A chemical investigation of secondary metabolites (SMs) from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine (DKP)-diphenyl ether hybrids, designated as diphenylemestrins A-E (1-5). These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures, with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component. The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism (ECD) calculations. Notably, diphenylemestrin C (3) exhibited moderate cytostatic activity against NB4 cells, with a half maximal inhibitory concentration (IC₅₀) value of 21.99 μmol·L^-1, and induced apoptosis at higher concentrations.
Aspergillus nidulans/metabolism* ; Diketopiperazines/pharmacology* ; Molecular Structure ; Phenyl Ethers/pharmacology* ; Humans ; Apoptosis/drug effects* ; Cell Line, Tumor

Pediatric idiopathic nephrotic syndrome (INS) is characterized by massive albuminuria, hypoproteinemia, edema and hyperlipidemia, with a long course and high probability of relapse and prolongation. Long-term complications caused by long-term usage of hormones and immunosuppressants in children with INS seriously affect their physical and mental health and quality of life. Most children with steroid-sensitive nephrotic syndrome can be cured before adulthood, while some of them relapse in adulthood. Long-term prognosis of children with steroid-resistant nephrotic syndrome is poor. There have been few studies in China followed the long-term outcomes and its related factors of children with INS over 10 years. The paper reviewed the literatures on the long-term outcomes of children with INS, including renal survival, growth, mental health, learning and work, marriage and fertility, disease recurrence and long-term related complications, to explore the factors related to the poor long-term outcomes of children with INS and to assist in clinical decision-making and follow-up management.

Objective:To explore the mediating effect of family function between first aid literacy and mental health of caregivers of children with asthma.Methods:This study was a cross-sectional survey. From August 2020 to January 2021, convenience sampling was used to recruit 350 caregivers of children with asthma in the Pediatric Internal Medicine Clinic in a ClassⅢ Grade A hospital in Qingdao. The survey was carried out using the General Information Questionnaire, the Safety and First Aid of the China Residents Health Literacy Questionnaire, the General Function Subscale of the Family Assessment Device, and the Chinese version of the General Health Questionnaire. Structural equation model was used to analyze the mediating effect of family function between first aid literacy and mental health. A total of 350 questionnaires were distributed, of which 337 were valid, with a valid rate of 96.29%.Results:Among 337 caregivers of children with asthma, the total score of the Chinese version of the General Health Questionnaire, the scores of the first aid literacy and the General Function Subscale of the Family Assessment Device were (2.52±2.33) , (12.28±1.31) , and (28.61±3.71) , respectively. Structural equation model showed that first aid literacy could directly affect mental health ( β=0.542) , and it could also indirectly affect mental health ( β=0.239) through the partial mediating effect of family function, and the mediating effect of family function accounted for 30.06% of the total effect. Conclusions:First aid literacy is an important factor affecting the mental health of caregivers of children with asthma. Family function plays a partial mediating role between first aid literacy and mental health of caregivers of children with asthma. Medical and nursing staff should pay attention to first aid literacy and family function to improve the mental health of caregivers.

