OBJECTIVE:To investigate the characteristics and regulations of antibacterials-induced adverse drug reactions (ADR) in our hospital,and to provide reference for promoting rational drug use. METHODS:233 patients with antibacterials-in-duced ADR in our hospital from Oct. 2013 to Jun. 2015 were selected and analyzed statistically according to patient's age and gen-der,route of administration,the type of antibacterials,occurrence time,organs/systems involved in ADR,etc. RESULTS:There were a large number of ADR in patients age ≤18 and ≥70 years,accounting for 19.3% and 18.5%;the male was more than the female;the incidence of ADR induced by intravenous route was the highest,accounting for 94.0%. Most of ADR was caused by cephalosporins,accounting for 33.9%;ADR often occurred within 1 d after medication,accounting for 63.9%;lesion of skin and its appendants injury was main ADR,accounting for 39.3%. CONCLUSIONS:Adhere to theclear indications,a detailed inqui-ry about allergy history before drug use,right dose,suitable route of administration and course,and timely ADR disposal can re-duce the damage caused by ADR.

AIM:Tostudywhe ther theangiotens in-(1-7)[Ang-(1-7)]/Mas receptor axis protects cardio-myocytes against high glucose (HG)-induced injury by inhibiting nuclear factor-κB (NF-κB) pathway.METHODS:The cell viability was measured by CCK-8 assay.The intracellular levels of reactive oxygen species ( ROS) were detected by DCFH-DA staining .The number of apoptotic cells was tested by Hoechst 33258 nuclear staining .Mitochondrial membrane potential ( MMP) was examined by JC-1 staining.The levels of NF-κB p65 subunit and cleaved caspase-3 protein were de-termined by Western blotting.RESULTS: Treatment of H9c2 cardiac cells with 35 mmol/L glucose (HG) for 30, 60, 90, 120 and 150 min significantly enhanced the levels of phosphorated ( p) NF-κB p65, peaking at 60 min.Co-treatment of the cells with 1 μmol/L Ang-(1-7) and HG for 60 min attenuated the up-regulation of p-NF-κB p65 induced by HG. Co-treatment of the cells with Ang-(1-7) at concentrations of 0.1~30μmol/L and HG for 24 h inhibited HG-induced cy-totoxicity, evidenced by an increase in cell viability .On the other hand, 1 μmol/L Ang-(1-7) ameliorated HG-induced apoptosis, oxidative stress and mitochondrial damage , indicated by decreases in the number of apoptotic cells , cleaved caspase-3 level, ROS generation and MMP loss .However, the above cardioprotective effects of Ang-(1-7) were markedly blocked by A-779, an antagonist of Ang-(1-7) receptor (Mas receptor).Similarly, co-treatment of H9c2 cardiac cells with 100 μmol/L PDTC ( an inhibitor of NF-κB) and HG for 24 h also obviously reduced the above injuries induced by HG.CONCLUSION:Ang-(1-7)/Mas receptor axis prevents the cardiomyocytes from the HG-induced injury by inhibiting NF-κB pathway .

