1.Analysis of Chemical Components of Yin-Qiao-Qing-Re Tablets by UPLC-Q-TOF-MS/MS and GC-MS
Zerong CAI ; Yumei HU ; Wenjun LIU ; Shulin WANG ; Xinyu KONG ; Yifan YANG ; Mengyu QIAN ; Li-ang CAO ; Zhenzhong WANG
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(9):1198-1212
OBJECTIVE The non-volatile and volatile chemical components in Yin-Qiao-Qing-Re Tablets were analyzed sepa-rately using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS)and Gas Chromatography Mass Spectrometry(GC-MS).METHODS The non-volatile components were analyzed using a Waters ACQUITY UPLC BEH C18 column(2.1 mm×100 mm,1.7 μm),with a mobile phase consisting of 0.1%formic acid aqueous solution(A)and acetonitrile(B)for gradient elution,a flow rate of 0.35 mL·min-1,an injection volume of 5 μL,and a column temperature of 30 ℃;the volatile components were analyzed using an Agilent SH-I-5MS column(5%Phenyl Methyl Silox,30 m×250 μm,0.25 μm);the procedure was temperature-programmed,with an injection volume of 1 μL,a split ratio of 10∶1,a flow rate of 1.0 mL·min-1,and an inlet temperature of 200 ℃.RESULTS A total of 134 non-volatile chemical components and 23 volatile components were analyzed and identified from Yin-Qiao-Qing-Re Tablets,among which 49 compounds were confirmed through comparison with reference stand-ards.The non-volatile components mainly include 27 flavonoids,21 organic acids,15 lignans,14 iridoids,12 phenylethanoid glyco-sides,11 saponins,10 alkaloids,5 terpenes,4 amino acids,3 phenylpropanoids,3 nucleosides,3 xanthones,3 phenolic glycosides,2 chromones and 1 carbohydrate.The volatile components mainly include 11 monoterpenes,5 alcohols and phenols,3 alkenes,2 ke-tones,1 ester,and 1 hydrocarbon.CONCLUSION This study rapidly identifies the chemical components of Yin-Qiao-Qing-Re Tablets,laying a preliminary foundation for research on the pharmacodynamic substances of Yin-Qiao-Qing-Re Tablets and the im-provement of quality control standards.
2.Analysis of Chemical Components of Yin-Qiao-Qing-Re Tablets by UPLC-Q-TOF-MS/MS and GC-MS
Zerong CAI ; Yumei HU ; Wenjun LIU ; Shulin WANG ; Xinyu KONG ; Yifan YANG ; Mengyu QIAN ; Li-ang CAO ; Zhenzhong WANG
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(9):1198-1212
OBJECTIVE The non-volatile and volatile chemical components in Yin-Qiao-Qing-Re Tablets were analyzed sepa-rately using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS)and Gas Chromatography Mass Spectrometry(GC-MS).METHODS The non-volatile components were analyzed using a Waters ACQUITY UPLC BEH C18 column(2.1 mm×100 mm,1.7 μm),with a mobile phase consisting of 0.1%formic acid aqueous solution(A)and acetonitrile(B)for gradient elution,a flow rate of 0.35 mL·min-1,an injection volume of 5 μL,and a column temperature of 30 ℃;the volatile components were analyzed using an Agilent SH-I-5MS column(5%Phenyl Methyl Silox,30 m×250 μm,0.25 μm);the procedure was temperature-programmed,with an injection volume of 1 μL,a split ratio of 10∶1,a flow rate of 1.0 mL·min-1,and an inlet temperature of 200 ℃.RESULTS A total of 134 non-volatile chemical components and 23 volatile components were analyzed and identified from Yin-Qiao-Qing-Re Tablets,among which 49 compounds were confirmed through comparison with reference stand-ards.The non-volatile components mainly include 27 flavonoids,21 organic acids,15 lignans,14 iridoids,12 phenylethanoid glyco-sides,11 saponins,10 alkaloids,5 terpenes,4 amino acids,3 phenylpropanoids,3 nucleosides,3 xanthones,3 phenolic glycosides,2 chromones and 1 carbohydrate.The volatile components mainly include 11 monoterpenes,5 alcohols and phenols,3 alkenes,2 ke-tones,1 ester,and 1 hydrocarbon.CONCLUSION This study rapidly identifies the chemical components of Yin-Qiao-Qing-Re Tablets,laying a preliminary foundation for research on the pharmacodynamic substances of Yin-Qiao-Qing-Re Tablets and the im-provement of quality control standards.
