1.Preparation of polyphenol-mediated copper ion coating on titanium surface and antibacterial and antioxidant properties
Zhenju GUAN ; Yonglin XIE ; Shougang XIANG ; Chengdong ZHANG ; Xiaolong LI ; Xingping LI ; Chao PU ; Bo ZHANG ; Xuwei LUO ; Dongqin XIAO
Chinese Journal of Tissue Engineering Research 2025;29(10):1997-2005
BACKGROUND:Titanium implants are widely used in clinical practice because of their high strength and good biocompatibility.However,during implantation,bacterial infection and tissue damage environment produce a large number of reactive oxygen species,which can easily lead to delayed tissue healing and surgical failure.Consequently,the development of titanium implants with antimicrobial and antioxidant properties becomes paramount. OBJECTIVE:Considering the potent antimicrobial attributes of copper ions and the remarkable antioxidant qualities of polyphenols,we proposed the fabrication of polyphenol-mediated copper ion coatings on titanium surfaces.These coatings were subsequently assessed for their in vitro antimicrobial and antioxidant properties. METHODS:Nanostructures were generated on the titanium surface using the alkali thermal method.The titanium was immersed in a solution containing tannic acid and copper ions to achieve polyphenol-mediated copper ion coatings.The surface morphology and water contact angle were detected.The loading and release of copper ions were examined using atomic absorption spectroscopy.Staphylococcus aureus was inoculated on the surface of pure titanium sheet(blank group),alkali heat treated titanium sheet(control group),and polyphenol mediated copper ion modified titanium sheet(experimental group)to observe the bacterial survival status.Osteoblast precursor cells MC3T3-E1 were co-cultivated on the surface of three groups of titanium sheets to assess their antioxidant properties and bioactivity. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the polyphenol-mediated copper ion modified titanium sheet had rod-like nanostructures and no cracks on the surface.The surface hydrophilicity of copper ion modified titanium sheet mediated by polyphenol was close to that of pure titanium sheet.Atomic absorption spectrometry results showed a 51%increase in the loading capacity of copper ions after polyphenol mediation,with a uniform release of copper ions.(2)The antibacterial rates of titanium sheets in the blank group,control group,and experimental group were 0%,21.65%,and 93.75%,respectively.The live/dead staining and CTC staining showed that the live bacteria on the surface of titanium plates in the blank group were the most,and the live bacteria on the surface of titanium plates in the experimental group were the least.(3)The results of live/dead staining and CCK-8 assay showed that the three groups of titanium sheets had good cytocompatibility,and the titanium sheets in the experimental group were more conducive to the proliferation of MC3T3-E1 cells.Active oxygen fluorescence probe detection exhibited that compared with the other two groups,the fluorescence intensity of active oxygen on the surface of the experimental group was significantly reduced.The results of alkaline phosphatase and alizarin red S staining showed that the osteogenic differentiation and extracellular matrix mineralization of MC3T3-E1 cells on the surface of titanium sheets in the experimental group were stronger than those in the other two groups.(4)These results show that the polyphenol-mediated copper ion coating has strong antibacterial and antioxidant properties and promotes osteogenic differentiation.
