BACKGROUND Surgical site infections(SSIs)increase mortality,hospital stays,additional medical treatment,and medical costs.Subcutaneous drains prevent SSIs in gynecological and breast surgeries;however,their clinical i...BACKGROUND Surgical site infections(SSIs)increase mortality,hospital stays,additional medical treatment,and medical costs.Subcutaneous drains prevent SSIs in gynecological and breast surgeries;however,their clinical impact in abdominal surgery remains unclear.AIM To investigate whether subcutaneous drains were beneficial in abdominal surgery using a systematic review and meta-analysis.METHODS The database search used PubMed,MEDLINE,and the Cochrane Library.The following inclusion criteria were set for the systematic review:(1)Randomized controlled trial studies comparing SSIs after abdominal surgery with or without subcutaneous drains;and(2)Studies that described clinical outcomes,such as SSIs,seroma formation,the length of hospital stays,and mortality.RESULTS Eight studies were included in this meta-analysis.The rate of total SSIs was significantly lower in the drained group(54/771,7.0%)than in the control group(89/759,11.7%),particularly in gastrointestinal surgery.Furthermore,the rate of superficial SSIs was slightly lower in the drained group(31/517,6.0%)than in the control group(49/521,9.4%).No significant differences were observed in seroma formation between the groups.Hospital stays were shorter in the drained group than in the control group.CONCLUSION Subcutaneous drains after abdominal surgery prevented SSIs and reduced hospital stays but did not significantly affect seroma formation.The timing of drain removal needs to be reconsidered in future studies.展开更多
BACKGROUND The results of intensive statin pretreatment before percutaneous coronary intervention(PCI)is inconsistent between Chinese and Western populations,and there are no corresponding meta-analyses involving hard...BACKGROUND The results of intensive statin pretreatment before percutaneous coronary intervention(PCI)is inconsistent between Chinese and Western populations,and there are no corresponding meta-analyses involving hard clinical endpoints in the available published literature.AIM To evaluate the efficacy and safety of high-dose statin loading before PCI in Chinese patients through a meta-analysis.METHODS Relevant studies were identified by searching the electronic databases of PubMed,Embase and Cochrane’s Library to December 2019.The outcomes included an assessment of major adverse cardiovascular event(MACE),non-fatal myocardial infarction(MI),cardiac death,target vessel revascularization(TVR),myalgia/myasthenia and abnormal alanine aminotransferase(ALT)in all enrolled patients.Random effect model and fixed effect model were applied to combine the data,which were further analyzed byχ2 test and I2 test.The main outcomes were then analyzed through the use of relative risks(RR)and its 95%confidence interval(95%CI).RESULTS Eleven studies involving 3123 individuals were included.Compared with patients receiving placebo or no statin treatment before surgery,intensive statin treatment was associated with a clear reduction of risk of MACE(RR=0.44,95%CI:0.31-0.61,P<0.00001).However,compared with the patients receiving moderateintensity statin before surgery,no advantage to intensive statin treatment was seen(RR=1.04,95%CI:0.82-1.31,P=0.74).In addition,no significant difference was observed between intensive statin therapy and non-intensive statin therapy on the incidence of TVR(RR=0.43,95%CI:0.18-1.02,P=0.06),myalgia/myasthenia(RR=1.35,95%CI:0.30-5.95,P=0.69)and abnormal alanine aminotransferase(RR=1.47,95%CI:0.54-4.02,P=0.45)except non-fatal MI(RR=0.54,95%CI:0.33-0.88,P=0.01).CONCLUSION Compared with placebo or no statin pretreatment,intensive statin before PCI displayed reduced incidence of MACE.However,there was no significant benefit between high and moderate-intensity statin.In addition,no significant difference was observed between intensive statin therapy and non-intensive statin therapy on the incidence of TVR,myalgia/myasthenia and abnormal alanine aminotransferase except non-fatal MI.展开更多