3.Optimization of the Extraction Process of Changyan Heji Ⅱ Based on UPLC-Q-TOF-MS/MS Combined with Response Surface Method and Principal Component Analysis
Shulin WANG ; Jing SHANG ; Wenjun LIU ; Zerong CAI ; Mengyu QIAN ; Xiaoxin HU ; Liang CAO ; Zhenz-hong WANG ; Wei XIAO
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(4):501-512
OBJECTIVE To establish a extraction process of Changyan Heji Ⅱ(CYHJ-Ⅱ)based on UPLC-Q-TOF-MS/MS technology combined with response surface analysis,and to optimize the extraction process.METHODS The chemical components in CYHJ-Ⅱ were qualitatively analyzed by UPLC-Q-TOF-MS/MS technology,and the chemical components with good linear relation-ship in mass spectrometry response were selected as process investigation indicators;the extraction process parameters(water addition amount,extraction time and soaking time)were investigated by Box-Behnken design;the comprehensive score was obtained by princi-pal component analysis(PCA),and the optimal process was determined by the comprehensive score combined with response surface a-nalysis.RESULTS Through qualitative analysis,110 components were inferred and identified from CYHJ-Ⅱ,including 2 organic acids,82 flavonoids,13 terpenoids,and 13 alkaloids.Based on the results of qualitative analysis,48 index components with good lin-ear relationships were derived by UPLC-Q-TOF-MS/MS combined with Masshunter mass spectrometry data analysis software.PCA was performed and the comprehensive score was calculated.Response surface analysis was performed with the comprehensive score as an indicator.The optimal extraction process obtained by combining the response surface prediction results and actual production was:soaking for 45 min,8 times the amount of solvent,2 extractions,each time for 120 min.CONCLUSION This study provides a new idea for the investigation of the extraction process of traditional Chinese medicine compound prescriptions and expands a new method for the development of traditional Chinese medicine compound prescriptions.
4.Optimization of the Extraction Process of Changyan Heji Ⅱ Based on UPLC-Q-TOF-MS/MS Combined with Response Surface Method and Principal Component Analysis
Shulin WANG ; Jing SHANG ; Wenjun LIU ; Zerong CAI ; Mengyu QIAN ; Xiaoxin HU ; Liang CAO ; Zhenz-hong WANG ; Wei XIAO
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(4):501-512
OBJECTIVE To establish a extraction process of Changyan Heji Ⅱ(CYHJ-Ⅱ)based on UPLC-Q-TOF-MS/MS technology combined with response surface analysis,and to optimize the extraction process.METHODS The chemical components in CYHJ-Ⅱ were qualitatively analyzed by UPLC-Q-TOF-MS/MS technology,and the chemical components with good linear relation-ship in mass spectrometry response were selected as process investigation indicators;the extraction process parameters(water addition amount,extraction time and soaking time)were investigated by Box-Behnken design;the comprehensive score was obtained by princi-pal component analysis(PCA),and the optimal process was determined by the comprehensive score combined with response surface a-nalysis.RESULTS Through qualitative analysis,110 components were inferred and identified from CYHJ-Ⅱ,including 2 organic acids,82 flavonoids,13 terpenoids,and 13 alkaloids.Based on the results of qualitative analysis,48 index components with good lin-ear relationships were derived by UPLC-Q-TOF-MS/MS combined with Masshunter mass spectrometry data analysis software.PCA was performed and the comprehensive score was calculated.Response surface analysis was performed with the comprehensive score as an indicator.The optimal extraction process obtained by combining the response surface prediction results and actual production was:soaking for 45 min,8 times the amount of solvent,2 extractions,each time for 120 min.CONCLUSION This study provides a new idea for the investigation of the extraction process of traditional Chinese medicine compound prescriptions and expands a new method for the development of traditional Chinese medicine compound prescriptions.
