1.Edaravone in the treatment of acute ischemic stroke:a rapid health technology assessment
Fang YU ; Lu ZENG ; Anhua WEI ; Xuepeng GONG ; Lu WANG
Chinese Journal of Pharmacoepidemiology 2024;33(10):1147-1155
Objective To rapidly evaluate the effectiveness,safety and economy of edaravone in treating acute ischemic stroke(AIS),and to provide the evidence-based basis for clinical decision-making.Methods PubMed,Embase,Web of Science,Cochrane Library,CNKI and WanFang Data databases and the official website of health technology assessment(HTA)agency were electronically searched to collect HTA reports,systematic reviews/Meta-analysis and pharmacoeconomic studies of edaravone in the treatment of AIS from the inception to October 1,2024.Two reviewers independently screened the literature,extracted data,evaluated the quality,summarized the results,and qualitatively described and analyzed the results.Results A total of 12 literature were included,involving 9 systematic reviews/Meta-analysis and 3 pharmacoeconomic studies.In terms of efficacy,edaravone alone or in combination with conventional therapy(alteplase,ozagrel)increased efficiency,improved short-term neurological deficit scores and improved patients'ability to perform activities of daily living compared with placebo or conventional therapy(alteplase,ozagrel)(P<0.05).There was no significant difference in the incidence of adverse reactions between edaravone and placebo,routine treatment,or other neuroprotectants(P>0.05).Combined with alteplase,it could reduce the incidence of intracranial hemorrhage compared to alteplase alone(P<0.05),with no statistically significant difference in all-cause mortality(P<0.05).Pharmacoeconomic studies showed that,edaravone does not have a cost-effectiveness advantage in the short term,but it may have a cost-effectiveness advantage from limited long-term studies.Conclusion Edaravone is effective and safe in the treatment of AIS,but there is limited research evidence and the conclusion still needs to be confirmed by further studies and clinical trials,and the economics need to be further evaluated.
2.Therapy Updates of 2024 Guidelines for the Diagnosis and Treatment of Heart Failure in China
Juan WU ; Ping LONG ; Lu ZENG ; Lu WANG ; Xuepeng GONG ; Anhua WEI
Herald of Medicine 2024;43(11):1718-1722
Heart failure is a severe manifestation or advanced stage of various heart diseases,with high mortality and readmission rates.The 2024 guidelines for the diagnosis and treatment of heart failure,which are on the 2018 guidelines,combined with new evidence and China's national conditions,provide a comprehensive and systematic description and recommendation on the classification,diagnosis,prevention,treatment,comorbidity,and management of heart failure.This article reviewed the update of the therapeutic drugs section.
3.Impact of cecal ligation and puncture-induced sepsis on the proliferation and differentiation of intestinal stem cells
Xuepeng ZHANG ; Jianlei FU ; Maoxia LIU ; Geng ZHANG ; Tong QIU ; Jiangyuan ZHOU ; Zixin ZHANG ; Xue GONG ; Qinyi FU ; Yi JI ; Siyuan CHEN
Chinese Critical Care Medicine 2024;36(5):496-502
Objective:To analyze the impact of cecal ligation and puncture (CLP)-induced sepsis on the proliferation and differentiation of intestinal epithelial cells.Methods:① Animal experiment: sixteen male C57BL/6 mice were divided into sham operation group (Sham group) and CLP-induced sepsis model group (CLP group) by random number table method, with 8 mice in each group. After 5 days of operation, the jejunal tissues were taken for determination of leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) and intestinal alkaline phosphatase (IAP) by polymerase chain reaction (PCR). The translation of LGR5 was detected by Western blotting. The expression of proliferating cell nuclear antigen (Ki67) was analyzed by immunohistochemistry. IAP level was detected by modified calcium cobalt staining and colorimetry. Immunofluorescence staining was used to detect the expression of Paneth cell marker molecule lysozyme 1 (LYZ1) and goblet cell marker molecule mucin 2 (MUC2). ② Cell