011;10(6):430-435
Objective To analyze the clinicopathological factors on the prognosis and investigate the necessity of adjuvant chemotherapy for patients with stage Ⅱ colorectal cancer.Methods The clinical data of 255 patients with stage Ⅱ colorectal cancer who were admitted to the First Affiliated Hospital of Sun Yat-Sen University from January 2000 to December 2005 were collected.The survival curve was drawn by Kaplan-Meier method,and the survival rate of the patients were analyzed by Log-rank test.Factors influencing the survival were analyzed by Cox regression model.Results All patients were followed up till April 23,2010,and the mean time of follow-up was (63 ± 22)months.The median survival time was 63 months.The 5-year and tumor-free survival rates were 85.3% and 83.7%,respectively.The 5-year overall and tumor-free survival rates of patients without preoperative bowel obstruction or perforation were 86.9% and 85.6%,which were sigaificantly higher than 72.7%and 68.4% of patients with preoperative bowel obstruction or perforation(x2 =4.546,4.573,P < 0.05 ).The 5-year overall and tumor-free survival rates of patients with negative resection margin were 85.5% and 83.9%,which were significantly higher than 75.0% and 75.0% of patients with positive resection margin(x2 =7.020,6.009,P < 0.05 ).The result of multivariate analysis revealed that preoperative bowel obstruction or perforation were the independent risk factors for patients with stage Ⅱ colorectal cancer(Wald =4.477,relative risk =2.371,95 % confidence interval:1.066-5.275,P < 0.05 ).The 5-year overall and tumor-free survival rates were 87.3% and 86.0% for patients who received adjuvant chemotherapy,and were 82.2% and 80.3% for patients who did not receive adjuvant chemotherapy (P > 0.05 ).Conclusions Preoperative bowel obstruction or perforation are independent risk factors for the survival of patients with stage Ⅱ colorectal cancer.Adjuvant chemotherapy could not improve the prognosis of patients with stage Ⅱ colorectal cancer.
4.Kansui root therapy for severe acute pancreatitis with high intra-abdominal pressure
Junming HE ; Shixia CAI ; Xiaosheng ZHONG ; Chengjiang QIU ; Youxing HUANG ; Song WANG ; Xianfeng LIU ; Zhijian TAN ; Bingqin CAI
Chinese Journal of Pancreatology 2010;10(6):392-394
Objective To investigate the treatment effects of Kansui root on severe acute pancreatitis (SAP) with abdominal compartment syndrome (ACS).Methods 16 cases of SAP were randomly divided into kansui root treatment group and control group according to random number table.Patients in control group received routine treatment including fasting, anti-shock, antibiotics and nutritional support.And the patients in kansui root group received routine treatment plus kansui root therapy.The clinical and laboratory parameters were determined and compared between the two groups.Results The relieving time of abdominal pain, bowel sound, the recovery time of hyperamylasemia, body temperature and leukocyte count in treatment group was (7.6±2.3)d, (6.1 ±3.1)d, (5.9±3.3)d, (5.2 ±3.2) d, (6.3 ±2.1)d, which were significantly shorter than those in control group [ ( 11.7 ± 2.1 ) d, ( 11.2 ± 2.3d, ( 10.2 ± 2.7) d, (9.2 ± 3.5 ) d, ( 11.1 ±3.3)d, P<0.01 ) ].At the 3rd, 4th and 5th day, the intra-abdominal pressure in treatment group were also significantly lower than those in control group[ ( 19.8 ±3.1 )cmH2O vs(23.7 ±2.9) cmH2O, ( 12.3 ±2.7) cmH2O vs (21.3±1.5)cmH2O,(8.2±3.1)cmH2O vs (17.3 ±2.3)cmH2O,P<0.05].Conclusions Severe acute pancreatitis has close relationship with Jiexiong syndrome in traditional chinese medicine.Kansui root is an effective therapy for alleviating high intra-abdominal pressure.
5.Hasubanan type alkaloids in Stephania hernandifolia.
Lijia TANG ; Yuanhu ZHANG ; Xiaoyan HAO ; Li HE ; Shaohui SONG ; Xiaojiang HAO ; Xiaosheng YANG
China Journal of Chinese Materia Medica 2010;35(15):1973-1977
OBJECTIVETo study the hasubanan type alkaloids in Stephania hernandifolia.
METHODThe dried herbs of S. hernandifolia. were extracted with 95% ethanol. After removal of the solvent, the residue was first partitioned between acid water and petroleum ether, then the aqueous layer was basified and extracted with chloroform to obtain crude alkaloids. Column chromatograghic methods with on silica gel, Rp-18, MCI CHP 20P, Sephadex LH-20 were applied for the isolation and purification of the crude alkaloid fraction. The structures were elucidated by their physicochemical properties and spectral data.
RESULTNine hasubanan type alkaloids were obtained and identified as aknadinine(1), longanone(2), stephasunoline (3), N-methylstephuline(4), epistephamiersine(5), prostephabyssine(6), aknadilactam(7), dihydroepistephamiersine(8), hasubanonine(9).
CONCLUSIONCompounds 2-8 were isolated from this plant for the first time.
