Determination of polymyxin B concentration in plasma and its application in critically ill patients / 中国药房

OBJECTIVE To establish a method for the determination of polymyxin B concentration in plasma and apply it to clinical practice. METHODS After precipitated with 5% trichloroacetic acid solution， using polymyxin E2 as internal standard， the concentrations of polymyxin B1 and B2 in plasma sample were determined by UPLC-MS/MS. The determination was performed on BEH C18 chromatographic column with water （0.1% formic acid）-acetonitrile （0.1% formic acid） as mobile phase （gradient elution） at the flow rate of 0.5 mL/min. The sample size was 10 µL. The detection was accomplished with electrospray ionization operated in positive ion scanning by multi-reaction monitoring mode. The ion pairs for quantitative analysis were m/z 603.2→101.2 （polymyxin B1）， m/z 595.7→101.1 （polymyxin B2） and m/z 578.5→101.1 （internal standard）. The plasma concentration of polymyxin B in 79 critically ill patients was measured by the above method， the occurrence of acute renal injury （AKI） was recorded and the relationship of polymyxin B concentration in plasma with AKI was analyzed. RESULTS The linear ranges of polymyxin B1 and polymyxin B2 were 200-20 000， 50-5 000 ng/mL （r＞0.995）， and the lower limits of quantification were 200 and 50 ng/mL， respectively. RSDs of intra‐day and inter‐day precision tests were not higher than 12.06%， the average extraction recovery was 103.04%-117.44%， and RSDs of matrix effect test and stability test were all not higher than 7.42%. Steady state trough and peak plasma concentration were （2.54±2.52） and （8.17±5.20） mg/L for 79 clinical patients using polymyxin B. Eighteen patients out of 27 included patients developed AKI， with an incidence of 66.67%. The peak concentration of polymyxin B of patients without AKI was significantly lower than that of patients with AKI （P＜0.05）， but there was no significant difference in the trough concentration between two groups （P＞0.05）. CONCLUSIONS The established UPLC-MS/MS has the advantages of simple operation and high sensitivity， and can be used to monitor the plasma concentration of polymyxin B in patients. The occurrence of AKI is correlated with the peak concentration of polymyxin B.

Analysis of influencing factors for the metabolism of voriconazole in adult patients / 中国药房

OBJECTIVE To analyze the influencing factors for the metabolism of voriconazole in adult patients， and to provide reference for the rational use of voriconazole in clinic. METHODS The clinical data of adult patients admitted in our hospital receiving voriconazole and therapeutic drug monitoring from April 2021 to March 2022 were collected. The trough concentration of voriconazole （c0） and plasma concentration of voriconazole-N-oxide concentration （cN） were determined， and voriconazole-to-voriconazole N-oxide concentration ratio （c0/cN） was calculated. Pearson’s correlation analysis was used to analyze the influencing factors for c0 and c0/cN of voriconazole. Multiple linear regression models were used to analyze the independent influencing factors for c0 and c0/cN of voriconazole. RESULTS The underlying diseases of the patients were mainly pneumonia， kidney disease and leukemia. The detected fungi were mainly Aspergillus， Candida and yeast-like fungi. Voriconazole was mainly administered by intravenous drip， especially in patients who used proton pump inhibitor in combination. The levels of C-reactive protein （CRP）， total bilirubin （TBIL）， direct bilirubin （DBIL） and indirect bilirubin （IBIL） were positively correlated with c0 of voriconazole， while platelet count and albumin levels were negatively correlated with voriconazole c0. The levels of CRP， TBIL and DBIL were positively correlated with c0/cN， while albumin levels were negatively correlated with c0/cN. Multiple linear regression analysis showed that the independent influencing factors of voriconazole c0 included the levels of CRP and IBIL， route of administration and dose of voriconazole， and the independent influencing factors of voriconazole c0/cN were the levels of CRP and DBIL and age. CONCLUSIONS The levels of CRP and IBIL， route of administration and dose of voriconazole are independent influencing factors of voriconazole c0； the levels of CRP and DBIL and age are independent influencing factors of voriconazole c0/cN. The influence of above indexes on the metabolism of voriconazole should be considered when using voriconazole clinically； and the route of administration and dose of voriconazole should be adjusted reasonably.