2.Analysis of the incidence and risk factors of low anterior resection syndrome after radical sphincter-preserving surgery for locally advanced rectal cancer treated with neoadjuvant immunotherapy: a single-center retrospective study
Yonglin HUANG ; Xingyu XIE ; Minghe ZHAO ; Tingting SUN ; Yunfeng YAO ; Tiancheng ZHAN ; Lin WANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2025;28(6):653-661
Objective:To explore the impact of neoadjuvant immunotherapy on the occurrence of low anterior resection syndrome (LARS) in patients with locally advanced rectal cancer who underwent restorative anterior resection, and to analyze associated risk factors.Methods:This study was an observational study. Patients with adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma of the rectum located 0-10 cm from the anal verge who received neoadjuvant immunotherapy followed by curative restorative anterior resection at Peking University Cancer Hospital between November 2019 and February 2024 were retrospectively examined. Exclusion criteria were as follows: (1) metastasis detected preoperatively;(2) follow-up <1 year or stoma closure <6 months; (3) local recurrence or metastasis during follow-up; and (4) stoma without closure or stoma re-creation. The Chinese version of the LARS questionnaire was used to assess bowel function by telephone interview, and patients were classified based on score into no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30–42 points). The incidence of LARS, major LARS, and associated risk factors were analyzed.Results:A total of 52 patients (34 men) were included for analysis. Mean age was 58.0 ± 9.8 years and mean body mass index was 25.1 ± 2.6 kg/m 2. Median follow-up was 27.5 months (range, 12.0-63.7). Median LARS score was 21 (range, 1-41). Twenty-six patients (50.0%) developed LARS after surgery, and half of these (13 cases) were classified as major LARS. Stool clustering (repeated defecation within 1 hour) was observed in 80.8% (42/52) of patients. Distance between the tumor edge and the dentate line [odds ratio (OR), 3.597; 95% confidence interval (CI), 1.140-11.360; P=0.026], management of the left colic artery (OR, 0.133; 95% CI, 0.026-0.691; P=0.008), and interval of stoma closure (OR, 5.250; 95%CI, 1.381-19.960; P=0.011) were significantly associated with LARS. Interval of stoma closure was significantly associated with major LARS (OR, 4.200; 95%CI, 1.064–16.584; P=0.040). In multivariate logistic regression, ≤3.5 cm between the tumor edge and the dentate line (OR, 7.407; 95%CI, 1.377-40.000; P=0.020), non-preservation of the left colic artery (OR, 8.403; 95%CI, 1.183-58.823; P=0.033) and interval of stoma closure >6 months (OR, 10.865; 95% CI, 2.039-57.896; P=0.005) were independent risk factors for LARS. Interval of stoma closure >6 months (OR, 4.356; 95% CI, 1.105-17.167; P=0.035) were independent risk factors for major LARS. Conclusion:Patients with locally advanced rectal cancer treated with neoadjuvant immunotherapy experienced a high incidence of LARS after curative surgery, with stool clustering as the predominant symptom. Tumor edge–dentate line distance ≤3.5 cm, non-preservation of the left colic artery, and interval of stoma closure >6 months were risk factors for LARS.
3.Analysis of the incidence and risk factors of low anterior resection syndrome after radical sphincter-preserving surgery for locally advanced rectal cancer treated with neoadjuvant immunotherapy: a single-center retrospective study
Yonglin HUANG ; Xingyu XIE ; Minghe ZHAO ; Tingting SUN ; Yunfeng YAO ; Tiancheng ZHAN ; Lin WANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2025;28(6):653-661
Objective:To explore the impact of neoadjuvant immunotherapy on the occurrence of low anterior resection syndrome (LARS) in patients with locally advanced rectal cancer who underwent restorative anterior resection, and to analyze associated risk factors.Methods:This study was an observational study. Patients with adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma of the rectum located 0-10 cm from the anal verge who received neoadjuvant immunotherapy followed by curative restorative anterior resection at Peking University Cancer Hospital between November 2019 and February 2024 were retrospectively examined. Exclusion criteria were as follows: (1) metastasis detected preoperatively;(2) follow-up <1 year or stoma closure <6 months; (3) local recurrence or metastasis during follow-up; and (4) stoma without closure or stoma