Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
Toll-Like Receptor 4/chemistry* ; Animals ; Acute Lung Injury/chemically induced* ; Mice ; Humans ; Ilex/chemistry* ; Molecular Docking Simulation ; Male ; NF-kappa B/immunology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; RAW 264.7 Cells ; Disease Models, Animal

[Purpose]To analyze the trends of incidence and age at onset of bone malignant tumors in cancer registration areas of Jiangsu Province from 2009 to 2019.[Methods]Incidence data of bone malignant tumors from 2009 to 2019 were collected from 16 consecutive and quality-con-trolled cancer registries in Jiangsu Province.The incidence rates,average age at onset,and inci-dence composition of bone malignant tumors were calculated.A birth cohort model was constructed to analyze the changes in the incidence of bone malignant tumors in the population born from 1929 to 2019.Joinpoint regression models were used to analyze the average annual percentage change(AAPC)in the incidence rates and the incidence composition of bone malignant tumors for each year in those aged 60 years old and above.A general linear regression model was used to ana-lyze the trend of the average age of onset.[Results]The crude incidence rate of bone malignant tumors in women in Jiangsu cancer registration areas decreased from 2009 to 2019,with an AAPC of-2.62％(P=0.025).After adjusting the population composition,except for urban areas,the incidence of bone malignant tumors in the whole province,men,women and rural areas all decreased significantly,with AAPC of-3.15％,-2.49％,-4.31％and-2.23％,respectively.The average age at onset of bone malignant tumors in the whole province,men and urban areas de-creased significantly yearly,with an average annual decrease of 0.365,0.504 and 0.469 years old,respectively.In the same period,the incidence of malignant bone tumors in the whole province,men,women and urban areas of age groups of 50～59,60～69 and 70～79 years old showed a decreasing trend,the AAPC ranged from-9.06％to-4.14％(all P＜0.05),and the inci-dence decreased gradually with the year of birth.The incidence of malignant bone tumors in men＜30 years old increased yearly with an AAPC of 4.30％(P＜0.05).Compared with 2009,the com-position of incidence in men aged 15～39 years old and in urban population increased in 2019,while the incidence of bone malignant tumors in the age group of 60～79 years old in the province generally decreased.After age structure adjustment,the incidence of bone malignant tumors in people over 60 years old in urban areas decreased with an AAPC of-1.42％(P＜0.05).[Conclu-sion]The incidence of bone malignant tumors in Jiangsu Province is decreasing and the age at on-set is moving forward,indicating that the prevention and control measures of bone malignant tu-mors should be adjusted accordingly.

In the context of an aging society,the number of elderly cancer patients is constantly increasing,and geriatric oncology has garnered significant attention in recent years.Given the heterogeneity in the health status of older patients,it has become increasingly important to provide individualized diagnosis,treatment,follow-up,and care.Thus,it must be emphasized the Comprehensive Geriatric Assessment(CGA)for elderly patients,which encompasses their physical function,nutritional status,cognitive function,emotional state,comorbidities,polypharmacy,social situation,and treatment preferences.This article provides consensus recommendations on CGA tools for elderly patients prior to anticancer treatment,offering valuable references and insights for clinical practice in China.

OBJECTIVE: To explore the clinical presentation and genetic etiology of a case with Xeroderma pigmentosum in conjunct with basal cell carcinoma and melanoma. METHODS: A male patient with Xeroderma pigmentosum treated at Xinxiang Central Hospital in October 2022 was selected as study subject. Whole exome sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing of his family members. This study was approved by the Ethics Committee of the hospital (Ethics No.: 2021-167). RESULTS: Magnetic resonance imaging showed that the patient has a solid soft tissue mass in the anterior and lower part of his right eyeball and a small nodule on the left nasal wing. Histopathological biopsy showed that the periocular tumor was basal cell carcinoma in conjunct with malignant melanoma, and the nasal wing tumor was basal cell carcinoma. WES and Sanger sequencing revealed that he has harbored compound heterozygous variants of the XPC gene, namely c.2391delT (p.F797Lfs*11) and IVS1+1G>A, which were inherited from his father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were rated as likely pathogenic (PVS1+PM2_Supporting+PM3) and pathogenic (PVS1+PM2_Supporting+PM3+PP5), respectively. The c.2391delT variant was unreported previously. Bioinformatic analysis suggests that it could significantly affect the tertiary structure of XPC protein. CONCLUSION The c.2391delT(p.F797Lfs*11) and IVS1+1G>A compound heterozygous variants probably underlay the pathogenesis in this patient. The detection of the novel variant has enriched the mutational spectrum of the XPC gene.
Humans ; Male ; Xeroderma Pigmentosum/genetics* ; Basal Cell Carcinoma/genetics* ; DNA-Binding Proteins/genetics* ; Melanoma/genetics* ; Mutation ; Skin Neoplasms/genetics* ; Middle Aged ; Exome Sequencing ; Pedigree

