Objective To study the pharmacokinetic profile of zidovudine and lamivudine tablets(ZL)in Chinese healthy subjects and to evaluate its bioequivalence and safety.Methods A randomized,open,single-dose,two-sequence,four-cycle and fully replicated crossover bioequivalence trial was conducted in 32 healthy subjects both fasting and postprandial,and two preparations of ZL tablets were administered orally in each cycle,with a washout period of 5 days.The concentrations of zidovudine and lamivudine in plasma were determined using high performance liquid chromatography-tandem mass spectrometry.The pharmacokinetic evaluation index parameters were statistically analyzed using Phoenix WinNonlin version 8.1 data statistical software to evaluate bioequivalence.Results The Cmax of zidovudine under fasting and postprandial conditions between ZL and the reference drugs after a single dose were(3 782.499±1 921.649)vs.(3 543.164±1 946.076)ng·mL-1 and(1 585.827±914.246)vs.(1 667.595±862.945)ng·mL-1,respectively.And the AUC0-t for fasting and postprandial conditions of zidovudine was(3 177.091±819.538)vs.(3 071.375±972.145)h·ng·mL-1 and(2 437.999±478.147)vs.(2 402.725±477.792)h·ng·mL-1,respectively;while the AUC0-∞ were(3 225.674±825.131)vs.(3 093.448±972.340)h·ng·mL-1and(2 464.310±480.790)vs.(2 427.693±477.933)h·ng·mL-1,respectively.The Cmax of a single dose of lamivudine under fasting and postprandial conditions between ZL and the reference drugs were(1 923.329±490.572)vs.(1 830.570±476.947)ng·mL-1 and(1 922.711±589.130)vs.(1 881.857±527.577)ng·mL-1,respectively.The AUC0-t for preprandial and postprandial lamivudine was(7 598.265±1 376.774)vs.(7 283.422±1 356.146)h·ng·mL-1 and(7 554.169±958.379)vs.(7 329.376±924.075)h·ng·mL-1,respectively,whereas the AUC0-∞ were(7 734.038±1 326.907)vs.(7 405.088±1 340.036)h·ng·mL-1 and(7 660.916±958.694)vs.(7 435.102±930.448)h·ng·mL-1,in fasting and fed tests,the 90％confidence intervals(CI)of the geometric mean ratios of the main pharmacokinetic parameters between test and reference preparations were all within the range of 80％-125％,respectively.A total of 37 adverse events occurred during the trial period,including 21 in the fasting group and 16 in the postprandial group,and no serious adverse events occurred.Conclusion The test formulations of zidovudine and lamivudine tablets were bioequivalent and well tolerated in healthy Chinese subjects under fasting and fed conditions compared to the reference tablets.

Objective To study the pharmacokinetic profile of zidovudine and lamivudine tablets(ZL)in Chinese healthy subjects and to evaluate its bioequivalence and safety.Methods A randomized,open,single-dose,two-sequence,four-cycle and fully replicated crossover bioequivalence trial was conducted in 32 healthy subjects both fasting and postprandial,and two preparations of ZL tablets were administered orally in each cycle,with a washout period of 5 days.The concentrations of zidovudine and lamivudine in plasma were determined using high performance liquid chromatography-tandem mass spectrometry.The pharmacokinetic evaluation index parameters were statistically analyzed using Phoenix WinNonlin version 8.1 data statistical software to evaluate bioequivalence.Results The Cmax of zidovudine under fasting and postprandial conditions between ZL and the reference drugs after a single dose were(3 782.499±1 921.649)vs.(3 543.164±1 946.076)ng·mL-1 and(1 585.827±914.246)vs.(1 667.595±862.945)ng·mL-1,respectively.And the AUC0-t for fasting and postprandial conditions of zidovudine was(3 177.091±819.538)vs.(3 071.375±972.145)h·ng·mL-1 and(2 437.999±478.147)vs.(2 402.725±477.792)h·ng·mL-1,respectively;while the AUC0-∞ were(3 225.674±825.131)vs.(3 093.448±972.340)h·ng·mL-1and(2 464.310±480.790)vs.(2 427.693±477.933)h·ng·mL-1,respectively.The Cmax of a single dose of lamivudine under fasting and postprandial conditions between ZL and the reference drugs were(1 923.329±490.572)vs.(1 830.570±476.947)ng·mL-1 and(1 922.711±589.130)vs.(1 881.857±527.577)ng·mL-1,respectively.The AUC0-t for preprandial and postprandial lamivudine was(7 598.265±1 376.774)vs.(7 283.422±1 356.146)h·ng·mL-1 and(7 554.169±958.379)vs.(7 329.376±924.075)h·ng·mL-1,respectively,whereas the AUC0-∞ were(7 734.038±1 326.907)vs.(7 405.088±1 340.036)h·ng·mL-1 and(7 660.916±958.694)vs.(7 435.102±930.448)h·ng·mL-1,in fasting and fed tests,the 90％confidence intervals(CI)of the geometric mean ratios of the main pharmacokinetic parameters between test and reference preparations were all within the range of 80％-125％,respectively.A total of 37 adverse events occurred during the trial period,including 21 in the fasting group and 16 in the postprandial group,and no serious adverse events occurred.Conclusion The test formulations of zidovudine and lamivudine tablets were bioequivalent and well tolerated in healthy Chinese subjects under fasting and fed conditions compared to the reference tablets.

