Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.
Humans ; Immune Checkpoint Inhibitors ; Neoplasm Recurrence, Local ; Lung Neoplasms/genetics* ; Thoracic Neoplasms/pathology* ; Adenocarcinoma ; DNA Helicases ; Nuclear Proteins ; Transcription Factors

OBJECTIVE: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. METHODS: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. RESULTS: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. CONCLUSION These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
Female ; Humans ; Male ; Middle Aged ; Brucellosis ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome ; Case Reports as Topic

Reduced levels of retinal dopamine, a key regulator of eye development, are associated with experimental myopia in various species, but are not seen in the myopic eyes of C57BL/6 mice, which are deficient in melatonin, a neurohormone having extensive interactions with dopamine. Here, we examined the relationship between form-deprivation myopia (FDM) and retinal dopamine levels in melatonin-proficient CBA/CaJ mice. We found that these mice exhibited a myopic refractive shift in form-deprived eyes, which was accompanied by altered retinal dopamine levels. When melatonin receptors were pharmacologically blocked, FDM could still be induced, but its magnitude was reduced, and retinal dopamine levels were no longer altered in FDM animals, indicating that melatonin-related changes in retinal dopamine levels contribute to FDM. Thus, FDM is mediated by both dopamine level-independent and melatonin-related dopamine level-dependent mechanisms in CBA/CaJ mice. The previously reported unaltered retinal dopamine levels in myopic C57BL/6 mice may be attributed to melatonin deficiency.
Animals ; Disease Models, Animal ; Dopamine ; Melatonin ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Myopia ; Retina ; Sensory Deprivation

Objective:To explore the current status and influencing factors of psychological resilience in in-service nurses in Hunan Province, and provide a certain reference for the development of nursing human resource management and occupational mental health.Methods:A mixed study method was adopted. Quantitative study: in August 2018, a total of 749 in-serve nurses from hospitals in Hunan Province were selected by convenient sampling and investigated with the general information questionnaire and Conner-Davidson Resilience Scale (CD-RISC) . SPSS 23.0 was used for statistical analysis. Qualitative study: totally 21 in-service nurses who participated in the quantitative study were randomly selected for semi-structured interviews. Based on the principle of data saturation, the subject analysis method was used to organize the data.Results:The total CD-RISC score of the 749 in-service nurses was (87.28±13.28) , higher than (65.40±13.90) of the domestic norm, and the difference was statistically significant ( P<0.01) ; the average score of each dimension in descending order was (3.69±0.55) for strength, (3.41±0.58) for toughness, and (3.34±0.60) for optimism. There were statistically significant differences between the total CD-RISC score of in-service nurses with different ages, educational levels, working years, type of affiliation, form of employment, and professional title ( F=7.295, 5.446, 6.915, 3.238, 4.342, 7.914; P<0.05) ; Multi-factor analysis showed that age and education level were the main influencing factors ( P<0.05) . Two themes were extracted from the qualitative study, namely internal factors and external factors. The internal factors included the lack of personal adaptability and mental health guidance awareness, while the external factors included differences in hospital management culture, and lack of psychological service institutions, professionals and trust. Conclusions:The psychological resilience of in-service nurses in Hunan Province is higher than that of domestic norms, and is affected by both internal and external factors. It is recommended to enhance the nurses' rights protection bill in future organization and management, attach importance to their on-the-job education and provide personalized psychological service channels for employees, and further strengthen the hospital's internal psychosocial service construction.

OBJECTIVE: To study the feasibility and clinical application value of laparoscopic surgery via suprapubic small incision in the treatment of gynecological benign diseases.METHODS: A total of 80 patients who received laparoscopic surgery through suprapubic small incison in Wuhan First Hospital from Jan. 2017 to Oct. 2018 were collected as the new-operative group,and 82 patients who received the traditional 4-hole laparoscopic surgery during the same period were included as the controls(traditional group).Their clinical data were analyzed retrospectively.Operative methods included ovarian cyst removal,oviduct fenestration,oviduct resection,salpingostomy,etc.RESULTS: The operation was secessful in both groups.There were no significant differences in operation time[(45.31±7.35)min vs.(52.46±9.21)min],bleeding[(30.79±7.74)mL vs.(32.58±5.21)mL],getting out of bed time[(12.93±3.95)h vs.(14.47±8.51)h],anal exhaust time[(14.29±4.19)h vs.(20.03±4.34)h]or hospitalization time[(5.76±1.43)d vs.(9.08±2.57)d]between the new operative group and the traditional group(P>0.05),but there were significant differences in pain score(3.14±1.12 vs.6.54±1.27)and cosmetic score(4.7±0.3 vs. 2.5±0.8)between the new operative group and the traditional group(P<0.05).CONCLUSION: Laparoscopic surgery via suprapubic small incision is safe and effective in the treatment of some gynecological benign diseases. The scar is hidden or no scar is present.It is worth popularizing and applying in clinic because of its low cost and full use of existing equipment and instruments.