experiment: IEC6 cells in logarithmic growth stage were divided into blank control group and lipopolysaccharide (LPS) group (LPS 5 μg/mL). Twenty-four hours after treatment, PCR and Western blotting were used to analyze the transcription and translation of LGR5. The proliferation of IEC6 cells were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining. The transcription and translation of IAP were detected by PCR and colorimetric method respectively.Results:① Animal experiment: the immunohistochemical results showed that the positive rate of Ki67 staining in the jejunal tissue of CLP group was lower than that of Sham group [(41.7±2.5)% vs. (48.7±1.4)%, P = 0.01]. PCR and Western blotting results showed that there were no statistical differences in the mRNA and protein expressions of LGR5 in the jejunal tissue between the CLP group and Sham group (Lgr5 mRNA: 0.7±0.1 vs. 1.0±0.2, P = 0.11; LGR5/β-actin: 0.83±0.17 vs. 0.68±0.19, P = 0.24). The mRNA (0.4±0.1 vs. 1.0±0.1, P < 0.01) and protein (U/g: 47.3±6.0 vs. 73.1±15.3, P < 0.01) levels of IAP in the jejunal tissue were lower in CLP group. Immunofluorescence saining analysis showed that the expressions of LYZ1 and MUC2 in the CLP group were lower than those in the Sham group. ②Cell experiment: PCR and Western blotting results showed that there was no significant difference in the expression of LGR5 between the LPS group and the blank control group (Lgr5 mRNA: 0.9±0.1 vs. 1.0±0.2, P = 0.33; LGR5/β-actin: 0.71±0.18 vs. 0.69±0.04, P = 0.81). The proliferation rate of IEC6 cells in the LPS group was lower than that in the blank control group, but there was no significant difference [positivity rate of EdU: (40.5±3.8)% vs. (46.5±3.6)%, P = 0.11]. The mRNA (0.5±0.1 vs. 1.0±0.2, P < 0.01) and protein (U/g: 15.0±4.0 vs. 41.2±10.4, P < 0.01) of IAP in the LPS group were lower than those in the blank control group. Conclusion:CLP-induced sepsis inhibits the proliferation and differentiation of intestinal epithelial cells, impairing the self-renewal ability of intestinal epithelium.
4.Simultaneous determination of lacosamide and perampanel concentration in human plasma by LC-MS/MS
Hengyi YU ; Yanjiao XU ; Dong XIANG ; Lu LIU ; Xiping LI ; Dong LIU ; Xuepeng GONG
China Pharmacy 2023;34(16):1979-1983
OBJECTIVE To establish a method for simultaneous determination of two third-generation anti-epileptic medicines such as lacosamide and perampanel in human plasma and apply this method in clinical practice. METHODS Using clozapine as internal standard, the concentrations of lacosamide and perampanel of plasma samples in 10 epileptic patients were determined by LC-MS/MS after protein precipitation with acetonitrile and dilution with acetonitrile-water (20∶80,V/V), and the plasma minimum concentrations were obtained by dilution of multiple. The determination was performed on Welch Ultimate XB-C18 column, with mobile phase A consisted of 10 mmol/L ammonium formate and mobile phase B consisted of methanol-acetonitrile-isopropanol (0.2% formic acid) mixed solution (7∶1.5∶1.5, V/V/V) for gradient elution at the flow rate of 0.4 mL/min. The column temperature was set at 40 ℃ , and the sample size was 5 μL. The electrospray ion source and multi-reaction monitoring mode were used for positive iron scanning. The ion pair used for quantitative analysis of lacosamide, perampanel and internal standard were m/z 251.2→ 144.1, m/z 350.2→219.2 and m/z 327.2→270.0, respectively. RESULTS The linear ranges of lacosamide and perampanel were 0.001 25-0.125 μg/mL(r>0.99), 0.037 5-3.75 ng/mL (r>0.99); the limits of quantification were 0.001 25 μg/mL and 0.037 5 ng/mL, respectively. The precision and accuracy within and between batches, extraction recovery rate, matrix effect, and stability all met relevant requirements. The minimum concentrations of lacosamide in No. 1-5 patients were 5.3-12.2 μg/mL, and the minimum concentrations of perampanel in No.6-10 patients were 208-510 ng/mL, respectively. CONCLUSIONS The established method is simple, rapid and suitable for the therapeutic drug monitoring of lacosamide and perampanel.