5.Real-world research on Panlongqi tablets in the treatment of fractures
Shiyuan FANG ; Jian QIN ; Liyong ZHANG ; Zerong WU ; Tuanmao GUO ; Ting DONG ; Wei XU ; Jiazhao YANG ; Lei CHEN ; Bin LIU
China Pharmacy 2024;35(24):3046-3051
OBJECTIVE To evaluate the effectiveness and safety of Panlongqi tablets in the treatment of fractures based on real-world research.METHODS From September 2021 to September 2023,fracture patients admitted to 33 medical institutions were collected retrospectively.Patients who received conventional treatment were divided into control group(n=3 750),and patients who received combination of Panlongqi tablets on the basis of conventional treatment were divided into observation group(n=3 706).Self-reported indicators of patients were collected through telephone follow-up at 0,4,7 and 14 days after treatment.The improvement values of pain score,swelling score and health utility value,as well as effective rate and adverse drug reactions were compared between 2 groups.The propensity matching score(PSM)method was adopted to perform baseline matching on patient's age,gender,fracture site,fracture severity,surgical type,type of hospital,and other indicators.Statistical analysis was performed on each therapeutic effect indicator.RESULTS After PSM,a total of 6 425 patients were included,of which 3 055 were in the observation group and 3 370 were in the control group.After 14 days of treatment,the observation group showed significant improvement in pain score(4.768 vs.4.353),swelling grading score(2.979 vs.2.391),and life quality utility value(0.430 vs.0.363),as well as effective rate(87.20%vs.75.99%)compared to the control group(P<0.05).The results of subgroup analyses conducted by gender,age,hospital type,and fracture site were consistent with the aforementioned results.In terms of safety,the observation group had no serious adverse reactions,with a total of 29 cases of mild adverse reactions such as dizziness,stomach pain,and allergies,with an incidence rate of 0.78%.CONCLUSIONS Panlongqi tablets combined with conventional treatment are significantly better than conventional treatment in improving pain,swelling,quality of life,and effective rate in patients with fractures,and have good safety.
6.Absolute bioavailability,dose proportionality,and tissue distribution of rotundic acid in rats based on validated LC-QqQ-MS/MS method
Haihua SHANG ; Xiaohan DAI ; Mi LI ; Yueyi KAI ; Zerong LIU ; Min WANG ; Quansheng LI ; Yuan GU ; Changxiao LIU ; Duanyun SI
Journal of Pharmaceutical Analysis 2022;12(2):278-286
Rotundic acid(RA),an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb.(Aquifoliaceae),possesses diverse bioactivities.To further study its pharmacokinetics,a simple and sensitive liquid chromatography with triple quadrupole mass spectrometry(LC-QqQ-MS/MS)method was developed and validated to quantify RA concentration in rat plasma and tissue using etofesalamide as an internal standard(IS).Plasma and tissue samples were subjected to one-step protein precipitation.Chromatographic separation was achieved on a ZORBAX Eclipse XDB-C18 col-umn(4.6 mm×50 mm,5 μm)under gradient conditions with eluents of methanol:acetonitrile(1∶1,V/V)and 5mM ammonium formate:methanol(9∶1,V/V)at 0.5mL/min.Multiple reaction monitoring transitions were performed at m/z 487.30 → 437.30 for RA and m/z 256.10 → 227.10 for IS in the negative mode.The developed LC-QqQ-MS/MS method exhibited good linearity(2-500 ng/mL)and was fully validated in accordance with U.S.Food and Drug Administration bioanalytical guidelines.Dose proportionality and bioavailability in rats were determined by comparing pharmacokinetic data after single oral(10,20,and 40 mg/kg)and intravenous(10 mg/kg)administration of RA.Tissue distribution was studied following oral administration at 20 mg/kg.The results showed that the absolute bioavailability of RA after administration at different doses ranged from 16.1%to 19.4%.RA showed good dose proportionality over a dose range of 10-40 mg/kg.RA was rapidly absorbed in a dose-dependent manner and highly distributed in the liver.In conclusion,this study is the first to systematically elucidate the absorption and distribution characteristics of RA in rats,which can provide additional information for further development and evaluation of RA in drug metabolism and pharmacokinetic studies.