Objective To analyze the interaction between voriconazole(VRC)and immunosuppressants such as tacrolimus and cyclosporine and the effect of CYP2C19 gene polymorphism on the interaction and adverse reactions(ADR)based on the results of CYP2C19 gene polymorphism and therapeutic drug monitoring,so as to provide a basis for the development of individualized VRC combined with immunosuppressants.Methods Two-dimensional liquid chromatography and pyrosequencing was used to detect the concentration of VRC and the CYP2C19 gene pol-ymorphism,respectively.And the concentration of immunosuppressants was detected at the same time.The rela-tionship among CYP2C19 gene polymorphism,the concentration of VRC and immunosuppressant and ADR was an-alyzed.Results A total of 61 patients were enrolled in this study,and the mutation rates of CYP2C19*2 and CYP2C19*3 were 54.1％(33/61)and 9.84％(6/61),respectively.The concentrations of VRC in patients with extensive metabolism(EMs),intermediate metabolism(IMs)and poor metabolism(PMs)were(4.44±3.46),(3.62±3.02)and(10.05±1.46)μg/ml(P＜0.05),respectively.The concentration of tacrolimus af-ter combined with VRC significantly increased compared to tacrolimus alone[(13.4±9.2)ng/ml vs(6.5±3.6)ng/ml;P=0.002],and the concentration of tacrolimus increased along with an increasing of VRC concentration.The concentration of VRC in patients combined with tacrolimus was lower than that in patients without immunosup-pressants[(3.81±3.48)μg/ml vs(5.84±3.71)μg/ml;P=0.032].The concentration of VRC inpatients with cyclosporine significantly decreased(P＜0.01),while tacrolimus and mycophenolate mofetil had no signifi-cant effect on the concentration of VRC.45.90％(28/61)of the patients had adverse reactions,the concentration of VRC in patients with ADR was significantly higher than that in patients without ADR[(7.07±3.43)μg/ml vs(3.06±2.90)μg/ml;P＜0.001].And the concentration of VRC in patients with ADR was higher than patients without ADR with based on CYP2C19 genotype.Conclusion CYP2C19 gene polymorphism can significantly affect the concentration and adverse reactions of VRC,and VRC has significant interaction with immunosuppressants such as tacrolimus.CYP2C19 gene polymorphism combined with therapeutic drug monitoring can improve the individual-ized treatment of tacrolimus and voriconazole,and is expected to minimize toxicity and improve treatment effects.

