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.

To investigate the effects of zearalenone(ZEA)on the proliferation and apoptosis of sika deer antler chondrocytes,the chondrocytes were isolated and cultured in vitro and treated with 50μmol/L ZEA for 24 h.Flow cytometry was used to assess cell proliferation,cell cycle,apoptosis,mitochondrial membrane potential,and intracellular levels of reactive oxygen species(ROS).The expression changes of hypertrophic cartilage cell marker genes Col X,Runx2,Alpl,and apoptosis-related genes Casp-3,Bax,Bcl-2 were measured using quantitative PCR.Additionally,glutathione reductase(GR)activity and the levels of the oxidative stress marker malondialdehyde(MDA)were determined.The results showed that after 24 h of ZEA treatment,cell proliferation was sig-nificantly inhibited,with an increase in the number of cells in the G0/G1 phase and a decrease in the S phase.The expression levels of hypertrophic chondrocyte marker genes Col X,Runx2 and Al-pl were significantly increased.Apoptosis rate was significantly increased,with elevated expression of pro-apoptotic genes Casp-3,Bax and reduced expression of the anti-apoptotic gene Bcl-2.The content of MDA in the antler chondrocytes increased,ROS levels rose,and GR activity decreased.The mitochondrial membrane potential reduced.The results suggested that ZEA could inhibit the proliferation of antler chondrocytes and promote the apoptosis by regulating cellular oxidative stress responses and the expression of apoptosis-related genes.

Objective:To analyze the status of registration of clinical trials of radiopharmaceuticals in China, and to provide reference for the development and clinical application of radiopharmaceuticals.Methods:By searching the clinical trial registration and information disclosure platform of the Center for Drug Evaluation of the National Medical Products Administration (NMPA), the data on clinical trials of radiopharmaceuticals registered from 2014 to 2024 were collected and analyzed for trial design, administered dose, common indications, and geographical distribution.Results:A total of 77 clinical trials were included. The Compound Annual Growth Rate for the number of projects from 2014 to 2024 was 40%. Diagnostic radiopharmaceuticals were predominantly based on 18F and 99Tc m, while therapeutic radiopharmaceuticals primarily utilized 177Lu and 90Y. All indications were concentrated in the field of oncology. Regarding trial design, non-randomized (71.4%), open-label (89.6%), and single-arm (66.2%) trials accounted for the highest proportions. Geographical distribution showed Beijing (29 trials), Shanghai (18 trials), and Jiangsu province (14 trials) as the regions with the highest concentration of clinical trials. Conclusions:Radiopharmaceutical clinical trials in China have shown rapid growth. However, research remains predominantly focused on oncology, with a relatively high proportion of early-stage trials. In order to fully utilize the potentials of radiopharmaceuticals and improve the quality of clinical trials, nuclear medicine researches should broaden therapeutic applications, implement prudently administerd dose in clinical trials, and implement optimized radiation protection procedures across all clinical trial centers.

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 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 T o explore the prevention and control measures for the hospital-acquired pulmonary mu-cormycosis caused by Cunninghamella bertholletiae.METHODS One case of patient with pulmonary mucormyco-sis caused by Cunninghamella bertholletiae who was treated in pediatric intensive care unit(PICU)of a three-A general hospital was enrolled in the study,the process of clinical diagnosis and treatment was summarized.A ret-rospective survey regarding four aspects including people,machine,materials and environment was conducted.The related factors leading to the hospital-acquired infections in the patient were analyzed.RESULTS The child was diagnosed with severe aplastic anemia and underwent hematopoietic stem cell transplantation,the child was treated with various invasive procedures during the treatment period and was infected with pulmona-ry mucormycosis caused by the rare Cunninghamella bertholletiae.The occurrence of the pulmonary mucormyco-sis was associated with the poor management of medical textile,insufficient environmental cleaning and disinfec-tion and nonstandard invasive procedures.CONCLUSIONS The Cunninghamella bertholletiae infection is less com-mon,but the risk of death is high.It is necessary for the medical institutions to complete the prevention and con-trol measures and intensify the health care workers'capabilities in identification of the pathogenic fungus so as to reduce the incidence of pulmonary mucormycosis caused by the pathogen.

