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.Minimally invasive technique for tibial plateau bicondylar fracture repair using the double reverse traction repositor
Zhimeng ZHAO ; Fulin TAO ; Dawei WANG ; Lin LI ; Dongsheng ZHOU ; Lianxin LI
Chinese Journal of Orthopaedics 2023;43(22):1509-1516
Objective:To assess the efficacy of a minimally invasive technique for repairing tibial plateau bicondylar fractures utilizing the double reverse traction repositor.Methods:A retrospective analysis was performed of the data of 31 patients (Schatzker V 17 cases, Schatzker VI 14 cases) who had been admitted to trauma center of Shandong provincial hospital affiliated to Shandong first medical university for tibial plateau bicondylar fractures from January 2017 to January 2022. There were 21 males and 10 females, aged from 18 to 67 years (average, 32.4±6.5 years). The intervention strategy comprised the use of a double reverse traction repositor and was augmented by precise screw fixation. A comprehensive set of parameters were measured, including time interval between injury and operation, operation time, blood loss, hospital stay, fracture healing time, incision complications. Postoperative assessments were made immediately and at the 12-month mark, including the evaluation of articular step-off height, medial tibial plateau angle, and posterior tibial slope angle. The evaluation also included thTime interval between injury and operation ranged from 5 to 11 days, with an average of 6.1±1.3 days. The surgical procedures varied in length from 70 to 160 minutes, averaging at 109.2±15.6 minutes. The volume of blood loss was noted to be between 90 to 380 ml, averaging at 176.5±20.8 ml. Hospitalization spanned from 10 to 15 days, with an average stay of 12.2 ±0.8 days. Over a follow-up duration of 12 to 20 months, averaging at 13.5±1.1 months, all patients achieved fracture union within a period of 11 to 20 weeks, with an average time of 14.6±1.5 weeks. The postoperative articular step-off was recorded at 0.45±0.13 mm immediately after surgery and 0.58±0.21 mm at the one-year follow-up. Similarly, the medial tibial plateau angle and posterior tibial slope angle showed marginal changes from the immediate postoperative period to the 12-month evaluation. Knee joint mobility at the one-year mark ranged impressively from 0° to 135°, with an average of 125.6°±2.1°. Functional outcomes as reflected by Rasmussen scores ranged from 18 to 28 points, with an average of 25.4±1.7 points. Pain, as assessed by the VAS, had a low score range of 0 to 2 points, averaging at 0.7±0.2 points. Notably, there were no postoperative complications associated with the incisions, such as fat liquefaction, infection, skin necrosis, or exposure of internal fixations. Additionally, no cases of delayed union or fixation failure were observed. Six patients had traumatic arthritis 1 year after operation.Conclusion:The minimally invasive double reverse traction repositor technique for tibial plateau bicondylar fracture repair is effective, warranting its broader application in orthopedic surgery.
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. Huatanjiangqi capsule regulates Nrf2/HDAC2 and improves glucocorticoid resistance of 16HBE cells
Mengwen WANG ; Chongyang WANG ; Fulin TAO ; Wentao ZHU ; Zhili HAN ; Nianxia SUN ; Dianlei WANG ; Yan GUO ; Zegeng LI ; Dianlei WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2021;26(12):1360-1369
AIM: To explore the effect of Huatanjiangqi capsule medicated serum (HTJQ) on the resistance of human bronchial epithelial cells (16HBE) to glucocorticoid (GC) stimulated by cigarette smoke extract (CSE). METHODS: After 16HBE cells were treated with HTJQ, the effects of different concentrations of HTJQ on the viability of 16HBE cells were determined by CCK-8 method. 16HBE cells were pretreated with HTJQ, and then cultured with dexamethasone (DEX) and lipopolysaccharide (LPS) for 24 hours, the effect of HTJQ on glucocorticoid (GC) resistance of 16HBE cells was determined by Enzyme-linked immunosorbent assay (ELISA). The effects of HTJQ, sulforaphane (SFN) and glutathione (GSH) on the expression of NF-E2-related factors 2 (Nrf2), Heme oxygenase-1 (HO-1) and histone deacetylase 2 (HDAC2) in 16HBE cells stimulated by CSE were measured by Western blot, and the effects of HTJQ, SFN and GSH on interleukin-8 (IL-8) in 16HBE cells were measured by ELISA. RESULTS: HTJQ promoted the proliferation of 16HBE cells at 1 h, 2 h and 4 h, the results of ELISA and Western blot showed that CSE induced GC resistance and decreased the expression of Nrf2, HO-1 and HDAC2 in 16HBE cells, HTJQ significantly decreased IL-8 and improved GC sensitivity of 16HBE cells (P<0.01), and up-regulated the expression of Nrf2, HO-1 and HDAC2 (P<0.01). In addition, HTJQ significantly up-regulated the level of GSH in 16HBE cells (P<0.01). Nrf2 agonists SFN and GSH significantly improved the glucocorticoid sensitivity of 16HBE cells (P<0.01), and up-regulated the expression of Nrf2, HO-1 and HDAC2 (P<0.01). CONCLUSION: HTJQ improves the GC resistance of 16HBE cells by up-regulating the expression of Nrf2/HDAC2 protein and the level of intracellular GSH.