BACKGROUND Liver resection has become safer as it has become less invasive.However,the minimum residual liver volume(RLV)required to maintain homeostasis is unclear.Furthermore,the formulae used to calculate standard ...BACKGROUND Liver resection has become safer as it has become less invasive.However,the minimum residual liver volume(RLV)required to maintain homeostasis is unclear.Furthermore,the formulae used to calculate standard liver volume(SLV)are complex.AIM To review previously reported SLV formulae and the methods used to evaluate the minimum RLV,and explore the association between liver volume and mortality.METHODS A systematic review of Medline,PubMed,and grey literature was performed.References in the retrieved articles were cross-checked manually to obtain further studies.The last search was conducted on January 20,2019.We developed an SLV formula using data for 86 consecutive patients who underwent hepatectomy at our institution between July 2009 and August 2011.RESULTS Linear regression analysis revealed the following formula:SLV(mL)=822.7×body surface area(BSA)?183.2(R2=0.419 and R=0.644,P<0.001).We retrieved 25 studies relating to SLV formulae and 12 studies about the RLV required for safe liver resection.Although the previously reported formulae included various coefficient and constant values,a simplified version of the SLV,the common SLV(cSLV),can be calculated as follows:cSLV(mL)=710 or 770×BSA.The minimum RLV for normal and damaged livers ranged from 20%-40%and 30%-50%,respectively.The Sapporo score indicated that the minimum RLV ranges from 35%-95%depending on liver function.CONCLUSION We reviewed SLV formulae and the minimum RLV required for safe liver resection.The Sapporo score is the only liver function-based method for determining the minimum RLV.展开更多
Background: Several studies have shown that twice-daily injections of premixed insulin analogs (MIX) could achieve comparable HbA1c levels to basal-bolus (BB) therapy. However, HbA1c does not necessarily reflect short...Background: Several studies have shown that twice-daily injections of premixed insulin analogs (MIX) could achieve comparable HbA1c levels to basal-bolus (BB) therapy. However, HbA1c does not necessarily reflect short-term glycemic fluctuations that may contribute to the onset or progression of diabetic complications. Therefore, in this study, we compared MIX and BB therapies in terms of their effects on glycemic variability. Methods: We performed a crosssectional observational study of patients attending our outpatient clinics to compare the effects of two insulin regimens on glycemic variability. We recruited patients treated with MIX or BB with HbA1c < 8.4%. A total of 27 patients (11 treated with BB and 16 treated with MIX) were enrolled and wore a continuous glucose monitor (CGM) for 72 h, while continuing their usual lifestyle and insulin doses. Results: No significant differences in CGM-determined glycemic markers were observed between the two groups. However, the post-lunch duration of glucose levels > 180 mg/dL (t > 180) was significantly shorter with BB therapy (88 ± 76 min) than with MIX therapy (145 ± 54 min;p < 0.05). After classification according to HbA1c levels, markers of glycemic variability were better in patients treated with BB than in those treated with MIX in better control group. Conclusion: These results suggest that BB therapy achieves better glucose profiles than MIX therapy in patients with type 2 diabetes, particularly after lunch.展开更多
