1.Signal interference between drugs and metabolites in LC-ESI-MS quantitative analysis and its evaluation strategy
Jiang FULIN ; Liu JINGYU ; Li YAGANG ; Lu ZIHAN ; Liu QIAN ; Xing YUNHUI ; Zhu JANSHON ; Huang MIN ; Zhong GUOPING
Journal of Pharmaceutical Analysis 2024;14(7):1024-1034
Liquid chromatography-electrospray ionization tandem mass spectrometry(LC-ESI-MS)is a widely utilized technique for in vivo pharmaceutical analysis.Ionization interference within electrospray ion source,occurring between drugs and metabolites,can lead to signal variations,potentially compromising quantitative accuracy.Currently,method validation often overlooks this type of signal interference,which may result in systematic errors in quantitative results without matrix-matched calibration.In this study,we conducted an investigation using ten different groups of drugs and their corresponding me-tabolites across three LC-ESI-MS systems to assess the prevalence of signal interference.Such in-terferences can potentially cause or enhance nonlinearity in the calibration curves of drugs and metabolites,thereby altering the relationship between analyte response and concentration for quanti-fication.Finally,we established an evaluation scheme through a step-by-step dilution assay and employed three resolution methods:chromatographic separation,dilution,and stable labeled isotope internal standards correction.The above strategies were integrated into the method establishment process to improve quantitative accuracy.
2.Efficacy comparison between modified two-window and conventional single-window posteromedial inverted L-shaped approach for reduction and internal fixation of flexion-inversion tibial plateau fractures
Zhiyuan LIU ; Weibo ZHOU ; Jianfeng HUANG ; Wei CHEN ; Fulin ZHOU
Chinese Journal of Trauma 2024;40(9):793-800
Objective:To compare the efficacy of reduction and internal fixation of flexion-inversion tibial plateau fractures with a modified two-window and conventional single-window posteromedial inverted L-shaped approach.Methods:A retrospective cohort study was used to analyze the clinical data of 44 patients with flexion-inversion tibial plateau fractures admitted to the Affiliated Changzhou No.2 People′s Hospital of Nanjing Medical University from January 2018 to December 2022, including 22 males and 22 females, aged 31-58 years [(44.4±9.1)years]. Among them, 25 patients were injured on the left side and 19 on the right. A total of 23 patients were treated with the conventional single-window posteromedial inverted L-shaped approach (conventional single-window approach group), while the other 21 with the modified two-window posteromedial inverted L-shaped approach (modified two-window approach group). The length of surgical incision, operation time, intraoperative blood loss, postoperative drainage volume, and postoperative hospital stay were compared between the two groups. The articular step-offs, medial tibial plateau angles (mTPA), tibial posterior slope angles (PSA), and Rasmussen radiological scores at 3 days, 3 months after surgery and at the last follow-up were evaluated in the two groups. The visual analogue scale (VAS) scores before surgery, at 7 days and 3 months after surgery, data of extension-flexion motion of the knee joint at 7 days after surgery and Hospital for Special Surgery (HSS) knee function scores at 3 and 6 months after surgery and at the last follow-up were compared between the two groups. At the last follow-up, the fracture healing was observed. The postoperative incidence of complications such as thrombosis and poor wound healing was compared between the two groups.Results:All the patients were followed up for 12-18 months [(15.7±3.2)months]. The operation time of the modified two-window approach group was (121.6±19.2)minutes, significantly shorter than (149.5±22.4)minutes of the conventional single-window approach group ( P<0.01). There were no statistically significant differences in the length of surgical incision, intraoperative blood loss, postoperative drainage volume, or postoperative hospital stay