Objective:This study aims to explore the application value of the "liftoff" modular method in robot-assisted laparoscopic surgery for complex adrenal tumors.Methods:We retrospectively analyzed the clinical data of 15 patients with complex adrenal tumors treated at the General Hospital of Southern Theater Command from May 2022 to June 2023. The cohort comprised 5 males and 10 females with an average age of (47.6±7.8) years and a body mass index (BMI) of 26.5 (23.8-27.9) kg/m 2. Among the patients, 3 had a BMI ≥28 kg/m 2, 2 had diabetes, 6 had hypertension, and 1 had coronary heart disease. Preoperative endocrine hormone examination revealed abnormal blood catecholamines in 5 cases and abnormal blood cortisol in 2 cases. Ultrasound and CT scans indicated that 9 tumors were located on the left side and 6 on the right, with 4 cases showing tumor compression on adjacent large blood vessels or organs. The average tumor diameter was (7.61±2.79) cm, with 10 cases having a diameter ≥ 6 cm. All patients underwent laparoscopic adrenalectomy assisted by robots through the transperitoneal approach. The surgeries were performed in a lateral position under general anesthesia. The "liftoff" modular method was utilized to separate the treatment of adrenal tumors into lateral, medial, dorsal, cephalic, and adrenal renal plane sides. Tumors were appropriately manipulated during the operations to achieve a "liftoff" shape. Different modular dissociation steps were adopted based on the size and location of the left and right adrenal tumors. The left adrenal gland was dissected in the order of medial and dorsal, adrenal renal plane side, and lateral and cephalic sides, while the right adrenal gland was dissected in the order of lateral and dorsal, adrenal renal plane side, and medial and cephalic sides. Postoperative related indicators and follow-up status of patients were recorded and analyzed. Results:All 15 surgeries were successfully completed without any conversions to open adrenalectomy, with an average operation time of 118 (102-130) minutes and an average intraoperative blood loss of 102 (69-163) ml. The postoperative drainage time was 4 (3-5) days, and the postoperative hospital stay was 6 (4-7) days. The postoperative pathological diagnoses included 5 cases of pheochromocytoma, 3 cases of macronodular adrenal hyperplasia, 6 cases of adrenocortical adenoma, and 1 case of myelolipoma. Follow-up for 6-12 months after surgery showed good recovery and no recurrence.Conclusions:The application of the "liftoff" modular method in robot-assisted laparoscopic surgery for complex adrenal tumors is safe and feasible. It efficiently aids in tumor removal and holds significant clinical application value.

AIM:To investigate the risk factors af-fecting serum digoxin concentration and the rela-tionship between the level of the concentration and adverse reactions(ADR),and to provide a basis for the safe and rational use of digoxin.METHODS:The serum digoxin concentration(SDC)was moni-tored by enzyme amplification immunoassay tech-nology.The basic data,laboratory indicators,con-comitant medication and adverse reactions of pa-tients were collected through the medical record system.RESULTS:Among the 55 patients,12.73％,76.36％and 10.91％of the patients were treated with＜0.125 mg/d,0.125 mg/d and 0.25 mg/d di-goxin,respectively.And the serum digoxin concen-tration increased in a dose dependent manner.Eleven patients(20％)developed ADR,the most common of which were arrhythmias.The SDC of patients with ADR was(2.55±1.59)ng/mL,which was significantly higher than that of the non-ADR group(0.93±0.63 ng/mL)(P＜0.000 1).The SDC in the patients with increased serum creatinine was higher than that in the normal creatinine group,and patients with severe renal impairment demon-strated significantly higher concentration of digoxin than that in patients with normal renal function(P＜0.05).The effect of concomitant administration of other drugs on the SDCof digoxin was not ob-served.CONCLUSION:The SDC varies greatly among individuals,and is associated with dosage and renal function.The higher the concentration of digoxin in serum,the higher the incidence of ADR.Therefore,monitoring the SDC of digoxin should be strengthened,so as to improve the level of individ-ual treatment.

