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 investigate the nicotine dependence of patients with chronic obstructive pulmonary disease (COPD) who smoke and analyze its influencing factors, so as to provide insights into targeted smoking cessation interventions for smoking COPD patients. Methods: The smoking COPD patients were selected from three hospitals in Lanzhou City using the convenience sampling method from October 2022 to April 2023. Demographic data, smoking status, and willingness to quit smoking were collected using questionnaire surveys. Nicotine dependence was assessed according to Fagerstrom Test for Nicotine Dependence. The influencing factors of nicotine dependence in smoking COPD patients were analyzed using a multiple linear regression model. Results: A total of 200 questionnaires were distributed, and 171 valid questionnaires were collected, with a response rate of 85.50%. The median age was 48.00 (interquartile range, 10.00) years. There were 158 males, accounting for 92.40%; 53 cases with a college degree or above, accounting for 30.99%. The median smoking duration was 15.00 (interquartile range, 11.00) years. There were 73 patients (42.69%) smoking 21 to 30 cigarettes per day, and 159 patients (92.98%) with the willingness to quit smoking. The median nicotine dependence score was 3.00 (interquartile range, 1.00) points. There were statistically significant differences in nicotine dependence scores among smoking COPD patients with different ages, educational levels, occupations, interpersonal relationships, smoking duration, daily cigarette consumption, awareness of smoking hazards and willingness to quit smoking (all P<0.05). Multiple linear regression analysis revealed that nicotine dependence was related with educational level (β=-0.251), interpersonal relationship (β=-0.246), smoking duration (β=0.038), daily cigarette consumption (β=0.518) and willingness to quit smoking (β=-0.173) among smoking COPD patients (all P<0.05). Conclusion The nicotine dependence among smoking COPD patients was influenced by educational level, interpersonal relationships, smoking duration, daily cigarette consumption and willingness to quit smoking.

ObjectiveTo determine the resistance of adult Culex quinquefasciatus and Musca domestica to commonly used insecticides in Dazhu District of Chongqing in 2023， and provide scientific evidence for rational use of hygienic insecticides. MethodsDrug resistance was determined by using adult mosquito contact tube method and adult fly drop method. ResultsIn 2023， the 24-hour mortality rate of adult Culex quinquefasciatus in Dazu District， Chongqing， against permethrin （0.25%）， beta-cypermethrin （0.025%）， deltamethrin （0.025%）， malathion （5%） and propoxur （0.1%） was 37.35%， 21.92%， 28.33%， 96.43%， and 95.38%， respectively. The median lethal dose （LD₅₀） value of female adult Musca domestica against beta-cypermethrin （95.8%）， chlorpyrifos （97%）， deltamethrin （90%） and dichlorvos （95%） was 2.572 μg， 0.329 μg， 0.406 μg， and 0.492 μg， respectively， with resistance of 829.68， 7.65， 53.42， and 46.42 folds to the above tested insecticides． ConclusionAdult Culex quinquefasciatus and Musca domestica in Dazu District show various degrees of resistance to commonly used insecticides. It warrants suspending the insecticides with high resistance， whereas mixedly and alternatively administering the insecticides with possible resistance and low resistance. Additionally， we should continue to monitor the resistance and guide the rational use of insecticides.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Background::Pathological scars are a disorder that can lead to various cosmetic, psychological, and functional problems, and no effective assessment methods are currently available. Assessment and treatment of pathological scars are based on cutaneous manifestations. A two-photon microscope (TPM) with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo. This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients. Methods::Fifteen patients with pathological scars and three healthy controls were recruited. Imaging was performed using a portable handheld TPM. Five indexes were extracted from two dimensional (2D) and three dimensional (3D) perspectives, including collagen depth, dermo-epidermal junction (DEJ) contour ratio, thickness, orientation, and occupation (proportion of collagen fibers in the field of view) of collagen. Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images. We assessed index differences between scar and normal skin and changes before and after treatment.Results::Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers. Five indexes were employed to distinguish between normal skin and scar tissue. Statistically significant differences were found in average depth ( t = 9.917, P <0.001), thickness ( t = 4.037, P <0.001), occupation ( t= 2.169, P <0.050), orientation of collagen ( t = 3.669, P <0.001), and the DEJ contour ratio ( t = 5.105, P <0.001). Conclusions::Use of portable handheld TPM can distinguish collagen from skin tissues; thus, it is more suitable for scar imaging than reflectance confocal microscopy. Thus, a TPM may be an auxiliary tool for scar treatment selection and assessing treatment efficacy.