between the two groups ( P>0.05). At 3 days, 3 months after surgery and at the last follow-up, the articular step-offs of the modified two-window approach group were 0.7(0.5, 0.9)mm, 1.0(0.8, 1.1)mm and 0.9(0.8, 1.0)mm respectively, significantly shorter than 1.0(0.7, 1.2)mm, 1.1(1.0, 1.3)mm and 1.1(0.9, 1.2)mm of the conventional single-window approach group ( P<0.05 or 0.01); the mTPA of the modified two-window approach group was 87.0(86.0, 87.0)°, 87.0(86.0, 87.0)° and 86.0(85.5, 87.0)° respectively, significantly larger than 85.0(84.0, 86.0)°, 85.0(84.0, 86.0)°and 85.0(84.0, 86.0)°of the conventional single-window approach group ( P<0.01); the Rasmussen radiological scores of the modified two-window approach group were (17.0±0.9)points, 16.0(15.0, 17.0)points and 16.0(15.0, 16.0)points respectively, significantly higher than (16.4±1.1)points, 13.0(13.0, 15.0)points and 14.0(13.0, 15.0)points of the conventional single-window approach group ( P<0.05 or 0.01); no significant differences in the PSA were found between the two groups ( P>0.05). There were no significant differences in VAS scores between the two groups before surgery and at 3 months after surgery ( P>0.05), while the VAS score at 7 days after surgery was 3.0(3.0, 3.0)points in the modified two-window approach group, significantly lower than 3.0(3.0, 4.0)points of the conventional single-window approach group ( P<0.05). There was no significant difference in the VAS score at 3 months after surgery between the two groups ( P>0.05). The extension-flexion motion of the knee joint at 7 days after surgery was 90.0(85.0, 95.0)° in the modified two-window approach group, higher than 80.0(75.0, 85.0)° of the conventional single-window approach group ( P<0.01). The HSS knee function score at 3 months after surgery was (67.9±2.8)points in the modified two-window approach group, higher than (66.1±2.7)points of the conventional one-window approach group ( P<0.05). There were no significant differences in the HSS knee function scores at 6 months after surgery and at the last follow-up between the two groups ( P>0.05). At the last follow-up, bone union was observed in both groups. One patient in the conventional single-window approach group developed partial popliteal vein thrombosis, with a complication rate of 4.4% (1/23); while one patient in the modified two-window approach group had poor healing of the incision postoperatively, with a complication rate of 4.8%(1/21) ( P>0.05). Conclusion:Compared with the conventional single-window approach, the modified two-window posteromedial inverted L-shaped approach has the advantages of shorter operation time, better reduction quality, early pain relief, and better restoration of knee joint extension-flexion motion and joint function in the reduction and internal fixation of flexion-inversion tibial plateau fractures.
3.Simultaneous determination of 5 kinds of pentacyclic triterpenoids in Chaenomeles speciosa by quantitative analysis of multi-components by single-marker
Tingting ZHANG ; Haoning HU ; Pingyuan LI ; Yongmei HUANG ; Junzhi WANG ; Haiming TANG ; Yonghong YIN
China Pharmacy 2022;33(20):2477-2480
OBJECTIVE To establish a method for simultan eous determination of 5 kinds of pentacyclic triterpenoids as 3-O- acetyl-pomolic acid in Chaenomeles speciosa ,and to analyze the difference in the contents of C. speciosa from different producing areas by different processing technologies . METHODS HPLC method was adopted . The determination was performed on COSMOSIL 5 C18-MS-Ⅱ column with mobile phase consisted of acetonitrile -0.005 mol/L ammonium dihydrogen phosphate solution (pH value adjusted to 6.5 with phosphoric acid )(70∶30,V/V)at the flow rate of 1.0 mL/min. The column temperature was set at 30 ℃. The detection wavelength was set at 210 nm,and sample size was 20 μL. The contents of the other four pentacyclic triterpenoids were calculated according to quantitative analysis of multi -components by single -marker(QAMS)using oleanolic acid as internal reference . The results were compared with those determined by external