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.

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）］

As human deep space exploration enters a practical phase, ensuring astronaut health and safety has become a critical determinant of mission success. The cerebrovascular system, essential for maintaining brain function, is highly sensitive to environmental changes. Cerebrovascular diseases represent one of the characteristic adverse effects of deep space conditions such as microgravity and high-energy radiation, and have emerged as a frontier challenge in space medicine. Based on experiences from manned space missions, major research challenges persist, particularly the lack of experimental data specific to the lunar environment and the unclear threshold for low-dose radiation-induced injury. Elucidating the mechanisms and multifactorial interactions by which deep space environments impact cerebrovascular structure and function, and summarizing the key risk factors, pathological processes, and recent advances in monitoring and early-warning technologies for cerebrovascular diseases in lunar astronauts, and of crucial importance. A comprehensive understanding of the interplay between deep space environmental stressors and cerebrovascular injury, as well as the development of personalized prevention and intervention strategies, will provide both theoretical and practical foundations for safeguarding cerebrovascular health in future Chinese deep space missions, while promoting progress in related biomedical research, technological innovation, and international collaboration.
Humans ; Astronauts ; Cerebrovascular Disorders/etiology* ; Space Flight ; Weightlessness/adverse effects* ; Risk Factors ; Moon

Objective To apply a random forest model combined with logistic regression in the understudied area of pneumoconiosis complications,and to investigate the incidence and risk factors of pneumoconiosis complicated by bacterial pneumonia,and the effect of concomitant bacterial pneumonia on the survival and prognosis of patients with pneumoconiosis.Methods Pneumoconiosis patients admitted to the West China Fourth Hospital,Sichuan University,between January 2018 and April 2022 were enrolled and divided into a group of those with only pneumoconiosis and another group of those with pneumoconiosis complicated by bacterial pneumonia.Univariate analyses,including chi-squared test,t-test,or rank sum test,were conducted to examine the differences between the groups.A random forest model was used to screen the variables,and the risk factors of pneumoconiosis complicated by bacterial pneumonia were identified by stepwise forward logistic regression method.Cox regression was applied to the survival data to assess the effect of concomitant bacterial pneumonia on the survival and prognosis of pneumoconiosis patients.Results Among the 742 pneumoconiosis patients,536 cases(72.24%)had concomitant bacterial pneumonia.Among the 55 deaths,36 cases(65.45%)had concomitant bacterial pneumonia.Univariate analysis showed statistically significant differences in age,duration of disease,lung function,duration of exposure,lung lavage,pulmonary tuberculosis,and emphysema between the two groups(P<0.05).The variables were screened using the random forest model,and the risk factors were ranked in a descending order of their importance—the types of dust,duration of exposure,lung function,lung lavage,and pulmonary tuberculosis.After screening,multivariate logistic regression analysis showed that the types of dust(compared with silica dust,silicate dust:odd ratio[OR]=8.100,95%CI,1.386-47.331;carbon dust:OR=1.728,95%CI,1.034-2.887;artificial inorganic dust:OR=2.138,95%CI,1.146-3.988),impaired lung function(compared with undamaged lung function group,the group of patients with mild,moderate,and moderately severe damage:OR=2.292,95%CI,1.482-3.544),and pulmonary tuberculosis(OR=1.559,95%CI,1.071-2.271)were risk factors for pneumoconiosis complicated by bacterial pneumonia.The median follow-up was 30.0 months,ranging from 1.0 month to 64.0 months.Cox regression analysis showed that the mortality risk for pneumoconiosis patients with concomitant bacterial pneumonia was 2.369 times higher than that for patients without bacterial pneumonia(95%CI,1.286-4.367).Conclusion Pneumoconiosis patients are susceptible to bacterial pneumonia and are influenced by multiple risk factors.Concomitant bacterial pneumonia markedly affects the patient prognosis.