re-creation. The Chinese version of the LARS questionnaire was used to assess bowel function by telephone interview, and patients were classified based on score into no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30–42 points). The incidence of LARS, major LARS, and associated risk factors were analyzed.Results:A total of 52 patients (34 men) were included for analysis. Mean age was 58.0 ± 9.8 years and mean body mass index was 25.1 ± 2.6 kg/m 2. Median follow-up was 27.5 months (range, 12.0-63.7). Median LARS score was 21 (range, 1-41). Twenty-six patients (50.0%) developed LARS after surgery, and half of these (13 cases) were classified as major LARS. Stool clustering (repeated defecation within 1 hour) was observed in 80.8% (42/52) of patients. Distance between the tumor edge and the dentate line [odds ratio (OR), 3.597; 95% confidence interval (CI), 1.140-11.360; P=0.026], management of the left colic artery (OR, 0.133; 95% CI, 0.026-0.691; P=0.008), and interval of stoma closure (OR, 5.250; 95%CI, 1.381-19.960; P=0.011) were significantly associated with LARS. Interval of stoma closure was significantly associated with major LARS (OR, 4.200; 95%CI, 1.064–16.584; P=0.040). In multivariate logistic regression, ≤3.5 cm between the tumor edge and the dentate line (OR, 7.407; 95%CI, 1.377-40.000; P=0.020), non-preservation of the left colic artery (OR, 8.403; 95%CI, 1.183-58.823; P=0.033) and interval of stoma closure >6 months (OR, 10.865; 95% CI, 2.039-57.896; P=0.005) were independent risk factors for LARS. Interval of stoma closure >6 months (OR, 4.356; 95% CI, 1.105-17.167; P=0.035) were independent risk factors for major LARS. Conclusion:Patients with locally advanced rectal cancer treated with neoadjuvant immunotherapy experienced a high incidence of LARS after curative surgery, with stool clustering as the predominant symptom. Tumor edge–dentate line distance ≤3.5 cm, non-preservation of the left colic artery, and interval of stoma closure >6 months were risk factors for LARS.
4.Reassessment of practice of Chinese surgeons since introduction of the watch and wait strategy after neoadjuvant therapy for rectal cancer
Minghe ZHAO ; Tingting SUN ; Lin WANG ; Yonglin HUANG ; Xingyu XIE ; Yun LU ; Guohua ZHAO ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2024;27(4):383-394
Objective:To investigate perspectives and changes in treatment selection by Chinese surgeons since introduction of the watch-and-wait approach after neoadjuvant therapy for rectal cancer.Methods:A cross-sectional survey was conducted using a questionnaire distributed through the "Wenjuanxing" online survey platform. The survey focused on the recognition and practices of Chinese surgeons regarding the strategy of watch-and-wait after neoadjuvant therapy for rectal cancer and was disseminated within the China Watch-and-Wait Database (CWWD) WeChat group. This group targets surgeons of deputy chief physician level and above in surgical, radiotherapy, or internal medicine departments of nationally accredited tumor-specialist or comprehensive hospitals (at provincial or municipal levels) who are involved in colorectal cancer diagnosis and treatment. From 13 to 16 December 2023, 321 questionnaires were sent with questionnaire links in the CWWD WeChat group. The questionnaires comprised 32 questions encompassing: (1) basic physician characteristics (including surgical volume); (2) assessment methods and criteria for clinical complete response (cCR); (3) patients eligible for watch-and-wait; (4) neoadjuvant therapies and other measures for achieving cCR; (5) willingness to implement watch-and-wait and factors influencing that willingness; (6) risks and monitoring of watch-and-wait; (7) subsequent treatment and follow-up post watch-and-wait; (8) suggestions for development of the CWWD. Descriptive statistics were employed for data analysis, with intergroup comparisons conducted using the χ 2 or Fisher's exact probability tests. Results:The response rate was 31.5%, comprising 101 responses from the 321 individuals in the WeChat group. Respondents comprised 101 physicians from 70 centers across 23 provinces, municipalities, and autonomous regions nationwide, 85.1% (86/101) of whom represented provincial tertiary hospitals. Among the respondents, 87.1% (88/101) had implemented the watch-and-wait strategy. The approval rate (65.6%, 21/32) and proportion of patients often informed (68.8%, 22/32) were both significantly higher for doctors in oncology hospitals than for