Objective:To quantitatively analyze right ventricular reverse remodeling in patients with severe tricuspid regurgitation after transcatheter tricuspid edge-to-edge repair (T-TEER) by two-dimensional speckle tracking echocardiography, and to preliminarily evaluate the clinical efficacy of this procedure.Methods:This study was a prospective single-center cohort study. Patients diagnosed with severe tricuspid regurgitation at the Xiamen Cardiovascular Hospital Xiamen University from March 2021 to June 2023 were enrolled. All patients underwent transthoracic echocardiography and transesophageal three-dimensional echocardiography before T-TEER, and transthoracic echocardiography at 30 days, 6 months, and 9 months after T-TEER. The primary endpoint was major adverse cardiovascular and cerebrovascular events, including death, stroke, myocardial infarction, reoperation, arrhythmia, and conduction block. Other clinical evaluation indicators included New York Heart Association (NYHA) functional classification and tricuspid regurgitation grade.Results:A total of 34 patients were enrolled, aged (67.9±9.3) years, and 71% (24/34) were female. The median follow-up duration was 9 months. All patients achieved a reduction of tricuspid regurgitation by ≥2 grades at 9 months after T-TEER, with 79% (27/34) of them having mild to moderate tricuspid regurgitation. Transthoracic echocardiography at 9 months after T-TEER showed that the vena contracta width of tricuspid regurgitation ((5.42±2.33) mm vs. (11.54±4.05) mm, P<0.001), effective regurgitant orifice area ((0.24±0.09) cm2 vs. (0.52±0.14) cm2, P<0.001), regurgitant jet area ((7.95±4.02) cm2 vs. (13.93±6.10) cm2, P<0.001), inferior vena cava diameter ((19.38±2.63) mm vs. (23.56±3.31) mm, P<0.001), right ventricular end-diastolic diameter ((28.03±6.26) mm vs. (33.21±8.24) mm, P=0.001), and tricuspid annular diameter ((36.47±4.40) mm vs. (41.44±7.08) mm, P<0.001) were all reduced compared with baseline; while the tricuspid annular plane systolic excursion ((18.08±5.25) mm vs. (14.91±3.42) mm, P=0.005) and right ventricular fractional area change ((37.61±7.52)% vs. (30.79±9.06)%, P=0.004) were both increased compared with baseline. At 9 months after T-TEER, all patients had a NYHA functional classification of grade Ⅰ or Ⅱ, and no major adverse cardiovascular and cerebrovascular event occurred during the follow-up period. Conclusion:It is preliminarily confirmed that T-TEER is safe and effective in the treatment of severe tricuspid regurgitation, with significant right ventricular reverse remodeling observed in patients at 9 months after T-TEER.

OBJECTIVE To analyze the ethanol extracts,total phenols,total flavonoids contents and HPLC fingerprints of typi-cal propolis samples from 6 foreign countries and 5 domestic regions,optimize the extraction process and evaluate the antioxidant activi-ty,so as to provide data support for improving the quality control system of propolis.METHODS The optimization of the propolis ex-traction process utilized flavonoid content as an indicator.Three flavonoid detection methods-namely,the aluminum trichloride meth-od,aluminum nitrate method,and polyamide method-were compared.The content of ethanol extract,total phenol content,and the scavenging ability of DPPH free radicals for each sample were determined.Further analysis was conducted using HPLC fingerprint pro-filing.RESULTS The propolis extract with the highest flavonoid content was obtained using 80%ethanol as the extraction solvent,operating at 50℃,with a stirring time of 3 h,ultrasonic power of 180 W,and ultrasonic time of 15 min.The aluminum trichloride method was proved to be the most effective for determining total flavonoids in propolis.While the ethanol extract,total flavonoids,and total phenols of propolis from Xinjiang,China were relatively low,their antioxidant activity exhibited superiority.HPLC analysis re-vealed,Brazilian red propolis lacked of chrysin,galangin,caffeic acid phenethyl ester and Brazilian green propolis lacked ferulic acid,apigenin,p-coumaric acid,chrysin,and pinocembrin.In contrast,the content of these four compounds in other samples varied,with the antioxidant capacity of the extracts not precisely corresponding to the compound content.CONCLUSION Propolis exhibits a complex chemical composition with significant variations among varieties.Key quality control indexes must be comprehensively consid-ered,encompassing physicochemical characteristics and biological activity.Establishing a multi-angle assessment system with a mate-rial basis-functional linkage is essential.This approach facilitates the realization of high quality and cost-effectiveness,thereby promo-ting the healthy development of the industry.