7.Risk factors of peritoneal metastasis in primary appendiceal tumor
Xuming HUANG ; Xuanhui LIU ; Lingyu HUANG ; Zerong CAI ; Yufeng CHEN ; Xiaojian WU
Chinese Journal of Oncology 2021;43(7):806-809
Objective:To investigate the risk factors of peritoneal metastasis in primary appendiceal tumor.Methods:The clinic data of 71 patients with primary appendiceal tumor admitted in the Sixth Affiliated Hospital of Sun Yat-sen University between Dec 2012 and Jan 2019 were enrolled retrospectively. Multivariate logistic regression analysis were carried out to evaluate the risk factors of appendiceal tumor with peritoneal metastasis.Results:Of the 71 patients, 33 were peritoneal metastasis (peritoneal metastasis group) and 38 were non-peritoneal metastasis (no peritoneal metastasis group). Twenty-one patients in the peritoneal metastasis group had increased preoperative cancer embryo antigen (CEA), while 3 cases in the non-peritoneal metastasis group, with statistically significant difference ( P<0.001). Sixteen cases in peritoneal metastasis group had increased preoperative carbohydrate antigen 199, while only 2 cases in the non-peritoneal metastasis group, the difference was statistically significant ( P<0.001). The pathological type of 30 cases in the peritoneal metastasis group was adenocarcinoma (including mucus adenocarcinoma and colon adenocarcinoma), while 12 cases of adenocarcinoma in the non-peritoneal metastasis group, with statistically significant difference ( P<0.001). Twelve cases in the peritoneal metastasis group had lymph node metastasis, while 3 cases in the non-peritoneal metastasis group, the difference is statistically significant ( P=0.003). Preoperative CEA elevation and pathological type is adenocarinoma were independent risk factors for peritoneal metastasis of appendiceal cancer ( P<0.05). Conclusions:The propensity of peritoneal metastasis in primary appendiceal tumor is high and the outcome is poor. Patients with increased preoperative CEA, adenocarcinoma histopathology are more inclined to have peritoneal metastasis.
8.Risk factors of peritoneal metastasis in primary appendiceal tumor
Xuming HUANG ; Xuanhui LIU ; Lingyu HUANG ; Zerong CAI ; Yufeng CHEN ; Xiaojian WU
Chinese Journal of Oncology 2021;43(7):806-809
Objective:To investigate the risk factors of peritoneal metastasis in primary appendiceal tumor.Methods:The clinic data of 71 patients with primary appendiceal tumor admitted in the Sixth Affiliated Hospital of Sun Yat-sen University between Dec 2012 and Jan 2019 were enrolled retrospectively. Multivariate logistic regression analysis were carried out to evaluate the risk factors of appendiceal tumor with peritoneal metastasis.Results:Of the 71 patients, 33 were peritoneal metastasis (peritoneal metastasis group) and 38 were non-peritoneal metastasis (no peritoneal metastasis group). Twenty-one patients in the peritoneal metastasis group had increased preoperative cancer embryo antigen (CEA), while 3 cases in the non-peritoneal metastasis group, with statistically significant difference ( P<0.001). Sixteen cases in peritoneal metastasis group had increased preoperative carbohydrate antigen 199, while only 2 cases in the non-peritoneal metastasis group, the difference was statistically significant ( P<0.001). The pathological type of 30 cases in the peritoneal metastasis group was adenocarcinoma (including mucus adenocarcinoma and colon adenocarcinoma), while 12 cases of adenocarcinoma in the non-peritoneal metastasis group, with statistically significant difference ( P<0.001). Twelve cases in the peritoneal metastasis group had lymph node metastasis, while 3 cases in the non-peritoneal metastasis group, the difference is statistically significant ( P=0.003). Preoperative CEA elevation and pathological type is adenocarinoma were independent risk factors for peritoneal metastasis of appendiceal cancer ( P<0.05). Conclusions:The propensity of peritoneal metastasis in primary appendiceal tumor is high and the outcome is poor. Patients with increased preoperative CEA, adenocarcinoma histopathology are more inclined to have peritoneal metastasis.
