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

Objective To establish a nomogram model for efficiently predicting overall survival(OS)and cancer-specific survival(CSS)in patients with CRCHBM.Method 2239 patients from 2010 to 2019 were retrospectively analyzed from the Surveillance,Epidemiology,and End Results Program(SEER)databases and Wuhan Union Hospital Cancer Center.SEER is randomly assigned to the training and internal validation cohorts,and the Wuhan database serves as the external validation.Cox regression analyses were used to determine the independent clinicopathological prognosis factors affecting OS and CSS,and a nomogram was constructed to predict OS and CSS.The clinical utility of columnar plots was assessed using calibration curves,area under the curve(AUC),and decision curve analysis(DCA).Result OS column line graphs were constructed based on nine independent predictors:age,tumor location,degree of differentiation,tumor size,TNM stage,chemotherapy,primary focus surgery,number of lymph nodes sampled,and serum carcinoembryonic antigen(CEA)level.The C-index of the nomogram to predict the 1-,3-,and 5-year OS were 0.764,0.790,and 0.805 in the training group,0.754,0.760,and 0.801 in the internal validation group,and 0.822,0.874,and 0.906 in the external validation group.CSS column line graphs were constructed based on 3 independent predictors of TNM staging,radiotherapy and chemotherapy.The 1-,3-,and 5-year CSS AUROC values of the training group were 0.791,0.757,and 0.782,respectively.0.682,0.709,0.625 in the internal validation group and 0.759,0.702,0.755 in the external validation group,respectively.The results of receiver operating characteristic curve(ROC),ROC and DCA showed that the use of our model was more effective in predicting OS and CSS than other single clinicopathological features.Conclusion In summary,the nomogram based on significant clinicopathological features can be conveniently used to predict OS and CSS individually in patients with CRCHBM.

Objective:To assess the understanding level of Family Resilience Scale for Schizophrenic Patients among respondents using cognitive interviews and revise the items accordingly.Methods:Using the purposive sampling method, two cognitive interviews were conducted on schizophrenia patients admitted to Chifeng An Ding Hospital from April to June 2023. A Question Appraisal System (QAS-99) was used to encode the interview data to find the problems existing in the scale structure, and at the same time, the scale items were revised based on expert opinions.Results:The first round of cognitive interviews showed ten questions, mainly focusing on "clarification"questions. The results of the second round of cognitive interviews showed that all respondents could correctly understand the scale items revised by the first round of lognitive interviews, and no further revision was required. The final Family Resilience Scale for Schizophrenic Patients included 24 items.Conclusions:Cognitive interviews can help to find and solve the differences in the understanding of items between researchers and interviewees in the compilation of the Family Resilience Scale for Schizophrenic Patients so as to improve the accuracy and reliability of the scale.

Objective:To elucidate the primary elements pertaining to the perception of relapse risk and to in-vestigate the characteristics and alterations of perception of the risk of recurrence in patients with schizophrenia.Methods:By using the method of phenomenological study,semi-structured in-depth interviews were conducted among schizophrenic patients with first onset,first recurrence and multiple recurrences.Twenty-three 23 outpatient and inpatient cases that met the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)were included,and all patients had PANSS scores below 60.The interview data were collated and analyzed according to Colaizzi analysis.Results:The perception of recurrence risk in patients with schizophrenia en-compassed 4 major themes and 11 sub-themes,namely susceptibility(limited overall understanding,transition from optimism to objectivity),detection of early warning symptoms(dynamic escalation,assistance from family mem-bers in identification),understanding risk factors(lack of understanding,the relationship between psychosocial fac-tors and relapse,dynamic understanding of medication-relapse relationship),and apprehension of the consequences of recurrence(care burden and financial constraints,impaired social functioning and maladjustment,impact on pub-lic safety,personal health risks).Conclusion:The content of risk perception of recurrence in patients with schizo-phrenia is relatively substantial.The overall level of risk perception of recurrence in patients with schizophrenia is low.

