Fungal infections have emerged as a critical public health issue endangering human health. However, the existing arsenal of antifungal agents is limited in diversity and is commonly plagued by drawbacks including narrow antimicrobial spectrums and the frequent emergence of drug resistance, which severely compromises the efficacy of clinical treatments. Pathogenic fungi can develop extensive adaptability to currently available drugs through multiple mechanisms, which are mainly manifested in three aspects: drug resistance, tolerance and persistence. The molecular mechanisms and regulatory pathways underlying drug resistance, tolerance and persistence in pathogenic fungi were systematically summarized in this review, and the counteractive strategies such as combination therapy and the development of novel antifungal agents were further discussed, which aimed to provide theoretical basis and practical reference for the precision treatment of fungal infections.

Objective To investigate the combined effect of berberine （BBR） and fluconazole （FLC） on FLC-tolerant Candida albicans in vitro. Methods The sensitivity of 8 strains of Candida albicans to FLC was assessed by determining their minimal inhibitory concentration （MIC） using broth microdilution method. FLC-tolerant strains were screened from FLC-sensitive strains by disk diffusion assay. The effect of BBR combined with FLC on FLC-tolerant Candida albicans was investigated by disk diffusion assay. Results All eight strains of Candida albicans exhibited sensitivity to FLC, with minimal inhibitory concentration （MIC₅₀） values below 0.5 μg/ml. Strains Y0109, 9821, 7879, 7654, and 9296 displayed colony growth in the inhibition zone after 48 h of constant temperature incubation, indicating FLC tolerance. When strains Y0109 and 9821 were subjected to a combination of BBR and FLC, the number of colonies within the inhibition zone decreased progressively with the increase of BBR concentration following a 48 h constant temperature culture. The inhibition zone became clear with the increasing of BBR concentration and increased with the increase of FLC loading, which showed a dose-dependent relationship. Conclusion The BBR combined with FLC demonstrated efficacy against FLC-tolerant strains.

AIM:To understand the efficacy and safety of amikacin(AMK)for the treatment of car-bapenem-resistant Klebsiella pneumoniae pneu-moniae(CRKP)in preterm infants and to establish a management process for the use of amikacin in preterm infants.METHODS:CRKP-infected preterm infants treated with amikacin between January 2019 and December 2021 were retrospectively ana-lyzed,and parametric data paired t-tests were used to assess the efficacy and safety of amikacin for the included infectious and safety indicators,and to es-tablish a management process for amikacin use in preterm infants.RESULTS:Eight cases of CRKP in-fection were included,with the main diagnosis of pneumonia and sepsis.eight preterm infants were screened for the AMK ototoxicity gene mitochon-drial gene MT-RNR1(MT-RNR1 1494C＞T and MT-RNR11555A＞G)before amikacin treatment,and none of them were found to have the gene variant.after receiving amikacin sulphate injection treat-ment for 7 days,the indicators of infectivity were improved,and was statistically significant(P＜0.01).No clinical ototoxicity or nephrotoxicity was ob-served in the children before or after treatment.CONCLUSION:Aminoglycosides are still the main antibiotics used for the empirical treatment of sus-pected infections in preterm infants,especially drug-resistant bacterial infections.Despite the risk of ototoxicity and nephrotoxicity,we provide man-agement procedures and recommendations for neonatal treatment with amikacin to reduce the risk of ototoxicity and nephrotoxicity in AMK.

OBJECTIVE To observe the efficacy and safety of hydromorphone in patient-controlled intravenous analgesia(PCIA)after uvulopalatopharyngoplasty.METHODS A total of 90 patients who received uvulopalatopharyngoplasty in Central Theater General Hospital from January 2022 to June 2023 were selected and divided into three groups(n=30 in each group)by using random number table method.Control group was given sufentanil 2.0 μg/kg,group A was given hydromorphone 0.20 mg/kg and group B was given hydromorphone 0.30 mg/kg.The analgesic parameters of three groups were background infusion rate of 1.2 ml/h,PCA amount of 2 ml,and lock-up time of 10 min.VAS score and Ramsay sedation score at 2 h,6 h,12 h,24 h and 48 h after surgery were recorded,as well as the number of compressions within 48 h after surgery,and the incidence of adverse reactions were analyzed.RESULTS There were no significant differences in intraoperative blood loss,operation time and intraoperative urine volume among the three groups(P>0.05).VAS score in group A and group B at 2 h(2.0±0.3,2.2±0.4),6 h(1.8±0.4,1.9±0.4),12 h(1.8±0.4,1.7±0.4),24 h(1.6±0.3,1.5±0.4)and 48 h(1.1±0.3,1.2±0.4)were significantly lower than those in control group(2.8±0.5,2.3±0.5,2.1±0.4,2.0±0.5,1.7±0.5)(P<0.05),but there was no significant difference between group A and group B(P>0.05).The Ramsay score of group A and group B at 2 h,6 h,12 h,24 h,and 48 h after operation was significantly lower than that of the control group(P<0.05).There was no significant difference in Ramsay score between group A and group B(P>0.05).The total number of compressions and effective number of compressions in group A and group B at 12 h,24 h and 48 h after surgery were lower than those in control group(P<0.05),but there was no significant difference between group A and group B(P>0.05).The incidence of total adverse reactions in group B was higher than that in group A and control group(P<0.05).There was no significant difference in the incidence of total adverse reactions between group A and control group(P<0.05).CONCLUSION Hydromorphone can effectively be used for postoperative self-controlled analgesia in patients with uvulopalatopharyngoplasty,and the efficacy is better than sufentanil,but the dose of 0.20 mg/kg hydromorphone has better safety than that of 0.3 mg/kg hydromorphone.