9. Association between the time of neutrophils to the lowest and prognosis of patients with esophageal squamous cell carcinoma treated with non-operative therapy
Shuang LIU ; Liping HUANG ; Zheng LIN ; Yanfang LIU ; Zerong ZHENG ; Xiane PENG ; Weilin CHEN ; Zhijian HU
Chinese Journal of Oncology 2019;41(2):124-128
Objective:
To investigate the association between the time of neutrophils to the lowest and prognosis of patients with esophageal squamous cell carcinoma (ESCC) treated with non-operative therapy.
Methods:
The clinical data of 325 non-operative treated ESCC patients were collected in this study. The X-title software was applied to establish optimal threshold of neutrophil reduction to the lowest value. According to the optimal threshold, the patients were divided into early group (115 cases) and late group (210 cases). The clinical features and survival time of the two groups were compared, and the factors of prognosis were analyzed by Cox regression model with univariate and multivariate analysis.
Results:
The X-title software demonstrated the optimal cutoff values for the time of neutrophils to the lowest was 39 days. The median overall survival time was 21.0 months in the early group which was significantly higher than that in the late group (16.0 months). Multivariate Cox regression analysis showed that the treatment methods and the time of neutrophils to the lowest were independent factors for overall survival of patients with ESCC treated by non-surgical therapy. Compared with radiotherapy alone, concurrent chemoradiation could benefit the survival (
10.The combined therapeutic effects of iodine-labeled multifunctional copper sulfide-loaded microspheres in treating breast cancer.
Qiufang LIU ; Yuyi QIAN ; Panli LI ; Sihang ZHANG ; Zerong WANG ; Jianjun LIU ; Xiaoguang SUN ; Michael FULHAM ; Dagan FENG ; Zhigang CHEN ; Shaoli SONG ; Wei LU ; Gang HUANG
Acta Pharmaceutica Sinica B 2018;8(3):371-380
Compared to conventional cancer treatment, combination therapy based on well-designed nanoscale platforms may offer an opportunity to eliminate tumors and reduce recurrence and metastasis. In this study, we prepared multifunctional microspheres loading I-labeled hollow copper sulfide nanoparticles and paclitaxel (I-HCuSNPs-MS-PTX) for imaging and therapeutics of W256/B breast tumors in rats. F-fluordeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) imaging detected that the expansion of the tumor volume was delayed (<0.05) following intra-tumoral (i.t.) injection with I-HCuSNPs-MS-PTX plus near-infrared (NIR) irradiation. The immunohistochemical analysis further confirmed the anti-tumor effect. The single photon emission computed tomography (SPECT)/photoacoustic imaging mediated by I-HCuSNPs-MS-PTX demonstrated that microspheres were mainly distributed in the tumors with a relatively low distribution in other organs. Our results revealed that I-HCuSNPs-MS-PTX offered combined photothermal, chemo- and radio-therapies, eliminating tumors at a relatively low dose, as well as allowing SPECT/CT and photoacoustic imaging monitoring of distribution of the injected agents non-invasively. The copper sulfide-loaded microspheres, I-HCuSNPs-MS-PTX, can serve as a versatile theranostic agent in an orthotopic breast cancer model.

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