those in general hospitals (27.7%, 18/65; 32.4%, 22/68) (χ 2=12.83, P<0.001; χ 2=11.70, P=0.001, respectively). The most used methods for diagnosing cCR were digital rectal examination (90.1%, 91/101), colonoscopy (91.1%, 92/101), and rectal T2-weighted magnetic resonance imaging (86.1%, 87/101). Criteria used to identify cCR comprised absence of a palpable mass on digital rectal examination (87.1%, 88/101), flat white scars or new capillaries on colonoscopy (77.2%, 78/101), absence of evident tumor signals on rectal T2-weighted sequences or T2WI low signals or signals equivalent to the intestinal wall (83.2%, 84/101), and absence of tumor hyperintensity on diffusion-weighted imaging with no corresponding hypointensity on apparent diffusion coefficient maps (66.3%, 67/101). As for selection of neoadjuvant regimen and assessment of cCR, 57.4% (58/101) of physicians preferred a long course of radiotherapy with or without induction and/or consolidation capecitabine + oxaliplatin, whereas 25.7% (26/101) preferred immunotherapy in combination with chemotherapy and concurrent radiotherapy. Most (96.0%, 97/101) physicians believed that the primary lesion should be assessed ≤12 weeks after completion of radiotherapy. Patients were frequently informed about the possibility of achieving cCR after neoadjuvant therapy and the strategy of watch-and-wait by 43.6% (44/101) of the responding physicians and 38.6% (39/101) preferred watch-and-wait for patients who achieved cCR or near cCR after neoadjuvant therapy for rectal cancer. Capability for multiple follow-up evaluations (70.3%, 71/101) was a crucial factor influencing physicians' choice of watch-and-wait after cCR. The proportion who patients who did not achieve cCR and underwent surgical treatment was lower in provincial tertiary hospitals (74.2%, 23/31) than in provincial general hospitals (94.5%, 52/55) and municipal hospitals (12/15); these differences are statistically significant (χ 2=7.43, P=0.020). The difference between local recurrence and local regrowth was understood by 88.1% (89/101) of respondents and 87.2% (88/101) agreed with monitoring every 3 months for 5 years. An increase in local excision or puncture rates to reduce organ resections in patients with pCR was proposed by 64.4% (65/101) of respondents. Conclusion:Compared with the results of a previous survey, Chinese surgeons' awareness of the watch-and-wait concept has improved significantly. Oncologists in oncology hospitals are more aware of the concept of watch-and-wait.
5.Reassessment of practice of Chinese surgeons since introduction of the watch and wait strategy after neoadjuvant therapy for rectal cancer
Minghe ZHAO ; Tingting SUN ; Lin WANG ; Yonglin HUANG ; Xingyu XIE ; Yun LU ; Guohua ZHAO ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2024;27(4):383-394
Objective:To investigate perspectives and changes in treatment selection by Chinese surgeons since introduction of the watch-and-wait approach after neoadjuvant therapy for rectal cancer.Methods:A cross-sectional survey was conducted using a questionnaire distributed through the "Wenjuanxing" online survey platform. The survey focused on the recognition and practices of Chinese surgeons regarding the strategy of watch-and-wait after neoadjuvant therapy for rectal cancer and was disseminated within the China Watch-and-Wait Database (CWWD) WeChat group. This group targets surgeons of deputy chief physician level and above in surgical, radiotherapy, or internal medicine departments of nationally accredited tumor-specialist or comprehensive hospitals (at provincial or municipal levels) who are involved in colorectal cancer diagnosis and treatment. From 13 to 16 December 2023, 321 questionnaires were sent with questionnaire links in the CWWD WeChat group. The questionnaires comprised 32 questions encompassing: (1) basic physician characteristics (including surgical volume); (2) assessment methods and criteria for clinical complete response (cCR); (3) patients eligible for watch-and-wait; (4) neoadjuvant therapies and other measures for achieving cCR; (5) willingness to implement watch-and-wait and factors influencing that willingness; (6) risks and monitoring of watch-and-wait; (7) subsequent treatment and follow-up post watch-and-wait; (8) suggestions for development of the CWWD. Descriptive statistics were employed for data analysis, with intergroup comparisons conducted using the χ 2 or Fisher's exact probability tests. Results:The response rate was 31.5%, comprising 