Objective To develop and validate an efficient and simple liquid chromatography with tandem mass spectrometry(LC-MS/MS)method for determination of polymyxin E in human plasma,and apply the established method in therapeutic drug monitoring(TDM)of polymyxin E.Methods The LC-MS/MS platform was based on AB SCIEX HPLC-4500MD system.Gradient elution was performed with 0.2％formic acid in water and 0.2％formic acid in acetonitrile.Phenomenex Kinetex XB-C18 column(100 mm × 2.1 mm,2.6 μm)were used.The analytes were detected by electrospray ionization(ESI)positive multiple reaction monitoring mode.The ion pairs for analytes(polymyxins E1,E2)and internal standard(polymyxins B1)were m/z 390.7→101.3,m/z 386.0→101.2,and m/z 402.3→101.2,respectively.Plasma samples were processed with protein precipitation method.Results Polymyxin E1 and E2 showed good linearity in the range of 0.031 2-6.24 mg/L and 0.006 15-1.23 mg/L,respectively.The within-run accuracy of polymyxin E1 and E2 in plasma ranged from 89.4％to 99.8％and 91.5％to 108.2％,respectively,while the between-run accuracy ranged from 91.8％to 104.7％and 95.6％to 105.2％,respectively.The within-run precision of polymyxin E1 and E2 in plasma ranged from 4.9％to 8.9％and 2.8％to 8.5％,respectively,while the between-run precision ranged from 4.1％to 7.6％and 4.2％to 9.8％,respectively.The average internal standard normalized matrix effect factors of polymyxins E1 and E2 were 96.9％-111.2％and 106.1％-112.8％in blank plasma samples from 6 different sources,102.5％-106.8％and 98.8％-105.2％in lipemic plasma,respectively,107.8％-108.9％and 106.9％-1 07.4％in hemolyzed plasma,respectively.The precision of matrix effects was less than 15.0％.The average recovery rate was 102.9％-107.5％for polymyxin E1 and E2,and 107.0％for internal standard polymyxin B1.The precision was less than 3.7％.Conclusions In this study,a simple and efficient LC-MS/MS method was established for determination of polymyxin E1 and E2 in human plasma,which is reliable in the therapeutic drug monitoring and pharmacokinetic study of polymyxin E.

Objective To develop and validate an efficient and simple liquid chromatography with tandem mass spectrometry(LC-MS/MS)method for determination of polymyxin E in human plasma,and apply the established method in therapeutic drug monitoring(TDM)of polymyxin E.Methods The LC-MS/MS platform was based on AB SCIEX HPLC-4500MD system.Gradient elution was performed with 0.2％formic acid in water and 0.2％formic acid in acetonitrile.Phenomenex Kinetex XB-C18 column(100 mm × 2.1 mm,2.6 μm)were used.The analytes were detected by electrospray ionization(ESI)positive multiple reaction monitoring mode.The ion pairs for analytes(polymyxins E1,E2)and internal standard(polymyxins B1)were m/z 390.7→101.3,m/z 386.0→101.2,and m/z 402.3→101.2,respectively.Plasma samples were processed with protein precipitation method.Results Polymyxin E1 and E2 showed good linearity in the range of 0.031 2-6.24 mg/L and 0.006 15-1.23 mg/L,respectively.The within-run accuracy of polymyxin E1 and E2 in plasma ranged from 89.4％to 99.8％and 91.5％to 108.2％,respectively,while the between-run accuracy ranged from 91.8％to 104.7％and 95.6％to 105.2％,respectively.The within-run precision of polymyxin E1 and E2 in plasma ranged from 4.9％to 8.9％and 2.8％to 8.5％,respectively,while the between-run precision ranged from 4.1％to 7.6％and 4.2％to 9.8％,respectively.The average internal standard normalized matrix effect factors of polymyxins E1 and E2 were 96.9％-111.2％and 106.1％-112.8％in blank plasma samples from 6 different sources,102.5％-106.8％and 98.8％-105.2％in lipemic plasma,respectively,107.8％-108.9％and 106.9％-1 07.4％in hemolyzed plasma,respectively.The precision of matrix effects was less than 15.0％.The average recovery rate was 102.9％-107.5％for polymyxin E1 and E2,and 107.0％for internal standard polymyxin B1.The precision was less than 3.7％.Conclusions In this study,a simple and efficient LC-MS/MS method was established for determination of polymyxin E1 and E2 in human plasma,which is reliable in the therapeutic drug monitoring and pharmacokinetic study of polymyxin E.

