Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

【Objective】 To summarize the clinicopathological features and prognosis of young patients (18-40 years old) with non-clear cell renal cell carcinoma (nccRCC) treated in a single center to provide reference for the diagnosis and treatment of similar patients. 【Methods】 Clinical data of 113 nccRCC patients treated during Jan. 2012 and Aug. 2022 were retrospectively analyzed, including 57 males (50.4%) and 56 females (49.6%). The average age of onset was (31.6±5.8) years. Among all patients, 57 had lesions (50.4%) on the left side, and 56 (49.6%) on the right side. Young patients undergoing renal cancer surgery accounted for approximately 12.4% of the total number of renal cancer patients undergoing surgery, and nccRCC accounted for 34.8% of the total number of cases. 【Results】 Minimally invasive surgery (laparoscopic or robot-assisted) was performed in 102 cases (90.3%), and open surgery in 11 cases (9.7%). Fifty-five cases (48.7%) underwent partial nephrectomy and 58 (51.3%) radical nephrectomy. Among them, 11 patients (9.7%) developed tumor thrombi. All surgeries were successful with no serious complications. The pathological types included 32 cases (28.3%) of chromophobe renal cell carcinoma, 25 cases (22.1%) of MiT family translocation renal cell carcinoma, and 20 cases (17.7%) of papillary renal cell carcinoma. The total proportion of the three pathological subtypes reached 68.1%. After 46 (2-115) months of follow-up, 8 cases (7.8%, 8/102) developed tumor metastasis and 2 died. 【Conclusion】 The nccRCC is rare in young patients. The major pathological type is chromophobe, and the major treatment method is minimally invasive surgery. Most pathological types have good long-term prognosis, while patients with tumor thrombi have a high risk of metastasis and poor prognosis.

Objective:To analyze the total expendition,developmental changes and flow of the total cost of traditional Chinese medicine(TCM)in China from 2016 to 2021,and to study the development of the total cost of TCM in different medical institutions.Methods:Institutional flow method and case-base aggregation method were used to account for the total TCM costs.Results:From 2016 to 2021,the total amount of total TCM costs flowed to TCM-type hospitals was the highest in China,the proportion of total TCM costs in primary healthcare organizations was increased,and TCM-type clinics and outpatient clinics were developed more rapidly.The share of Chinese medicine drug costs in total Chinese medicine costs has been declined,and the share of county hospitals in their total health costs has been risen overall Conclusion:In the future,it would increase the TCM investment,attach importance to the development of TCM services in non-Chinese medicine hospitals,improve the capacity of primary Chinese medicine services,continue to consolidate the policy of"strengthening the primary",and maintain the rapid development of Chinese medicine clinics and outpatient clinics;the value of Chinese medicine technical labor should be emphasized,and the driving force of county hospitals should be brought into full play.

Objective:To analyze the total expendition,developmental changes and flow of the total cost of traditional Chinese medicine(TCM)in China from 2016 to 2021,and to study the development of the total cost of TCM in different medical institutions.Methods:Institutional flow method and case-base aggregation method were used to account for the total TCM costs.Results:From 2016 to 2021,the total amount of total TCM costs flowed to TCM-type hospitals was the highest in China,the proportion of total TCM costs in primary healthcare organizations was increased,and TCM-type clinics and outpatient clinics were developed more rapidly.The share of Chinese medicine drug costs in total Chinese medicine costs has been declined,and the share of county hospitals in their total health costs has been risen overall Conclusion:In the future,it would increase the TCM investment,attach importance to the development of TCM services in non-Chinese medicine hospitals,improve the capacity of primary Chinese medicine services,continue to consolidate the policy of"strengthening the primary",and maintain the rapid development of Chinese medicine clinics and outpatient clinics;the value of Chinese medicine technical labor should be emphasized,and the driving force of county hospitals should be brought into full play.

Objective:To analyze the total expendition,developmental changes and flow of the total cost of traditional Chinese medicine(TCM)in China from 2016 to 2021,and to study the development of the total cost of TCM in different medical institutions.Methods:Institutional flow method and case-base aggregation method were used to account for the total TCM costs.Results:From 2016 to 2021,the total amount of total TCM costs flowed to TCM-type hospitals was the highest in China,the proportion of total TCM costs in primary healthcare organizations was increased,and TCM-type clinics and outpatient clinics were developed more rapidly.The share of Chinese medicine drug costs in total Chinese medicine costs has been declined,and the share of county hospitals in their total health costs has been risen overall Conclusion:In the future,it would increase the TCM investment,attach importance to the development of TCM services in non-Chinese medicine hospitals,improve the capacity of primary Chinese medicine services,continue to consolidate the policy of"strengthening the primary",and maintain the rapid development of Chinese medicine clinics and outpatient clinics;the value of Chinese medicine technical labor should be emphasized,and the driving force of county hospitals should be brought into full play.