101 responses from the 321 individuals in the WeChat group. Respondents comprised 101 physicians from 70 centers across 23 provinces, municipalities, and autonomous regions nationwide, 85.1% (86/101) of whom represented provincial tertiary hospitals. Among the respondents, 87.1% (88/101) had implemented the watch-and-wait strategy. The approval rate (65.6%, 21/32) and proportion of patients often informed (68.8%, 22/32) were both significantly higher for doctors in oncology hospitals than for those in general hospitals (27.7%, 18/65; 32.4%, 22/68) (χ 2=12.83, P<0.001; χ 2=11.70, P=0.001, respectively). The most used methods for diagnosing cCR were digital rectal examination (90.1%, 91/101), colonoscopy (91.1%, 92/101), and rectal T2-weighted magnetic resonance imaging (86.1%, 87/101). Criteria used to identify cCR comprised absence of a palpable mass on digital rectal examination (87.1%, 88/101), flat white scars or new capillaries on colonoscopy (77.2%, 78/101), absence of evident tumor signals on rectal T2-weighted sequences or T2WI low signals or signals equivalent to the intestinal wall (83.2%, 84/101), and absence of tumor hyperintensity on diffusion-weighted imaging with no corresponding hypointensity on apparent diffusion coefficient maps (66.3%, 67/101). As for selection of neoadjuvant regimen and assessment of cCR, 57.4% (58/101) of physicians preferred a long course of radiotherapy with or without induction and/or consolidation capecitabine + oxaliplatin, whereas 25.7% (26/101) preferred immunotherapy in combination with chemotherapy and concurrent radiotherapy. Most (96.0%, 97/101) physicians believed that the primary lesion should be assessed ≤12 weeks after completion of radiotherapy. Patients were frequently informed about the possibility of achieving cCR after neoadjuvant therapy and the strategy of watch-and-wait by 43.6% (44/101) of the responding physicians and 38.6% (39/101) preferred watch-and-wait for patients who achieved cCR or near cCR after neoadjuvant therapy for rectal cancer. Capability for multiple follow-up evaluations (70.3%, 71/101) was a crucial factor influencing physicians' choice of watch-and-wait after cCR. The proportion who patients who did not achieve cCR and underwent surgical treatment was lower in provincial tertiary hospitals (74.2%, 23/31) than in provincial general hospitals (94.5%, 52/55) and municipal hospitals (12/15); these differences are statistically significant (χ 2=7.43, P=0.020). The difference between local recurrence and local regrowth was understood by 88.1% (89/101) of respondents and 87.2% (88/101) agreed with monitoring every 3 months for 5 years. An increase in local excision or puncture rates to reduce organ resections in patients with pCR was proposed by 64.4% (65/101) of respondents. Conclusion:Compared with the results of a previous survey, Chinese surgeons' awareness of the watch-and-wait concept has improved significantly. Oncologists in oncology hospitals are more aware of the concept of watch-and-wait.
6.Exosomal miR-17-5p derived from epithelial cells is involved in aberrant epithelium-fibroblast crosstalk and induces the development of oral submucosal fibrosis
Xie CHANGQING ; Zhong LIANG ; Feng HUI ; Wang RIFU ; Shi YUXIN ; Lv YONGLIN ; Hu YANJIA ; Li JING ; Xiao DESHENG ; Liu SHUANG ; Chen QIANMING ; Tao YONGGUANG
International Journal of Oral Science 2024;16(4):671-684
Oral submucous fibrosis(OSF)is a chronic and inflammatory mucosal disease caused by betel quid chewing,which belongs to oral potentially malignant disorders.Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development.The epithelium,which is the first line of defense against the external environment,can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment.However,the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear.In this study,we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes.MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts,where it promoted cell secretion,contraction,migration and fibrogenic marker(α-SMA and collagen type I)expression.The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1(TGFBR1)through the E3 ubiquitination ligase WWP1,thus facilitating downstream TGF-β pathway signaling.Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes.Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts.In conclusion,we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway,which provided a new perspective and strategy for the diagnosis and treatment of OSF.