Clinical Characteristics of Voriconazole-induced Neurological ADR and the Occurrence of Hypokalemia and Hyponatremia / 中国药房

OBJECTIVE：To explo re the clinical characteristics of voriconazole-induced neurological ADR and the occurrence of hypokalemia and hyponatremia before ADR. METHODS ：The medical records of 411 patients receiving voriconazole therapy ， who admitted to our hospital from January 2018 to November 2020，were retrospectively analyzed. The general information of all patients，including sex ，age，body weight ，type of infection ，underlying disease ，type of pathogenic fungal infection and administration route of voriconazole ，maintenance dose ，blood drug concentration ，were collected. The basic information of patients with neurological ADR ，including sex ，age，types of infection ，underlying disease ，drug combination ，occurrence time and clinical manifestations ，were collected . The levels of blood potassium ，blood sodium and liver function indexes （ALT，AST， γ-GT，ALP，total bilirubin ，direct bilirubin ）within 3 days before the neurological ADR were also collected. The relationship of neurological ADR with voriconazole trough concentration ，blood potassium and blood sodium levels was analyzed. RESULTS ： Among 411 patients，31（7.54％）patients suffered from neurological ADR ，which were higher in male （64.52％）than in female （35.48％），mainly in patients aged 50 and over （74.20％）. The major infection type was lung infection （96.77％）. Among 31 patients with neurological ADR ，26 patients suffered from neurological ADR after 1-7 days after voriconazole administration ， accounting for 83.87％. Thirty patients received intravenous drip ，accounting for 96.77％. The incidence of neurological ADR in patients with voriconazole trough concentration ＞5.0 μ g/mL （8.99％）was significantly higher than that in patients with trough concentration ≤5.0 μg/mL（3.42％，χ2＝4.91，P＝0.027）. The clinical manifestations of the patients were mainly 023-68766797。E-mail：cheng7zhu@163.com hallucinations（32.35％），irritability（32.35％）and poor sleep （17.65％），etc. Within 3 days before 30 patients，receiving related indexes test ，suffered from neurological ADR ，16 patients（53.33％）had hypokalemia and 12 patients（40.00％） had hyponatremia ，which w ere significantly higher than the incidence of hypokalemia （24.74％，P＝0.001）and hyponatremia （12.89％，P＜0.001）in those without neurological ADR . There were 8，10，7，13，7 and 10 patients with ALT ，AST，ALP， γ-GT，total bilirubin and direct bilirubin increased. In 31 patients with neurological ADR ，the neurological ADR were relieved or disappeared after reducing the dosage or discontinuing voriconazole. CONCLUSIONS ：The neurological ADR of voriconazole mostly occurs 1-7 days after voriconazole administration ，mainly by intravenous drip ，mostly in male and people aged 50 and over. The occurrence of neurological ADR may be related to trough concentration of voriconazole ，and most patients suffer from hypokalemia or hyponatremia before the occurrence of ADR .

Analysis of Clinical Distribution and Drug Resistance of Acinetobacter baumannii in a Third-grade Class-A Hospital from Chongqing during 2015 to 2018 / 中国药房

OBJECTIVE：To provide reference for clinical treatment of Acinetobacter baumannii infection and rational use of antibiotics. METHODS ：By retrospective analysis ，64 500 strains of bacteria were isolated from the inpatients of our hospital during Jan. 2015 to Dec. 2018. WHONET 5.6 software was used to analyze the detection rate ，specimen type ，departments of A. baumannii. The resistance of A. baumannii to 18 commonly used antibiotics in 4 years was analyzed by RxC table χ 2 test. RESULTS：A total of 2 072，2 040，2 017 and 2 143 strains of A. baumannii were isolated during 2015-2018，accounting for 12.85％，13.38％，13.60％，11.71％ of positive specimens. The main specimen types of 8 272 strains of A. baumannii were sputum（4 368 strains，52.81％），pus（1 106 strains，13.37％），ascites（804 strains，9.72％）. The main departments were burn department（1 605 strains，19.40％），hepatobiliary department （1 200 strains，14.51％），brain surgery department （977 strains， 11.81％）. The drug resistance rate to 18 kinds of antibiotics showed a wave-like decreasing trend （P＜0.001）. In 2018，drug resistance rate to ampicillin and aztreonam was more than 80％，and that to ampicillin/sulbactam ，ceftazidime，levofloxacin， Compound sulfamethoxazole ，gentamicin，amikacin，tobramycin and tegacyclin was less than 50％ ，among which the drug resistance rate to amikacin and tegacyclin were 14.7％ and 0，respectively. CONCLUSIONS ：There is no significant change in the number of isolates and detection rate of A. baumannii in our hospital between 2015 and 2018. The bacteria mainly cause respiratory tract infection. Amikacin or tegacyclin are recommended for treatment.