The Chinese herb Ephedra(also known as Mahuang)has been extensively utilized for the prevention and treatment of coronavirus-induced diseases,including coronavirus disease 2019(COVID-19).However,the specific anti-SARS...The Chinese herb Ephedra(also known as Mahuang)has been extensively utilized for the prevention and treatment of coronavirus-induced diseases,including coronavirus disease 2019(COVID-19).However,the specific anti-SARS-CoV-2 compounds and mechanisms have not been fully elucidated.The main protease(M~(pro))of SARS-CoV-2 is a highly conserved enzyme responsible for proteolytic processing during the viral life cycle,making it a critical target for the development of antiviral therapies.This study aimed to identify naturally occurring covalent inhibitors of SARS-CoV-2 M~(pro)from Ephedra and to investigate their covalent binding sites.The results demonstrated that the non-alkaloid fraction of Ephedra(ENA)exhibited a potent inhibitory effect against the SARS-CoV-2 M~(pro)effect,whereas the alkaloid fraction did not.Subsequently,the chemical constituents in ENA were identified,and the major constituents'anti-SARS-CoV-2 M~(pro)effects were evaluated.Among the tested constituents,herbacetin(HE)and gallic acid(GA)were found to inhibit SARS-CoV-2 M~(pro)in a time-and dose-dependent manner.Their combination displayed a significant synergistic effect on this key enzyme.Additionally,various techniques,including inhibition kinetic assays,chemoproteomic methods,and molecular dynamics simulations,were employed to further elucidate the synergistic anti-M~(pro)mechanisms of the combination of HE and GA.Overall,this study deciphers the naturally occurring covalent inhibitors of SARS-CoV-2 M~(pro)from Ephedra and characterizes their synergistic anti-M~(pro)synergistic effect,providing robust evidence to support the anti-coronavirus efficacy of Ephedra.展开更多
In order to comply with the requirements for a drug listed in China, the study was developed to compare the pharmacokinetics and relative bioavailability of two different enteric formulations of omeprazole (OPZ) in he...In order to comply with the requirements for a drug listed in China, the study was developed to compare the pharmacokinetics and relative bioavailability of two different enteric formulations of omeprazole (OPZ) in healthy Chinese subjects. A total of 32 volunteers participated in the study. Plasma concentrations were analyzed by non- stereospecific liquid chromatography/tandem mass spectrometric (LC-MS/MS) method. After administration of a single 40-mg dose of the two OPZ formulations, the comparative bioavailability was assessed by calculating individual AUC0-t (the area under the concentration-time curve from time zero to the last measurable concentration), AUC0-∞ (the area under the concentration-time curve extrapolated to infinity), Cmax (the maximum observed concentration), and Tpeak (the time to Cmax) values of OPZ, 5-hydroxyomeprazole (OH-OPZ), and omeprazole sulfone (OPZ-SFN), respectively. The 90% confidence intervals (CIs) of AUC0-t, AUC0-∞, and Cmax were 85.4%-99.0%/88.8%-98.6%/87.6%-99.4%, 85.5%-99.2%/89.0%-98.6%/88.5%-101.3%, and 72.3%-87.6%/79.6%-91.1%/88.4%-99.1% for OPZ/OH-OPZ/ OPZ-SFN, respectively, and Tpeak values did not differ significantly. In this study, the test formulation of OPZ in fasting healthy Chinese male volunteers met the Chinese bioequivalance standard to the reference formulation based on AUC, Cmax, and Tpeak.展开更多
In the present study, we developed a simple, sensitive, precise, and accurate liquid chromatography-tandem mass spectrometric(LC-MS/MS) method and validated such approach for simultaneous determination of flupirtine a...In the present study, we developed a simple, sensitive, precise, and accurate liquid chromatography-tandem mass spectrometric(LC-MS/MS) method and validated such approach for simultaneous determination of flupirtine and its active metabolite D-13223 in human plasma. The flupirtine, D-13223, and stable isotope internal standard(IS) were extracted from plasma samples by liquid-liquid extraction and chromatographed on a C18 column with a mobile phase consisting of acetonitrile–water–ammonia(55:45:0.1, v/v/v) at a flow rate of 0.25 m L/min. Detection was performed on a triple quadrupole tandem mass spectrometer with an electrospray ionization source(ESI) by multiple reaction monitoring(MRM) in positive ion mode. The linear calibration curves were obtained within the concentration range of 10.00–2000.00 ng/m L for flupirtine and 2.00–400.00 ng/m L for D-13223. The intra-and inter-run RSD, calculated from quality control(QC) samples, was less than 9.26% for flupirtine and D-13223. The accuracy was –5.80%–3.31% for flupirtine and D-13223. The extraction recoveries of flupirtine, D-13223, and their IS were all between 88.3%–97.2%. The method was successfully applied to investigate the pharmacokinetic profiles of flupirtine and its active metabolite D-13223 in human plasma following peroral administration of 100 mg flupirtine maleate capsules in healthy male Chinese volunteers.展开更多