7.Exosomal miR-17-5p derived from epithelial cells is involved in aberrant epithelium-fibroblast crosstalk and induces the development of oral submucosal fibrosis
Xie CHANGQING ; Zhong LIANG ; Feng HUI ; Wang RIFU ; Shi YUXIN ; Lv YONGLIN ; Hu YANJIA ; Li JING ; Xiao DESHENG ; Liu SHUANG ; Chen QIANMING ; Tao YONGGUANG
International Journal of Oral Science 2024;16(4):671-684
Oral submucous fibrosis(OSF)is a chronic and inflammatory mucosal disease caused by betel quid chewing,which belongs to oral potentially malignant disorders.Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development.The epithelium,which is the first line of defense against the external environment,can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment.However,the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear.In this study,we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes.MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts,where it promoted cell secretion,contraction,migration and fibrogenic marker(α-SMA and collagen type I)expression.The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1(TGFBR1)through the E3 ubiquitination ligase WWP1,thus facilitating downstream TGF-β pathway signaling.Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes.Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts.In conclusion,we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway,which provided a new perspective and strategy for the diagnosis and treatment of OSF.
8.Association of ticagrelor with risk of infection:a two-sample Mendelian randomization study based on the GWAS database
Guifeng XU ; Yonglin WU ; Gongjie GUO ; Junhong HUANG ; Zhipeng XIE ; Wenwei LUO ; Shilong ZHONG ; Weihua LAI
China Pharmacy 2023;34(7):859-862
OBJECTIVE To investigate the causal association between ticagrelor and risk of infection METHODS Two-sample Mendelian randomization was adopted. Genetic instrumental variables were selected based on the results of the largest genome-wide association analysis to in vivo exposure of ticagrelor and its major active metabolite AR-C124910XX. The causal associations of ticagrelor and its major active metabolite AR-C124910XX with drug indications (coronary artery disease, unstable angina pectoris, myocardial infarction, stroke and ischemic stroke)were analyzed by inverse variance weighted Mendelian randomization model as a positive control for genetic instrumental variables. The causal relationship between ticagrelor and bacterial infection, acute lower respiratory infection, bacterial pneumoniae, pneumoniae,acute upper respiratory infection and sepsis were furtheranalyzed by using this method, and the robustness of the results was assessed by using heterogeneity tests and horizontal 202002030415) pleiotropy tests. RESULTS The increase of area under the curve at steady state (AUCss) of the genetic surrogated ticagrelor significantly reduced the risk of coronary artery disease, myocardial infarction and unstable angina pectoris (P<0.001). AUCss genetic instrument variables of its main active metabolite AR-C124910XX failed to pass positive control. Further analysis showed that the increase of the genetic surrogated ticagrelor exposure suggestively reduced the risk of bacterial infection [OR(95%CI)=0.80(0.65,0.99),P=0.040] and sepsis [OR (95%CI)=0.84(0.73, 0.98), P=0.023]. The results of the heterogeneity tests showed that there was no heterogeneity in the causal association of the genetic surrogated ticagrelor AUCss with bacterial infection and sepsis (P>0.05). The results of horizontal pleiotropy tests showed that the causal association of genetic surrogated ticagrelor AUCss with bacterial infection and sepsis had no effects on horizontal pleiotropy (P>0.05). CONCLUSIONS Ticagrelor has a potential role in reducing the risk of sepsis and bacterial infections.
