1.In vivo pharmacological efficacy of intravenously administered cepharanthine hydrochloride in rats based on its exposures
Zengxu YANG ; Bohong ZHENG ; Mengran WANG ; Fengxu CHENG ; Wenpeng ZHANG ; Chunyan LIU ; Junhai XIAO ; Xiaomei ZHUANG
Chinese Journal of Pharmacology and Toxicology 2025;39(1):46-57
OBJECTIVE To establish a liquid chromatography massspectrometry(LC-MS/MS)method for quantitatively determining the concentration of cepharanthine in rat plasma and tissue samples after intravenous injection of cepharanthine hydrochloride.METHODS ①The LC-MS/MS method was adopted.A Phenomenex C18(3.0 mm×50 mm,2.6 μm)column was employed with a mobile phase consisting of 0.05%formic acid-2 mmol·L-1 ammonium acetate-water solution and 0.1%formic acid-acetonitrile solution under gradient elution at a flow rate of 0.6 mL·min-1.The determination was performed using positive ion multiple reaction monitoring mode assays:cepharanthine(m/z:607.3→365.1)and buspirone(IS)(m/z:386.4→122.2).② Blood samples were collected from 6 SD rats at different time points following a single iv administration of cepharanthine to determine the concentration of the drug.The main pharmacokinetic parameters were calculated using a non-compartmental model.③72 SD rats were subjected to tissue distribution experiments after a single and multiple iv administra-tion of cepharanthine,and tissue samples were collected at six different time points(n=6)for the quanti-fication of drug concentrations.④ The whole blood plasma distribution ratio(Rb/p)of cepharanthine hydrochloride(7.5 mg·kg-1)in 3 SD rats was determined 2 h after iv administration.⑤The protein binding of cepharanthine to rat plasma and lung tissue homogenates was determined by equilibrium dialysis before the concentration of the free drug within the lungs was calculated.RESULTS ① An LC-MS/MS method for quantitatively determining cepharanthine in rat plasma and tissue homogenates was devel-oped,which demonstrated an excellent linear relationship(r2>0.999)within the concentration range of 2 to 1000 μg·L-1,with a lower limit of quantification at 2 μg·L-1.The obtained results met all the require-ments for accurate quantitative detection.②The main pharmacokinetic parameters of cepharanthine in rats following a single iv administration were as follows:C0=(686.91±238.43)μg·L-1,t1/2=(29.70±6.29)h,Vz=(62.70±7.93)L·kg-1,Vss=(62.55±11.28)L·kg-1,CL=(1.50±0.23)L·h-1·kg-1 and AUC(0-t)=(4.52±0.61)h·mg·L-1.③ Concentrations in tissues exceeded those in plasma after both a single and multiple iv administration,with the highest levels in the lung.The values of AUC(0-t)in lungs were(2 547.35±156.56)and(4 481.35±479.21)h·mg·L-1 after a single and multiple iv administration,respectively.④ The content of cepharanthine in blood cells was higher than that in plasma,and Rb/p was 3.5±0.8.⑤ After correction by the protein-binding rate,the minimum concentration of free drugs in the lungs(95.04 μg·L-1)exceeded the reported antiviral activity threshold against coronaviruses(EC50=60.67 μg·L-1).CONCLUSION An LC-MS/MS method has been established to rapidly and sensitively determine the concentration of cepharanthine in rat plasma and tissues.Following intravenous administration of ceph-aranthine hydrochloride,the pulmonary exposure level of the drug is significantly higher in plasma and other tissues,providing data for evaluating its in vivo pharmacological activities.