Hepatic stellate cells(HSCs)represent a significant component of hepatocellular carcinoma(HCC)microenvironments which play a critical role in tumor progression and drug resistance.Tumor-ona-chip technology has provide...Hepatic stellate cells(HSCs)represent a significant component of hepatocellular carcinoma(HCC)microenvironments which play a critical role in tumor progression and drug resistance.Tumor-ona-chip technology has provided a powerful in vitro platform to investigate the crosstalk between activated HSCs and HCC cells by mimicking physiological architecture with precise spatiotemporal control.Here we developed a tri-cell culture microfluidic chip to evaluate the impact of HSCs on HCC progression.Onchip analysis revealed activated HSCs contributed to endothelial invasion,HCC drug resistance and natural killer(NK)cell exhaustion.Cytokine array and RNA sequencing analysis were combined to indicate the iron-binding protein LIPOCALIN-2(LCN-2)as a key factor in remodeling tumor microenvironments in the HCC-on-a-chip.LCN-2 targeted therapy demonstrated robust anti-tumor effects both in vitro 3D biomimetic chip and in vivo mouse model,including angiogenesis inhibition,sorafenib sensitivity promotion and NK-cell cytotoxicity enhancement.Taken together,the microfluidic platform exhibited obvious advantages in mimicking functional characteristics of tumor microenvironments and developing targeted therapies.展开更多
Quantum process may conduce to brain function.Particularly,it was proposed that the Posner molecules,Cag(PO4)6,can serve as neural qubits,which can maintain quantum entanglement between phosphorus nuclei for quite a l...Quantum process may conduce to brain function.Particularly,it was proposed that the Posner molecules,Cag(PO4)6,can serve as neural qubits,which can maintain quantum entanglement between phosphorus nuclei for quite a long time.We study the process from entangled Posner molecules to the synchronized activities of brain.A diffusion model of Posner molecules with appropriate boundary conditions and the mean first arriving time of Posner molecules from one area of brain to another are obtained.We establish linkages between the quantum entangled connectivity of brain and the remaining time of entangled Posner molecules before decoherence.Based on these results,we find direct correlations between entangled Posner molecules and the functional connectivity of human brain.Furthermore,we discover that the quantum entangled connectivity depends on age.展开更多
Non-suicidal self-injury (NS SI) refers to any intentional,self-inflicted behavior that causes direct damage to body tissues (Kerr et al.,2010),and has emerged as a challenging public health issue worldwide,especially...Non-suicidal self-injury (NS SI) refers to any intentional,self-inflicted behavior that causes direct damage to body tissues (Kerr et al.,2010),and has emerged as a challenging public health issue worldwide,especially among adolescents.The most common presentations of NSSI include skin-cutting,severe scratching,and burning (Whitlock et al,2006).展开更多
基金Supported by Grants-in-Aid from JSPS KAKENHI,No.JP 21K10715 and No.JP 20K10404Northern Advancement Center for Science&Technology,No.T-2-2+9 种基金the Yasuda Medical Foundation,No.31010316the Okawa Foundation for Information and Telecommunications,No.41111042Taiju Life Social Welfare Foundation,No.50811490Japan Keirin Autorace Foundation,No.2023M-378Project Mirai Cancer Research Grants,No.31010269Takahashi Industrial and Economic Research Foundation,No.50411278Sapporo Doto Hospital,No.50311211Noguchi Hospital,No.40310551Doki-kai Tomakomai Hospital,No.40710739Tsuchida Hospital,No.50811478.
