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.

Primary aldosteronism(PA) is the most common endocrine cause of secondary hypertension and is characterized by hypertension, hypokalemia, suppressed renin, and inappropriately elevated aldosterone. Increasing evidence indicates disturbances in calcium homeostasis among patients with PA. The calcium-regulatory system encompasses calcium and phosphate, parathyroid hormone(PTH), and vitamin D. Patients with PA frequently exhibit hypocalcemia, hypophosphatemia, elevated PTH, and reduced vitamin D levels. Clarifying the contribution of calcium dysregulation to PA pathogenesis is clinically relevant for mitigating target-organ damage. This review summarizes: (1) the role of aberrant calcium signaling in the development of PA; (2) characteristic features of calcium homeostasis in PA; and (3) the interactions between the renin-angiotensin-aldosterone system(RAAS) and calcium-regulatory pathways. Overall, abnormalities in calcium signaling appear integral to the pathogenesis of PA, and disrupted calcium homeostasis may aggravate target-organ injury in affected patients.

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.

Objective:To evaluate the application effectiveness of a training program for a nutritional support training base from the perspective of clinical nurses, and to provide a reference for optimizing and improving the training program.Methods:In October 2022, a clinical training program for nutritional support nurses was established based on the core competencies. The clinical training program was carried out from July to September 2023. The trainees who completed the training course were invited to participate in qualitative interviews to evaluate the course. The interview content was recorded, transcribed, and encoded using NVivo 11.0 software. The data were sorted and analyzed using thematic framework analysis.Results:Semi-structured qualitative interviews were conducted with 10 clinical nurses until data saturation was achieved. Three general themes and 10 sub-themes were extracted, including overall evaluation of the training course (rich, comprehensive, and reasonable training content; professional and skilled teaching team), changes brought by the course (improvement of clinical work confidence, strengthening of peer learning, enhancement of the initiative of independent learning, and identification of the factors that hinder the development of specialty), and recommendations for the course (the diversity of teaching forms, reasonable arrangement of practical training departments, increase in operational practice opportunities, establishment of online courses).Conclusions:The students had high overall evaluation on the training course of the nutritional support base. Based on their suggestions, the course can be optimized in the future by diversifying the teaching forms, rationally arranging the practical training departments, strengthening operational practices, and constructing online courses.

Objective:To evaluate the application effectiveness of a training program for a nutritional support training base from the perspective of clinical nurses, and to provide a reference for optimizing and improving the training program.Methods:In October 2022, a clinical training program for nutritional support nurses was established based on the core competencies. The clinical training program was carried out from July to September 2023. The trainees who completed the training course were invited to participate in qualitative interviews to evaluate the course. The interview content was recorded, transcribed, and encoded using NVivo 11.0 software. The data were sorted and analyzed using thematic framework analysis.Results:Semi-structured qualitative interviews were conducted with 10 clinical nurses until data saturation was achieved. Three general themes and 10 sub-themes were extracted, including overall evaluation of the training course (rich, comprehensive, and reasonable training content; professional and skilled teaching team), changes brought by the course (improvement of clinical work confidence, strengthening of peer learning, enhancement of the initiative of independent learning, and identification of the factors that hinder the development of specialty), and recommendations for the course (the diversity of teaching forms, reasonable arrangement of practical training departments, increase in operational practice opportunities, establishment of online courses).Conclusions:The students had high overall evaluation on the training course of the nutritional support base. Based on their suggestions, the course can be optimized in the future by diversifying the teaching forms, rationally arranging the practical training departments, strengthening operational practices, and constructing online courses.

Primary aldosteronism(PA) is the most common endocrine cause of secondary hypertension and is characterized by hypertension, hypokalemia, suppressed renin, and inappropriately elevated aldosterone. Increasing evidence indicates disturbances in calcium homeostasis among patients with PA. The calcium-regulatory system encompasses calcium and phosphate, parathyroid hormone(PTH), and vitamin D. Patients with PA frequently exhibit hypocalcemia, hypophosphatemia, elevated PTH, and reduced vitamin D levels. Clarifying the contribution of calcium dysregulation to PA pathogenesis is clinically relevant for mitigating target-organ damage. This review summarizes: (1) the role of aberrant calcium signaling in the development of PA; (2) characteristic features of calcium homeostasis in PA; and (3) the interactions between the renin-angiotensin-aldosterone system(RAAS) and calcium-regulatory pathways. Overall, abnormalities in calcium signaling appear integral to the pathogenesis of PA, and disrupted calcium homeostasis may aggravate target-organ injury in affected patients.