standard method . The total content of oleanolic acid and ursolic acid ,the total content of 5 components in C. speciosa from different producing areas and different processing technologies were compared . RESULTS The linear range of 3-O-acetyl-pomolic acid ,betulinic acid ,oleanolic acid ,ursolic acid and 3-O-acetyl ursolic acid were 4.06-81.2,2.12-42.4,9.62-192.3,7.77-155.4,4.21-84.1 μg/mL,respectively(R2>0.999). RSDs of precision ,reproducibility and stability (24 h)tests were all lower than 3%. The average recoveries were 98.29%-101.38% (RSDs<3%,n=6). The mass fraction of 3-O-acetyl-pomolic acid ,betulinic acid ,ursolic acid and 3-O-acetyl ursolic acid measured by QAMS w ere 0.023%-0.060%,0.044%-0.528%,0.101%-0.368%,0.067%-0.221%,respectively;the deviations from the results measured by external standard method were all within 8%. The total content of oleanolic acid and ursolic acid, the total content of 5 components in C. speciosa processed by fresh -cut technology from the same producing area were higher than those in C. speciosa processed by traditional technology ,and the total content of 5 components in C. speciosa from Chongqing Qianjiang were significantly higher than those from other producing areas (P<0.05). CONCLUSIONS QAMS method is established for the simultaneous determination of 3-O-acetyl-pomolic acid ,betulinic acid ,oleanolic acid ,ursolic acid and 3-O-acetyl ursolic acid in C. speciosa. Established method is simple ,rapid and accurate . The total content of 5 components in C. speciosa produced in Chongqing Qianjiang is higher ,and the total content of C. speciosa processed by fresh -cut technology from the same origin is higher than C. speciosa processed by traditional technology .
4.Application of OPT101 sensor in ICU-specific near-infrared spectroscopy instrumentation
Ting LI ; Fulin ZHONG ; Boan PAN ; Zebin LI ; Chong HUANG ; Zishan DENG
International Journal of Biomedical Engineering 2018;41(1):11-18,43
The OPT101 photoelectric sensor has the characteristics of good photoelectric response,buih-in transimpedance amplifier and small size,which meet the needs of accurately near-infrared spectral measurement in medical near-infrared spectroscopy (NIRS) range.Our research team has developed a series of portable NIRS instruments for NIRS measuring in intensive care units (ICU).The characteristics and advantages of OPT101 in the development of clinical ICU-specific NIRS instruments were introduced.The research progress of our team on the development of ICU-NIRS instruments using OPT101 was reviewed.The prospect of OPT101 in clinical noninvasive detection was discussed.
5. extract (Wuzhi Tablet) protects against chronic-binge and acute alcohol-induced liver injury by regulating the NRF2-ARE pathway in mice.
Xuezhen ZENG ; Xi LI ; Chenshu XU ; Fulin JIANG ; Yufei MO ; Xiaomei FAN ; Yaoting LI ; Yiming JIANG ; Dongshun LI ; Min HUANG ; Huichang BI
Acta Pharmaceutica Sinica B 2017;7(5):583-592
Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ), a preparation of extract fromthat is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding. The activities of ALT and AST in serum were assessed as well as the level of GSH and the activity of SOD in the liver. The expression of CYP2E1 and proteins in the NRF2-ARE signaling pathway including NRF2, GCLC, GCLM, HO-1 were measured, and the effect of WZ on NRF2 transcriptional activity was determined. We found that both models resulted in liver steatosis accompanied by increased transaminase activities, but that liver injury was significantly attenuated by WZ. WZ administration also inhibited CYP2E1 expression induced by alcohol, and elevated the level of GSH and the activity of SOD in the liver. Moreover, the NRF2-ARE signaling pathway was activated by WZ and the target genes were all upregulated. Furthermore, WZ significantly activated NRF2 transcriptional activity. Collectively, our study demonstrates that WZ protected against alcohol-induced liver injury by reducing oxidative stress and improving antioxidant defense, possibly by activating the NRF2-ARE pathway.