Objective:To explore the correlation between psychological resilience, self-neglect and depression among community empty-nest elderly people, and to analyze the mediating role of depression between psychological resilience and self-neglect.Methods:This study was a cross-sectional study. From July to October 2020, a stratified multi-stage sampling was used to select 560 community empty-nest elderly people from 6 community health service centers in Qingdao as the research object. The survey was carried out using the General Information Questionnaire, the Chinese version of the Connor-Davidson Resilience Scale (CD-RISC) , the simplified version of the Geriatric Depression Scale, and the Geriatric Self-neglect Scale. Pearson correlation was used to analyze the correlation between variables. The structural equation model was constructed using AMOS 24.0. A total of 560 questionnaires were distributed, and 549 valid questionnaires were recovered, with the valid recovery rate of 98.04%.Results:Among 549 empty-nest elderly people, the total score of Chinese version of CD-RISC was (64.30±14.57) , and the average score of the Geriatric Self-neglect Scale was (3.72±2.67) . There were 174 elderly people (31.70%) with depressive symptoms. The total score and the scores of each dimension of the Chinese version of the CD-RISC in the community empty-nest elderly people were negatively correlated with the total score of the simplified version of the Geriatric Depression Scale ( P<0.01) . Except for the dimension of safety self-neglect, the scores of other dimensions and the total score of the Geriatric Self-neglect Scale were negatively correlated with the total score and the scores of each dimension of the Chinese version of the CD-RISC ( P<0.01) , and were positively correlated with the total score of the simplified version of the Geriatric Depression Scale ( P<0.01) . Depression played a mediating role between the psychological resilience and self-neglect of empty-nest elderly in the community, and the mediating effect accounted for 53.85% of the total effect. Conclusions:Psychological resilience of community empty-nest elderly can directly affect self-neglect, and can also indirectly affect self-neglect through depression. Attention should be paid to the improvement of the psychological resilience of the empty-nest elderly in the community, to reduce the occurrence of self-neglect, and to promote their healthy aging.

Objective:To explore the mediating effects of resilience and depression on the relationship between social support and self-neglect.Methods:From July to October 2020, a cross-sectional survey was conducted among 549 empty-nest community-dwelling elderly in the community using the social support rating scale, Connor and Davidson resilience scale, geriatric depression scale and elderly self-neglect scale. SPSS 22.0 and AMOS 24.0 were used for data analysis, including descriptive analysis, correlation analysis and structural equation modeling.Results:The scores of social support, resilience and self-neglect of the empty-nest elderly were (38.63±7.47), (64.30±14.57) and (3.72±2.67) respectively, and 31.70% (174/549) of the subjects had depressive symptoms. The score of self-neglect was negatively correlated with the score of social support ( r=-0.597, P<0.01) and resilience ( r=-0.557, P<0.01), and positively correlated with depression score ( r=0.675, P<0.01). The score of social support was positively correlated with resilience score ( r=0.531, P<0.01) and negatively correlated with depression ( r=-0.597, P<0.01). Social support could affect self-neglect directly ( β=-0.485, P<0.05), and it could also influence self-neglect indirectly through the partial mediating effect of resilience ( β=-0.451, P<0.05). The mediating effect of resilience and depression accounted for 12.18% and 36.00% of the total effects respectively. Conclusion:Social support could influence self-neglect directly or indirectly through resilience and depression. The empty-nesters should be encouraged to participate more in social activities so as to improve their resilience, reduce the occurrence of self-neglect.

Objective:To investigate the efficacy and safety of adrenocorticotropic hormone (ACTH) in treating primary nephrotic syndrome in children with dual resistance to glucocorticoids and calcineurin inhibitors (CNIs).Methods:Clinical data of 6 children with primary nephrotic syndrome treated with ACTH in the Children's Hospital of Zhejiang University School of Medicine from January 1, 2015 to December 31, 2019 were retrospectively collected. All the enrolled patients were children with primary nephrotic syndrome with dual resistance to glucocorticoids and CNIs. All the 6 children were given 0.4-1.0 IU·kg -1·d -1 ACTH (total ≤25 IU)+5% glucose 500 ml intravenous infusion for 8 h during the hormone reduction process, with a course of treatment for 5 days, once a month, and continuous treatment for 3-6 months. Clinical data such as 24 h urinary protein quantification, serum albumin, serum cholesterol, estimated glomerular filtration rate (eGFR) level and glucocorticoid dosage were collected at equal time points at 6 months before treatment, at the beginning of treatment, at the end of treatment and at 6 months of follow-up after treatment of ACTH to evaluate the efficacy and adverse reactions. Results:The onset age of 6 children was (4.89±1.77) years, and the age of the first treatment with ACTH was (9.49±3.06) years. All the 6 children completed 3 to 6 months of ACTH treatment, with 2 cases of complete remission, 2 cases of partial remission and 2 cases of no remission. At the end of ACTH treatment, 24 h urinary protein was significantly decreased ( P=0.026), serum albumin level was significantly increased ( P=0.003), and glucocorticoid dosage was significantly decreased ( P<0.001) than before treatment. At 6 months after the end of ACTH treatment, there was no statistical significance in 24 h urinary protein, serum albumin and hormone dosage compared with the end of ACTH treatment (all P>0.05), and the blood cholesterol level continued to decrease ( P=0.039). There was no significant change in eGFR during observation period ( P>0.05). In the process of ACTH infusion, all the 6 children showed transient decrease in urine output, rash in 2 cases, and elevated blood glucose in 1 case, which could be spontaneously relieved after drug withdrawal. There were no serious cardiovascular events, renal impairment, infection and other adverse reactions. Conclusions:ACTH has a good effect on children with primary nephrotic syndrome who are dual resistant to glucocorticoids and CNIs. ACTH can reduce proteinuria, decrease the dosage of glucocorticoids, improve the clinical remission rate, and has good security.