Purpose To analyze the impact of clinicopatho-logical factors on residual tumor burden(RCB)grading system and Miller-Payne(MP)grading system in non-specific invasive breast cancer patients after neoadjuvant chemotherapy,and to explore the predictive value of the two grading systems for patient survival.Methods The clinical data of 177 patients with non-specific invasive breast cancer diagnosed by preoperative punc-ture and treated with neoadjuvant chemotherapy were retrospec-tively analyzed.The relationship of RCB grading system or MP grading system with disease free survival(DFS)and overall sur-vival(OS)was studied,and the value of the two systems in predicting prognosis was analyzed and compared.Results RCB grading was related to menstrual status,histological grading be-fore treatment,and lymph node metastasis after treatment;MP grading was related to pre-treatment histological grading,post-treatment lymph node metastasis,and pre-treatment molecular typing.By evaluating the ROC curve of recurrence and survival and comparing the area under curve(AUC),it was shown that RCB grading system was superior to MP grading system in pre-dicting recurrence and evaluating survival.Univariate and multi-variate survival analysis showed that pre-treatment clinical stag-ing,post-treatment lymph node metastasis,and RCB grading were independent factors for DFS.Pre-treatment clinical stag-ing,pre-treatment molecular typing,and RCB grading were in-dependent factors for OS,while MP grading was not an inde-pendent factor for DFS and OS.Conclusion RCB grading sys-tem has a higher predictive value for patient survival than MP grading system.RCB grading evaluation system is recommended as evaluation system for non-specific invasive breast cancer after neoadjuvant chemotherapy.

Objective:To investigate the current situation of medical equipment allocation in 103 tertiary public hospitals,analyze and compare the proportion of medical equipment in different regional hospitals in our country,and provide basis for scientific and reasonable allocation of medical equipment.Methods:A questionnaire was designed by literature research and expert consultation,and an electronic questionnaire was released through the public account of"China Medical Equipment"and the platform of"Good Medical Workers"to analyze the correlation between the number of medical equipment configuration,the proportion of domestic products,the region where the hospital was located and the number of hospital beds.Results:A total of 103 valid questionnaires were collected,involving 103 tertiary public hospitals in East China,North China,Central China,South China,Southwest,Northwest and Northeast China,of which 18%were in North China,37%were in East China and 9%were in South China.In North China,South China and East China,the average number of medical equipment in the tertiary public hospitals in the region was 9785 units per hospital,9245 units per hospital and 8153 units per hospital,and the number of the expensive equipment was relatively small,which had no correlation with the number of beds.There were statistically significant differences between North China and East China in the number of beds,the number of pieces of equipment per 100 beds and the amount of equipment per 100 beds(t=-2.582,2.939,4.653,P＜0.05).The number of life support equipment configuration was significantly positively correlated with the number of beds,and the domestic share,especially the domestic share of life support equipment,increased.Conclusion:The analysis of medical equipment allocation in public hospitals in China can provide data support for hospitals to better adapt to the adjustment of the new expensive medical equipment catalogue,provide reference for the demonstration and promotion of large medical equipment allocation and localization in tertiary hospitals,and provide reference for relevant health management departments.