Objective:In order to truly realize the deep integration of ideological and political education and professional edu-cation in the course of Animal Immunology and effectively improve the comprehensive quality of students.Methods:The experiment adopts the teaching method of integrating the online and offline hybrid teaching of Animal Immunology into the ideology and politics of the course,studies the course design concept,teaching objectives,teaching design and teaching implementation,and will conduct an evaluation of the teaching effect from the examination results and ideological and political effect.Results:The results show that the teaching model has stimulated students'interest in learning and improved their overall ability.Conclusion:It shows that the teaching effect of this method is good and the basic task of moral education is realized.

AIM:To understand the efficacy and safety of amikacin(AMK)for the treatment of car-bapenem-resistant Klebsiella pneumoniae pneu-moniae(CRKP)in preterm infants and to establish a management process for the use of amikacin in preterm infants.METHODS:CRKP-infected preterm infants treated with amikacin between January 2019 and December 2021 were retrospectively ana-lyzed,and parametric data paired t-tests were used to assess the efficacy and safety of amikacin for the included infectious and safety indicators,and to es-tablish a management process for amikacin use in preterm infants.RESULTS:Eight cases of CRKP in-fection were included,with the main diagnosis of pneumonia and sepsis.eight preterm infants were screened for the AMK ototoxicity gene mitochon-drial gene MT-RNR1(MT-RNR1 1494C＞T and MT-RNR11555A＞G)before amikacin treatment,and none of them were found to have the gene variant.after receiving amikacin sulphate injection treat-ment for 7 days,the indicators of infectivity were improved,and was statistically significant(P＜0.01).No clinical ototoxicity or nephrotoxicity was ob-served in the children before or after treatment.CONCLUSION:Aminoglycosides are still the main antibiotics used for the empirical treatment of sus-pected infections in preterm infants,especially drug-resistant bacterial infections.Despite the risk of ototoxicity and nephrotoxicity,we provide man-agement procedures and recommendations for neonatal treatment with amikacin to reduce the risk of ototoxicity and nephrotoxicity in AMK.

Objective:To establish a set of scientific and reasonable indicator system of common prosperity in the field of health, so as to promote the construction and evaluation of the demonstration area of common prosperity with high quality of health.Methods:According to the requirements of promoting common prosperity demonstration area with high quality of health in Zhejiang province, the initial indicator pool was established through literature research and theoretical analysis in July 2021, and experts were convened to carry out expert brainstorming to determine indicator system in the form of meetings. Delphi method was used to conduct two rounds of expert consultation on the indicator system.Finally, the analytic hierarchy process and percentage weight method were used to calculate the indicator weight value.Results:The final indicator system included 4 first-level indicators and 30 second-level indicators. Among the first-level indicators, the weight values of the development, equilibrium, inclusiveness, and sustainability were 0.326 4, 0.242 8, 0.245 8, and 0.185 0. There were 8 second-level indicators in developmental indicator dimension, of which the indicator with the highest weight was the per capita health expectancy. The balance indicator dimension included 6 second-level indicators, of which the indicator with the highest weight was the per capita financing difference of basic medical insurance between the urban workers with the urban-rural residents. The inclusive indicator dimension included 6 second-level indicators, and the proportion of personal health expenditure to total health expenditure had the highest weight. The sustainability indicator dimension included 10 second-level indicators, and the proportion of government health expenditure in fiscal expenditure had the highest weight.Conclusions:The indicator system constructed in this research could provide certain guidance and reference for promoting the construction of common prosperity in health, and provide some reference for follow-up research in this field.