【Objective】 To analyze the data of non-small cell lung cancer (NSCLC) gene chip using the bioinformatics method, screen differential expression genes (DEGs), and explore the biomarkers related to the prognosis of NSCLC so as to provide a new target for the treatment of NSCLC. 【Methods】 The NSCLC gene chip data were downloaded from the GEO database and the common DEGs in the two datasets were screened by GEO2R tool and FunRich3.1.3 software. The DAVID database was used in GO analysis and KEGG analysis of the DEGs. The protein-protein interaction (PPI) network was constructed using the STRING database; Cytoscape 3.8.0 software was used to select the top 20 hub genes. Then Kaplan-Meier plotter was used to analyze the prognosis of the identified hub genes, and multiple external databases were used to verify the expressions of the hub genes and their relationship with prognosis. 【Results】 A total of 159 intersect DEGs were screened from the two datasets. A total of 20 hub genes were identified via PPI network. Survival analysis and validation results from multiple external databases showed that SPP1 was highly expressed in NSCLC tumor tissues and was significantly correlated with the patients’ poor prognosis (P<0.05). The subgroup analysis showed that SPP1 might cause the poor prognosis by affecting lymph node metastasis. 【Conclusion】 SPP1 may be a biomarker for evaluating the prognosis of NSCLC patients, providing a new idea for the targeted therapy of NSCLC.

Objective:To investigate the causes and outcomes in the children who did not immediately receive glucocorticoids therapy after initial diagnosis of primary nephrotic syndrome (PNS).Methods:The clinical data of PNS patients not immediately receiving glucocorticoids therapy after initial diagnosis at the Department of Nephrology, the Children's Hospital, Zhejiang University School of Medicine from January 1, 2005 to December 31, 2014 were retrospectively analyzed.Results:A total of 1 431 cases were initially diagnosed with PNS, including 1 061 males and 370 females. Among them, 130 cases did not receive conventional glucocorticoids treatment immediately, accounting for 9.1%. Of whom, 75 cases were found showing spontaneous remission after symptomatic treatment; 23 cases were directly treated with adrenocorticotropic hormone (ACTH), one case with mycophenolate mofetil (MMF), and 31 cases not given glucocorticoids or immunosuppressants because of parental refusal. Among 75 cases with spontaneous remission, 16 cases were found in sustained remission; 39 cases were treated with glucocorticoids and 6 cases with ACTH at relapse; 14 cases were lost. Among 29 cases using ACTH, 7 cases were found in sustained remission. Among the 31 cases who refused glucocorticoids or immunosuppressants therapy, one died. The case treated with MMF, later were given with halved hormone because of no-effective response.Conclusions:Spontaneous remission is found in a small proportion of PNS patients at first-onset, but most subsequently relapse. Hormone therapy should be routinely given unless remission has occurred before application. Some children's parents refuse hormone therapy, and need further communication. Some cases initially treated with ACTH are found in sustained remission, which should be further observed and studied to clear the efficacy and safety of ACTH.