Objective:To analyze the clinical outcomes of the first frozen-thawed embryo transfer (FET) in patients <35 years old applying natural cycle (NC) and hormone replacement therapy (HRT).Methods:A retrospective cohort study was conducted to analyze 4 814 young infertility patients who underwent the first FET in Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2016 to June 2021. According to different endometrial preparation protocols, they were divided into 2 groups: NC group and HRT group, who were matched the baseline data using 1∶1 propensity score matching (PSM). After the matching, the two groups of their baseline data, pregnancy outcomes and perinatal outcomes were compared, and then we adjusted the confounding factors which affect live birth rate by univariate and multivariate logistic regression analysis. Based on antral follicle count (AFC), number of embryos transferred and number of high-quality embryos transferred, the effect of NC and HRT on the live birth rate were further analyzed.Results:Before PSM, 2 131 patients in NC group and 2 683 patients in HRT group were included. The differences in female age, male age, body mass index (BMI), basal follicle-stimulating hormone (bFSH), anti-Müllerian hormone (AMH), AFC, endometrial thickness on conversion day, and number of embryos transferred were all statistically significant between the two groups (all P<0.05). And the differences in number of high-quality embryos transferred and type of embryos transferred between the two groups were not statistically significant (all P>0.05). After PSM, 1 441 patients in each of NC group and HRT group were included, and there were no significant differences in their baseline characteristics such as female age, male age and BMI between the two groups (all P<0.05). The live birth rate [50.66% (730/1 441)] and the clinical pregnancy rate [60.31% (869/1 441)] in NC group were significantly higher than those in HRT group [44.69% (644/1 441), P=0.001; 54.27% (782/1 441), P=0.001], and the incidence of very low birth weight in NC group was significantly lower than that in HRT group, and there were no statistical significances in other indicators between the two groups (all P>0.05). After adjusting confounders including bFSH, AMH, AFC, endometrial thickness on conversion day, number of embryos transferred and high-quality embryos transferred using multivariate logistic regression analysis, the results showed that NC was an independent protective factor for live birth rate in the first FET cycle ( aOR=1.280, 95% CI: 1.103-1.486, P=0.001). Stratified analysis showed that those with AFC<11, AFC 11-12, 2 embryos transferred and 2 high-quality embryos tranferred in NC group had significantly higher live birth rate [49.03% (151/308), 49.09% (349/711), 56.38% (442/784), 57.85% (350/605)] than those in HRT group [36.36% (120/330), P=0.001; 43.14% (286/663), P=0.027; 48.97% (379/774), P=0.003; 48.68% (294/604), P=0.001]. Conclusion:NC-FET had higher live birth rate and clinical pregnancy rate than HRT-FET in young patients.