5.Rapid Health Technology Assessment of the Efficacy,Safety and Economics of Empagliflozin in the Treatment of Type 2 Diabetes Mellitus
Lu WANG ; Anhua WEI ; Lu ZENG ; Ling GUI ; Xuepeng GONG ; Dong LIU
Herald of Medicine 2023;42(12):1841-1849
Objective To rapidly evaluate the efficacy,safety and economics of empagliflozin in the treatment of type 2 diabetes mellitus(T2DM)and to provide evidence-based medical evidence for clinical decision.Methods PubMed,Embase,the Cochrane Library,CNKI,Wangfang,VIP database and major health technology assessment(HTA)websites were searched from the construction of the databases to Nov 30th,2022.Two researchers independently screened,extracted the data,evaluated the quality and analyzed the results according to inclusion and exclusion criteria.Results A total of 23 literatures were included,including 3 HTA reports,10 systematic review/Meta-analyses and 10 pharmacoeconomic studies.The results of efficacy showed that empagliflozin reduced HbA1c,blood pressure,body weight and all-cause mortality compared with the control group.Safety studies showed that empagliflozin was generally well tolerated,and significantly reduced MACEs and the relative risk of the renal primary outcomes,but increased the risk of genital infections and electrolyte abnormality compared with placebo and other oral antidiabetic drugs.The economic evaluation results showed that empagliflozin was more cost-effective in high risk patients with comorbid cardiovascular or kidney disease.Conclusion Empagliflozin is effective and safe in the treatment of T2DM,but the pharmacoeconomic studies focusing on chinese populations are urgently needed.
6.Analysis of clinical diagnosis and treatment of complex lymphatic anomalies
Tong QIU ; Jiangyuan ZHOU ; Xue GONG ; Kaiying YANG ; Zixin ZHANG ; Yuru LAN ; Xuepeng ZHANG ; Zilong ZHOU ; Geng ZHANG ; Jianlei FU ; Siyuan CHEN ; Yi JI
Chinese Journal of Plastic Surgery 2023;39(11):1167-1174
Objective:To analyze the clinical features, differential diagnosis, treatment and prognosis of complex lymphatic malformations.Methods:The clinical data of patients with complex lymphatic malformation were retrospectively analyzed from April 2010 to April 2022 in the Multidisciplinary Outpatient Department of the Vascular Disease Team of West China Hospital, Sichuan University. All patients were diagnosed with complex lymphatic malformation after consultation with multidisciplinary experts in pediatric surgery, radiology, plastic surgery, pathology, rehabilitation and other departments. The clinical manifestations, blood routine, coagulation function, magnetic resonance imaging and treatment methods of the patients were analyzed. According to the follow-up and disease results, the patients were divided into improvement, stability, progress and death.Results:A total of 18 patients with complex lymphatic malformations were included in the study, including 6 males and 12 females. The age of first diagnosis ranged from 1 month to 29 years old, and the median age was 2.5 years old. Patients were followed up and treated for 0.4 to 12.0 years, with an average follow-up of 3.5 years. Ten patients had pleural and pericardial effusion; 15 patients had visceral involvement which showed multifocal changes in imaging examinations; 9 cases were accompanied by bone destruction, which in Gorham-Stout disease patients broke through the cortex while in generalized lymphatic anomalies it did not; 14 patients had various degrees of coagulation abnormalities, of which 8 patients with severe coagulation dysfunction were all diagnosed as kaposiform lymphangiomatosis. Of the 18 patients, one kaposiform lymphangiomatosis patient died; six patients progressed; eight patients were stable; and three patients improved.Conclusion:The clinical characteristics of patients with complex lymphatic malformations are systemic, diverse and complex. The clinical symptoms of patients with diffuse lymphatic malformation accompanied by involvement of bone and multiple internal organs, chest and abdominal effusion, and coagulation dysfunction should be considered as complex lymphatic malformation. However, due to overlapping clinical characteristics of each subtypes, it is difficult to distinguish patients with complex lymphatic malformation, and the curative effect and prognosis are poor. Precision targeted drugs are the future research direction for the treatment of such diseases.