2.In vivo pharmacological efficacy of intravenously administered cepharanthine hydrochloride in rats based on its exposures
Zengxu YANG ; Bohong ZHENG ; Mengran WANG ; Fengxu CHENG ; Wenpeng ZHANG ; Chunyan LIU ; Junhai XIAO ; Xiaomei ZHUANG
Chinese Journal of Pharmacology and Toxicology 2025;39(1):46-57
OBJECTIVE To establish a liquid chromatography massspectrometry(LC-MS/MS)method for quantitatively determining the concentration of cepharanthine in rat plasma and tissue samples after intravenous injection of cepharanthine hydrochloride.METHODS ①The LC-MS/MS method was adopted.A Phenomenex C18(3.0 mm×50 mm,2.6 μm)column was employed with a mobile phase consisting of 0.05%formic acid-2 mmol·L-1 ammonium acetate-water solution and 0.1%formic acid-acetonitrile solution under gradient elution at a flow rate of 0.6 mL·min-1.The determination was performed using positive ion multiple reaction monitoring mode assays:cepharanthine(m/z:607.3→365.1)and buspirone(IS)(m/z:386.4→122.2).② Blood samples were collected from 6 SD rats at different time points following a single iv administration of cepharanthine to determine the concentration of the drug.The main pharmacokinetic parameters were calculated using a non-compartmental model.③72 SD rats were subjected to tissue distribution experiments after a single and multiple iv administra-tion of cepharanthine,and tissue samples were collected at six different time points(n=6)for the quanti-fication of drug concentrations.④ The whole blood plasma distribution ratio(Rb/p)of cepharanthine hydrochloride(7.5 mg·kg-1)in 3 SD rats was determined 2 h after iv administration.⑤The protein binding of cepharanthine to rat plasma and lung tissue homogenates was determined by equilibrium dialysis before the concentration of the free drug within the lungs was calculated.RESULTS ① An LC-MS/MS method for quantitatively determining cepharanthine in rat plasma and tissue homogenates was devel-oped,which demonstrated an excellent linear relationship(r2>0.999)within the concentration range of 2 to 1000 μg·L-1,with a lower limit of quantification at 2 μg·L-1.The obtained results met all the require-ments for accurate quantitative detection.②The main pharmacokinetic parameters of cepharanthine in rats following a single iv administration were as follows:C0=(686.91±238.43)μg·L-1,t1/2=(29.70±6.29)h,Vz=(62.70±7.93)L·kg-1,Vss=(62.55±11.28)L·kg-1,CL=(1.50±0.23)L·h-1·kg-1 and AUC(0-t)=(4.52±0.61)h·mg·L-1.③ Concentrations in tissues exceeded those in plasma after both a single and multiple iv administration,with the highest levels in the lung.The values of AUC(0-t)in lungs were(2 547.35±156.56)and(4 481.35±479.21)h·mg·L-1 after a single and multiple iv administration,respectively.④ The content of cepharanthine in blood cells was higher than that in plasma,and Rb/p was 3.5±0.8.⑤ After correction by the protein-binding rate,the minimum concentration of free drugs in the lungs(95.04 μg·L-1)exceeded the reported antiviral activity threshold against coronaviruses(EC50=60.67 μg·L-1).CONCLUSION An LC-MS/MS method has been established to rapidly and sensitively determine the concentration of cepharanthine in rat plasma and tissues.Following intravenous administration of ceph-aranthine hydrochloride,the pulmonary exposure level of the drug is significantly higher in plasma and other tissues,providing data for evaluating its in vivo pharmacological activities.
3.Clinical efficacy of mini plate internal fixation through lateral elbow joint approach for Dubberley 3B distal humeral coronal fractures
Qingwei WANG ; Huasong WANG ; Huafeng SHI ; Shouyong HU ; Qihuang ZHOU ; Junhai WANG
Chinese Journal of Orthopaedics 2024;44(23):1532-1540
