Case analysis of a patient with isavuconazonium-caused pancytopenia / 中国药房

OBJECTIVE To correctly identify and deal with the adverse drug reaction as pancytopenia caused by isavuconazonium and to provide reference for the safe use of isavuconazonium. METHODS Clinical pharmacists analyzed a case of severe infection and renal insufficiency who experienced pancytopenia after using isavuconazonium. Clinical pharmacists screened the drugs used during hospitalization and evaluated the relationship between this adverse drug reaction and isavuconazonium， as well as the possible mechanisms， based on the half-life of the drugs and relevant literature. RESULTS & CONCLUSIONS The relationship between pancytopenia and isavuconazonium was assessed as “possibly related”. When using isavuconazonium， attention should be paid to avoiding the combination of drugs with the same mechanism or potential interaction. For patients who have a course of treatment for more than 2 weeks， have hematological abnormalities or complicated with liver and renal insufficiency， or should use it combined with other drug with same mechanism， it may be considered to increase the frequency of blood routine monitoring.

Expression of a Lactobacillus casei L-lactate dehydrogenase mutant in Pichia pastoris for asymmetric reduction of phenylpyruvate / 生物工程学报

To improve the productivity of L-phenyllactic acid (L-PLA), L-LcLDH1(Q88A/I229A), a Lactobacillus casei L-lactate dehydrogenase mutant, was successfully expressed in Pichia pastoris GS115. An NADH regeneration system in vitro was then constructed by coupling the recombinant (re) LcLDH1(Q88A/I229A) with a glucose 1-dehydrogenase for the asymmetric reduction of phenylpyruvate (PPA) to L-PLA. SDS-PAGE analysis showed that the apparent molecular weight of reLcLDH1(Q88A/I229A) was 36.8 kDa. And its specific activity was 270.5 U/mg, 42.9-fold higher than that of LcLDH1 (6.3 U/mg). The asymmetric reduction of PPA (100 mmol/L) was performed at 40 °C and pH 5.0 in an optimal biocatalytic system, containing 10 U/mL reLcLDH1(Q88A/I229A), 1 U/mL SyGDH, 2 mmol/L NAD⁺ and 120 mmol/L D-glucose, producing L-PLA with 99.8% yield and over 99% enantiomeric excess (ee). In addition, the space-time yield (STY) and average turnover frequency (aTOF) were as high as 9.5 g/(L·h) and 257.0 g/(g·h), respectively. The high productivity of reLcLDH1(Q88A/I229A) in the asymmetric reduction of PPA makes it a promising biocatalyst in the preparation of L-PLA.

Translational research on gastric cancer: Ruijin experience / 中华胃肠外科杂志

Translational medicine refers to translating basic research achievements into the clinical application for diagnosis and treatment. There are still many issues of gastric cancer to be solved in clinical diagnosis and treatment. We need to focus on clinical questions, by means of basic research and multidisciplinary intersection approach, to further improve the overall efficacy of gastric cancer. Based on Ruijin Hospital′s translational research experiences, in this paper, the authors describe the future direction in the field of translational research, such as the etiology and pathogenesis of gastric cancer, tumor markers for early diagnosis, prediction of recurrence and metastasis, classification criteria, evaluation of chemotherapy, tumor heterogeneity, targeted therapy, immunotherapy and research platform establishment. In addition, here we share our perspective of the research on serum biomarkers, specific antibodies and improvement of drug delivery for gastric cancer.

Value of semi-quantitative indices of 68Ga-PSMA-11 PET/CT in differential diagnosis of malignant and benign prostate lesions / 中华核医学与分子影像杂志