Objective To assess the value of susceptibility-weighted imaging (SWI) in staging hepatic fibrosis (HF) in rabbits. Methods Sixty healthy rabbits were randomly divided into HF group (n=44), control group (n=16). Rabbits in the HF group and supplementary group were injected subcutaneously with 50%CCl4 oily solution to establish hepatic fibrosis model. On the basis of preliminary test, 8 rabbits in the HF group and 4 rabbits in the control group were selected randomly at the 4th, 5th, 6th, 10th week after CCL4 injection ,respectively , to undergo liver MR scan,including conventional axial T1WI, T2WI and axial SWI, DWI scan. All rabbits were sacrificed after MR scan and the tissue of liver were sampled for pathological test and hepatic fibrosis staging. Rabbits were classified into group F0, F1-2 and F3-4 based on pathological results. Liver signal intensity (SI), and liver-to-muscle SI ratio were measured on SWI images and ADC values were measured on DWI images correspondently. One-way ANOVA analysis was performed to compare difference in liver SI, liver-to-muscle SI ratio and ADC values among group F0 (no fibrosis), F1-2 (mild-moderate fibrosis) and F3-4 (severe fibrosis) . Spearman correlation analysis was performed to correlate pathological staging and liver SI, liver-to-muscle SI ratio and ADC values. Receiver operating characteristic (ROC) curve analysis was performed to compare the diagnostic performance of SWI and DWI for staging HF. Results Two and 5 rabbits in the HF group died at the 5th and the 6th week after CCL4 injection , respectively due to acute hepatic necrosis, hepatorrhexis and systemic failure. Seven rabbits in supplementary group were used as supplement. Of the 16 rabbits in the control group, 1 was excluded from the study due to liver fibrosis. Fifteen rabbits in group F0, sixteen rabbits in group F1-2 and sixteen rabbits in group F3-4 underwent MRI and were included into this study. Liver-to-muscle SI ratio in group F0, F1-2 and F3-4 were 0.973 ± 0.020, 0.880 ± 0.090 and 0.649 ± 0.140, respectively. Liver SI were 378 ± 45, 374 ± 19 and 317 ± 34. ADC values were (1.473 ± 0.320) × 10-3, (1.311 ± 0.310) × 10-3 and (0.942 ± 0.180) × 10-3mm2/s. There were statistically significant differences in liver SI, liver-to-muscle SI ratio and ADC values among group F0, F1-2 and F3-4 (F=46.571,15.803 and 15.317, P< 0.01). Liver-to-muscle SI ratio was highly negatively correlated with HF staging (r=-0.818,P<0.01), while liver SI and ADC values were moderately correlated with HF staging (r=-0.565,-0.630;P<0.01). Area under ROC curve (AUC) of liver-to-muscle SI ratio, liver SI and ADC value for differentiating hepatic fibrosis stage F0 and stage F1-4 were 0.916, 0.695 and 0.768, while the AUC for differentiating hepatic fibrosis stage F0-2 and stage F3-4 were 0.951, 0.904 and 0.900. Conclusion Liver-to-muscle SI ratio on SWI provide added diagnostic value and could be an useful parameter for staging hepatic fibrosis.

AIM:To investigate the roles of ATP-sensitive potassium ( KATP ) channels in high glucose-induced cardiac injury and the inhibitory effect of hydrogen sulfide ( H2 S) on the cardiomyocyte injury.METHODS:The expres-sion level of KATP channel protein was tested by Western blot.The cell viability was measured by CCK-8 assay.The number of apoptotic cells was observed by Hoechst 33258 nuclear staining.Mitochondrial membrane potential ( MMP) was exam-ined by JC-1 staining.RESULTS:After the H9c2 cells were treated with 35 mmol/L glucose ( high glucose, HG) for 1~24 h, the protein level of KATP channel was significantly reduced at 6 h, 9 h, 12 h and 24 h, reaching the minimum level at 12 h and 24 h.Pretreatment of the cells with 400μmol/L NaHS ( a donor of H2 S) prior to exposure to HG for 12 h con-siderably blocked the down-regulation of KATP channels induced by HG.Pretreatment of the cells with 100 μmol/L mito-chondrial KATP channel opener diazoxide, 50μmol/L non-selective KATP channel opener pinacidil or NaHS obviously inhibi-ted HG-induced injuries, leading to an increase in the cell viability, and decreases in the number of apoptotic cells and the MMP loss.Pretreatment with 100μmol/L mitochondrial KATP channel antagonist 5-hydroxydecanoic acid or 1 mmol/L non-selective KATP channel antagonist glibenclamide attenuated the above cardioprotective effects of NaHS.CONCLUSION:KATP channels mediate the inhibitory effect of H2 S on HG-induced cardiac injury.