Objective:Evaluate the application of Fourier transform infrared spectroscopy in the identification of homology of carbapenem-resistant Escherichia coli(CREC). Methods:A total of 26 carbapenem-resistant Escherichia coli strains were isolated from 9 provinces in China in 2018. The 900-1 200 cm -1 was selected as a spectral region for the Euclidean distance calculating and average linkage clustering between all isolates.The single nucleotide polymorphism (SNP) was analyzed by whole genome sequencing (WGS). Results:Twenty-six CREC strains were divided into 14 infrared spectros copy(IR) types by FTIR. The same IR type belonged to the same sequence type type.Compared with cluster analysis based on WGS, the consistency of FTIR cluster analysis was 92.3% (24/26).Conclusions:FTIR presented excellent performance in identification of homology of CREC.Besides, with the advantages of simple operation and rapid acquisition of results, FTIR may be a useful tool in clinical labs.

Objective To study the protective effects and preliminary mechanisms of endothelial progenitor cells-derived microvesicles (EPC-MVs) on hypoxic-ischemic brain damage (HIBD) in newborn rats by using the HIBD model.Method Rat endothelial progenitor cells (EPCs) were cultured and microvesicles were extracted from EPCs culture medium by ultracentrifugation.A total of 60 neonatal SD rats were randomly assigned into control group,HIBD group,saline group and EPC-MVs group.The HIBD model was prepared in HIBD group,saline group and EPC-MVs group.After the preparation of the HIBD model,rats in saline group and EPC-MVs group received intraventricular injection with saline and EPC-MVs,respectively.After 72 hours,the rats were sacrificed for brain tissue,cerebral infarction was detected by TTC staining,vascular endothelial growth factor (VEGF) mRNA was tested by real-time PCR,protein western blot was used to detect changes in VEGF protein expression.Result Cells extracted and cultured from the spleen of 12-week-old SD rats were confirmed as EPCs by morphology and flow cytometry.EPC-MVs isolated by high-speed centrifugation from EPCs culture supernatant met the morphological characteristics of microvesicles by transmission electron microscopy.The infarcted brain tissue was not detected in the control group.The cerebral infarction volume ratios of HIBD group,saline group and EPC-MVs group were (80.3 ± 6.3) ％,(77.9 ± 8.9) ％,(35.2 ± 7.7) ％,respectively.The infarct volume of EPC-MVs group was significantly lower than that of HIBD group and saline group (P ＜ 0.001).The expression of VEGF mRNA and protein in HIBD group,saline group and EPC-MVs group were higher than those in control group (P ＜0.001).Among them,EPC-MVs group had the most significant increase,compared with the other three experimental groups,and the difference was statistically significant (P ＜ 0.001).There was no significant difference between saline group and HIBD group in the expression of VEGF mRNA and protein (P ＞ 0.05).Conclusion Intraventricular injection of EPC-MVs can attenuate HIBD in neonatal rats,and the mechanism may be related to up-regulation of VEGF expression.

Objective: To evaluate the ability of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in identifying the rmpA2-carrying hypervirulentKlebsiella pneumoniae. Methods: A total of 57nonduplicateKlebsiella pneumoniae isolates were collected from the Second Affiliated Hospital of Zhejiang University and Henan Provincial People′s Hospital. Virulence gene rmpA2 and capsule K serotype-specific genes were detected by PCR, multilocus sequence typing (MLST) was performed for molecular typing, and string test was conducted to identify the hypermucoviscous phenotype. The ClinProTools software was used for peak analysis. Four standard algorithms, including support vector machine (SVM), genetic algorithm (GA), supervised neural network (SNN), and quick classifier (QC), were tested for their power to differentiate between rmpA2-positive and rmpA2-negative strains. Results: Among the 57 Klebsiella pneumoniae isolates, 28 isolates belonged to sequence type (ST) 11 and carried the virulence gene rmpA2, of which 5 isolates were positive for string test; while the other 29 isolates were not detected rmpA2, and MLST divided them into five STs including ST11 (n=23), ST15 (n=3), ST1 (n=1), ST76 (n=1), and ST473 (n=1). The results of four standard algorithms were similar, while the sensitivity and specificity of SVM was the highest at 93.23% and 100% respectively. Analysis results of ClinProTools software suggested that the specific peaks for differentiating the rmpA2-positive and rmpA2-negative strains were 7 168.9 and 7 280.76, however, the peak intensity of themwere variant. Conclusion The sensitivity and specificity ofMALDI-TOF MS for rapid identification of rmpA2-carrying hypervirulentKlebsiella pneumoniae werehigher than 90% and there was a difference on the peak intensity of two specific peaks, which needs further study.(Chin J Lab Med, 2018, 41: 571-675)