Objective:To compare the clinical efficacy of using micro steel plate internal fixation through the lateral elbow joint approach and traditional posterior olecranon osteotomy approach for the treatment of Dubberley 3B distal humeral coronal fracture.Method:A retrospective analysis was conducted on the data of 35 patients with Dubberley 3B distal humeral coronal fractures admitted to the Orthopedics Department of Jingmen Central Hospital (15 cases) and the Central Theater Command General Hospital of the People's Liberation Army (20 cases) from January 2018 to May 2023. Among them, 23 cases were treated with micro steel plate internal fixation through the lateral elbow joint approach (study group), and 12 cases were treated with traditional posterior olecranon osteotomy approach internal fixation (control group). There were 24 males and 11 females aging from 32 to 64 years old with 18 left elbows and 17 right ones. All of them were fresh fracture cases. The surgical incision length, surgical time, intraoperative bleeding, hospital stay, fracture healing, and incidence of complications between the two groups were recorded and compared. Visual analog scale (VAS) was recorded at 1 week and 1 month after surgery. Function recovery was assessed using Mayo elbow joint function score (Mayo elbow performance score, MEPS) at 3 months and the last follow-up.Result:There was no significant difference in preoperative baseline data between the study group and control group ( P>0.05). Patients in the study group were followed up for 18.7±3.9 months (range 12-47 months) while those in the control group were followed up for 22.3±4.7 months (range 12-52 months). There were significant differences between the study group and control group in the surgical incision length (10.5±0.9 cm vs. 21.2±1.7 cm), surgical time (76.3±4.7 min vs. 98.8±6.1 min), intraoperative blood loss (65.6±10.2 vs. 148.5±14.9 ml), length of stay( 10.4±1.5 vs. 15.8±1.6 d), and fracture healing time (4.2±0.9 months vs. 5.7±1.1 months) ( P<0.05). At the follow-up of 1 week and 1 month, the VAS of the study group (2.7±0.4, 1.3±0.4) were significantly lower compared to the control group ( 3.1±0.5, 1.8±0.6), ( t=2.577, 2.288; P=0.015, 0.029). At the follow up of 3 months, the MEPS of the study group were significantly higher compared to the control group (83.6±1.7 vs. 60.3±4.2, t=23.418, P<0.001). With time, the VAS of both groups decreased significantly, and the MEPS increased significantly ( P<0.05). At the last follow-up, there was no significant difference in MEPS between the two groups (92.3±3.8 vs. 89.5±5.7, P>0.05). At the last follow-up, there were 3 cases of joint degeneration in the study group with no complications of nerve or vascular damage, screw cutting, nonunion of fractures, loss of reduction, joint stiffness, or ectopic ossification, while in the control group, there was one case of delayed healing at the olecranon osteotomy site, one case of poor reduction of the fracture, both treated with immobilization and showing varying degrees of joint stiffness; one case showed ectopic ossification, and a total of four patients experienced elbow joint stiffness. The incidence of complications between the two groups [13.0% (3/23) vs. 33.3% (4/12)] showed significant difference ( P<0.05). Conclusion:The treatment of Dubberley 3B distal humeral coronal fracture through the lateral approach of elbow joint with mini steel plate internal fixation yielded good clinical results with the advantages of short surgical time, reliable internal fixation, satisfying joint function and fewer complications.
4.Interpretation of the progress in esophageal cancer treatment in the 2024 American Society of Clinical Oncology Gastrointestinal Cancer Symposium
Xuxu ZHANG ; Junhai LI ; Xinyao XU ; Jiahe LI ; Jipeng ZHANG ; Wei LI ; Lei WANG ; Qiang LU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(06):807-813
The 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO-GI) was held in San Francisco, the USA from January 18th to 20th, 2024 (local time). The multiple studies presented in this symposium will have a significant impact on the clinical practice of esophageal cancer. This article will focus on the surgical methods of esophageal cancer, perioperative immunotherapy, drug therapy for advanced esophageal cancer, rescue treatment after immunotherapy resistance, and other relevant aspects. It aims to summarize and interpret the significant advancements in the field of esophageal cancer presented in this symposium.