Objective:To compare the diagnostic efficacy of MR elastography (MRE), Gd-EOB-DTPA dynamic contrast-enhanced MRI (DCE-MRI) in early quantitative evaluation of liver fibrosis (LF) staging of experimental rabbits.Methods:From April to December 2019, 200 healthy rabbits were randomly divided into LF group ( n=160) and control group ( n=40). LF group were injected subcutaneously with 50% CCl 4 oil solution, while control group were injected with normal saline solution. The LF group ( n=40) and control group ( n=10) were randomly selected at the end of the 4th, 8th, 12th and 16th weeks respectively to undergo axial MRI scan including MRE and Gd-EOB-DTPA DCE-MRI. The quantitative parameter values were obtained, including liver stiffness (LS), volume transfer constant (K trans), reflux rate constant (K ep), volume fraction of extravascular extracellular space (V e) and volume fraction of plasma (V p). Histopathological LF staging was based on Scheuer staging. One-way ANOVA analysis was used to evaluate the differences of LS, K trans, K ep, V e and V p among different LF stages. The Spearman correlation analysis was used to evaluate the correlations between pathological LF staging and quantitative parameter values. The ROC curve was used to compare the diagnositic performance of all quantitative parameter values. Results:Among the final qualified 150 rabbits, there were 32 in F0, 32 in F1, 35 in F2, 30 in F3, 21 in F4. Significant differences of LS, K trans, K ep, V e and V p were found among different LF stages. There was correlation between LS, K trans, K ep and LF stages ( r=0.832, 0.730, -0.617, all P<0.001), respectively. However, no statistically correlation was found between V e, V p and LF stages ( r=-0.074, P=0.367; r=-0.078, P=0.342). The area under the ROC curve (AUCs) of LS were the greatest (0.920 for F0 vs F1-F4, 0.900 for F0 vs F1-F2, 0.945 for F0 vs F3-F4, 0.926 for F1-F2 vs F3-F4), while the AUCs of K trans were 0.897, 0.863, 0.942, 0.809, respectively. Conclusion:The early quantitative diagnostic efficacy for LF staging by MRE was superior to Gd-EOB-DTPA DCE-MRI in rabbits.

Objective:To investigate the prognostic risk factors of young patients with upper gastrointestinal bleeding (UGIB) in emergency department (ED), so as to improve the efficiency of emergency treatment and diversion of these patients.Methods:A retrospective analysis was performed on the clinical data of young patients with UGIB in the ED of Hainan Provincial People's Hospital from January 1, 2019 to December 30, 2020. In-hospital mortality was the primary endpoint of the study, and admission to the Intensive Care Unit (ICU) and length of hospital stay were the secondary endpoints. Inclusion criteria: (1) patients met the diagnostic criteria of acute UGIB; (2) age ranged from 18 to 40 years old; and (3) complete clinical data. Exclusion criteria: (1) bleeding and hemoptysis from the mouth, nose and throat; (2) gastrointestinal bleeding occurred in hospital; (3) lower gastrointestinal bleeding; (4) incomplete clinical data.Results:Among the 383 patients, 268 (70.0%) underwent upper gastrointestinal endoscopy, and the most frequent endoscopic diagnoses were duodenal ulcer (64.6%) and esophageal-gastric varices bleeding (16.8%). Seventy-one (18.5%) patients required endoscopic treatment, 5 (1.3%) patients required surgical treatment, and 7 (1.8%) patients required intervention treatment. The mortality rate was 2.1%, the ICU admission rate was 2.3%, and the length of hospital stay was 5 (3, 6) d. The ICU admission rate and mortality rate were significantly higher in patients with liver disease and in patients with syncope/coma (all P<0.05). Patients with thrombocyte levels (<120×10 9/L) had a significantly longer length of hospital stay than that of patients with normal platelets [8 (5, 11) d vs. 4 (3, 6) d, P<0.001]. The dead patients had significantly higher white blood cell count, urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase and activated partial thrombin time levels (all P<0.05), and significantly lower hemoglobin, albumin, SpO 2 and Glasgow coma score (GCS) levels (all P<0.05). Low GCS was an independent risk factor of ICU admission ( OR=33.973, 95% CI: 1.582~729.417, P=0.024) and mortality ( OR=20.583, 95% CI: 1.368~309.758, P=0.029). Conclusions:The poor prognostic factors of young patients with UGIB in ED are concomitant liver disease, syncope/coma, co-infection, hyperazotemia, impaired kidney function, liver dysfunction, coagulopathy, anemia, and low SpO 2, low GCS, and low hypoproteinemia on admission.