6.Study on efficacy and safety of sequential rivaroxaban use in reducing blood loss after applying tranexamic acid in total hip arthroplasty
Fulin LI ; Dong YIN ; Bingfeng MO ; Yu HUANG ; Xiao HUANG ; Qiang LU ; Wenhui LIU
Chongqing Medicine 2017;46(16):2193-2197
Objective To research the efficacy and safety of sequential rivaroxaban use in reducing blood loss after applying tranexamic acid(TXA)in total hip arthroplasty(THA).Methods According to the design by the random control principle,150 pa tients undergoing unilateral primary THA from September 2012 to June 2015 were selected and randomly divided into the group A,B,C,D and E (n=30).The group A did not use TXA,the group B received intravenous drip of 10 mg/kg TXA at 10 min before skin incision,the group Creceived intravenous drip of 15 mg/kg TXA at 10 min before skin incision,the group D respectively received intravenous drip of 15mL/kg TXA at 10 min before skin incision and after 3 h,the group E received intravenous drip of 15 mL/kg TXA at 10 min before skin incision and articular cavity use of 1 g TXA before closing the incision.Oral 10 mg rivaroxaban was given at postoperative 6-12 h when the drainage volume was less than 30 mL/h and then the conventional dose was used until postoperative 35 d.The intraoperative blood loss,postoperative drainage volume,hidden blood loss,blood transfusion rate,postoperative anticoagulation time,time of removing drainage tube,postoperative prothrombin time on postoperative 1 d,activated partial thromboplastin time,descend value of hemoglobin,and occurrence rates of postoperative deep vein thrombosis (DVT) and pulmonary embolism (PE) were observed in the group A,B,C,D and E.Results The intraoperative blood loss,postoperative drainage volume,hidden blood loss,blood transfusion rate and descend value of hemoglobin on postoperative 1 d had statistical differences among 5 groups(P<0.05).The are significant differences between the group D and A in the intraoperative blood loss,postoperative drainage volume,hidden blood loss,blood transfusion rate,descend value of hemoglobin on postoperative 1 d,postoperative anticoagulation time and removal drainage tube time(P<0.05).All cases had no symptomatic DVT and PE during the perioperative period and postoperative 3-month outpatient or telephone follow-up.Conclusion Sequential rivaroxaban use after applying TXA during THA perioperative period is safe and effective.Moreover intravenous drip of 15 mL/kg TXA at 10 min before skin incision and after 3 h has most significant effect in reducing bleeding volume during THA perioperative period.
7.Cytoreductive surgery and hyperthermic intraperitoneal chemo-therapy improve survival of patients with peritoneal carcinomato-sis from colorectal cancer:a retrospective case-control study
Chaoqun HUANG ; Yunfeng ZHOU ; Conghua XIE ; Xiaojun YANG ; Fulin CHENG ; Bin XIONG ; Guoliang YANG ; Yan LI
Chinese Journal of Clinical Oncology 2013;(16):979-983
Objective:To evaluate the efficacy and safety of cytoreductive surgery (CRS) in conjunction with hyperthermic intra-peritoneal chemotherapy (HIPEC) for treating patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC). Methods:A total of 62 CRC patients with complication of PC were divided into the CRS group, namely, Group One (n=29, CRS and systemic adju-vant chemotherapy) and the CRS+HIPEC group, namely, Group Two (n=33, CRS+HIPEC). The primary end point of the study was overall survival (OS) and the secondary end point was serious adverse events (SAE). Results:Patients' clinicopathologic characteris-tics, peritoneal carcinomatosis index, and completeness of cytoreduction therapy were well balanced and comparable between the two groups. The median follow-up was 41.9 mo (6.5 mo to 110.0 mo) in Group One and 32.0 mo (10.5 mo to 95.9 mo) in Group Two. The median OS was 8.5 mo (95%CI:4.9 mo to 12.1 mo) in Group One and 14.5 mo (95%CI:11.9 mo to 17.1 mo) in Group Two (P=0.007). Within 30 days after the surgery, SAE occurred in 3 of the 29 patients in Group One, and 9 of the 33 patients in Group Two (P=0.126). Multivariate analysis revealed that HIPEC, CC0-1 score, and chemotherapy over six cycles were the independent factors for OS improvement. Conclusion:The CRS+HIPEC method improves the OS of patients with PC from CRC, suggesting an acceptable safety.