AIM:To investigate the risk factors af-fecting serum digoxin concentration and the rela-tionship between the level of the concentration and adverse reactions(ADR),and to provide a basis for the safe and rational use of digoxin.METHODS:The serum digoxin concentration(SDC)was moni-tored by enzyme amplification immunoassay tech-nology.The basic data,laboratory indicators,con-comitant medication and adverse reactions of pa-tients were collected through the medical record system.RESULTS:Among the 55 patients,12.73％,76.36％and 10.91％of the patients were treated with＜0.125 mg/d,0.125 mg/d and 0.25 mg/d di-goxin,respectively.And the serum digoxin concen-tration increased in a dose dependent manner.Eleven patients(20％)developed ADR,the most common of which were arrhythmias.The SDC of patients with ADR was(2.55±1.59)ng/mL,which was significantly higher than that of the non-ADR group(0.93±0.63 ng/mL)(P＜0.000 1).The SDC in the patients with increased serum creatinine was higher than that in the normal creatinine group,and patients with severe renal impairment demon-strated significantly higher concentration of digoxin than that in patients with normal renal function(P＜0.05).The effect of concomitant administration of other drugs on the SDCof digoxin was not ob-served.CONCLUSION:The SDC varies greatly among individuals,and is associated with dosage and renal function.The higher the concentration of digoxin in serum,the higher the incidence of ADR.Therefore,monitoring the SDC of digoxin should be strengthened,so as to improve the level of individ-ual treatment.

Objective : To construct folate modified D ⁃α ⁃tocopheryl polyethylene glycol 1000 succinate ( TPGS) oparticles on the cytotoxicity and spliced X ⁃box binding protein 1 ( XBP1s) of mouse leukemia cells of monocyte macrophage (RAW264. 7) . Methods : Mixed FA⁃TPGS and rhodamine B (RhB) labeled XBP1 siRNA solution in a proportion of 5 ∶ 1 and obtained the nano⁃complex coated with XBP1 siRNA(FT@ XBP1) . FT@ XBP1 nanocarriers were characterized by transmission electron microscope , dynamic light scattering , ultraviolet visible spectrum analysis and/or fluorescence analysis. And the release of siRNA from FA⁃TPGS nano⁃carriers was calculated simultaneously. The cell cytotoxicity of FT@ XBP1 nanomaterials were detected by scanning electron microscopy (SEM) , CCK⁃8 and flow cytometry. And the inhibited effect of XBP1 s of RAW264. 7 cells was checked by Western blot. Results FA modified TPGS could effectively bind XBP1 siRNA. And the average particle size of FT@ XBP1 nanocarriers were(200 ± 20) nm. The relative release assays showed that acidic environments (pH 5. 0) was beneficial for siRNA to release from FT@ XBP1 . Both CCK⁃8 and apoptosis assay showed that the effects of FT@ XBP1 on the proliferation and apoptosis of RAW264. 7 cells were relatively small , and FT@ XBP1 could significantly inhibit the expression of XBP1 s protein in RAW264. 7(P < 0. 001) . Conclusion TPGS nanoparticles modified with folic acid can effectively encapsulate XBP1 siRNA and inhibit XBP1 s expression of RAW264. 7 cells with good cellular compatibility.

Objective : To construct folate modified D ⁃α ⁃tocopheryl polyethylene glycol 1000 succinate ( TPGS) nanomaterials (FA⁃TPGS) , which can stably load and effectively release siRNA , and to observe the effects of nanoparticles on the cytotoxicity and spliced X ⁃box binding protein 1 ( XBP1s) of mouse leukemia cells of monocyte macrophage (RAW264. 7) . Methods : Mixed FA⁃TPGS and rhodamine B (RhB) labeled XBP1 siRNA solution in a proportion of 5 ∶ 1 and obtained the nano⁃complex coated with XBP1 siRNA(FT@ XBP1) . FT@ XBP1 nanocarriers were characterized by transmission electron microscope , dynamic light scattering , ultraviolet visible spectrum analysis and/or fluorescence analysis. And the release of siRNA from FA⁃TPGS nano⁃carriers was calculated simultaneously. The cell cytotoxicity of FT@ XBP1 nanomaterials were detected by scanning electron microscopy (SEM) , CCK⁃8 and flow cytometry. And the inhibited effect of XBP1 s of RAW264. 7 cells was checked by Western blot. Results : FA modified TPGS could effectively bind XBP1 siRNA. And the average particle size of FT@ XBP1 nanocarriers were(200 ± 20) nm. The relative release assays showed that acidic environments (pH 5. 0) was beneficial for siRNA to release from FT@ XBP1 . Both CCK⁃8 and apoptosis assay showed that the effects of FT@ XBP1 on the proliferation and apoptosis of RAW264. 7 cells were relatively small , and FT@ XBP1 could significantly inhibit the expression of XBP1 s protein in RAW264. 7(P < 0. 001) . Conclusion TPGS nanoparticles modified with folic acid can effectively encapsulate XBP1 siRNA and inhibit XBP1 s expression of RAW264. 7 cells with good cellular compatibility.