Objective:To analyze the positive detection rate, main genotypes of β-thalassemia in western region of Guangxi Zhuang Autonomous Region (referred to as Guangxi).Methods:Retrospective analysis of 26 189 individuals who underwent gene testing for thalassemia at the Affiliated Hospital of Youjiang Medical University for Nationalities from January 2013 to December 2019. Using the crossing breakpoint PCR (Gap-PCR) and reverse dot blot (RDB) techniques to detect Chinese common type of 7 kinds of α-thalassemia and 17 kinds of β-thalassemia genotypes, high-throughput sequencing(Sanger) was performed for suspected rare β-thalassemia. Gap-PCR was used for suspected deletion β-thalassemia types.Results:β-thalassemia was diagnosed in 4 495 (17.16%) of 26 189 samples. A total of 6 177 alleles of 20 types of β-thalassemia were detected, mainly CD17 (2 712 cases, 43.90%) and CD41-42 (2 240 cases, 36.26%), including 7 rare alleles: Gγ +( Aγδβ) 0, SEA-HPFH, Hb New York, Hb G-Taipei, Hb Hezhou, Hb G-Coushatta and IVS-Ⅱ-81. There were 3 903 case (86.83%) heterozygous, 273 case (6.07%) double heterozygous, and 319 case (7.10%) homozygous among 4 495 β-thalassaemia subjects. A total of 48 genotypes were detected. The two most common genotypes were CD17/β N (1 890 cases, 42.05%) and CD41-42/β N (1 212 cases, 26.96%), accounted for 69.01% (3 102/4 495). Seven rare genotypes were detected: Gγ +( Aγδβ) 0/β N in 3 cases, Hb New York/β N in 3 cases, Hb G-Taipei/β N in 2 cases, SEA-HPFH/β N, Hb Hezhou/β N, Hb G-Coushatta/β N and IVS-Ⅱ-81/β N in 1 case each. A total of 1 041 cases (3.97%, 1 041/26 189) of 116 types of αβ-thalassemia were detected, mainly -- SEA/αα composite CD17/β N (144 cases, 13.83%), followed by -α 3.7/αα composite CD17/β N (112 cases, 10.76%). Conclusions:Western region of Guangxi is a high prevalence area of β-thalassemia, CD17/β N and CD41-42/β N are the main genotypes. The variation spectrum of β-thalassemia is complex and diverse, with rich genotype.

Over the past 30 years, Yarrowia lipolytica, Kluyveromyces, Pichia, Candida, Hansenula and other non-conventional yeasts have attracted wide attention because of their desirable phenotypes, such as rapid growth, capability of utilizing multiple substrates, and stress tolerance. A variety of synthetic biology tools are being developed for exploitation of their unique phenotypes, making them potential cell factories for the production of recombinant proteins and renewable bio-based chemicals. This review summarizes the gene editing tools and the metabolic engineering strategies recently developed for non-conventional yeasts. Moreover, the challenges and future perspectives for developing non-conventional yeasts into efficient cell factories for the production of useful products through metabolic engineering are discussed.
Gene Editing ; Metabolic Engineering ; Pichia/genetics* ; Synthetic Biology ; Yarrowia/genetics* ; Yeasts