Objective:To analyze the clinical outcomes of the first frozen-thawed embryo transfer (FET) in patients <35 years old applying natural cycle (NC) and hormone replacement therapy (HRT).Methods:A retrospective cohort study was conducted to analyze 4 814 young infertility patients who underwent the first FET in Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2016 to June 2021. According to different endometrial preparation protocols, they were divided into 2 groups: NC group and HRT group, who were matched the baseline data using 1∶1 propensity score matching (PSM). After the matching, the two groups of their baseline data, pregnancy outcomes and perinatal outcomes were compared, and then we adjusted the confounding factors which affect live birth rate by univariate and multivariate logistic regression analysis. Based on antral follicle count (AFC), number of embryos transferred and number of high-quality embryos transferred, the effect of NC and HRT on the live birth rate were further analyzed.Results:Before PSM, 2 131 patients in NC group and 2 683 patients in HRT group were included. The differences in female age, male age, body mass index (BMI), basal follicle-stimulating hormone (bFSH), anti-Müllerian hormone (AMH), AFC, endometrial thickness on conversion day, and number of embryos transferred were all statistically significant between the two groups (all P<0.05). And the differences in number of high-quality embryos transferred and type of embryos transferred between the two groups were not statistically significant (all P>0.05). After PSM, 1 441 patients in each of NC group and HRT group were included, and there were no significant differences in their baseline characteristics such as female age, male age and BMI between the two groups (all P<0.05). The live birth rate [50.66% (730/1 441)] and the clinical pregnancy rate [60.31% (869/1 441)] in NC group were significantly higher than those in HRT group [44.69% (644/1 441), P=0.001; 54.27% (782/1 441), P=0.001], and the incidence of very low birth weight in NC group was significantly lower than that in HRT group, and there were no statistical significances in other indicators between the two groups (all P>0.05). After adjusting confounders including bFSH, AMH, AFC, endometrial thickness on conversion day, number of embryos transferred and high-quality embryos transferred using multivariate logistic regression analysis, the results showed that NC was an independent protective factor for live birth rate in the first FET cycle ( aOR=1.280, 95% CI: 1.103-1.486, P=0.001). Stratified analysis showed that those with AFC<11, AFC 11-12, 2 embryos transferred and 2 high-quality embryos tranferred in NC group had significantly higher live birth rate [49.03% (151/308), 49.09% (349/711), 56.38% (442/784), 57.85% (350/605)] than those in HRT group [36.36% (120/330), P=0.001; 43.14% (286/663), P=0.027; 48.97% (379/774), P=0.003; 48.68% (294/604), P=0.001]. Conclusion:NC-FET had higher live birth rate and clinical pregnancy rate than HRT-FET in young patients.

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

Objective:To investigate the clinical characteristics, diagnosis and treatment of dermatomyositis with kidney neoplasm.Methods:The data of two patients with dermatomyositis complicated with kidney neoplasm in Tongji Hospital from January to February 2022 were retrospectively analyzed. The first case was a 55-year-old female, who was admitted with the chief complaints of recurrent erythema of upper extremities for 2 months and facial erythema for 1 month. Physical examination: erythema can be seen on upper limbs and face, no tenderness or percussion pain in kidney area. Myositis enzyme profile test showed that anti-Mi-2 antibody and anti-SSA /Ro-52 antibody were positive. Contrast CT showed nodular uneven enhancement in the right kidney with a size of 50 mm×41 mm. The second case was a 58-year-old female, who was admitted with the chief complaints of kidney occupying for a month. Physical examination: flaky erythema on face, no tenderness or percussion pain in kidney area. Myositis enzyme profile test showed that anti-Ro-52 antibody and anti-MDA5 antibody were positive. Contrast CT showed a significantly uneven enhanced mass with a size of about 50 mm×41 mm on left kidney. Both patients were diagnosed with kidney neoplasm before surgery and underwent laparoscopic partial nephrectomy in Tongji Hospital.Results:Both patients received regular oral prednisone after surgery. The pathological presentation of case 1 was papillary renal cell carcinoma, the facial erythema subsided 1 month after surgery, and there was no tumor recurrence for 13 months. The pathological presentation of case 2 was clear cell renal cell carcinoma, facial erythema subsided 2 weeks after surgery, and there was no tumor recurrence for 12 months.Conclusions:The diagnosis of dermatomyositis should be combined with clinical manifestations and laboratory examination, and the possibility of malignant tumor should be excluded due to the high likelihood of concomitant malignancy. For patients with dermatomyositis with kidney neoplasm, the main treatment is still surgery, and supplemented with glucocorticoid therapy.