Objective To evaluate the value of semi-quantitative indices of 68Ga-prostate specific membrane antigen (PSMA)-11 PET/CT in differentiating malignant and benign prostate lesions.Methods From November 2017 to June 2018,30 patients (age:52-86 years) who underwent 68Ga-PSMA-11 PET/CT imaging in the Third Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed,and the serum total prostate specific antigen (tPSA) and free prostate specific antigen (fPSA) were examined within 1 week before PET/CT imaging.Semi-quantitative indices of 68Ga-PSMA-11 PET/CT on prostate lesions were measured by automatic segmentation algorithm method,including PSMA-related lesion volume (VPSMA),maximum standardized uptake value (SUVmax),mean standardized uptake value (SUVmean),peak standardized uptake value (SUVpeak) and total lesion uptake value of PSMA (TLUPSMA).The indices were compared between malignant and benign prostate lesions,and the optimal cut-off values for differentiating malignant and benign prostate lesions were obtained by receiver operating characteristic (ROC) curve analysis.Results According to the pathological results,19 patients had malignant lesions and 11 were with benign diseases.The differences of tPSA,SUVmax,SUVmean SUVpeak and TLUPSMA between malignant and benign prostate lesions were statistically significant (u values:17.00-48.00,all P＜0.05),but there were no significant differences of fPSA,fPSA/tPSA and VPSMA between 2 groups (u values:64.00-99.00,all P＞0.05).The optimal cut-off value of tPSA was 18.30 μg/L for differentiating malignant and benign prostate lesions,with sensitivity of 13/17 (PSA of 2 patients were missing),specificity of 9/11 and area under curve (AUC) of 0.743.The optimal cut-off values of SUVmax,SUVmean and SUVpeak were 5.50,3.09 and 3.56,respectively,with all corresponding sensitivity of 18/19,all specificity of 9/11,and AUC of 0.902,0.907 and 0.919,respectively.The optimal cut-off value of TLUPSMA was 54.81 cm3,with sensitivity of 14/19,specificity of 9/11 and AUC of 0.804.Conclusion The semi-quantitative indices of 68Ga-PSMA-11 PET/CT are valuable for differentiating malignant and benign prostate lesions,in which SUVpeak is superior to other indices.

Prognostic value of metabolic tumor volume and total lesion glycolysis from ¹⁸F-FDG PET/CT in lymph node metastases and risk stratification of endometrial carcinoma / 부인종양

OBJECTIVE: To investigate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG), measured by preoperative ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT), in risk stratification of patients with endometrial carcinoma (EC). METHODS: The patients with pathological diagnosis of EC who underwent preoperative ¹⁸F-FDG PET/CT imaging were retrospectively selected for analysis of the prognostic values of PET parameters in risk classification and lymph node metastases (LNMs). Receiver-operating-characteristic analysis was used to analyze the correlation of PET parameters cutoff values with deep myometrial invasion (MI), lymphovascular space involvement and LNM for prognostic values in risk stratification. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for detection of LNM are 83.3%, 99.7%, 90.9%, 99.5% and 99.2%, respectively. The MTV and TLG of primary lesion of EC in the patients with LNM are notably higher than those in patients without LNM, p<0.010. The MTV and TLG of the EC primary lesions in high-risk patients are significantly higher than those in low-risk patients (p<0.010), but the maximum standardized uptake value (SUVmax) is not. The MTV and TLG of primary lesions were superior to SUVmax for predicting of deep MI, LNM and high-risk of EC (p<0.005). CONCLUSION: MTV and TLG of primary lesions are more valuable in predicting risk stratification of EC patients. Preoperative ¹⁸F-FDG PET/CT imaging is useful in predicting the LNM of EC and may help guide pelvic lymphadenectomy to avoid unnecessary pelvic lymphadenectomy in EC patients with low-risk stratification.

Clinical application of laparoscopic Roux-en-Y gastric bypass in patients with type 2 diabetes mellitus / 中华内分泌外科杂志

Objective To evaluate the clinical effects of the laparoscopic Roux-en-Y gastric bypass (LRYGB) on patients with type 2 diabetes mellitus (T2DM).Methods From Dec.2013 to Dec.2015,83 cases with T2DM received LRYGB were enrolled to this study.They were divided into low body mass index group (LBMI,25≤BMI＜28),intermediate body mass index group (IBMI,28≤BMI＜32) and high body mass index group (HBMI,BMI≥33).Meanwhile,the clinical effects and side-effects were evaluated among three groups.The factors of adverse effects were evaluated by Cox multivariate analysis.Results Only one patient in HBMI was conversed to open surgery,all the others received LRYGB.The surgery time,intraoperative blood loss and complica tion were positively related to BMI,and the difference was statistically significant between the 3 groups(P＜0.05).The main side-effect of LRYGB was gastrointestinal reaction.The level of fasting blood-glucose,postprandial 2 hours blood sugar,HbA1c and cholesterol total in three groups were lower than baseline (P＜0.05),however,there was no significant difference among the three groups (P＞0.05).The rate of clinical effects in three groups was 89.5％,89.3％ and 91.7％.There was no significant difference among the three groups(P＞0.05);In Cox multivariate analysis,cholesterol total and BMI were independent prognostic indicator for LRGB adverse.Conclusions LRYGB is a safe and effective method for patients with T2DM,which can effectively improve glucose and lipid metabolism.The increased BMI can increase the incidence of LRYGB complications.Total cholesterol is an independent prognostic indicator for the adverse of LRYGB.