Alkaloids ; chemistry ; isolation & purification ; Chemical Phenomena ; Molecular Structure ; Plant Extracts ; chemistry ; isolation & purification ; Stephania ; chemistry
6.Correlation between paraspinal muscle atrophy, morphological changes of facet joints and adjacent segment degeneration after lumbar fusion
Dachuan LI ; Xiao LU ; Guangyu XU ; Jian SONG ; Minghao SHAO ; Feizhou LYU ; Xiaosheng MA ; Xinlei XIA ; Hongli WANG ; Jianyuan JIANG
Chinese Journal of Orthopaedics 2022;42(19):1292-1300
Objective:To investigate the correlation between paraspinal muscle atrophy, morphological changes of facet joints and adjacent segment disease (ASDis) after lumbar fusion operation.Methods:A retrospective study was conducted among 195 patients who underwent posterior lumbar fusion again for ASDis at this institution from January 2014 to December 2020, including 29 patients with ASDis whose initial surgical fusion segment was L 4,5. According to Roussouly's staging, there were 5 cases of type I, 9 cases of type II, 10 cases of type III, and 5 cases of type IV. Another 29 cases were selected from patients without ASDis after lumbar fusion as a control group. The control group was paired 1∶1 with the ASDis group according to gender, fusion segment, and Roussouly typing of the lumbar spine. The cross-sectional area (CSA) and fat infiltration (FI) of paravertebral muscle, facet joint angle (F-J) and pedicle facet (P-F) angle before the first (second) operation were measured and compared between the two groups. Then logistic regression analysis was used to determine the predictors of ASDis after posterior lumbar fusion. Finally, the receiver operation characteristic (ROC) curve was described, and the area under the curve (AUC) and cut-off point were calculated. At the same time, the paraspinal muscle atrophy before the second operation in ASDis group was measured. Results:The average follow-up time of 98 patients was 59.25±6.38 months (range, 49-73 months). The average body mass index (BMI) of ASDis group was 24.76±3.64 kg/m 2, which was higher than that in control group (22.24±2.92 kg/m 2) ( t=2.481, P=0.041). The average CSA and relative cross-sectional area (rCSA) of paraspinal muscle in ASDis group were 3 214.32± 421.15 mm 2 and 1.69±0.36 respectively, which were less than 3 978.91±459.87 mm 2 and 2.26±0.29 in control group ( t=10.22, P=0.012; t=9.47, P=0.038). The FI degree of paraspinal muscle in ASDis group (21.95%±5.89%) was significantly higher than that in control group (14.64%±7.11%) ( t=7.32, P=0.002). The F-J angle in ASDis group was 35.06°±3.45°, which was less than 38.39°±4.67° in control group ( t=4.76, P=0.027). The P-F angle in ASDis group was 117.39°±8.13°, which was greater than 111.32°±4.78° in control group ( t=5.25, P=0.031). Multivariate logistic regression analysis showed that higher BMI ( OR=1.34, P=0.038), smaller rCSA of paraspinal muscle ( OR=0.02, P=0.017) and higher FI of paraspinal muscle ( OR=1.58, P=0.032) were the risk factors of postoperative ASDis. The ROC curve showed that the AUC of BMI was 0.680 and the cut-off point was 22.58 kg/m 2; The AUC of the FI of paraspinal muscle was 0.716 and the cut-off point was 15.69%; The AUC of rCSA of paraspinal muscle was 0.227 and the cut-off point was 1.92. For ASDis patients, the paraspinal muscle before the second operation had a higher degree of FI (25.47%±6.59% vs. 21.95%±5.89%, t=3.99, P=0.042) and a smaller rCSA (1.52±0.28 vs. 1.69±0.36, t=3.85, P=0.038) than that before the first operation. The difference between the FI degree of paraspinal muscle before the second operation and the first operation was negatively correlated with the occurrence time of ASDis ( r=-0.53, P=0.039) , and the difference of rCSA was positively correlated with the occurrence time of ASDis ( r=0.64, P=0.043) . Conclusion:When BMI >22.58 kg/m 2, FI of paraspinal muscle >15.69%, and rCSA of paraspinal muscle <1.92, it suggests that ASDis is more likely to occur after operation. And the more obvious paraspinal muscle atrophy after the first operation, the earlier ASDis may occur. Morphological changes of facet joints cannot be used as an index to predict the occurrence of ASDis.
7.A unique binding pocket induced by a noncanonical SAH mimic to develop potent and selective PRMT inhibitors.
Youchao DENG ; Xiaosheng SONG ; Iredia D IYAMU ; Aiping DONG ; Jinrong MIN ; Rong HUANG
Acta Pharmaceutica Sinica B 2023;13(12):4893-4905
Protein arginine methyltransferases (PRMTs) are attractive targets for developing therapeutic agents, but selective PRMT inhibitors targeting the cofactor SAM binding site are limited. Herein, we report the discovery of a noncanonical but less polar SAH surrogate YD1113 by replacing the benzyl guanidine of a pan-PRMT inhibitor with a benzyl urea, potently and selectively inhibiting PRMT3/4/5. Importantly, crystal structures reveal that the benzyl urea moiety of YD1113 induces a unique and novel hydrophobic binding pocket in PRMT3/4, providing a structural basis for the selectivity. In addition, YD1113 can be modified by introducing a substrate mimic to form a "T-shaped" bisubstrate analogue YD1290 to engage both the SAM and substrate binding pockets, exhibiting potent and selective inhibition to type I PRMTs (IC50 < 5 nmol/L). In summary, we demonstrated the promise of YD1113 as a general SAH mimic to build potent and selective PRMT inhibitors.