文摘BACKGROUND Surgical site infections(SSIs)increase mortality,hospital stays,additional medical treatment,and medical costs.Subcutaneous drains prevent SSIs in gynecological and breast surgeries;however,their clinical impact in abdominal surgery remains unclear.AIM To investigate whether subcutaneous drains were beneficial in abdominal surgery using a systematic review and meta-analysis.METHODS The database search used PubMed,MEDLINE,and the Cochrane Library.The following inclusion criteria were set for the systematic review:(1)Randomized controlled trial studies comparing SSIs after abdominal surgery with or without subcutaneous drains;and(2)Studies that described clinical outcomes,such as SSIs,seroma formation,the length of hospital stays,and mortality.RESULTS Eight studies were included in this meta-analysis.The rate of total SSIs was significantly lower in the drained group(54/771,7.0%)than in the control group(89/759,11.7%),particularly in gastrointestinal surgery.Furthermore,the rate of superficial SSIs was slightly lower in the drained group(31/517,6.0%)than in the control group(49/521,9.4%).No significant differences were observed in seroma formation between the groups.Hospital stays were shorter in the drained group than in the control group.CONCLUSION Subcutaneous drains after abdominal surgery prevented SSIs and reduced hospital stays but did not significantly affect seroma formation.The timing of drain removal needs to be reconsidered in future studies.
基金Supported by the Scientific Research Project of Nanjing Clinical Medical Centre,No.1 Ning Health Science Education[2020].
文摘BACKGROUND The results of intensive statin pretreatment before percutaneous coronary intervention(PCI)is inconsistent between Chinese and Western populations,and there are no corresponding meta-analyses involving hard clinical endpoints in the available published literature.AIM To evaluate the efficacy and safety of high-dose statin loading before PCI in Chinese patients through a meta-analysis.METHODS Relevant studies were identified by searching the electronic databases of PubMed,Embase and Cochrane’s Library to December 2019.The outcomes included an assessment of major adverse cardiovascular event(MACE),non-fatal myocardial infarction(MI),cardiac death,target vessel revascularization(TVR),myalgia/myasthenia and abnormal alanine aminotransferase(ALT)in all enrolled patients.Random effect model and fixed effect model were applied to combine the data,which were further analyzed byχ2 test and I2 test.The main outcomes were then analyzed through the use of relative risks(RR)and its 95%confidence interval(95%CI).RESULTS Eleven studies involving 3123 individuals were included.Compared with patients receiving placebo or no statin treatment before surgery,intensive statin treatment was associated with a clear reduction of risk of MACE(RR=0.44,95%CI:0.31-0.61,P<0.00001).However,compared with the patients receiving moderateintensity statin before surgery,no advantage to intensive statin treatment was seen(RR=1.04,95%CI:0.82-1.31,P=0.74).In addition,no significant difference was observed between intensive statin therapy and non-intensive statin therapy on the incidence of TVR(RR=0.43,95%CI:0.18-1.02,P=0.06),myalgia/myasthenia(RR=1.35,95%CI:0.30-5.95,P=0.69)and abnormal alanine aminotransferase(RR=1.47,95%CI:0.54-4.02,P=0.45)except non-fatal MI(RR=0.54,95%CI:0.33-0.88,P=0.01).CONCLUSION Compared with placebo or no statin pretreatment,intensive statin before PCI displayed reduced incidence of MACE.However,there was no significant benefit between high and moderate-intensity statin.In addition,no significant difference was observed between intensive statin therapy and non-intensive statin therapy on the incidence of TVR,myalgia/myasthenia and abnormal alanine aminotransferase except non-fatal MI.