Isolation, culture and identification of bacterial strains from tree shrews feces / 中国比较医学杂志

Objective Study the fecal flora diversity of the tree shrew , to provide a basis data of fecal bacteria of feeding the tree shrew .Methods Ten tree shrews were used in this study .The Stools of the animals were respectively cultured with oxygen and without oxygen to isolate the bacterial .Then the PCR-amplified 16S rRNA of the bacterial was sequenced and analyzed .Results 25 bacterial strains belonging to ten bacterial species were isolated by anaerobic incubation , and 25 bacterial strains belonging to twelve bacterial species were isolated by aerobic incubation .Proteus vulgaris, Enterococcus faecalis, Escherichia fergusonii, Enterococcus faecium, Shigella flexneri, Shigella sonnei, Staphylococcus aureus , Aeromonas salmonicida subsp .masoucida , Rahnella aquatilis , Exiguobacterium aquaticum , Raoultella terrigena , and Escherichia coli were identified in this study .Conclusions There is a fecal flora diversity of the tree shrew, and the Proteus vulgaris , Escherichia fergusonii and Enterococcus faecium may be the major parasitic flora .

Effect of siRNA-mediated silencing of Notch2 on proliferation of the HepG2 human hepatocellular carcinoma cells / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the effect of silencing the Notch2 gene by small interfering (si)RNA on the proliferation of the HepG2 human hepatocellular carcinoma (HCC) cells.</p><p><b>METHODS</b>Notch2-siRNA was transfected as a liposomal formulation into HepG2 cells. The non-HCC cell lines SG07901 (gastric cancer) and SW620 (colon cancer) were used as controls. The mRNA expression of Notch2 and Hesl were detected by RTPCR, and the protein expression of Notch2 was detected by western blotting. The proliferation of transfected HepG2 cells was assessed by the cell counting kit-8 (CCK8) colorimetric assay.</p><p><b>RESULTS</b>The untransfected HepG2 cells showed significantly upregulated transcript expression of Notch2, and not of Notch1, Notch3 or Notch4, compared to the other non-HCC cell lines. Following transfection of Noteh2-siRNA into HepG2 cells, the mRNA expression of Notch2 and Hes1 and the protein expression of Notch2 were significantly decreased. The rales of proliferation inhibition in HepG2 following transfection of Notch2-siRNA showed an increasing time-related trend, with 2.64% ± 1620% at 12 h, 38.34% ± 8.80% at 24 h, 70.05% ± 7.80% at 48 h, 70.78% ± 10.00% at 72 h, and 74.22% ± 4.80% at 96 h.The inhibition rate at 24 h of transfection was significantly different from that of the groups of control cells.</p><p><b>CONCLUSION</b>Notch2 is upregulated in the common HCC cultured cell line HepG2. siRNA-mediated silencing of Notch2 exerts inhibition effects on HepG2 proliferation, suggesting the potential for this approach as targeted therapy for treating HCC.</p>

Evaluation of procalcitonin for the prediction of bacteremia / 国际检验医学杂志

Objective To evaluate the diagnostic value of procalcitonin (PCT)in bacteremia.Methods Clinical data of adult pa-tients with suspected bacteremia were retrospectively analyzed for white blood cell counts(WBC),neutrophil absolute (NEU)and PCT levels in blood samples collected at the first time of blood culture.Receiver operating characteristic (ROC)curve was used to evaluate the values of different indexes for the prediction of bacteremia.Results A total of 120 patients were enrolled,including 47 patients (39.2%)with bacteremia and 73 patients (60.8%)without bacteremia.PCT,WBC and NEU levels were significantly higher in bacteremia patients than patients without bacteremia (P0.05).Taking 0.43 ng/mL as cutoff value,the negative predictive value of PCT was 94.7%.The best cutoff value of PCT was 2.27 ng/mL,which was associated with sensitivity of 74.47%,specificity of 90.00%,positive predictive value of 83.3% and negative predictive value of 84.0%.Conclusion PCT might be with more clinical value for the prediction of bacteremi than WBC and NEU.