8.Clinicopathological study on secretory meningioma
Fulin SONG ; Haiming QIN ; Wenchen HUANG
Chinese Journal of Practical Internal Medicine 2006;0(16):-
Objective To study the clinicopathological characteristics and ultrastructural features of secretory meningioma.Methods A total of 19 cases of secretory meningioma were studied by clinicopathology,immunohistochemical and ultrastructural observation.Results Eosinophilic hyaline inclusions with different sizes were found in cytoplasm of tumor cell,which were positive to PAS and alcian blue stains.These inclusions were secreted by microvesicles in cytoplasm of tumor cell under electron microscopy.Conclusion Immunohistochemistry and ultrastructural observation play important roles in the diagnosis and differential diagnosis of this tumor.
9.High dose tamoxifen in the reversal treatment of multidrug resistance to EP regimen in patients with non-small cell lung cancer.
Zhuan HONG ; Xiuli ZHENG ; Xiaofeng SUN ; Hongxia XU ; Zhaofei ZHOU ; Li WANG ; Xia XU ; Liangxi PAN ; Jifeng FENG ; Fulin HUANG
Chinese Journal of Lung Cancer 2002;5(3):201-203
BACKGROUNDTo evaluate the reversal effect of high dose tamoxifen on multidrug resistance to EP regimen in patients with non-small cell lung cancer.
METHODSA total of 41 patients with NSCLC were studied, who were resistant to EP regimen and were proved to have P-gp protein overexpression. All patients were randomizedly divided into two arms. Reversal group (n=21) received oral tamoxifen 100?mg, 2 times everyday on D1-5, together with EP regimen. Control group (n=20) were only given EP regimen.
RESULTSIn reversal group, complete response occurred in 1 patient, and partial response in 5; disease remained stable in 11 patients, and tumor progression occurred in 4 patients. The response rate was 28.6%(6/21). In control group, no response occurred; 9 patients had stable diseases, and the other 11 progressed. There was a significant difference in response rate between the two groups (P=0.012?1). In reversal and control groups, the median survivals were 8.4 and 4.6 months respectively (P < 0.01), and 1-year survial rates were 38.1% and 35.0% respectively. Reversal of P-gp occurred in 7 cases of reversal group (33.3%),and none in control group (P= 0.005?2) . There was no significant difference in toxicities between the two groups (P > 0.05).
CONCLUSIONSHigh dose tamoxifen can remarkably downregulate the expression of P-gp and partially reverse the multidrug resistance to EP regimen for non-small cell lung cancer.
10.Biweekly regimen of high-dose leucovorin, fluorouracil and oxaliplatin for advanced and refractory colorectal cancer
Jianwei LU ; Liangxi PAN ; Fulin HUANG ;
China Oncology 2001;0(03):-
Purpose:To evaluate the efficacy and toxicity of the biweekly regimen of high dose leucovorin (CF), continuous central venous infusion(ccvi) of fluorouracil (5 FU) and oxaliplatin (OXA)for advanced and refractory colorectal cancer.Methods:28 patients (12 in rectum,16 in colon) received biweekly CF/5 FU/OXA (CF: 200 mg/m 2,ccvi 2 hour,days 1~2;5 FU:400mg/m 2,iv.,day 1; 5 FU: 1.6 g/m 2,ccvi.22 hours, days 1~2; OXA: 135 mg/m 2,ccvi.4 hour,day 1,every two weeks).Four treatment courses were carried out with an interval of one month.Results:The overall response rate was 39.28%.The response rates of rectal,colonic cancers were 33.33%% and 43.13%, respectively.Median duration of 11 partial responses were 5.0 months.Median survival of all patients was 7.0 months. Median survival of responsive patients,and non responsive was 11.0 and 7.0 months,respectively( P

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