Objective:To investigate the effect of microRNA-27b-3p (miR-27b-3p)/nuclear factor-E2-related factor 2 (Nrf2) on metabolic memory impairment of human retinal pigment epithelial (RPE) cells and to explore its regulatory mechanism.Methods:ARPE-19 cells were divided into normal control group, metabolic memory group, miR-27b-3p control group, miR-27b-3p inhibitor group, and liraglutide group.Cells in normal control group were cultured in 5.5 mmol/L normal glucose medium for 6 days.Cells in metabolic memory group were cultured in 30 mmol/L glucose for 3 days and changed to 5.5 mmol/L for 3 days.Cells in miR-27b-3p inhibitor group were added with puromycin after lentiviral transfection to select the successfully transfected cells, and were cultured in 30 mmol/L glucose for 3 days then 5.5 mmol/L glucose for 3 days.Cells in liraglutide group were cultured in 30 mmol/L glucose with liraglutide for 3 days then 5.5 mmol/L glucose for 3 days.The regulatory relationship between miR-27b-3p and Nrf2 was verified by lentiviral transfection.Expressions of miR-27b-3p, Nrf2, NAD(P)H dehydrogenase[quinone]1 (NQO1), heme oxygenase-1 (HO-1) mRNA and protein levels were analyzed by real-time quantitative PCR.Total and nuclear Nrf2 protein expressions were detected by Western blot.The cell proliferation rates of various groups were determined by cell counting kit-8 (CCK-8).The reactive oxygen species (ROS) level was detected by the DHE kit.Results:The miR-27b-3p mRNA relative expression of normal control group, metabolic memory group, miR-27b-3p control group, miR-27b-3p inhibitor group was 1.000±0.000, 1.881±0.034, 1.683±0.088 and 0.111±0.008, respectively, with a statistically significant difference ( F=850.815, P<0.001).The miR-27b-3p mRNA relative expression level was lower in normal control group than in metabolic memory group, lower in miR-27b-3p inhibitor group than in normal control group, and the differences were statistically significant (both at P<0.01).The expression levels of Nrf2 mRNA, total protein, and nuclear protein were decreased in metabolic memory group in comparison with normal control group and were significantly increased in miR-27b-3p inhibitor group in comparison with miR-27b-3p control group, showing statistically significant differences (all at P<0.01).The NQO1 and HO-1 mRNA expressions were decreased in metabolic memory group in comparison with normal control group, and were significantly higher in miR-27b-3p inhibitor group compared with miR-27b-3p control group, showing statistically significant differences (all at P<0.01).The fluorescence intensity of Nrf2, NQO1, and HO-1 was lower in metabolic memory group than in normal control group, and was higher in miR-27b-3p inhibitor group than in miR-27b-3p control group, showing statistically significant differences (all at P<0.01).Compared with metabolic memory group, the relative expression of miR-27b-3p mRNA declined in liraglutide group, with a statistically significant difference ( P<0.05).The relative expression levels of Nrf2 mRNA, NQO1 mRNA, HO-1 mRNA, total and nuclear Nrf2 protein of liraglutide group were enhanced in comparison with metabolic memory group, with statistically significant differences (all at P<0.05).The fluorescence intensity of Nrf2, NQO1, and HO-1 was enhanced in liraglutide group in comparison with metabolic memory group, and the differences were statistically significant (all at P<0.05).Compared with normal control group and liraglutide group, the cell proliferation viability was decreased in metabolic memory group, and the differences were statistically significant (both at P<0.01).The relative content of ROS was higher in metabolic memory group than in normal control group and liraglutide group, and the difference was significant (all at P<0.01). Conclusions:Liraglutide reverses the inhibition of metabolic memory on Nrf2, NQO1, and HO-1 by downregulating miR-27b-3p.

Objective:To explore the correlation between the length of peripherally inserted central catheter (PICC) through upper and lower extremities of premature infants and their body parameters, and to deduce the formula of the different length of PICC of premature infants, so as to improve the accuracy of the tip of PICC in premature infants.Methods:This study was a retrospective case series study.From January 2016 to September 2021, 758 premature infants with PICC hospitalized in Neonatal Intensive Care Unit (NICU) of Shanghai Children's Hospital were selected retrospectively by convenience sampling. We recorded the sex, gestational age, catheterization age, catheterization vessel location, birth length, length on the day of catheterization, birth weight and weight on the day of catheterization of premature infants. Pearson correlation analysis and simple linear regression were used to find the most relevant body parameters, and formula fitting was carried out to derive the optimal length of PICC for premature infants.Results:In 652 premature infants (86.02%, 652/758) , the PICC was placed in the lower limb vein, and the proportion of great saphenous vein was the highest, accounting for 41.42% (314/758) . Simple linear regression showed that the weight and length had the highest correlation with the optimal length of PICC in the superficial veins of the upper and lower extremities. The formula for the length of PICC with the puncture points of median vein, basilic vein, axillary vein, great saphenous vein, small saphenous vein, popliteal vein and femoral vein was derived.Conclusions:The formula derived from the weight and length of premature infants can provide a reference for clinical measurement of PICC length of premature infants.