OBJECTIVE To analyze the ethanol extracts,total phenols,total flavonoids contents and HPLC fingerprints of typi-cal propolis samples from 6 foreign countries and 5 domestic regions,optimize the extraction process and evaluate the antioxidant activi-ty,so as to provide data support for improving the quality control system of propolis.METHODS The optimization of the propolis ex-traction process utilized flavonoid content as an indicator.Three flavonoid detection methods-namely,the aluminum trichloride meth-od,aluminum nitrate method,and polyamide method-were compared.The content of ethanol extract,total phenol content,and the scavenging ability of DPPH free radicals for each sample were determined.Further analysis was conducted using HPLC fingerprint pro-filing.RESULTS The propolis extract with the highest flavonoid content was obtained using 80%ethanol as the extraction solvent,operating at 50℃,with a stirring time of 3 h,ultrasonic power of 180 W,and ultrasonic time of 15 min.The aluminum trichloride method was proved to be the most effective for determining total flavonoids in propolis.While the ethanol extract,total flavonoids,and total phenols of propolis from Xinjiang,China were relatively low,their antioxidant activity exhibited superiority.HPLC analysis re-vealed,Brazilian red propolis lacked of chrysin,galangin,caffeic acid phenethyl ester and Brazilian green propolis lacked ferulic acid,apigenin,p-coumaric acid,chrysin,and pinocembrin.In contrast,the content of these four compounds in other samples varied,with the antioxidant capacity of the extracts not precisely corresponding to the compound content.CONCLUSION Propolis exhibits a complex chemical composition with significant variations among varieties.Key quality control indexes must be comprehensively consid-ered,encompassing physicochemical characteristics and biological activity.Establishing a multi-angle assessment system with a mate-rial basis-functional linkage is essential.This approach facilitates the realization of high quality and cost-effectiveness,thereby promo-ting the healthy development of the industry.

[Purpose]To analyze the trends of incidence and age at onset of bone malignant tumors in cancer registration areas of Jiangsu Province from 2009 to 2019.[Methods]Incidence data of bone malignant tumors from 2009 to 2019 were collected from 16 consecutive and quality-con-trolled cancer registries in Jiangsu Province.The incidence rates,average age at onset,and inci-dence composition of bone malignant tumors were calculated.A birth cohort model was constructed to analyze the changes in the incidence of bone malignant tumors in the population born from 1929 to 2019.Joinpoint regression models were used to analyze the average annual percentage change(AAPC)in the incidence rates and the incidence composition of bone malignant tumors for each year in those aged 60 years old and above.A general linear regression model was used to ana-lyze the trend of the average age of onset.[Results]The crude incidence rate of bone malignant tumors in women in Jiangsu cancer registration areas decreased from 2009 to 2019,with an AAPC of-2.62％(P=0.025).After adjusting the population composition,except for urban areas,the incidence of bone malignant tumors in the whole province,men,women and rural areas all decreased significantly,with AAPC of-3.15％,-2.49％,-4.31％and-2.23％,respectively.The average age at onset of bone malignant tumors in the whole province,men and urban areas de-creased significantly yearly,with an average annual decrease of 0.365,0.504 and 0.469 years old,respectively.In the same period,the incidence of malignant bone tumors in the whole province,men,women and urban areas of age groups of 50～59,60～69 and 70～79 years old showed a decreasing trend,the AAPC ranged from-9.06％to-4.14％(all P＜0.05),and the inci-dence decreased gradually with the year of birth.The incidence of malignant bone tumors in men＜30 years old increased yearly with an AAPC of 4.30％(P＜0.05).Compared with 2009,the com-position of incidence in men aged 15～39 years old and in urban population increased in 2019,while the incidence of bone malignant tumors in the age group of 60～79 years old in the province generally decreased.After age structure adjustment,the incidence of bone malignant tumors in people over 60 years old in urban areas decreased with an AAPC of-1.42％(P＜0.05).[Conclu-sion]The incidence of bone malignant tumors in Jiangsu Province is decreasing and the age at on-set is moving forward,indicating that the prevention and control measures of bone malignant tu-mors should be adjusted accordingly.