7.Analysis of clinical diagnosis and treatment of complex lymphatic anomalies
Tong QIU ; Jiangyuan ZHOU ; Xue GONG ; Kaiying YANG ; Zixin ZHANG ; Yuru LAN ; Xuepeng ZHANG ; Zilong ZHOU ; Geng ZHANG ; Jianlei FU ; Siyuan CHEN ; Yi JI
Chinese Journal of Plastic Surgery 2023;39(11):1167-1174
Objective:To analyze the clinical features, differential diagnosis, treatment and prognosis of complex lymphatic malformations.Methods:The clinical data of patients with complex lymphatic malformation were retrospectively analyzed from April 2010 to April 2022 in the Multidisciplinary Outpatient Department of the Vascular Disease Team of West China Hospital, Sichuan University. All patients were diagnosed with complex lymphatic malformation after consultation with multidisciplinary experts in pediatric surgery, radiology, plastic surgery, pathology, rehabilitation and other departments. The clinical manifestations, blood routine, coagulation function, magnetic resonance imaging and treatment methods of the patients were analyzed. According to the follow-up and disease results, the patients were divided into improvement, stability, progress and death.Results:A total of 18 patients with complex lymphatic malformations were included in the study, including 6 males and 12 females. The age of first diagnosis ranged from 1 month to 29 years old, and the median age was 2.5 years old. Patients were followed up and treated for 0.4 to 12.0 years, with an average follow-up of 3.5 years. Ten patients had pleural and pericardial effusion; 15 patients had visceral involvement which showed multifocal changes in imaging examinations; 9 cases were accompanied by bone destruction, which in Gorham-Stout disease patients broke through the cortex while in generalized lymphatic anomalies it did not; 14 patients had various degrees of coagulation abnormalities, of which 8 patients with severe coagulation dysfunction were all diagnosed as kaposiform lymphangiomatosis. Of the 18 patients, one kaposiform lymphangiomatosis patient died; six patients progressed; eight patients were stable; and three patients improved.Conclusion:The clinical characteristics of patients with complex lymphatic malformations are systemic, diverse and complex. The clinical symptoms of patients with diffuse lymphatic malformation accompanied by involvement of bone and multiple internal organs, chest and abdominal effusion, and coagulation dysfunction should be considered as complex lymphatic malformation. However, due to overlapping clinical characteristics of each subtypes, it is difficult to distinguish patients with complex lymphatic malformation, and the curative effect and prognosis are poor. Precision targeted drugs are the future research direction for the treatment of such diseases.
8.Analysis of factors associated with infantile hemangioma: a multicenter case-control study
Tong QIU ; Kaiying YANG ; Xue GONG ; Jiangyuan ZHOU ; Xuepeng ZHANG ; Yuru LAN ; Siyuan CHEN ; Yi JI
Chinese Journal of Dermatology 2022;55(9):772-777
Objective:To analyze demographic and clinical characteristics of infantile hemangioma (IH) , and to explore related risk factors for IH.Methods:A multicenter case-control study was conducted. IH patients (case group) and healthy children (control group) were collected from West China Hospital of Sichuan University, West China Second University Hospital of Sichuan University and Yulin Community Central Hospital of Chengdu from October 2018 to December 2020. The data on patients′ demographic characteristics, and risk factors during their mothers′ pre-pregnancy, pregnancy and perinatal period were collected and retrospectively analyzed. Univariate and multivariate analyses were performed using binary logistic regression.Results:A total of 1 479 patients with IH and 1 086 healthy children were included in this study. There were 456 males and 1 023 females in the case group, with the age being 3.74 ± 2.82 months, and there were 359 males and 727 females in the control group, with the age being 3.95 ± 2.77 months. There was no significant difference in the gender ratio, age, ethnic composition, birth weight or birth height between the case group and control group (all P > 0.05) . IH lesions mostly affected the head and face (564 cases, 38.1%) , followed by the trunk (449 cases, 30.6%) and limbs (356 cases, 24.1%) . At the visit, 1 109 (75.0%) patients presented with proliferating IH, 1 059 (71.6%) with superficial IH, and 1 306 (88.3%) with focal IH. The IH lesion area ranged from 0.01 to 168.00 (6.24 ± 12.91) cm 2, and the segmental IH area ranged from 7.50 to 168.00 (32.17 ± 26.94) cm 2. Univariate logistic regression analysis showed some factors influencing the occurrence of IH (all P < 0.05) , including pre-pregnancy factors (delivery history and miscarriage history) , pregnancy factors (fetal distress, cord entanglement, history of threatened abortion, placenta previa, oligohydramnios, gestational hypothyroidism, gestational anemia, history of progesterone supplementation, history of thyroxine drug use, history of uterus myomas) , and perinatal factors (including fetal position, gestational weeks, premature rupture of membranes and preterm premature rupture of membranes) . Multivariate binary logistic regression adjusted analysis showed that fetal breech presentation, preterm birth, cord entanglement and history of thyroxine drug use during pregnancy did not influence the occurrence of IH (all P > 0.05) ; the delivery history was the strongest independent risk factor for IH (adjusted OR = 5.624, 95% CI: 4.275 to 7.398, P < 0.001) , and gestational hypothyroidism and history of uterus myomas were protective factors for IH. Conclusions:In this study, the average age of IH patients at visit was 4 months, skin lesions mostly occurred on the head and face, and most were superficial and focal in the proliferative stage. The occurrence and development of IH may be associated with placental diseases, hypoxia, maternal hormone levels during pregnancy, etc.