To investigate the effects of zearalenone(ZEA)on the proliferation and apoptosis of sika deer antler chondrocytes,the chondrocytes were isolated and cultured in vitro and treated with 50μmol/L ZEA for 24 h.Flow cytometry was used to assess cell proliferation,cell cycle,apoptosis,mitochondrial membrane potential,and intracellular levels of reactive oxygen species(ROS).The expression changes of hypertrophic cartilage cell marker genes Col X,Runx2,Alpl,and apoptosis-related genes Casp-3,Bax,Bcl-2 were measured using quantitative PCR.Additionally,glutathione reductase(GR)activity and the levels of the oxidative stress marker malondialdehyde(MDA)were determined.The results showed that after 24 h of ZEA treatment,cell proliferation was sig-nificantly inhibited,with an increase in the number of cells in the G0/G1 phase and a decrease in the S phase.The expression levels of hypertrophic chondrocyte marker genes Col X,Runx2 and Al-pl were significantly increased.Apoptosis rate was significantly increased,with elevated expression of pro-apoptotic genes Casp-3,Bax and reduced expression of the anti-apoptotic gene Bcl-2.The content of MDA in the antler chondrocytes increased,ROS levels rose,and GR activity decreased.The mitochondrial membrane potential reduced.The results suggested that ZEA could inhibit the proliferation of antler chondrocytes and promote the apoptosis by regulating cellular oxidative stress responses and the expression of apoptosis-related genes.

BackgroundIn Sichuan Province， most healthcare institutions providing mental health services have adopted self-developed evaluation indicators for the quality of nursing care in psychiatric closed wards， lacking unified standards. This results in insufficient authority and homogeneity， which is unfavorable for the standardized assessment and continuous improvement of nursing quality. ObjectiveTo construct a standardized evaluation indicator system for nursing quality of psychiatric closed wards in Sichuan Province， so as to provide references for nursing quality management and assessment. MethodsBased on bio-psycho-social medical model and guided by "Structure-Process-Outcome" quality evaluation framework， preliminary evaluation indicators for nursing quality in psychiatric closed wards were developed through literature analysis， research team discussions and clinical experience. Through two rounds of Delphi expert consultation， the indicators were revised and finalized. ResultsThe response rates for two rounds of Delphi expert consultation questionnaire were 100%. The expert authority coefficients were 0.845 and 0.864， respectively， and the Kendall's coordination coefficients ranged from 0.119 to 0.210 （P<0.01）. Ultimately， a nursing quality evaluation index system for psychiatric closed wards was established， comprising 3 first-level indicators， 9 second-level indicators and 46 third-level indicators. ConclusionThe nursing quality evaluation indicators for psychiatric closed wards constructed based on the Delphi method can provide references for nursing quality management and evaluation in such wards. ［Funded by Research Project Fund of Sichuan Nursing Society （number， H20004）； Sichuan Hospital Association Hospital Management Research Special Fund （number， YG2323）］

Objective:To analyze the relationship between 24-hour urinary calcium (24 h UCa) level and the risk of end-stage kidney disease (ESKD), cardiovascular disease (CVD), and all-cause mortality.Methods:In the Chinese Cohort Study of Chronic Kidney Disease, we examined 3 375 patients aged 18-74 years with CKD stages 1-4. Kaplan-Meier survival and Cox proportional hazard regression models were used to test a time-to-event association between levels of 24 h UCa and incidence of ESKD, CVD, and all-cause mortality.Results:During a follow-up of 4.17 (3.37, 5.20) years, 179, 145, 104 and 38 ESKD events occurred in <0.60, 0.60-, 1.20-, ≥2.32 mmol 24 h UCa groups. Higher levels of 24 h UCa (1.20-,≥2.32 mmol) were independently associated with a lower incidence of ESKD events in patients with CKD, with HR (95% CI) of 0.71 (0.54-0.93) and 0.43 (0.29-0.64), respectively. No significant associations with CVD and all-cause mortality endpoints were detected. Conclusion:Among patients with CKD, levels of 24 h UCa displayed an association with the risk of ESKD among patients with CKD stages 1-4.

Objective:To analyze the status of registration of clinical trials of radiopharmaceuticals in China, and to provide reference for the development and clinical application of radiopharmaceuticals.Methods:By searching the clinical trial registration and information disclosure platform of the Center for Drug Evaluation of the National Medical Products Administration (NMPA), the data on clinical trials of radiopharmaceuticals registered from 2014 to 2024 were collected and analyzed for trial design, administered dose, common indications, and geographical distribution.Results:A total of 77 clinical trials were included. The Compound Annual Growth Rate for the number of projects from 2014 to 2024 was 40%. Diagnostic radiopharmaceuticals were predominantly based on 18F and 99Tc m, while therapeutic radiopharmaceuticals primarily utilized 177Lu and 90Y. All indications were concentrated in the field of oncology. Regarding trial design, non-randomized (71.4%), open-label (89.6%), and single-arm (66.2%) trials accounted for the highest proportions. Geographical distribution showed Beijing (29 trials), Shanghai (18 trials), and Jiangsu province (14 trials) as the regions with the highest concentration of clinical trials. Conclusions:Radiopharmaceutical clinical trials in China have shown rapid growth. However, research remains predominantly focused on oncology, with a relatively high proportion of early-stage trials. In order to fully utilize the potentials of radiopharmaceuticals and improve the quality of clinical trials, nuclear medicine researches should broaden therapeutic applications, implement prudently administerd dose in clinical trials, and implement optimized radiation protection procedures across all clinical trial centers.