基金Supported by a Grant-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science,and Technology,Japan,No.23591993 to TM,and No.24791437 to MM,No17K10672to T Mizuguchi+8 种基金supported by Astellas Pharma,Inc.,No.RS2018A000763,Tokyo,JapanDaiichi Sankyo Company,No.1800461,Tokyo,JapanShionogi&Co.,No.RS2018A000439931,Osaka,JapanMerk Serono,No.MSJS20180613001,Tokyo,JapanSapporo Doto Hospital,No.30037656,Sapporo,JapanNoguchi Hospital,No.30047663,Otaru,JapanDoki-kai Tomakomai Hospital,No.30047674,Tomakomai,JapanTsuchida Hospital,No.30057704,Sapporo,JapanIkuta Hospital,No.30057704,Shiraoi,Japan was given to TM
文摘BACKGROUND Liver resection has become safer as it has become less invasive.However,the minimum residual liver volume(RLV)required to maintain homeostasis is unclear.Furthermore,the formulae used to calculate standard liver volume(SLV)are complex.AIM To review previously reported SLV formulae and the methods used to evaluate the minimum RLV,and explore the association between liver volume and mortality.METHODS A systematic review of Medline,PubMed,and grey literature was performed.References in the retrieved articles were cross-checked manually to obtain further studies.The last search was conducted on January 20,2019.We developed an SLV formula using data for 86 consecutive patients who underwent hepatectomy at our institution between July 2009 and August 2011.RESULTS Linear regression analysis revealed the following formula:SLV(mL)=822.7×body surface area(BSA)?183.2(R2=0.419 and R=0.644,P<0.001).We retrieved 25 studies relating to SLV formulae and 12 studies about the RLV required for safe liver resection.Although the previously reported formulae included various coefficient and constant values,a simplified version of the SLV,the common SLV(cSLV),can be calculated as follows:cSLV(mL)=710 or 770×BSA.The minimum RLV for normal and damaged livers ranged from 20%-40%and 30%-50%,respectively.The Sapporo score indicated that the minimum RLV ranges from 35%-95%depending on liver function.CONCLUSION We reviewed SLV formulae and the minimum RLV required for safe liver resection.The Sapporo score is the only liver function-based method for determining the minimum RLV.
文摘Background: Several studies have shown that twice-daily injections of premixed insulin analogs (MIX) could achieve comparable HbA1c levels to basal-bolus (BB) therapy. However, HbA1c does not necessarily reflect short-term glycemic fluctuations that may contribute to the onset or progression of diabetic complications. Therefore, in this study, we compared MIX and BB therapies in terms of their effects on glycemic variability. Methods: We performed a crosssectional observational study of patients attending our outpatient clinics to compare the effects of two insulin regimens on glycemic variability. We recruited patients treated with MIX or BB with HbA1c < 8.4%. A total of 27 patients (11 treated with BB and 16 treated with MIX) were enrolled and wore a continuous glucose monitor (CGM) for 72 h, while continuing their usual lifestyle and insulin doses. Results: No significant differences in CGM-determined glycemic markers were observed between the two groups. However, the post-lunch duration of glucose levels > 180 mg/dL (t > 180) was significantly shorter with BB therapy (88 ± 76 min) than with MIX therapy (145 ± 54 min;p < 0.05). After classification according to HbA1c levels, markers of glycemic variability were better in patients treated with BB than in those treated with MIX in better control group. Conclusion: These results suggest that BB therapy achieves better glucose profiles than MIX therapy in patients with type 2 diabetes, particularly after lunch.