A case of adult spindle cell sarcoma with NTRK3-C22orf34 gene fusion is reported. The patient, a 35-year-old-male, developed lateral swelling of the right thigh without obvious inducement 7 months before admission and was not accompa-nied by limited movement. The patient was diagnosed with adult spindle cell sarcoma with NTRK3-C22orf34 gene fusion based on the medical history, imaging findings, histomorphology, immunohistochemistry and molecular phenotype. The patients underwent tumor resection without drug-targeted therapy and followed up for 8 months after tumor resection and survived without tumor. In recent years, the number of adult spindle cell sarcomas with neurotrophic tyrosine kinase receptor 3 (NTRK3) gene fusions have been increasing year by year, and most of them are difficult to diagnose based on HE sections due to the varied morphology and small number of these tumors. With the wide application of high-throughput sequencing in soft tissue tumors, the difficulty of diagnosis of spindle cell tumors with the NTRK fusion gene has decreased. High-throughput sequencing of the patient showed that NTRK3-C22orf34 (mutation abundance 5%) gene fusion combined with BRCA1 (mutation abundance 15%) rearrangement and deletion of CDKN2A and TP53 genes were found to be of definite or potential clinical significance. The morphologic spectrum of NTRK fusion spindle cell tumors, especially sarcomas, is still evolving. Treatment of NTRK fusion gene spindle cell tumors is based on surgical resection in combination with tropomyosin receptor kinase (TRK) inhibitors. The emergence of secondary or acquired resistance is primarily associated with point mutations associated with the structural domain of the kinase, and mutations may reduce the efficacy of TRK inhibitors.

Objective To investigate the risk factors of postoperative severe hypocalcemia (SH) occur-rence in the patients with secondary hyperparathyroidism (SHPT) treated by ultrasound-guided radiofrequen-cy ablation (RFA).Methods A total of 41 patients with SHPT receiving RFA treatment in the Affiliated Nanchong Central Hospital of North Sichuan Medical College from May 2019 to March 2023 were selected as the study subjects.The retrospective analysis was adopted to collect the data such as the basic information,disease information,laboratory and imagiological examination.The patients were divided into the SH group and non-SH group according to whether or not the corrected serum calcium level being lower than 1.8 mmol/L on 1 d after RFA.The univariate and multivariate logistic regression models were used to analyze the related risk factors of SH occurrence after RFA.The receiver operating characteristic (ROC) curve was drawn to test the predictive efficiency of the related risk factors.Results There were 41 patients with SHPT,inclu-ding 19 males and 22 females,with an average age of (49.56±13.64)years old,and 22 cases developed SH on 1 d after RFA.The univariate analysis results showed that preoperative alkaline phosphatase (ALP),C-reac-tive protein (CRP),parathyroid hormone (PTH) and serum calcium levels had statistical differences between the two groups.The multivariate logistic regression analysis results showed that ALP was an independent risk factor for postoperative SH occurrence.The area under the curve (AUC) of adopting ALP for predicting SH occurrence after RFA in the patients with SHPT was 0.895,and the best predicted cut-off value was 323.34 U/L.Conclusion Paying attention to the level of ALP before operation and correcting it reasonably could be conducive to reduce the incidence rate of postoperative SH.

[This corrects the article DOI: 10.1016/j.apsb.2021.09.004.].