Changes of bonemarrow and circulating endothelial progenitor cells in mice with acute pancreatitis / 国际外科学杂志

Objective To investigate changes in number of endothelial progenitor cells(EPCs)from bone marrow and circulation in mice with acute pancreatitis.Methods BALB/c mice were assigned randomly to saline group and cerulein group.Animals were sacrificed at 12, 24 and 48 hours after injection.Bone marrow and circulating EPCs were detected by flow cyzometric analysis.Plasma VEGF, TNF-α and ET-1 were determined by enzyme-linked immunosorbent assay.The expression of VEGF in the pancreas was assessed by Western blotting.Apoptosis in situ was detected by TUNEL.Results The amounts of EPCs in bone marrow and circulation increased remarkably after cerulein injection(P < 0.05), also the levels of plasma VEGF TNF-α and ET-1(P < 0.05), the EPCs levels in bone marrow and circulation seen in the study closely mirrors the levels of VEGF detected in the circulation(r = 0.77, 0.67 individually).VEGF expression in pancreas was up-regulated after 12 h of cerulein injection compared with that of control group.Apoptosis of endothelial cells also increased in the cerulein group.Conclusion EPCs were mobilized by acute pancreatitis, which may be due to the mobilizing effect of increased levels of VEGF, EPCs may participate in the repair process of injured endothelium induced by acute pancreatitis.

Research about the effect of pain-related education program on nurses' attitude, knowledge and as-sessment practices of pains / 中国实用护理杂志

Objective To know the influence of pain-related education program on nurses'attitude, knowledge and assessment practices of pains.Methods The effects of pain education program (PEP) were measured by a quasi-experimental design, 196 nurses were divided into the experimental group(106 cases)and the control group(90 cases)randomly.Pain education program was used only in the experimental group.Compared level of pain- related knowledge, attitude and assessement paractiees between the two groups.Results Nurses in the experimental group who received the PEP had a significant improvement in their pain knowledge and attitudes.Their scores on the NKAS increased from 15.67 at T1 to 26.13 at T2 and 35.14 at T3.The scores of nurses in the control group were unchanged (from 15.20 at T1 to 14.29 at T2 and 14.93 at T3).In addition, the percentage of experimental group nurses who correctly used the Changhai Pain Scale to assess patients' pain intensity increased significantly after the PEP, and the in-creased usage of the assessment tool between experimental and control groups also shows a statistical differ-ence in trend.Conclusions The PEP does impact on nurses' knowledge levels and clinical behavior.It can be concluded that PEP is effective in improving nurses' pain knowledge, attitude and assessment prac-tice.

Application and Evaluation of Reverse Dot Blot (RDB) Hybridization Assay for HBV YMDD Motif Mutants / 中山大学学报(医学科学版)

[Objective] To detect HBV YMDD motif mutants using RDB hybridization assay in lamivudine treated patients with chronic hepatitis B virus infection,as well as to evaluate the detection capability for clinical application.[Method] HBV DNA was extracted from serum for a total of 242 cases,after the PCR amplification,the hybridization was performed.By comparing the RDB assay results to sequence analysis,the concordant results were analyzed.The sensitivity and detection capability for mixed infection samples are also evaluated.[Results] There are 236 of concordant results for RDB assay and sequencing were obtained in a total of 242 cases,accounting for 97.5%.For all of the cases,there are 58 cases with coexisting mutant viruses in wild type viruses,accounting for 24%.The sensitivity of RDB hybridization assay for HBV YMDD motif mutants was 103 IU/mL,and approximately 10% mutant type strains can be detected from a mixed infection sample.[Conclusion] The RDB hybridization assay for HBV YMDD motif mutants is a simple,accurate,and economic method and it may be a promising tool for clinical application.