Background and purpose:Previous researches have shown that procalcitonin differentiates infec-tious from non-infectious fever and assesses the severity of infectious diseases. This study aimed to investigate the clin-ical value of procalcitonin in patients with chemotherapy-induced febrile neutropenia.Methods:A total of 147 patients with chemotherapy-induced febrile neutropenia admitted to intensive care unit from Jan. 2012 to Dec. 2014 were di-vided into infectious group and fever of unknown origin group according to clinical symptoms, signs and etiology. The infectious group was divided into sepsis, severe sepsis, and septic shock groups according to the severity of infection. The procalcitonin levels were compared between different groups.Results:A procalcitonin cut-off value>0.935 ng/mL provided a sensitivity of 90.0%, speciifcity of 90.0% and AUC=0.905. The procalcitonin level of the infectious group was signiifcantly higher than that of the fever of unknown origin group [1.805 (1.268-2.523) ng/mLvs 0.555 (0.398-0.818) ng/mL,P<0.001]. There is a signiifcant difference between the severe sepsis group and the sepsis group [13.885 (7.600-17.961) ng/mLvs 1.805 (1.268-2.563) ng/mL,P<0.001]. Compared with the severe sepsis group, the value of procalcitonin in the septic shock group was signiifcantly higher [23.800 (20.050-30.478) ng/mLvs 13.885 (4.955-19.133) ng/mL,P<0.001].Conclusion:Plasma procalcitonin is a useful marker for diagnosing neutropenia in patients with infection. Meanwhile, procalcitonin can be used to assess the severity of infection in patients with neutropenia.

Objective To explore the clinical significance and gene mutation profiles of renal transplant patients with unconjugated hyperbilirubinemia (Gilbert's syndrome).Methods Genomic DNA was extracted from peripheral blood samples of 8 renal transplant patients with Gilbert'S syndrome.UGT1A1 * 6 and UGT1A1 * 28 genotypes were identified through digital fluorescence molecular hybridization and DNA sequencing.Results There are 2 cases of UGT1A1 * 28 heterozygous mutant,3 cases of UGT1A1 * 6 homozygous mutant,2 case of UGT1A1 * 6 heterozygous mutant,1 case of UGT1A1 * 28 heterozygous mutant combined with UGT1A1 * 6 heterozygous mutant.Conclusion There is a higher heterozygous or homozygous gene mutation rate of UGT1A1 * 6 and UGT1A1 * 28 in renal transplant patients with Gilbert's syndrome.Genetic mutation of UGT1A1 * 6 and UGT1A1 * 28 may be the reason of Gilbert's syndrome after renal transplant.

ABSTRACT OBJECTIVE：To study the association between CYP3A5，CYP3A4，ABCB1 and POR*28 genetic polymorphisms and drug dosage（D）and steady blood concentration/dosage（c0/D）of tacrolimus in lung transplant recipients after one year of tacrolimus administration. METHODS：By retrospective analysis，a total of 46 recipients who underwent lung transplantation in China-Japan Friendship Hospital during May 2017-May 2018 were selected. The c0 and D of tacrolimus were measured and collected after one year of tacrolimus administration，and c0/D was calculated. Recipients’genotypes of CYP3A5（rs776746）， CYP3A4（rs2242480，rs28371759），ABCB1（rs1045642，rs2032582，rs1128503）and POR*28（rs1057868）were collected. The relationship between genetic polymorphism and D，c0/D was analyzed statistically. RESULTS：The genotype frequency in this study were all in accordance with Hardy-Weinberg equilibrium （P＞0.05）. While maintaining tacrolimus c0 within therapeutic range， genetic polymorphism of CYP3A5（rs776746）and CYP3A4（rs2242480）influenced D and c0/D of tacrolimus significantly（P＜ 0.05）. There was no statistical significance in D or c0/D among different genotypes of other sites（P＞0.05）. There was statistical significance in D or c0/D among extensive metabolism type recipients with CYP3A5（rs776746）*1 and CYP3A4（rs2242480）*1G alleles，normal metabolism type recipients with only CYP3A5 （rs776746） *1 or CYP3A4 （rs2242480） *1G alleles and poor metabolism type recipients without CYP3A5（rs776746）*1 and CYP3A4（rs2242480）* 1G alleles（P＜0.05）. D of tacrolimus was the highest in extensive metabolism type recipient and the lowest in poor metabolism type recipient. CONCLUSIONS：The detection of genetic polymorphism of CYP3A5（rs776746）and CYP3A4（rs2242480）has guiding significance for individualized medication of tacrolimus after one year of tacrolimus administration.