Objective To investigate influencing factors for failed cardiopulmonary resuscitation(CPR)in patients with respiratory and cardiac arrest.Methods A retrospective analysis was con-ducted on the clinical data of 204 patients with respiratory and cardiac arrest.All patients underwent CPR treatment and were divided into success group and failure group based on the CPR outcome.A matched case-control study based on matching design was carried out.The success and failure groups were matched at a ratio of 1 to 2 using gender,age,body mass index(BMI),and the presence or absence of hypertension,hyperlipidemia,and diabetes as covariates.Logistic regression analysis was employed to explore the influencing factors for failed CPR in patients with respiratory and cardiac ar-rest.Results Among the 204 patients,65(31.86％)had successful CPR and were included in success group,while 139(68.14％)had failed CPR and were included in failure group.After a rati-o of 1 to 2 matching design,62 patients in the success group and 124 patients in the failure group were finally included in the study.Multivariate logistic regression analysis revealed that cardiovascular disease as the cause of respiratory and cardiac arrest,CPR performed outside the hospital,a long time interval from the onset of the condition to the initiation of CPR,and a large dose of epinephrine were independent risk factors for failed CPR(P＜0.05).In contrast,the combined use of a bag-mask de-vice and endotracheal intubation during respiratory and cardiac arrest,a prolonged duration of CPR,and electrical defibrillation were independent protective factors for successful CPR(P＜0.05).Con-clusion Cardiovascular disease,out-of-hospital CPR,a long time interval from the onset of the condi-tion to the initiation of CPR,and a large dose of epinephrine are risk factors for failed CPR in patients with respiratory and cardiac arrest.The combined use of a bag-mask device and endotracheal intubation during respiratory and cardiac arrest,prolonging the duration of CPR,and electrical defibrillation are protective factors for successful CPR.The matched case-control study method based on a matc-hing design can reduce the interference of confounding factors,ensure the reliability of the results,and provide a reliable basis for the formulation of CPR intervention protocols.

Objective To explore the value of vesical imaging reporting and data system(VI-RADS)combined with absolute tumor-wall contact length(ABTCL)and actual tumor-wall contact length(ACTCL)in diagnosing muscle invasive bladder cancer(MIBC).Methods The MRI data of 113 patients with pathologically confirmed bladder cancer(BCa)were analyzed retrospectively.All patients underwent conventional MRI,diffusion weighted imaging(DWI)and dynamic contrast enhanced(DCE)MRI before sur-gery.Two radiologists independently evaluated MRI images based on VI-RADS score,and measured quantitative parameters,inclu-ding ABTCL and ACTCL.The Chi-square test was used to compare the difference of VI-RADS scores between MIBC and non-mus-cle invasive bladder cancer(NMIBC).Quantitative parameters between MIBC and NMIBC were compared by Mann-Whitney U test.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of VI-RADS,quantitative parameters and VI-RADS combined with quantitative parameters in the diagnosis of MIBC.Results VI-RADS,ABTCL and ACTCL had significant differences between MIBC and NMIBC(P＜0.05).The area under the curve(AUC)for VI-RADS,ABTCL and ACTCL in diagno-sing MIBC were 0.89,0.76 and 0.77,respectively.There was no significant difference between the AUC for ABTCL and ACTCL(P＞0.05).The AUC for VI-RADS combined with ABTCL or ACTCL in diagnosing MIBC was 0.93,higher than that of only VI-RADS(P＜0.05).Conclusion The combination of VI-RADS with either ABTCL or ACTCL can effectively improve the diagnostic performance of MIBC.ABTCL obtainedby linear measurement is easier to implement in clinical practice than ACTCL obtained by curved measurement.

BackgroundNurses' moral courage is a special type of altruistic behavior， which is considered to be a key factor to improve patient safety. Empathy level can positively predict altruistic behavior， and moral sensitivity exerts an obvious mediation role in the positive prediction. At present， there is no relevant research to explore the path role of moral sensitivity in the relationship between empathy and moral courage. ObjectiveTo verify the mediation role of moral sensitivity in the relationship between empathy and moral courage among nursing students， so as to provide references for increasing the moral courage among nursing students. MethodsFrom June 1 to June 30， 2022， a total of 602 nursing students were recruited via convenience sampling from a tertiary grade A hospital in Mianyang， and participants were assessed using Interpersonal Reactivity Index-Chinese （IRI-C）， Moral Sensitivity Questionnaire-Revised Chinese Version （MSQ-R-CV） and Nurses' Moral Courage Scale （NMCS）. Pearson correlation analysis was used to assess the correlation among above scales. The Process macro plug-in for SPSS was used to test the mediation effect of moral sensitivity on the relationship between empathy and moral courage. ResultsA total of 602 valid questionnaires were collected， with an effective recovery rate of 96.78%. IRI-C score of nursing students was positively correlated with MSQ-R-CV score and NMCS score （r=0.269， 0.146， P<0.01）. MSQ-R-CV score was positively correlated with NMCS score （r=0.722， P<0.01）. The mediation effect model was established with IRI-C score as independent variable， MSQ-R-CV score as intermediary variable， and NMCS score as dependent variable. Analysis showed that the direct effect of empathy on moral courage among nursing students was not significant （direct effect value of -0.052， 95% CI： -0.178~0.008）， while analysis yielded a significant indirect effect of empathy on moral courage via moral sensitivity （indirect effect value of 0.189， 95% CI： 0.209~0.407）. ConclusionThe moral sensitivity of nursing students plays a significant mediation role in the relationship between empathy and moral courage. ［Funded by 2022 Higher Education Teaching Research and Reform Project of Southwest Medical University （number， JG2022239）］

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.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.