5.Clinical efficacy of mini plate internal fixation through lateral elbow joint approach for Dubberley 3B distal humeral coronal fractures
Qingwei WANG ; Huasong WANG ; Huafeng SHI ; Shouyong HU ; Qihuang ZHOU ; Junhai WANG
Chinese Journal of Orthopaedics 2024;44(23):1532-1540
Objective:To compare the clinical efficacy of using micro steel plate internal fixation through the lateral elbow joint approach and traditional posterior olecranon osteotomy approach for the treatment of Dubberley 3B distal humeral coronal fracture.Method:A retrospective analysis was conducted on the data of 35 patients with Dubberley 3B distal humeral coronal fractures admitted to the Orthopedics Department of Jingmen Central Hospital (15 cases) and the Central Theater Command General Hospital of the People's Liberation Army (20 cases) from January 2018 to May 2023. Among them, 23 cases were treated with micro steel plate internal fixation through the lateral elbow joint approach (study group), and 12 cases were treated with traditional posterior olecranon osteotomy approach internal fixation (control group). There were 24 males and 11 females aging from 32 to 64 years old with 18 left elbows and 17 right ones. All of them were fresh fracture cases. The surgical incision length, surgical time, intraoperative bleeding, hospital stay, fracture healing, and incidence of complications between the two groups were recorded and compared. Visual analog scale (VAS) was recorded at 1 week and 1 month after surgery. Function recovery was assessed using Mayo elbow joint function score (Mayo elbow performance score, MEPS) at 3 months and the last follow-up.Result:There was no significant difference in preoperative baseline data between the study group and control group ( P>0.05). Patients in the study group were followed up for 18.7±3.9 months (range 12-47 months) while those in the control group were followed up for 22.3±4.7 months (range 12-52 months). There were significant differences between the study group and control group in the surgical incision length (10.5±0.9 cm vs. 21.2±1.7 cm), surgical time (76.3±4.7 min vs. 98.8±6.1 min), intraoperative blood loss (65.6±10.2 vs. 148.5±14.9 ml), length of stay( 10.4±1.5 vs. 15.8±1.6 d), and fracture healing time (4.2±0.9 months vs. 5.7±1.1 months) ( P<0.05). At the follow-up of 1 week and 1 month, the VAS of the study group (2.7±0.4, 1.3±0.4) were significantly lower compared to the control group ( 3.1±0.5, 1.8±0.6), ( t=2.577, 2.288; P=0.015, 0.029). At the follow up of 3 months, the MEPS of the study group were significantly higher compared to the control group (83.6±1.7 vs. 60.3±4.2, t=23.418, P<0.001). With time, the VAS of both groups decreased significantly, and the MEPS increased significantly ( P<0.05). At the last follow-up, there was no significant difference in MEPS between the two groups (92.3±3.8 vs. 89.5±5.7, P>0.05). At the last follow-up, there were 3 cases of joint degeneration in the study group with no complications of nerve or vascular damage, screw cutting, nonunion of fractures, loss of reduction, joint stiffness, or ectopic ossification, while in the control group, there was one case of delayed healing at the olecranon osteotomy site, one case of poor reduction of the fracture, both treated with immobilization and showing varying degrees of joint stiffness; one case showed ectopic ossification, and a total of four patients experienced elbow joint stiffness. The incidence of complications between the two groups [13.0% (3/23) vs. 33.3% (4/12)] showed significant difference ( P<0.05). Conclusion:The treatment of Dubberley 3B distal humeral coronal fracture through the lateral approach of elbow joint with mini steel plate internal fixation yielded good clinical results with the advantages of short surgical time, reliable internal fixation, satisfying joint function and fewer complications.
6.Comparison of nutrition and visual health between Tibetan migrant students and local students in Gannan of Lanzhou New District
ZHANG Yonghua,MA Cuiling, ZHANG Xiaoling ,SHI Ying,WANG Chunping,SU Junhai,ZHAO Ai
Chinese Journal of School Health 2021;42(7):1029-1032
Objective:
This paper studies the nutritional and vision health status of Tibetan migrant students and the differences between the local students in Lanzhou and them to provide a theoretical basis for nutrition intervention and vision protection for students.
Methods:
Cluster sampling method was used to select 2 434 students migrating from Gannan Tibetan Autonomous Prefecture to a boarding middle school, and 3 291 students from three middle schools in Qilihe District of Lanzhou from September to December 2020. All the students were administered physical and visual examination. Proportion of nutritional status, poor eyesight and myopia by gender and age groups between Tibetan migrant students and local students were analyzed.
Results:
The detection rate of overweight and obesity in Tibetan migrant boys(2.8%,5.7%) and girls(11.0%,8.3%) was lower than that of local students of the same sex(5.6%,8.3%;24.9%,20.9%) ( χ 2=12.17,7.21, P <0.05; χ 2=81.33,91.34, P <0.05); The detection rate of malnutrition in Tibetan migrant boys(9.9%) was higher than that in local boys(7.2%) ( χ 2=6.65, P <0.05). The detection rate of poor vision in Tibetan migrant boys was lower than that in local boys ( χ 2=3.93, P <0.05). The detection rate of myopia was significantly lower than that of local students ( χ 2=975.82, P <0.01). The detection rate of abnormal color vision in Tibetan migrant boys was higher than that in local boys ( χ 2=8.38, P <0.05). The detection rate of abnormal color vision in Tibetan migrant girls was lower than that in local girls ( χ 2=8.08, P <0.05). The detection rate of mild and moderate visual impairment was lower among Tibetan migrant boys than local boys ( χ 2=3.88, 8.32, P <0.05); the detection rate of mild, moderate and severe myopia was lower than local boys ( χ 2= 13.72 ,55.96, 338.50, P <0.05). The detection rate of mild, moderate and severe myopia was lower among Tibetan migrant girls than local girls ( χ 2=7.62, 37.79,424.00, P <0.05).