Objective:To establish a colloidal gold technique assay for the rapid detection of immunoglobulin(Ig)M and IgG antibodies against 2019 novel coronavirus (2019-nCoV) and to evaluate its clinical performance.Methods:A total of 278 patients who were respectively treated at Wuhan Hankou Hospital and the People′s Hospital of Honghu from February 12, 2020 to February 20, 2020 were collected. According to the diagnostic criteria, 89 patients were confirmed with positive 2019-nCoV nucleic acid, and 189 were 2019-nCoV nucleic acid-negative suspected patients. A total of 273 medical examiners from Nanfang Hospital, Southern Medical University from 2015 to 2018 were selected as controls. The serum samples of patients were collected. 2019-nCoV nucleic proteins were obtained from prokaryotic expression vectors. Indirect IgM and IgG colloidal gold techniques were established by using recombinant nuclear protein. 2019-nCoV nucleic acid detection by reverse transcription-polymerase chain reaction (RT-PCR) was used as control. Serum specimens were tested for 2019-nCoV IgM and IgG. The specificity and sensitivity of colloidal gold assay were analyzed.Results:The positive rates of IgM and IgG with the colloidal gold detection in confirmed patients with positive 2019-nCoV nucleic acid were 78.7%(70/89) and 73.0%(65/89), respectively. The positive rates of IgM and IgG in medical examiners were 1.8%(5/273) and 0.7%(2/273), respectively. The sensitivity and specificity of IgM detection reagents were 78.7% and 98.2%, respectively, those of IgG detection reagents were 73.0% and 99.3%, respectively, and those of IgM combined with IgG detection were 87.6% and 98.2%, respectively. For suspected patients with negative 2019-nCoV nucleic acid, the positive rates of IgM and IgG were 59.8%(113/189) and 52.9%(100/189), respectively, and the positive rate of IgM combined with IgG detection was 66.1%(125/189).Conclusion:This reagent of 2019-nCoV antibodies detection (colloidal gold technique) fulfills the requirement for clinical application with high specificity and sensitivity, which can be served as a supplementary detection method for 2019-nCoV nucleic acid detection by RT-PCR.

Objective: To establish a colloidal gold technique assay for the rapid detection of immunoglobulin(Ig) M and IgG antibodies against 2019 novel coronavirus (2019-nCoV) and to evaluate its clinical performance. Methods: A total of 278 patients who were treated at Wuhan Hankou Hospital and the People's Hospital of Honghu from February 12, 2020 to February 20, 2020 were collected. According to the diagnostic criteria, 89 patients were confirmed with 2019-nCoV nucleic acid positive diagnosis, and 189 were 2019-nCoV nucleic acid-negative suspected patients. A total of 273 medical examiners from Nanfang Hospital, Southern Medical University from 2015 to 2018 were selected as controls. The serum samples of patients were collected. 2019-nCoV nucleic proteins were obtained from prokaryotic expression vectors. Indirect IgM and IgG colloidal gold techniques were established by using recombinant N protein. 2019-nCoV nucleic acid detection by reverse transcription-polymerase chain reaction (RT-PCR) was used as control. Serum specimens were tested for 2019-nCoV IgM and IgG. The specificity and sensitivity of colloidal gold assay were analyzed. Results: The sensitivity and specificity of IgM detection reagents were 78.7% and 98.2%, respectively, those of IgG detection reagents were 73.0% and 99.3%, respectively, and those of IgM combined with IgG detection were 87.6% and 98.2%, respectively. For suspected patients with negative 2019-nCoV nucleic acid, the positive rates of IgM and IgG were 59.8% (113/189) and 52.9% (100/189), respectively, and the positive rate of IgM combined with IgG detection was 66.1% (125/189). Conclusion This reagent of 2019-nCoV antibodies detection (colloidal gold technique) fulfills the requirement for clinical application with high specificity and sensitivity, which can be served as a supplementary detection method for 2019-nCoV nucleic acid detection by RT-PCR.