9.Retrospective analysis of the cell therapy of inhibition of antigen-presentation attenuators combined with adjuvant chemotherapy in the treatment of colon cancer
Yonglin ZHU ; Ying HUANG ; Jinle WANG ; Bingshou XIE ; Hongwei DONG
Chinese Journal of Primary Medicine and Pharmacy 2018;25(24):3175-3179
Objective To investigate the clinical effect and safety of the cell therapy of inhibition of antigen -presentation attenuators ( iAPA ) combined with adjuvant chemotherapy in the treatment of colon cancer . Methods From February 2014 to October 2015,the clinical data of 40 patients with colon cancer in the People's Hospital of Wenzhou were analyzed retrospectively.They were divided into control group and study group by the random digital table,with 20 cases in each group.The control group received mFOLFOX6 chemotherapy(treatment for 6 months),and the study group was treated with iAPA on the basis of the control group (treatment for 6 cycle).The clinical efficacy,levels of immune function indicators ( CD+3,CD+4,CD+8,CD+4/CD+8) before treatment and after treatment,the incidence of toxic and side effects and quality of life (QOL) score of the two groups were recorded.And the survival rates were statistically analyzed.Results The total effective rate of the study group was higher than that of the control group (85.0% vs.55.0%,χ2=4.286,P<0.05).After treatment,the serum levels of CD +3,CD+4,CD+8,CD+4/CD+8in the study group were higher than those in the control group,while the serum level of CD +8was lower in the study group than that in the control group,the differences were statistically significant (t=2.657,3.160,5.700,2.326,all P<0.05).There were no side effects of the degree of Ⅳin the two groups.The incidence rates of diarrhea(25.0%),vomiting and nausea (20.0%),liver function damage (25.0%) and bone marrow suppression (25.0%) in the study group were lower than those in the control group (χ2=5.013,5.227,5.013,6.465,all P<0.05).After treatment,the QOL scores of the two groups were higher than those before treatment (all P<0.05),and the QOL score of the study group was higher than that of the control group (t=4.739,P<0.05).The survival rate of the study group was higher than that of the control group after 24 and 30 months of treatment(χ2=5.013,4.912,all P<0.05 ).Conclusion The iAPA combined with adjuvant chemotherapy in the treatment of colon cancer can regulate the immune function of the patients,and improve the treatment effect of the disease.It helps to improve the QOL and prolong the life period of the patients,reduce the incidence of side effects,and it is safe.
10.Inhibitory and inductive effects of Polygonum capitatum water extract on CYP450
Yuan LU ; Jie PAN ; Yumin XIE ; Lin ZHENG ; Yong HUNAG ; Yonglin WANG ; Yongjun LI
Chinese Pharmacological Bulletin 2015;(8):1147-1151,1152
Aim To evaluate the inhibitive and induc-tive effects of Polygonum capitatum water extract on main cytochrome P450 isoforms in human and liver mi-crosomes of mouse in vitro for predicting the herb-drug interactions in clinical application. Methods The in vitro inhibitory effect was evaluated by incubating Po-lygonum capitatum water extract with the probe sub-strates of main phase I metabolic enzymes in human liver microsomes, including CYP1A2, CYP2E1, CYP2C9,CYP2C19 and CYP3A4. Mice were adminis-tered with Polygonum capitatum water extract at dosage of 0 . 58 g · kg-1 and 1 . 16 g · kg-1 by gastric lavage for successive 7 days and 14 days, then the cocktail-LC-MS/MS method was applied to assess the inductive effect of main CYP450 isoforms in mouse liver micro-somes. Results The IC50 values of Polygonum capita-tum water extract on main CYP450 isoforms in human liver microsomes were from 849 . 6 mg · L-1 to 2 287 mg·L-1 . Compared with the blank control group, the activites of CYP2C9 and CYP3A4 in 1. 16 g·kg-1 7 d group were about 49 . 9 % and 21. 1 % higher ( P <0. 01, P < 0. 05 ) respectively, the activities of CYP2C9 and CYP3A4 in 0. 58 g·kg-1 7 d group were 27. 6 % and 15. 5 % higher ( P <0. 01 , P <0. 05 ) respectively, the activities of CYP2C9 and CYP3A4 in 1. 16 g·kg-1 14 d group were 67. 5 % and 32. 1 %higher (P<0. 01) respectively, while the activities of CYP1 A2 , CYP2 E1 and CYP2 C19 were not increased significantly in Polygonum capitatum treatment group. Conclusions Polygonum capitatum water extract do not show the inhibitory effect on main CYP450 in hu-man liver microsomes. There is induction on CYP2C9 and CYP3 A4 in mouse liver microsomes by Polygonum capitatum water extract.

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