Conclusion
Tibetan migrant students was lower than that of local students. More attention should be paid to nutrition intake of Tibetan boys to prevent malnutrition. The detection rate of myopia in Tibetan migrant students is low,but the detection rate of severe poor vision among Tibetan students in the junior high school group is higher than that of local students, and attention should be paid to the visual health of Tibetan students in junior high school.
7.Analysis of the efficacy of tirofiban in the treatment of transient ischemic attack with high risk of recurrence
Chunli FU ; Mengkun WANG ; Junhai WANG
Journal of Apoplexy and Nervous Diseases 2021;38(6):488-491
Objective To investigate the efficacy of tirofiban on transient ischemic attack with high risk of recurrence.Methods 156 patients with non-cardiogenic transient ischemic attack with ABCD2 score ≥ 4 points were hospitalized at the Department of Neurology,Sinopharm Tongmei General Hospital from Jan 2019 to Mar 2021.Eight patients were excluded due to incomplete data or drop-off from follow-up.The remaining 148 patients were randomly divided into two groups,78 in the observation group and 70 in the control group.The observation group was given tirofiban treatment (loading tirofiban via a micropump,and continuous intravenous pumping for 48 hours) and intensive lipid-lowering therapy.The control group was given intensive anti-platelet aggregation therapy with Aspirin enteric-coated tablets,hydroclopidogre and intensive lipid-lowering therapy.We made a comparative analysis between two groups about efficacy,safety and short-term stroke incidence.Results In the observation group,57 cases were cured,14 cases were effective,and 7 cases were ineffective;6 cases (7.69%) had a stroke (cerebral infarction) within 7 days,7 cases (8.97%) had a stroke within 30 days,and 7 cases (8.97%) had a stroke within 90 days.In the control group,39 cases were markedly effective,15 cases were effective,and 16 cases were ineffective;in the control group,13 cases (18.57%) had a stroke (cerebral infarction) within 7 days,15 cases (21.43%) had a stroke within 30 days,16 cases (22.86%) had a stroke within 90 days.No intracerebral hemorrhage occurred in either group within 90 days.The two groups had statistical significance in terms of effective treatment rate (P<0.05).However,there was no significant difference in the number of stroke cases between the observation group and the control group in the short-term 7 days,30 days,and 90 days (P>0.05).There was no significant difference in coagulation,platelet,liver and kidney function between the two groups after 48 hours of treatment (P>0.05).Conclusion For patients with transient ischemic attack at high risk of recurrence,tirofiban treatment can effectively control TIA attacks,but it cannot reduce the risk of stroke.
8.Risk Factors for Duodenal Stump Leakage after Laparoscopic Gastrectomy for Gastric Cancer
Lihu GU ; Kang ZHANG ; Zefeng SHEN ; Xianfa WANG ; Hepan ZHU ; Junhai PAN ; Xin ZHONG ; Parikshit Asutosh KHADAROO ; Ping CHEN
Journal of Gastric Cancer 2020;20(1):81-94
PURPOSE:
Duodenal stump leakage (DSL) is a potentially fatal complication that can occur after gastrectomy, but its underlying risk factors are unclear. This study aimed to investigate the risk factors and management of DSL after laparoscopic radical gastrectomy for gastric cancer (GC).
MATERIALS AND METHODS:
Relevant data were collected from several prospective databases to retrospectively analyze the data of GC patients who underwent Billroth II (B-II) or Roux-en-Y (R-Y) reconstruction after laparoscopic gastrectomy from 2 institutions (Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, and HwaMei Hospital, University of Chinese Academy of Sciences). The DSL risk factors were analyzed using univariate and multivariate analysis regression.