基金supported by the National Key Research and Development Program of China(No.2022YFC-3502000)the Basic Public Welfare Research Program of Zhejiang Province(No.LGF22H280012)+4 种基金Zhejiang Provincial TCM Science and Technology Plan Project(Nos.2023ZR064,GZY-ZJ-KJ-24004,2024ZL007 and 2022ZB017)the Medical Science and Technology Project of Zhejiang Province(Nos.2022495401,2021KY040 and2022KY069)Zhejiang Provincial Key Projects in Chinese Medicine(Nos.2020ZZ003 and 2021ZZ001)Shanghai Science and Technology Innovation Action Plans(Nos.21S21900600)Zhejiang Province"Ten Thousand People Plan"Science and Technology Innovation Leading Talents Project(No.2020R52029)。
文摘The Chinese herb Ephedra(also known as Mahuang)has been extensively utilized for the prevention and treatment of coronavirus-induced diseases,including coronavirus disease 2019(COVID-19).However,the specific anti-SARS-CoV-2 compounds and mechanisms have not been fully elucidated.The main protease(M~(pro))of SARS-CoV-2 is a highly conserved enzyme responsible for proteolytic processing during the viral life cycle,making it a critical target for the development of antiviral therapies.This study aimed to identify naturally occurring covalent inhibitors of SARS-CoV-2 M~(pro)from Ephedra and to investigate their covalent binding sites.The results demonstrated that the non-alkaloid fraction of Ephedra(ENA)exhibited a potent inhibitory effect against the SARS-CoV-2 M~(pro)effect,whereas the alkaloid fraction did not.Subsequently,the chemical constituents in ENA were identified,and the major constituents'anti-SARS-CoV-2 M~(pro)effects were evaluated.Among the tested constituents,herbacetin(HE)and gallic acid(GA)were found to inhibit SARS-CoV-2 M~(pro)in a time-and dose-dependent manner.Their combination displayed a significant synergistic effect on this key enzyme.Additionally,various techniques,including inhibition kinetic assays,chemoproteomic methods,and molecular dynamics simulations,were employed to further elucidate the synergistic anti-M~(pro)mechanisms of the combination of HE and GA.Overall,this study deciphers the naturally occurring covalent inhibitors of SARS-CoV-2 M~(pro)from Ephedra and characterizes their synergistic anti-M~(pro)synergistic effect,providing robust evidence to support the anti-coronavirus efficacy of Ephedra.
基金Project supported by the 12th Five-Year Significant New Drugs Creation Plan of the Ministry of Science and Technology of China(No. 2011ZX09302-003-03)the Zhejiang Provincial Medicine and Health Research Fund(No.2008A064)the Jiangsu Hengrui Medicine Co.,Ltd.,China
文摘In order to comply with the requirements for a drug listed in China, the study was developed to compare the pharmacokinetics and relative bioavailability of two different enteric formulations of omeprazole (OPZ) in healthy Chinese subjects. A total of 32 volunteers participated in the study. Plasma concentrations were analyzed by non- stereospecific liquid chromatography/tandem mass spectrometric (LC-MS/MS) method. After administration of a single 40-mg dose of the two OPZ formulations, the comparative bioavailability was assessed by calculating individual AUC0-t (the area under the concentration-time curve from time zero to the last measurable concentration), AUC0-∞ (the area under the concentration-time curve extrapolated to infinity), Cmax (the maximum observed concentration), and Tpeak (the time to Cmax) values of OPZ, 5-hydroxyomeprazole (OH-OPZ), and omeprazole sulfone (OPZ-SFN), respectively. The 90% confidence intervals (CIs) of AUC0-t, AUC0-∞, and Cmax were 85.4%-99.0%/88.8%-98.6%/87.6%-99.4%, 85.5%-99.2%/89.0%-98.6%/88.5%-101.3%, and 72.3%-87.6%/79.6%-91.1%/88.4%-99.1% for OPZ/OH-OPZ/ OPZ-SFN, respectively, and Tpeak values did not differ significantly. In this study, the test formulation of OPZ in fasting healthy Chinese male volunteers met the Chinese bioequivalance standard to the reference formulation based on AUC, Cmax, and Tpeak.