Objective:To quantitatively analyze right ventricular reverse remodeling in patients with severe tricuspid regurgitation after transcatheter tricuspid edge-to-edge repair (T-TEER) by two-dimensional speckle tracking echocardiography, and to preliminarily evaluate the clinical efficacy of this procedure.Methods:This study was a prospective single-center cohort study. Patients diagnosed with severe tricuspid regurgitation at the Xiamen Cardiovascular Hospital Xiamen University from March 2021 to June 2023 were enrolled. All patients underwent transthoracic echocardiography and transesophageal three-dimensional echocardiography before T-TEER, and transthoracic echocardiography at 30 days, 6 months, and 9 months after T-TEER. The primary endpoint was major adverse cardiovascular and cerebrovascular events, including death, stroke, myocardial infarction, reoperation, arrhythmia, and conduction block. Other clinical evaluation indicators included New York Heart Association (NYHA) functional classification and tricuspid regurgitation grade.Results:A total of 34 patients were enrolled, aged (67.9±9.3) years, and 71% (24/34) were female. The median follow-up duration was 9 months. All patients achieved a reduction of tricuspid regurgitation by ≥2 grades at 9 months after T-TEER, with 79% (27/34) of them having mild to moderate tricuspid regurgitation. Transthoracic echocardiography at 9 months after T-TEER showed that the vena contracta width of tricuspid regurgitation ((5.42±2.33) mm vs. (11.54±4.05) mm, P<0.001), effective regurgitant orifice area ((0.24±0.09) cm2 vs. (0.52±0.14) cm2, P<0.001), regurgitant jet area ((7.95±4.02) cm2 vs. (13.93±6.10) cm2, P<0.001), inferior vena cava diameter ((19.38±2.63) mm vs. (23.56±3.31) mm, P<0.001), right ventricular end-diastolic diameter ((28.03±6.26) mm vs. (33.21±8.24) mm, P=0.001), and tricuspid annular diameter ((36.47±4.40) mm vs. (41.44±7.08) mm, P<0.001) were all reduced compared with baseline; while the tricuspid annular plane systolic excursion ((18.08±5.25) mm vs. (14.91±3.42) mm, P=0.005) and right ventricular fractional area change ((37.61±7.52)% vs. (30.79±9.06)%, P=0.004) were both increased compared with baseline. At 9 months after T-TEER, all patients had a NYHA functional classification of grade Ⅰ or Ⅱ, and no major adverse cardiovascular and cerebrovascular event occurred during the follow-up period. Conclusion:It is preliminarily confirmed that T-TEER is safe and effective in the treatment of severe tricuspid regurgitation, with significant right ventricular reverse remodeling observed in patients at 9 months after T-TEER.

TROP-2, a tumor-associated antigen, has been implicated in the progression of various epithelial tumors. Due to its favorable expression profile, TROP-2 has emerged as a promising target for antibody-drug conjugates (ADCs) based anti-tumor therapies. Although ADCs have shown efficacy in cancer treatment, their application in solid tumors is hindered by their high molecular weight, poor tumor penetration, and release of cytotoxic molecules. Therefore, a recombinant immunotoxin was developed based on a shark-derived variable domain of immunoglobulin new antigen receptor (VNAR) antibody. VNARs are only one-tenth the size of IgG antibodies and possess remarkable tissue penetration capabilities and high stability. In this study, a shark VNAR phage display library was created, leading to the identification of shark VNAR-5G8 that targets TROP-2. VNAR-5G8 exhibited a high affinity and cellular internalization ability towards cells expressing high levels of TROP-2. Epitope analysis revealed that VNAR-5G8 recognizes a hidden epitope consisting of CRD and TY-1 on TROP-2. Subsequently, VNAR-5G8 was fused with a truncated form of Pseudomonas exotoxin (PE38) to create the recombinant immunotoxin (5G8-PE38), which exhibited significant anti-tumor activity in vitro and in vivo. Overall, this study highlights the promise of 5G8-PE38 as a valuable candidate for cancer therapy.