RESULTS:
A total of 810 patients were eligible for our analysis (426 with R-Y, 384 with B-II with Braun). Eleven patients had DSL (1.36%). Body mass index (BMI), elevated preoperative C-reactive protein (CRP) level, and unreinforced duodenal stump were the independent risk factors for DSL. DSL was diagnosed in 2–12 days, with a median of 8 days. Seven patients received conservative treatment, 3 patients received puncture treatment, and only 1 patient required reoperation. All patients recovered successfully after treatment.
CONCLUSIONS
The risk factors of DSL were BMI ≥24 kg/m², elevated preoperative CRP level, and unreinforced duodenal stump. Nonsurgical treatments for DSL are preferred.
9.Diagnosis and treatment of late spontaneous esophageal rupture:a report of 10 cases
Junhai LI ; Feng XUE ; Yingping LIANG ; Bo WANG ; Pengguo WANG ; Xiaoqi GUO ; Ming YU ; Jiansheng WANG
Chinese Journal of Primary Medicine and Pharmacy 2019;26(6):650-652
Objective To summarize and analyze the clinical features,diagnostic methods and treatment measures of patients with advanced spontaneous esophageal rupture. Methods Retrospective analysis of clinical characteristics of 10 patients with advanced spontaneous esophageal rupture was conducted. Results The average age of the patients was 49. 3 years old. The average time of diagnosis was 82. 6 hours. The cause of onset was drastic vomiting except for one case falling down. The main clinical manifestations were chest pain,abdominal pain,and shortness of breath,fever and elevation of hemogram,pleural effusion appeared in all patients,1 case was not treated in time,and 9 cases of the first checks were delayed for diagnosis and treatment in other specialties. Conservative treatment(closed thoracic drainage,gastrointestinal decompression,enteral nutrition support and antimicrobial therapy) was given to all patients. All 10 cases were cured by conservative treatment,the average time of hospitalization was 49. 4 days,followed up for 2 years, no chronic empyema, stricture of the esophagus and reflux esophagitis were observed. Conclusion Late spontaneous rupture of the esophagus is caused by delays in the diagnosis and treatment of the esophagus,the effect of comprehensive conservative treatment is satisfactory.
10.Torsion of testes in newborn:a study of 12 cases
Hao WANG ; Shoulin LI ; Wei ZHOU ; Junhai JIANG ; Xiaodong LIU ; Wanhua XU ; Jianchun YIN ; Qitao XU
Chinese Journal of Neonatology 2019;34(5):372-374
Objective To study the clinical features, diagnosis and treatment of torsion of testes in newborn. Method Neonates who were diagnosed with neonatal testicular torsion and admitted to Shenzhen Children's Hospital from March 2008 to July 2018 were studied. The clinical data such as days in age, time of onset, clinical manifestations, time of ultrasound examination, characteristics of ultrasound examination, surgery time, surgical types, postoperative conditions, pathological findings, and follow-up results were retrospectively analyzed. Result A total of 12 infants with torsion of testes were enrolled. The average onset time was 2.9 d, ranged from 1~10 d. The time of onset was within 24 h after birth in six infants. The median duration from onset to seeing a doctor was 3.5 d, ranged from 2 h to 28 d. First manifestations being reported grammer were scrotal swelling or mass, including 7 cases on the left side and 5 cases on the right side. Among them, 9 cases were associated with redness or cyanosis of the scrotum. Ultrasound was characterized by the disappearance or significant reduction of testicular parenchymal blood flow signal, and the sensitivity of ultrasound was 100%. The average time from admission to operation was (2.1±1.1) h. All the 12 infants had orchiectomy,after necrosis of unilateral testicle was confirmed. Eight of them underwent contralateral test icular fixation. The average operation time was 46 min. There was no wound bleeding or infection postoperatively, and the average hospital stay was 6.4 d. The pathological features were blurred residual contour of the seminiferous tubule (9 cases) or the disappearance of the seminiferous tubule structure (3 cases). After 3 to 24 months of follow-up, no contralateral testicular torsion or atrophy was found. Conclusion The rate of testicular necrosis in children with torsion of testes is high. The newborn with scrotal swelling should be diagnosed promptly with color Doppler ultrasound. If necessary, surgical exploration should be performed in time.


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