Objective:To investigate the effects of long non-coding RNA (lncRNA) Gm13568 on the activation of A1 astrocytes and the progress of experimental autoimmune encephalomyelitis (EAE) in mice.Methods:A recombinant lentiviral vector (LV-Inhibit-Gm13568) carrying astrocyte-specific promoter of glial fibrillary acidic protein (GFAP) was established to inhibit the function of endogenous Gm13568. A control vector (LV-ctrl) was established as well. The recombinant vectors were packaged. C57BL/6 mice were injected with 1×10 7 transforming units of viral suspension via the tail vein and 7 d after the injection, myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55) was used to establish the mouse model of EAE. Four groups, PBS group, EAE group, LV-ctrl+ EAE group and LV-Inhibit-Gm13568+ EAE group, were included in this study. Clinical signs of the mice were monitored daily in a double-blinded manner. The mice were sacrificed 23 d after the EAE model was established and the spinal cord tissues were collected. The expression of Serping 1, C3, Srgn and H2-T23 at mRNA level was detected by real-time PCR. Changes in the expression of IL-6, TNF-α, macrophage chemotactic protein-1 (MCP-1) and interferon-inducible protein-10 (IP-10) were measured. Western blot was used to investigate the expression of GFAP and Notch1 in spinal cord tissues and the phosphorylation of signal transduction and transcription activator 3 (STAT3). The expression of Notch1 intracellular domain (NICD) and GFAP in spinal cord tissues was detected by immunofluorescence. Furthermore, the infiltration of inflammatory cells and the demyelination of spinal cord were observed using HE and Luxol fast blue (LFB) staining methods. Results:Compared with PBS group, A1 astrocytes were activated and Notch1 expression was significantly up-regulated in EAE group and LV-ctrl+ EAE group. The clinical score of mice in LV-Inhibit-Gm13568+ EAE group was decreased from an average score of 3.5 to less than 1 on 23 d after antigen induction and the clinical symptoms were alleviated as compared with the mice in LV-ctrl+ EAE group. Meanwhile, the activation of A1 astrocytes was down-regulated, and the production of inflammatory cytokines and chemokines was also reduced. The expression of Notch1, GFAP and NICD at protein level and the phosphorylation of STAT3 were significantly reduced. Moreover, the infiltration of inflammatory cells and demyelination of spinal cord tissues were alleviated significantly.Conclusions:LncRNA Gm13568 might regulate the activation of A1 astrocytes via the Notch1/STAT3 pathway, thus affecting the production of inflammatory cytokines and chemokines and participating in the process of EAE.

The spread of coronavirus disease 2019 (COVID-19) throughout the world has resulted in stressful healthcare burdens and global health crises. Developing an effective measure to protect people from infection is an urgent need. The blockage of interaction between angiotensin-converting enzyme 2 (ACE2) and S protein is considered an essential target for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs. A full-length ACE2 protein could be a potential drug to block early entry of SARS-CoV-2 into host cells. In this study, a therapeutic strategy was developed by using extracellular vesicles (EVs) with decoy receptor ACE2 for neutralization of SARS-CoV-2. The EVs embedded with engineered ACE2 (EVs-ACE2) were prepared; the EVs-ACE2 were derived from an engineered cell line with stable ACE2 expression. The potential effect of the EVs-ACE2 on anti-SARS-CoV-2 was demonstrated by both in vitro and in vivo neutralization experiments using the pseudovirus with the S protein (S-pseudovirus). EVs-ACE2 can inhibit the infection of S-pseudovirus in various cells, and importantly, the mice treated with intranasal administration of EVs-ACE2 can suppress the entry of S-pseudovirus into the mucosal epithelium. Therefore, the intranasal EVs-ACE2 could be a preventive medicine to protect from SARS-CoV-2 infection. This EVs-based strategy offers a potential route to COVID-19 drug development.

Tumor metastasis is responsible for most mortality in cancer patients, and remains a challenge in clinical cancer treatment. Platelets can be recruited and activated by tumor cells, then adhere to circulating tumor cells (CTCs) and assist tumor cells extravasate in distant organs. Therefore, nanoparticles specially hitchhiking on activated platelets are considered to have excellent targeting ability for primary tumor, CTCs and metastasis in distant organs. However, the activated tumor-homing platelets will release transforming growth factor-β (TGF-β), which promotes tumor metastasis and forms immunosuppressive microenvironment. Therefore, a multitalent strategy is needed to balance the accurate tumor tracking and alleviate the immunosuppressive signals. In this study, a fucoidan-functionalized micelle (FD/DOX) was constructed, which could efficiently adhere to activated platelets through P-selectin. Compared with the micelle without P-selectin targeting effect, FD/DOX had increased distribution in both tumor tissue and metastasis niche, and exhibited excellent anti-tumor and anti-metastasis efficacy on 4T1 spontaneous metastasis model. In addition, due to the contribution of fucoidan, FD/DOX treatment was confirmed to inhibit the expression of TGF-β, thereby stimulating anti-tumor immune response and reversing the immunosuppressive microenvironment. The fucoidan-functionalized activated platelets-hitchhiking micelle was promising for the metastatic cancer treatment.