Objective:To analyze the vaccination recommendations and follow-up for children with special health status.Methods:In this retrospective cohort study, 509 children who attended the Consultation Clinic of Vaccination for Special Health Children in Beijing Children′s Hospital from August 2020 to February 2023 were selected, the children were given vaccination planning advice after the assessment. The clinical data were collected, including the general situation, special health conditions, vaccination recommendations and implementation status, occurrence and outcomes of suspected adverse events following immunization (AEFI) after vaccination. The vaccination situation and safety in these children were evaluated.Results:Among the 509 children, the most common special health conditions were cardiovascular system diseases (103 cases), followed by neurological diseases (88 cases) and neonatal problems (82 cases). After comprehensive evaluation and multidisciplinary collaboration, 399 children (78.4%) were recommended to receive vaccination/catch-up vaccination according to the immunization program, 63 children (12.4%) were recommended to receive some vaccines but temporarily suspend others, and 47 children (9.2%) were recommended to temporarily suspend vaccination. A total of 449 children (88.2%) were actually vaccinated, AEFI occurred in 49 children and 45 cases were considered as general reactions.Conclusions:The majority of children with special health status can be vaccinated, and the overall compliance and safety are high. The individualized immunization evaluation model of multidisciplinary collaboration is conducive to the completion of the immunization program of children with special health status.

Surgical resection and radiotherapy have been commonly applied to the treatment of early- and intermediate-stage Merkel cell carcinoma. In recent years, immunotherapy based on immunogenic characteristics of Merkel cell carcinoma has been proved to be effective in the treatment of advanced Merkel cell carcinoma. This review focuses on advances in the treatment of Merkel cell carcinoma, and provides a reference for its clinical diagnosis and treatment.

Objective:To systematically evaluate the effect of singing therapy on patients with chronic obstructive pulmonary disease.Methods:Randomized controlled trials on the effect of singing therapy in patients with chronic obstructive pulmonary disease were searched by computer from PubMed, Web of Science, Cochrane Library, CINAHL, Embase, China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine disc, and VIP. The search period was from the establishment of databases to June 30, 2023. Two researchers independently screened literature, performed a literature quality assessment, and extracted data. Meta-analysis was performed using RevMan 5.4 software.Results:A total of 11 articles were included. Meta-analysis showed that singing therapy for 10 weeks or more could improved anxiety ( MD=-5.01, 95% CI: -5.76~-4.25, P<0.001), and depression ( MD=-4.73, 95% CI: -8.82~-0.64, P=0.020). Singing therapy with a duration of less than 60 min per session and/or five interventions per week or more could improve FEV 1% predicted values ( MD=9.46, 95% CI: 7.66~11.26, P<0.001) in patients with chronic obstructive pulmonary disease. Conclusions:Singing therapy is best achieved at least five times a week, with each session lasting less than 60 minutes and lasting for at least ten weeks. However, more high-quality, multicenter and large sample studies are still needed for further validation.

Objective:To explore whether thyroxine (T 4) could promote differentiated thyroid cancer (DTC) progression by binding to integrin α vβ 3in vitro and its downstream mechanism. Methods:Papillary thyroid cancer cell lines TPC-1, K1 and follicular thyroid cancer (FTC) cell line FTC133 were cultured in vitro, and the expressions of integrin α vβ 3 in those 3 DTC cell lines were determined with immunofluorescence and flow cytometry analysis. After the treatment of T 4, tetraiodo thyroacetic acid (Tetrac) and Arg-Gly-Asp (RGD) peptide alone or in combination, the proliferation and metastatic potential of DTC cell lines were detected by cell counting kit-8 (CCK-8), Transwell migration and invasion assays. The small interfering RNA (siRNA) transfection was used to verify whether integrin α v or β 3 subunit knockdown could reverse the effect of T 4 on DTC cells. The expression levels of downstream signaling proteins phosphorylated extracellular signal-regulated kinase (p-ERK)1/2 and total extracellular signal-regulated kinase (ERK)1/2 were detected by Western blot. The effects of mitogen-activated protein kinase kinase (MEK)1/2 inhibitor (GSK1120212) on the proliferation, migration and invasion of T 4-treated cells were detected. One-way analysis of variance and Tukey test were used for data analysis. Results:The integrin α vβ 3 expressions in TPC-1, K1 and FTC133 cells were all positive, with the relative mean fluorescence intensity (MFI) of 61.93±18.61, 16.89±2.43 and 32.36±0.83, and the percentages of positive cells of (94.38±1.30)%, (74.11±3.87)% and (50.67±1.78)%, respectively ( F values: 13.36 and 217.30, P=0.006 and P<0.001). Compared with control group, the proliferation, migration and invasion in the three DTC cell lines treated with T 4 were significantly enhanced (96 h, F values: 62.67-297.50, q values: 13.15-20.73, all P<0.001). T 4-induced cell proliferation, migration and invasion were markedly reversed by Tetrac or RGD (96 h, q values: 8.61-17.54, all P<0.001). T 4-induced cell proliferation, migration and invasion were also significantly inhibited by the knockdown of integrin α v or β 3 subunit (72 h, F values: 7.75-70.98, q values: 4.77-15.21, all P<0.05). Western blot results showed that the phosphorylation levels of ERK1/2 in DTC cells were significantly increased by T 4 treatment, and the T 4-induced activation of ERK1/2 signaling pathway could be blocked by Tetrac, RGD, integrin α v or β 3 subunit knockdown. T 4-induced cell proliferation, migration and invasion were significantly reversed by GSK1120212 (96 h, F values: 47.53-151.40, q values: 10.32-16.65, all P<0.001). Conclusion:T 4 can promote cell proliferation and metastasis of DTC cells by binding to integrin α vβ 3 and activating the ERK1/2 pathway.

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.