Objective: To examine the effect of functional sports training on the development of spatial awareness in children aged 6-8 years old,to provide a reference to improve children s ability of spatial sense. Methods: A class of 125 children aged 6-8 years from first, second, and third grades of an elementary school in Zhengzhou City were conveniently selected by stratified random sampling, who were divided into the experimental group ( n =62) and the control group ( n =63) by random number tables. The experimental group received functional sports intervention for 8 weeks,3 times a week,20 min each time, and the control group received traditional sports game program. Results: After the intervention,the error values of depth perception, orientation perception, and space perception in the experimertal group of 6 and 7 year old children reduced by 1.98 cm, 2.88°, and 22.00 cm (6 year old children) and 1.61 cm, 2.34°, and 17.99 cm (7 year old children) compared with the control group, respectively. Compared with those in the control group of 8 year old after the intervention, and the differences were of statistical signifiance( t =-3.07, -2.94, -3.07 ; -3.25, -3.29, -3.15, P <0.01). There was no significant difference in the error values of depth perception, orientation perception and space perception between the experimental group and the control group after intervention ( P >0.05). In the experimental group, the error values of depth perception, orientation perception and space perception reduced by 2.30 cm, 3.88°, 28.05 cm (6 year old children), 2.16 cm, 2.15°, 17.45 cm (7 year old children) and 1.16 cm, 1.81°, 9.10 cm (8 year old children) in children aged 6-8 years after intervention, significant improvement were observed compared with before intervention ( t = 8.50 , 9.04, 7.35; 7.39, 10.30, 11.05; 4.67, 4.46, 14.14, P <0.01). Compared with before the intervention, children aged 6-8 in the control group only had significant differences in space perception( t =4.13, 6.71, 8.93, P <0.01). Conclusion Functional sports games can improve depth perception, orientation perception and spatial perception for children aged 6-8 years. It can be integrated into children s daily activities to play a positive role in promoting the healthy growth of children.

The pharmacodynamic (PD) and pharmacokinetic (PK) properties of Huangqin Tang (HQT) were investigated in yeast-induced febrile rats. Blood sample and rectal temperature data of the rats were collected at different times after single oral administration of HQT at 20 g x kg(-1). The plasma concentrations of paeoniflorin, baicalin, wogonoside, baicalein, wogonin, oroxylin A, glycyrrhizic acid and glycyrrhetinic acid were quantified by a sensitive liquid chromatography-tandem mass spectrometric (LC-MS) method. The blood concentrations of PGE2, 1L-1β and TNF-α were detected by radioimmunoassay (RIA). All pharmacokinetic parameters were processed by non-compartmental analysis using WinNonlin software. The potential relationship between the mean concentration of eight constituents and the antifebrile efficacy was investigated by calculating Pearson correlation coefficients. It was found that HQT had significant antifebrile efficacy in yeast-induced febrile rats, but had no effect to normal rats. The antifebrile effect of HQT can be attributed to the inhibition of PGE2, 1L-1β and TNF-α. The constituents (baicalin, wogonoside, baicalein, wogonin, oroxylin A, glycyrrhizic acid and glycyrrhetinic acid) in febrile rats had delayed absorption and elimination, a longer residence time in the body, and higher C(max) and AUC than those in normal rats. Febrile condition could affect the pharmacokinetic behaviour of HQT in vivo; the flavonoids with the same backbone showed the similar fate in the body; baicalein and wogonin had a strong positive correlation (R > 0.66, P ≤ 0.02) with the antifebrile efficacy determined. Together, these constituents demonstrated different pharmacokinetic properties in the febrile body.
Administration, Oral ; Animals ; Area Under Curve ; Chromatography, Liquid ; Dinoprostone ; blood ; Drugs, Chinese Herbal ; pharmacokinetics ; Fever ; metabolism ; Flavanones ; pharmacokinetics ; Flavonoids ; pharmacokinetics ; Glucosides ; pharmacokinetics ; Interleukin-1beta ; blood ; Mass Spectrometry ; Monoterpenes ; pharmacokinetics ; Rats ; Tumor Necrosis Factor-alpha ; blood

Decompression, Surgical ; Humans ; Lumbar Vertebrae ; surgery ; Spinal Fusion ; Spondylolisthesis ; diagnosis ; physiopathology ; surgery

OBJECTIVETo study the relationship between functional gene expression in Salvia miltiorrhiza from different producing areas and active principles, which might provide scientific basis for the gene regulation of tanshinones.

METHODThe quantitative determination of cryptotanshinone and tanshinone II A was carried out by using HPLC method, expression level of 3 functional genes of SmAACT, SmCMK and SmIPPI were investigated by real-time PCR method.

RESULTThe content of active principles together with expression level of SmAACT and SmCMK were higher in S. miltiorrhiza from genuine producing areas including Henan and Shanxi, but lower in samples from Beijing which was non-genuine producing area.

CONCLUSIONExpression level of SmAACT and SmCMK had close relationships involving tanshinones' accumulation, but the SmIPPI gene had not.