MiRNA,as a class of short non-coding RNA molecules,plays an important role in the post-transcriptional regula-tion of gene expression.miRNAs regulate gene expression by targeting specific mRNA sequences,thereby affecting various cellular bio-logical behaviors,including proliferation,apoptosis,migration,and invasion.In recent years,it has been found that miRNA may play an important role in the occurrence and development of hepatocellular carcinoma.This article provides a review of the research progress on the association between miRNA and the occurrence and development of hepatocellular carcinoma.

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.

MiRNA,as a class of short non-coding RNA molecules,plays an important role in the post-transcriptional regula-tion of gene expression.miRNAs regulate gene expression by targeting specific mRNA sequences,thereby affecting various cellular bio-logical behaviors,including proliferation,apoptosis,migration,and invasion.In recent years,it has been found that miRNA may play an important role in the occurrence and development of hepatocellular carcinoma.This article provides a review of the research progress on the association between miRNA and the occurrence and development of hepatocellular carcinoma.

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.

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.

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.

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