OBJECTIVE： To investigate pharmaceutical care of cancer pain therapy in medical institutions from Beijing area， and to provide reference for improving the quality of pharmaceutical care for cancer pain in medical institutions and formulating cancer pain therapy decision by public health administration departments at different levels. METHODS： Inspection results of standardized diagnosis and treatment for cancer pain were analyzed retrospectively in Beijing Pain Therapy Quality Control and Improvement Center during Feb.-Mar. 2018. Scoring results of pharmaceutical care （20 points） and its 5 sub-items （personnel participation， drug supply， drug management， outpatient prescription comment and inpatient prescription comment， 4 points each item） were analyzed statistically and classified according to hospital level and pharmaceutical care inspection results. RESULTS： A total of 64 hospitals in Beijing participated in the inspection， including 27 tertiary A hospitals （42.19％）， 21 tertiary B hospitals （32.81％）， 16 secondary hospitals or first-level hospitals （25.00％）. Pharmaceutical care in all hospitals met the inspection requirements with qualified rate of 100％. 52 hospitals performed excellently （81.25％）， and 12 hospitals were qualified for pharmaceutical care （18.75％）. Among 5 sub-items of personnel participation， drug supply， drug management， outpatient prescription comment and inpatient prescription comment， the average score of drug supply item was the highest （3.83±0.05）； the lowest was the personnel participation item （2.93±0.13）. The results of pharmaceutical care inspection in tertiary A hospitals （17.80±0.28） and tertiary B hospitals （17.78±0.30） were significantly better than those in secondary hospitals or first-level hospitals（16.16±0.50）（P＜0.01 or P＜0.05）； there was statistical significance only in the score of outpatient prescription comment among 5 sub-items（P＝0.026）. Total scores of the hospitals with excellent pharmaceutical care were significantly higher than those of the hospitals with qualified pharmaceutical care in terms of personnel participation， outpatient prescription comment and inpatient prescription comment （P＜0.01 or P＜0.05）. There was significant difference in the inspection results of pharmaceutical care among the excellent group， the qualified group and the unqualified group classified by the results of personnel participation item （P＜0.01 or P＜0.05）. CONCLUSIONS： The quality of pharmaceutical care for cancer pain therapy in medical institutions from Beijing area has reached the qualified level， but the participation of clinical pharmacists in cancer pain therapy and outpatient prescription comment still need improvement in further. The training of clinical pharmacists and information construction of narcotic drug management should be strengthened so as to improve the overall quality of pharmaceutical care for cancer pain.

Extracorporeal membrane oxygenation (ECMO) is a viable ultimate support therapy for patients with severe cardiorespiratory failure. Antimicrobial agents are commonly prescribed in critically ill patients with ECMO. However, an increasing number of studies have shown that ECMO circuit is associated with significant pharmacokinetic (PK) alterations, including the increased volume of distribution and reduced the clearance. In addition, the critical illness pathophysiology can also influence PK of antimicrobial, such as systemic inflammation, excessive fluid resuscitation, hypo-albuminemia, worsening hepatic or renal function. These PK alterations may increase the possibility of therapeutic failure or toxicity. Therefore, this study reviews published studies of the effects of ECMO on PK of antimicrobial agents in adults and makes preliminary recommendations on possible dosing regimen.