The effect of knockdown A20 expression on the proliferation, apoptosis and migration of MCF-7 cells / 安徽医科大学学报

Objective To study the effect of knockdown A20 expression on the proliferation, apoptosis and migra-tion of MCF-7 cells and to evaluate the potential value of the A20 gene as the therapeutic target of breast cancer. Methods Synthesized siRNA targeted to A20 gene or negative control siRNA were transfected into MCF-7 cells by using lipofectamine 2000. CCK8 assay, Annexin V and 7-AAD double staining cytometry, Transwell assay were performed to investigate the effect of knockdown A20 mRNA expression on the proliferation, apoptosis, migration of MCF-7 cells, respectively. Results It can inhibit the proliferation and migration as well as promote the apoptosis in MCF-7 cells by knockdown A20 mRNA expression. Conclusion A20 gene plays an important role in the prolif-eration, apoptosis and migration of MCF-7 cells and it could be a potential therapeutic target of breast cancer.

HbA1c is positively associated with pulse wave velocity and Flow-mediated dilation in the patients with type 2 diabetes / 中国综合临床

Objective To investigate the association between HbA1c status,arterial stiffness and endothelial function in subjects with type 2 diabetes mellitus(DM).Methods The study group consisted of 338 DM patients,including 74 subjects with normal HbA1c(≤ 6.0％)(Group A),102 subjects with mildly increased HbA1c(HbA1C increased by less than 6.5％)(Group B)and 162 patients with high HbA1c level (HbA1c increased by more than 6.5％)(Group C).All patients were evaluated for glucose,HbA1c,TC and TG.Pulse wave velocity(PWV)and flow-mediated dialation(FMD)were performed simultaneously.Results Compared with Group A,Group B and C had higher baPWV([1734 ± 343]cm/s vs.[1537 ± 313]cm/s and [1853 ± 364]cm/s vs.[1537 ± 313]cm/s).Patients in Group C had a higher baPWV than those in Group B ([1853 ± 364]cm/s vs.[1734 ± 343]cm/s,P =0.006).The patients in group A had a lower level of FMD than that of group B and C([4.20±3.13]％ vs[5.29±3.92]％,[4.09±2.79]％ vs.[5.29±3.92]％,P＜0.01).Leaner association analysis showed a positive correlation between baPWV and HbAlc(r =0.53,P ＜0.01).baPWV was negatively correlated with FMD(r =-0.25,P ＜0.01).Logistic regression analysis showed that HbA1c(OR32.19％,CI 11.26 ～53.12,P＜0.001),age(OR 14.21,95％ CI 11.43 ～ 17.00,P＜0.001),systolic blood pressure(OR 7.36,95％ CI 6.12-8.59)and TC(OR:0.31,95％ CI:9.97-70.64)were independent predictors for the increased arterial stiffness(baPWV).Conclusion Arterial stiffness parameters varied significantly across subgroups of patients with different levels of HbA1c and the arterial stiffness was positively associated with deranged glucose homeostasis.

Contrast of prostate cancer and breast cancer / 国际肿瘤学杂志

There are many cancers whose growth depend on some hormones,called hormone-related cancers,such as thyroid cancer,breast cancer,endometrium cancer and prostate cancer.Among them,breast cancer and prostate cancer,have higher incidences and share a lot of features.Companng prostate cancer with breast cancer will make great significance in treatment of prostate cancer.