5.Rapid Analysis of Chemical Components of Zhitong Huazheng Capsules Based on UPLC-Q-TOF/MS Technology Combined with UNIFI Database
Fulin WU ; Cuizhu WANG ; Qinghai DONG ; Han WANG ; Jing TAN ; Hongqiang LIN ; Jinping LIU ; Pingya LI
China Pharmacy 2019;30(17):2336-2342
OBJECTIVE: To rapidly identify chemical components of Zhitong huazheng capsules (shorted for “ZTHZC”), and to provide reference for further elucidating the pharmacodynamic material basis and overall quality control. METHODS: UPLC-Q-TOF/MS method was adopted to separate the chemical components of ZTHZC. By reviewing literatures that related to chemical components of ZTHZC and its single Chinese traditional medicinal crops, the chemical structure of the chemical components was saved into a .mol format file, and supplemented the UNIFI database. The chemical constituents of ZTHZC were qualitatively analyzed by UNIFI database screening, and validated according to their precise molecular mass, characteristic ions, neutral loss, secondary mass spectrometry cleavage, chromatographic retention behavior, combined reference information and literature reports. RESULTS: A total of 70 chemical components were identified in this experiment, including 38 organic acids and organic acid esters, 8 alkaloids, 9 flavonoids, 5 triterpenoid saponins, 5 aldehydes, 2 ketones, 1 quinone, 1 polyacetylene and 1 monoterpenoid. CONCLUSIONS: This study provides a rapid detection and identification method for chemical components of ZTHZC, and also provides a scientific basis for the clarification of ZTHZC’s quality control and pharmacodynamics.
6.Tibiocalcaneal arthrodesis via bone transport technique for traumatic talus infection or defect
Yonghui WANG ; Fulin TAO ; Baisheng FU ; Dawei WANG ; Qinghu LI ; Yongliang YANG
Chinese Journal of Trauma 2019;35(3):247-253
Objective To investigate the clinical efficacy of tibiocalcaneal arthrodesis using bone transport technique in the treatment of traumatic talus infection or loss. Methods A retrospective case series study was conducted to analyze the clinical data of 15 patients with talus infection or loss admitted to the provincial hospital affiliated to Shandong University from June 2011 to October 2017. There were 13 males and two females, aged from 19 to 47 years, with an average age of 27 years. Thirteen patients had talus infection and two patients had talus loss. All patients underwent tibiocalcaneal fusion with external fixator using bone transport technique, including four patients treated with annular external fixator and 11 with unilateral external fixator. Six patients with severe infection underwent debridement at stage I and osteotomy at stage II, and the other nine underwent debridement and osteotomy at the same time. The length of new bone, the fixation time of external fixator and complications were recorded. The American Orthopedic Foot and Ankle Society ( AOFAS ) score was used to evaluate the efficacy. Results All patients were followed up for 18-35 months, with an average of 26 months. The length of new bone in proximal tibial osteotomy area was 5-16 cm, with an average of 9 cm. The external fixators were removed after bone healing at docking site and maturation of new bone. The fixation time of external fixator ranged from 13 to 27 months, with an average of 18 months. No complications such as needle breakage, recurrence of infection and calcaneal varus occurred, and the length of both lower limbs was equal. AOFAS score was increased from preoperative (42. 0 ± 3. 6)points (31-55 points) to (76. 0 ± 4. 2)points (69-86 points ) at the last follow-up. Conclusion Tibiocalcaneal arthrodesis using bone transport technique is proved to be effective in treating traumatic talus infection or loss, which can repair the bone defect after debridement, improve the ankle-hindfoot function and improve the quality of life.
7.Study on the application of oral magnesium sulfate solution in split doses as bowel preparation for colonoscopy in elderly patients
Fulin GE ; Binbin SU ; Tingting LI ; Lili SHI ; Yue LYU ; Jun WAN
Chinese Journal of Internal Medicine 2019;58(3):181-184
Objective To evaluate the efficacy and safety of oral magnesium sulfate solution in split doses as bowel preparation in elderly patients undergoing colonoscopy.Methods A total of 368 elderly patients undergoing colonoscopy were enrolled at PLA General Hospital.The patients were randomly divided into magnesium sulfate solution orally in split doses group (group A,n=178) and single dose group (group B,n=190).Parameters including general information,defecation frequency,Boston bowel preparation score (BBPS),detection rate of lesions and adverse reactions.Results The frequency of defecations in group A was (7.6± 1.4),more than that in group B (6.6± 1.5) with statistical significance (P<0.05).The duration of bowel preparation in group A was (128.6±25.3) min,shorter than that of group B (165.4±29.7) min (P<0.05).The BBPS in group A was (8.09±0.67),better than that of group B (7.34±0.58) (P<0.05).The detection rates of intestinal polyps and micropolyps (diameter<0.5 cm) in group A were 73/178 (41.0%) and 51/178 (28.7%) respectively,compared with 58/190 (30.5%) and 37/190 (19.5%) in group B (both P<0.05).In group A,8 patients reported adverse reactions as abdominal distension and discomfort.One patient had ST-T abnormality of electrocardiogram (ECG).No nausea or vomiting occurred,yet 2 cases needed enema for inadequate bowel preparation.Twenty-one cases in group B reported adverse events including 7 with nausea and vomiting.There were 13 patients treated with enema.Abnormal ECG was found in 4 patients in group B.The satisfaction rate of group A was 97.8%,higher than that of group B (91.6%) (P<0.05).Conclusions The effect of bowel preparation of elderly patients with magnesium sulfate solution in split dose has a better tolerance,good cleaning effect and low incidence of adverse reactions.It is an ideal choice for the elderly to prepare colonoscopy.
8.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.
9. 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.
10.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.

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