OBJECTIVE：To analyze the occurrence of acute kidney injury （AKI）after lung transplantation and its possible influential factors . METHODS ：Medical records of 64 patients who received lung transplantation in our hospital from April 2017 to June 2018 were included in this retrospective study. Patients were divided into AKI group （44 cases）and non-AKI group （20 cases），according to whether AKI occurred after operation. According to diagnostic criteria for lung transplantation in our hospital ， all patients were given Methylprednisolone sodium succinate for injection or Methylprednisolone sodium succinate for injection combined with Basiliximab for injection ，and triple immunosuppressive therapy of Tacrolimus capsules+Mycophenolate mofetil dispersible tablets or Mycophenolate mofetil capsules or Mycophenolate sodium enteric-coated tablets+Methylprednisolone tablets or Prednisone acetate tablets were given after operation. The occurrence of AKI in AKI group within a week after operation were recorded. Intraoperative influential factors （operation type ， operation duration ， ECMO support ， immune inhibitor use ， intraoperative blood loss ），postoperative influential factors [days of ICU ，mechanical ventilation and ECMO support ，median value of Scr within one week after operation ，median tacrolimus concentration and the use of potential nephrotoxic drugs （≥4 kinds）， hospitalization days] and survival rate one year after operation were observed in 2 groups. RESULTS ：Within one week after lung transplantation，44 patients（68.8％）had experienced at least one episode of AKI ，among which 19 cases（29.7％）were stage 1， 17 cases（26.5％）were stage 2 and 8 cases（12.5％）were stage 3. The incidence of AKI was the highest on post-operative day 4 （57.4％）. The incidence of AKI at stage 3 exhibited growth trend within the first week after operation ，and reached the highest on median post-operative day 5（8.7％）. Operation duration ，median value of Scr within one week after operation ，median tacrolimus concentration in non-AKI group were significantly shorter or lower than AKI group ；there was no significant difference in operation type， ECMO support ， use of immunosuppressive agents ， intraoperative blood loss ，ICU days ，mechanical ventilation days，ECMO support days ，the utilization rate of potential nephrotoxic drugs （ ≥4 kinds） and hospitalization days between 2 groups （P＞0.05）. There was no statistical significance in the survival rate at stage 1 and 2 one year after operation between AKI group and non-AKI group （P＞0.05）. One year after operation ，survival rate of AKI group at stage 3 was significantly lower than that of non-AKI group （P＜0.05）. CONCLUSIONS：The incidence of AKI is high after lung transplantation. Operation duration ，median value of Scr within one week after operation ，median tacrolimus concentration were possible factors for the occurrence of AKI after operation.

OBJECTIVE： To study the correlation of tacrolimus concentrations among transplant patients’ whole blood， plasma and blood cells， analyze the effects of transplant types and ages on the their correlation， and to provide reference for rational drug use in clinic. METHODS： Totally 20 patients receiving tacrolimus anti-rejection therapy after transplantation and undergoing therapeutic drug monitoring （TDM） were randomly selected. According to the type of transplantation， they were divided into renal transplantation group and lung transplantation group （10 cases for each group）.  According to age， they were divided into three groups： 20-40 years old group， 41-60 years old group and 61-80 years old group （4， 9， 7 cases for each group）. Their residual blood after TDM was collected. Chemiluminescence microparticle immuno assay  （CMIA） was used to detect the concentration of tacrolimus in whole blood. UPLC-MS/MS was used to measure the concentrations of tacrolimus in plasma and blood cells. Pairs plots and Spearman rank correlation analysis were used to analyze the correlation of tacrolimus between whole blood and plasma， between whole blood and blood cells， between plasma and blood cells as well as the effects of transplant types and ages on tacrolimus concentrations among tansplant patient’s whole blood， plasma and blood cells. RESULTS： The correlation of tacrolimus concentrations in whole blood and plasma （r＝0.623，P＜0.01） was slightly stronger than that of whole blood and blood cells （r＝0.591， P＜0.01）； while  the correlation of tacrolimus concentration in plasma and blood cells was relatively weak （r＝0.497，P＜0.05）. Transplant type and age had an effect on the correlation of tacrolimus concentrations among patients’ whole blood， plasma， blood cells. The correlation of tacrolimus concen- tration in whole blood， blood cells and plasma in renal transplantation group was also weak （all r＜0.5）， and was weaker than that in lung transplantation group. The correlation of tacrolimus concentration among whole blood， plasma and blood cells was weak in patients of aged 20-40 years old group （all r＜0.3）， and was weaker than that of patients of aged 41-60 years old group and 61-80 years old group. CONCLUSION： Post-transplantation patients’ tacrolimus concentrations in whole blood， plasma and blood cell have a weak correlation. Rejections and adverse effects should be monitored in these patients， especially those renal transplantation patients or those patients aged 20 to 40.

The formation of most proteins consists of two steps: the synthesis of precursor proteins and the synthesis of functional proteins. In these processes, propeptides play important roles in assisting protein folding or inhibiting its activity. As an important polypeptide chain coded by a gene sequence in lipase gene, propeptide usually functions as an intramolecular chaperone, assisting enzyme molecule folding. Meanwhile, some specific sites on propeptide such as glycosylated sites, have important effect on the activity, stability in extreme environment, methanol resistance and the substrate specificity of the lipase. Studying the mechanism of propeptide-mediated protein folding, as well as the influence of propeptide on lipases, will allow to regulate lipase by alternating the propeptide folding behavior and in turn pave new ways for protein engineering research.
Lipase/metabolism* ; Molecular Chaperones/metabolism* ; Protein Folding ; Protein Precursors ; Substrate Specificity