Adult olfactory neurogenesis plays critical roles in maintaining olfactory functions. Newly-generated neurons in the subventricular zone migrate to the olfactory bulb (OB) and determine olfactory discrimination, but the mechanisms underlying the regulation of olfactory neurogenesis remain unclear. Our previous study indicated the potential of APPL2 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2) as a modulating factor for neurogenesis in the adult olfactory system. In the present study, we report how APPL2 affects neurogenesis in the OB and thereby mediates olfactory discrimination by using both in vitro neural stem cells (NSCs) and an in vivo animal model-APPL2 transgenic (Tg) mice. In the in vitro study, we found that APPL2 overexpression resulted in NSCs switching from neuronal differentiation to gliogenesis while APPL2 knockdown promoted neurogenesis. In the in vivo study, APPL2 Tg mice had a higher population of glial cells and dampened neuronal production in the olfactory system, including the corpus callosum, OB, and rostral migratory stream. Adult APPL2 Tg mice displayed impaired performance in olfactory discrimination tests compared with wild-type mice. Furthermore, we found that an interaction of APPL2 with Notch1 contributed to the roles of APPL2 in modulating the neurogenic lineage-switching and olfactory behaviors. In conclusion, APPL2 controls olfactory discrimination by switching the fate choice of NSCs via interaction with Notch1 signaling.

Objective To investigate the antimicrobial resistance profile of the clinical isolates collected from selected hospitals across China. Methods Twenty-nine general hospitals and five children's hospitals were involved in this program. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems. Results were interpreted according to CLSI 2017 breakpoints. Results A total of 190 610 clinical isolates were collected from January to December 2017, of which gram negative organisms accounted for 70.8％ (134 951/190 610) and gram positive cocci 29.2％ (55 649/190 610). The prevalence of methicillin-resistant strains was 35.3％ in S. aureus (MRSA) and 80.3％ in coagulase negative Staphylococcus (MRCNS) on average. MR strains showed much higher resistance rates to most of the other antimicrobial agents than MS strains. However, 91.6％ of MRSA strains were still susceptible to trimethoprim-sulfamethoxazole, while 86.2％ of MRCNS strains were susceptible to rifampin. No staphylococcal strains were found resistant to vancomycin. E. faecalis strains showed much lower resistance rates to most of the drugs tested (except chloramphenicol) than E. faecium. Vancomycin-resistant Enterococcus (VRE) was identified in both E. faecalis and E. faecium. The identified VRE strains were mainly vanA, vanB or vanM type based on phenotype or genotype. The proportion of PSSP or PRSP strains in the non-meningitis S.pneumoniae strains isolated from children decreased but the proportion of PISP strains increased when compared to the data of 2016. Enterobacteriaceae strains were still highly susceptible to carbapenems. Overall, less than 10％ of these strains (excluding Klebsiella spp.) were resistant to carbapenems. The prevalence of imipenem-resistant K. pneumoniae increased from 3.0％ in 2005 to 20.9％ in 2017, and meropenem-resistant K. pneumoniae increased from 2.9％ in 2005 to 24.0％ in 2017, more than 8-fold increase. About 66.7％ and 69.3％ of Acinetobacter (A. baumannii accounts for 91.5％) strains were resistant to imipenem and meropenem, respectively. Compared with the data of year 2016, P. aeruginosa strains showed decreasing resistance rate to carbapenems. Conclusions Bacterial resistance is still on the rise. It is necessary to strengthen hospital infection control and stewardship of antimicrobial agents. The communication between laboratorians and clinicians should be further improved in addition to surveillance of bacterial resistance.