Objective? To investigate the leadership status of new nurses, and to provide some reference for the training and education of new nurses and efficient quality nursing service. Methods? In September 2018, a total of 129 new nurses from a ClassⅢ Grade A hospital were randomly recruited by convenience sampling method. Questionnaire survey was conducted to compare the difference of leadership among new nurses with different characteristics by General Information Questionnaire and Nurse Leadership Questionnaire. A total of 129 questionnaires were sent out and 125 valid questionnaires were collected. Results? The average leadership score of the 125 new nurses was (3.59±0.67). The score of nursing professional ability dimension was the highest (3.73±0.64), and the score of critical thinking ability dimension was the lowest (3.47±0.71). The scores of five dimensions of interpersonal communication ability, communication ability, critical thinking ability, planning and organizing ability and self-care ability of new nurses of different genders in the nurse leadership questionnaire were compared, and the differences were statistically significant (t=-3.950,-3.145,-3.389,-3.451,-2.179;P＜0.05). The difference in critical thinking ability score of new nurses with different marital status was statistically significant (t=3.235,P＜ 0.01). Conclusions? The overall level of leadership status of new nurses is low. It is suggested that in the standardized training and education of newly recruited nurses, early education and training of career leadership should be emphasized, and the strengths of different groups of nurses should be brought into play, so as to improve their professional value and quality service.

Objective To explore the effects of massive open online courses (MOOC) teaching in new entry nurses standardized training of respiratory medicine. Methods A total of 33 new entry nurses of respiratory medicine at a hospital were selected as control group from 2013 to 2014 with the routine training method. A total of 34 new entry nurses were chosen as intervention group from 2015 to 2017. Nurses of intervention group accepted standardized training with the MOOC teaching method by formulating systematic online and offline training course. The training effects of two groups were evaluated. Results The specialized theoretical achievements and skill achievements of nurses were (72.68±9.44) and (75.78±10.32) in intervention group, and (67.33±8.89) and (62.64±5.8) in control group with significant differences (P< 0.05). After intervention, the degree of satisfaction of patients in intervention group was higher than that in control group with a significant difference (χ2=10.823, P< 0.05). Conclusions MOOC teaching can effectively improve the level of specialized skill in new entry nurses, contribute to linking theory with practice, fast role switching and improve the occupational satisfaction.

In order to study the microstructure characteristics of normal lunate bones,eight fresh cadaver normal lunates were scanned with micro-computed tomography.High-resolution images of the micro-structure of normal lunates were obtained and we analyzed the nutrient foramina.Then nine regions of interest (ROI) were chosen in the central sagittal plane so that we could obtain the parameters of trabecular bones of ROIs.The distal lamellar-like compact structure had statistically significant differences when it was compared with the ROIs in the volar and dorsal ends of the distal cortex.The difference of diameter between the volar and dorsal foramina was significant (P＜0.05).However,there was no significant difference regarding the number.The trabecular bones of the volar and dorsal distal ends had lower intensity than those of the distal central subchondral bone plate.The diameters of the nutrient foramina on the volar cortex were larger than those on the dorsal.This research provided more detailed information about microstructure of normal lunate and the nutrient foramina on cortex,and a reference for further study about diseased lunate.

We investigated the complete genome characteristic of the Hantaan virus strain AYW89-15 isolated in Jiangxi Province,China.Primers were designed and were used to amplify the complete S,M and L segments by RT-PCR.The PCR product were then cloned and sequenced,the gene sequences were analyzed with DNAStar and MEGA6.0 software.Result showed that the complete gene sequence was 11 848 nucleotides in length,the S,M and L segments were 1 699 nt,3 616 nt and 6 533 nt respectively,encoding 429,1 133 and 2 151 amino acids respectively.The sequence identities between stain AYW89-15 and other Hantaan virus were 79.7％-87.3％ at the nucleotide level and 92.3％-98.4％ at the amino acid level.Phylogenetic analysis of HV showed AYW89-15 belonged to a new HTNV lineage.AYW89-15 was a new subtype of HTNV that exists in Jiangxi Province.