文摘In the present study, we developed a simple, sensitive, precise, and accurate liquid chromatography-tandem mass spectrometric(LC-MS/MS) method and validated such approach for simultaneous determination of flupirtine and its active metabolite D-13223 in human plasma. The flupirtine, D-13223, and stable isotope internal standard(IS) were extracted from plasma samples by liquid-liquid extraction and chromatographed on a C18 column with a mobile phase consisting of acetonitrile–water–ammonia(55:45:0.1, v/v/v) at a flow rate of 0.25 m L/min. Detection was performed on a triple quadrupole tandem mass spectrometer with an electrospray ionization source(ESI) by multiple reaction monitoring(MRM) in positive ion mode. The linear calibration curves were obtained within the concentration range of 10.00–2000.00 ng/m L for flupirtine and 2.00–400.00 ng/m L for D-13223. The intra-and inter-run RSD, calculated from quality control(QC) samples, was less than 9.26% for flupirtine and D-13223. The accuracy was –5.80%–3.31% for flupirtine and D-13223. The extraction recoveries of flupirtine, D-13223, and their IS were all between 88.3%–97.2%. The method was successfully applied to investigate the pharmacokinetic profiles of flupirtine and its active metabolite D-13223 in human plasma following peroral administration of 100 mg flupirtine maleate capsules in healthy male Chinese volunteers.
基金funded by National Natural Science Foundation of China (Nos.31901010 and 81803916,China)Natural Science Foundation of Jiangsu Province (grant No.BK20180128,China)+3 种基金The Priority Academic Program Development of Jiangsu Higher Education Institutions (Integration of Chinese and Western Medicine,China)Jiangsu Specially Appointed ProfessorshipJiangsu Key Discipline Construction Fund of the 14th Five-Year Plan (Biology,China)The Graduate Research&Practice Innovation Program of Jiangsu Province (KYCX21_1743,KYCX22_1992,China)。
文摘Hepatic stellate cells(HSCs)represent a significant component of hepatocellular carcinoma(HCC)microenvironments which play a critical role in tumor progression and drug resistance.Tumor-ona-chip technology has provided a powerful in vitro platform to investigate the crosstalk between activated HSCs and HCC cells by mimicking physiological architecture with precise spatiotemporal control.Here we developed a tri-cell culture microfluidic chip to evaluate the impact of HSCs on HCC progression.Onchip analysis revealed activated HSCs contributed to endothelial invasion,HCC drug resistance and natural killer(NK)cell exhaustion.Cytokine array and RNA sequencing analysis were combined to indicate the iron-binding protein LIPOCALIN-2(LCN-2)as a key factor in remodeling tumor microenvironments in the HCC-on-a-chip.LCN-2 targeted therapy demonstrated robust anti-tumor effects both in vitro 3D biomimetic chip and in vivo mouse model,including angiogenesis inhibition,sorafenib sensitivity promotion and NK-cell cytotoxicity enhancement.Taken together,the microfluidic platform exhibited obvious advantages in mimicking functional characteristics of tumor microenvironments and developing targeted therapies.
基金supported by the National Natural Science Foundation of China(11671354)supported by the National Natural Science Foundation of China(81801644).
文摘Quantum process may conduce to brain function.Particularly,it was proposed that the Posner molecules,Cag(PO4)6,can serve as neural qubits,which can maintain quantum entanglement between phosphorus nuclei for quite a long time.We study the process from entangled Posner molecules to the synchronized activities of brain.A diffusion model of Posner molecules with appropriate boundary conditions and the mean first arriving time of Posner molecules from one area of brain to another are obtained.We establish linkages between the quantum entangled connectivity of brain and the remaining time of entangled Posner molecules before decoherence.Based on these results,we find direct correlations between entangled Posner molecules and the functional connectivity of human brain.Furthermore,we discover that the quantum entangled connectivity depends on age.
基金supported by the National Key Basic Research Program of China(No.2016YFC1307100)the Program of Health and Family Planning Commission in Zhejiang Province(No.2020KY548),China。
文摘Non-suicidal self-injury (NS SI) refers to any intentional,self-inflicted behavior that causes direct damage to body tissues (Kerr et al.,2010),and has emerged as a challenging public health issue worldwide,especially among adolescents.The most common presentations of NSSI include skin-cutting,severe scratching,and burning (Whitlock et al,2006).