Objective To establish and validate an ultra performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS)method for quantification of MRX-I,a new oxazolidinone antibacterial agent,in human plasma and urine.Methods Chromatographic separation was performed on a Waters ACQUITY UPLC BEH C8 column using an isocratic elution.The mo-bile phase consisted of acetonitrile and water (40∶60,v/v).Quantitative analysis was conducted in the multiple reaction moni-toring mode.Linezolid was used as an internal standard.Liquid-liquid extraction with ethyl acetate was used to remove impuri-ties in the plasma and urine samples.The method was validated in terms of matrix effect,recovery,precision,accuracy and stability.Results The calibration curves were linear within the range of 0.005 00-1 .00 mg/L.The lower limit of quantification was 0.005 00 mg/L for both plasma and urine samples.Retention time was less than 1 .5 min for both MRX-I and internal standard in plasma and urine.The ma-trix effect factors of plasma and urine for MRX-I was 90.4%±8.2% and 82.7%±7.9%,respectively.The recovery of MRX-I was 112.8% ± 13.4% from plasma and 105.6% ± 13.4% from urine samples,respectively.The inter- and intra-day accuracy of MRX-I was 98.9%-105.0% and 96.5%-102.6% in plasma samples,and 92.7%-98.6% and 95.1 %-105.7% in urine samples.MRX-I was stable for 24 h at room tem-perature,48 h in automatic sampler after pretreatment,and stable after 3 freeze-thaw cycles in plasma and urine.MRX-I was also stable at-40℃for eight months in plasma and six months in urine,respectively.Conclusions The UPLC-MS/MS method established in this study shows high sensitivity and specificity for determination of MRX-I in human plasma and urine.The re-sults of validation are consistent with the requirement of bioanalytical method validation.

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 establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for determination of tobramycin in human serum,and examine the utility of the method in a clinical pharmacokinetic study of tobramycin inhalation.Methods Serum samples were pretreated by solid phase extraction with tobramycin-D12 as internal standard.Chromatographic separation was performed on a TitankHilic(2.1 mm × 100 mm,3 μm)column.The mobile phase consisted of0.1％formic acid-acetonitrile and 0.1％formic acid aqueous solution at a flow rate of 0.4 mL/min.Electrospray ionization source and multiple reaction monitoring(MRM)scanning were used for monitoring the quantitative ion pairs with m/z 468.3→m/z 163.3(tobramycin)and m/z 480.6→m/z 166.2(tobramycin-D12).The established method was investigated in terms of selectivity,interaction,concomitant medication,standard curve and lower limit of quantitation,precision and accuracy,recovery,matrix effect,and stability of tobramycinin.Results The linear range of tobramycin was 0.050 0-10.0 mg/L(R2=0.999 5).The intra-and inter-batch precision was satisfactory(coefficient of variation[CV]≤3.6％).The accuracy ranged from-0.4％to 6.0％.The matrix effect factor(MF)in human serum samples(including hemolysis and lipemia)ranged from 92.2％to 94.9％(CV≤2.7％).The recovery of tobramycinin was 79.5％-81.9％in serum samples,while the recovery of internal standard was 78.9％.The analyte was stable in serum samples for 72 h at room temperature and for 274 days at-20℃/-70℃.The pharmacokinetic study of tobramycin inhalation in bronchiectasis patients showed that after continuous administration of tobramycin 300 mg twice a day to 3 patients,the mean Cmax of tobramycin was(0.72±0.61)mg/L on Day 1 and(0.76±0.73)mg/L on Day 28,respectively.The corresponding Tmax was(1.83±0.61)h and(1.50±0.50)h,respectively.Conclusions The UPLC-MS/MS method established in this study is sensitive,accurate and rapid.It is successfully applied to the clinical pharmacokinetic study of tobramycin inhalation.The method may be suitable for therapeutic drug monitoring of tobramycin in clinical practice.

Pyroptosis is a programmed death of inflammatory cells triggered by pathogen invasion,dependent on caspase activation,through both classical and non-classical pyroptosis pathways.Cell pyroptosis is related to the occurrence and development of a variety of animal infectious diseases caused by microbial infection.After microorganisms invading,cells are stimulated by pathology-re-lated molecular patterns,causing strong immune response,stimulating inflammatory signaling pathways,and then activating inflammasome,leading to pyroptosis.The immune system has e-volved multiple mechanisms to fight microbial infections and regulate inflammatory responses.The innate immune system,by recognizing microbial molecules in pathogens and responding quickly by producing inflammasome and activating pyroptosis,helps clear pathogens to prevent infection and maintain the normal functioning of the body.A thorough study of the pathogenesis and immune es-cape mechanism of cell pyroptosis in animal infectious diseases will provide a new direction for the treatment of animal infectious diseases.