Objective:To analyze the total expendition,developmental changes and flow of the total cost of traditional Chinese medicine(TCM)in China from 2016 to 2021,and to study the development of the total cost of TCM in different medical institutions.Methods:Institutional flow method and case-base aggregation method were used to account for the total TCM costs.Results:From 2016 to 2021,the total amount of total TCM costs flowed to TCM-type hospitals was the highest in China,the proportion of total TCM costs in primary healthcare organizations was increased,and TCM-type clinics and outpatient clinics were developed more rapidly.The share of Chinese medicine drug costs in total Chinese medicine costs has been declined,and the share of county hospitals in their total health costs has been risen overall Conclusion:In the future,it would increase the TCM investment,attach importance to the development of TCM services in non-Chinese medicine hospitals,improve the capacity of primary Chinese medicine services,continue to consolidate the policy of"strengthening the primary",and maintain the rapid development of Chinese medicine clinics and outpatient clinics;the value of Chinese medicine technical labor should be emphasized,and the driving force of county hospitals should be brought into full play.

Objective:To analyze the total expendition,developmental changes and flow of the total cost of traditional Chinese medicine(TCM)in China from 2016 to 2021,and to study the development of the total cost of TCM in different medical institutions.Methods:Institutional flow method and case-base aggregation method were used to account for the total TCM costs.Results:From 2016 to 2021,the total amount of total TCM costs flowed to TCM-type hospitals was the highest in China,the proportion of total TCM costs in primary healthcare organizations was increased,and TCM-type clinics and outpatient clinics were developed more rapidly.The share of Chinese medicine drug costs in total Chinese medicine costs has been declined,and the share of county hospitals in their total health costs has been risen overall Conclusion:In the future,it would increase the TCM investment,attach importance to the development of TCM services in non-Chinese medicine hospitals,improve the capacity of primary Chinese medicine services,continue to consolidate the policy of"strengthening the primary",and maintain the rapid development of Chinese medicine clinics and outpatient clinics;the value of Chinese medicine technical labor should be emphasized,and the driving force of county hospitals should be brought into full play.

Objective:To analyze the total expendition,developmental changes and flow of the total cost of traditional Chinese medicine(TCM)in China from 2016 to 2021,and to study the development of the total cost of TCM in different medical institutions.Methods:Institutional flow method and case-base aggregation method were used to account for the total TCM costs.Results:From 2016 to 2021,the total amount of total TCM costs flowed to TCM-type hospitals was the highest in China,the proportion of total TCM costs in primary healthcare organizations was increased,and TCM-type clinics and outpatient clinics were developed more rapidly.The share of Chinese medicine drug costs in total Chinese medicine costs has been declined,and the share of county hospitals in their total health costs has been risen overall Conclusion:In the future,it would increase the TCM investment,attach importance to the development of TCM services in non-Chinese medicine hospitals,improve the capacity of primary Chinese medicine services,continue to consolidate the policy of"strengthening the primary",and maintain the rapid development of Chinese medicine clinics and outpatient clinics;the value of Chinese medicine technical labor should be emphasized,and the driving force of county hospitals should be brought into full play.

Objective:To analyze the total expendition,developmental changes and flow of the total cost of traditional Chinese medicine(TCM)in China from 2016 to 2021,and to study the development of the total cost of TCM in different medical institutions.Methods:Institutional flow method and case-base aggregation method were used to account for the total TCM costs.Results:From 2016 to 2021,the total amount of total TCM costs flowed to TCM-type hospitals was the highest in China,the proportion of total TCM costs in primary healthcare organizations was increased,and TCM-type clinics and outpatient clinics were developed more rapidly.The share of Chinese medicine drug costs in total Chinese medicine costs has been declined,and the share of county hospitals in their total health costs has been risen overall Conclusion:In the future,it would increase the TCM investment,attach importance to the development of TCM services in non-Chinese medicine hospitals,improve the capacity of primary Chinese medicine services,continue to consolidate the policy of"strengthening the primary",and maintain the rapid development of Chinese medicine clinics and outpatient clinics;the value of Chinese medicine technical labor should be emphasized,and the driving force of county hospitals should be brought into full play.

Objective:To analyze the total expendition,developmental changes and flow of the total cost of traditional Chinese medicine(TCM)in China from 2016 to 2021,and to study the development of the total cost of TCM in different medical institutions.Methods:Institutional flow method and case-base aggregation method were used to account for the total TCM costs.Results:From 2016 to 2021,the total amount of total TCM costs flowed to TCM-type hospitals was the highest in China,the proportion of total TCM costs in primary healthcare organizations was increased,and TCM-type clinics and outpatient clinics were developed more rapidly.The share of Chinese medicine drug costs in total Chinese medicine costs has been declined,and the share of county hospitals in their total health costs has been risen overall Conclusion:In the future,it would increase the TCM investment,attach importance to the development of TCM services in non-Chinese medicine hospitals,improve the capacity of primary Chinese medicine services,continue to consolidate the policy of"strengthening the primary",and maintain the rapid development of Chinese medicine clinics and outpatient clinics;the value of Chinese medicine technical labor should be emphasized,and the driving force of county hospitals should be brought into full play.