9.Construction and practice of standardized workflow and informatization platform for centralized volume-based procurement
Yingying WEI ; Dong LIU ; Xiongzhang YIN ; Hongbin YANG ; Guofang HE ; Fei’e LI ; Shunda CHEN ; Xuepeng GONG
China Pharmacy 2022;33(9):1136-1140
OBJECTIVE To sum marize the pro cedure and informatization construction of centralized volume-based procurement(VBP)in our hospital ,in order to give references for normal development of centralized VBP. METHODS The standardized workflow system was established ,including using flow chart method to establish standardized workflow ,carrying out procedure training and inspection of procedure implementation , and continuously conducting procedure optimization. The information system was developed for the task links that needed a lot of calculation to improve the automation level of information processing. RESULTS & CONCLUSIONS Eight specific work procedures were established in our hospital ,including the work procedures of submitting the demand data of centralized VBP and the implementation of centralized VBP ,and has taken measures such as procedure training ,establishing supervision and inspection system and using auxiliary means to promote the implementation of the procedure ,so as to optimize the procedure and work form. An informatization platform for the clinical task allocation of the agreed purchase quantity of centralized VBP and a supervision platform for the daily use of VBP were also established in our hospital,then the two tasks with a large amount of calculation could be finished. Standardized workflow system and informatization platform construction has improved the operation and supervision efficiency of centralized VBP in our hospital ,ensured the completion of centralized purchase tasks and saved human resources ,which has a certain promotion value.
10.Biological Characteristics of Recombinant Arthrobotrys oligospora Chitinase AO-801
Shasha GONG ; Qingling MENG ; Jun QIAO ; Yunfu HUANG ; Wenqiang ZHONG ; Guowu ZHANG ; Kai ZHANG ; Ningxing LI ; Yunxia SHANG ; Zhiyuan LI ; Xuepeng CAI
The Korean Journal of Parasitology 2022;60(5):345-352
Chitinase AO-801 is a hydrolase secreted by Arthrobotrys oligospora during nematode feeding, while its role remained elusive. This study analyzed the molecular characteristics of recombinant chitinase of Arthrobotrys oligospora (reAO-801). AO-801 belongs to the typical glycoside hydrolase 18 family with conserved chitinase sequence and tertiary structure of (α/β)8 triose-phosphate isomerase (TIM) barrel. The molecular weight of reAO-801 was 42 kDa. reAO-801 effectively degraded colloidal and powdered chitin, egg lysate, and stage I larval lysate of Caenorhabditis elegans. The activity of reAO-801 reached its peak at 40˚C and pH values between 4-7. Enzyme activity was inhibited by Zn2+, Ca2+, and Fe3+, whereas Mg2+ and K+ potentiated its activity. In addition, urea, sodium dodecyl sulfate, and 2-mercaptoethanol significantly inhibited enzyme activity. reAO-801 showed complete nematicidal activity against C. elegans stage I larvae. reAO-801 broke down the C. elegans egg shells, causing them to die or die prematurely by hatching the eggs. It also invoked degradation of Haemonchus contortus eggs, resulting in apparent changes in the morphological structure. This study demonstrated the cytotoxic effect of reAO-801, which laid the foundation for further dissecting the mechanism of nematode infestation by A. oligospora.

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