Objective Objective To analyze the potential spatial factors affecting the genetic differentiation of Oncomelania hupensis robertsoni in Yunnan Province. Methods A total of 13 administrative villages were selected from schistosomiasis-endemic areas of Yunnan Province as O. hupensis snail sampling sites. At least 200 snails were collected in each site, and the spatial variable data of each site were recorded, including longitude, latitude and altitude. Thirty active and Schistosoma japonicum uninfected O. hupensis snails were selected from each sampling site by means of the crawling method and the cercarial shedding method. Genomic DNA was extracted from O. hupensis snails. Following PCR amplification, purification of PCR amplification products and sequencing, the gene sequences of O. hupensis snail samples were spliced and edited using the DNAstar software and the NCBI database to yield the complete mitochondrial sequences of O. hupensis snails at each sampling site, and the mitochondrial genetic distance matrix of O. hupensis robertsoni was calculated at each sampling site. The geographical coordinates of each sampling site were marked using the software ArcGIS 10.2, and the straight-line geographical distance between each sampling site was calculated. The altitude difference, longitude difference and latitude difference between each sampling site were calculated using the Excel software, and the correlation between the mitochondrial genetic distance matrix of O. hupensis robertsoni and each spatial variable matrix was examined by using the Mantel test at 13 sampling sites in Yunnan Province. Results Among the 13 O. hupensis snail sampling sites in Yunnan Province, the largest mitochondrial genetic distance of O. hupensis robertsoni snail populations was seen between Anding Village, Nanjian Yi Autonomous County and Caizhuang Village, Midu County (26.244 2), and the largest geographical distance was seen between Dongyuan Village, Gucheng District and Cangling Village, Chuxiong County (272.64 km). The highest altitude difference was seen between Anding Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1 086.10 m), and the largest longitude difference was found between Qiandian Village, Eryuan County and Cangling Village, Chuxiong County (1.86°), while the largest latitude difference was measured between Leqiu Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1.81°). In addition, the mitochondrial genetic distance of O. hupensis robertsoni snail populations was positively correlated with altitude at 13 snail sampling sites in Yunnan Province (r = 0.542 8, P < 0.001), and showed no significant correlations with geographical distance (r = 0.093 4, P > 0.05), longitude (r = −0.199 5, P > 0.05) or latitude (r = 0.205 7, P > 0.05). Conclusion Altitude may be a potential spatial factor affecting the genetic differentiation of O. hupensis robertsoni in Yunnan Province.

p21 (encoded by the CDKN1A gene) is a critical cell cycle regulatory protein endowed with versatile biological functions. In various sex hormone-related cancers, p21 exhibits a paradoxical dual role, capable of both inhibiting tumorigenesis and promoting cancer progression, exerting dual, often opposing, effects on cellular fate that are dictated by the specific context. The clinical targeting of p21 remains elusive, largely due to its functionally pleiotropic and context-dependent nature within intricate regulatory networks. During the initial, hormone-dependent phase of cancers like breast and prostate cancer, p21 expression and activity are largely governed by the transcriptional programs of estrogen or androgen receptor signaling. This hormonal regulation contributes to the control of tumor cell proliferation and underpins the initial efficacy of endocrine therapies. In contrast, as these diseases advance to late stages or evolve into non-hormone-dependent subtypes—exemplified by castration-resistant prostate cancer (CRPC) and specific forms of triple-negative breast cancer (TNBC)—these conventional hormonal control mechanisms often become dysfunctional or are entirely bypassed. This fundamental transition creates a critical therapeutic void, highlighting the urgent need to identify and exploit alternative molecular pathways to effectively target p21’s function. Promising strategies may include the precise modulation of its upstream transcriptional regulators, downstream effector proteins, or the intersecting parallel signaling networks that critically influence its activity. This review provides a systematic synthesis of the intricate and interconnected mechanisms that underpin the dual effects of p21 in sex hormone-related tumors. These mechanisms are categorized into three core, interrelated functional domains. (1) cell cycle regulation: p21 executes its canonical tumor-suppressive role by binding to and inhibiting cyclin-dependent kinases (CDKs) and by directly interacting with proliferating cell nuclear antigen (PCNA), thereby inducing cell cycle arrest, predominantly at the G1/S checkpoint; (2) apoptosis modulation: p21 exerts a highly context-dependent influence on programmed cell death, functioning either as a pro-apoptotic agent under severe genotoxic stress or as a pro-survival factor by inhibiting apoptosis through interactions with proteins like Bcl-2; (3) hormonal and signaling crosstalk: p21 is an integral node within broader cellular networks, engaging in direct physical interactions with hormone receptors(e.g., AR, ER) and participating in complex feedback loops with key oncogenic pathways, including PI3K/AKT, MAPK/ERK, and p53. Critically, the role of p21 is not static but highly dynamic. It can undergo a functional switch from tumor-suppressive to tumor-promoting in response to therapeutic pressures, metabolic alterations, or evolving tumor microenvironment cues. These adaptive shifts are frequently implicated in the development of therapy resistance and disease recurrence, particularly in advanced, hormone-resistant cancers. By synthesizing these insights, this review aims to establish a coherent theoretical framework to guide the future development of novel therapeutic strategies that target the p21 pathway. It underscores the necessity of moving beyond a simplistic, binary view of p21 and emphasizes the forthcoming challenges, such as the discovery of reliable biomarkers to predict its functional state and the rational design of context-specific pharmacological modulators to selectively harness its therapeutic potential.

ObjectiveTo investigate the characteristics of gray matter structure and clinical symptoms in patients with Alzheimer's disease （AD） comorbid with apathy （AD-A）. MethodsThe study included 30 patients with AD-A， 30 AD disease patients without apathy （AD without apathy， AD-NA）， and 30 healthy controls （HCs） matched in gender， age， and years of education. All participants underwent a comprehensive neuropsychological assessment and magnetic resonance imaging （MRI） scans. Voxel-based morphometry （VBM） was used to analyze changes in gray matter volume among the three groups. Additionally， the correlation between the identified abnormal brain regions and apathy scale scores was analyzed. ResultsThere were no statistically significant differences among the three groups in terms of age， gender， years of education， or total intracranial volume. Compared with the HCs group， both the AD-A and AD-NA groups showed significantly lower scores in cognitive function （P<0.001）. The AD-A group exhibited significantly higher apathy scale scores compared with the AD-NA group （P<0.001）. Compared with the AD-NA group， the AD-A group showed reduced gray matter volume in the bilateral caudate nucleus， left orbitofrontal cortex， lingual gyrus， inferior frontal gyrus， superior frontal gyrus， entorhinal cortex， right middle frontal gyrus and posterior cingulate cortex （FWE-corrected， P<0.05 for all）. Compared with the HCs group， the AD-A group exhibited reduced gray matter volume in the bilateral middle temporal gyrus， left fusiform gyrus， calcarine sulcus， postcentral gyrus， right inferior frontal gyrus and supramarginal gyrus （FWE-corrected， P<0.05 for all）. Compared with the HCs group， the AD-NA group showed reduced gray matter volume in the left precuneus， inferior temporal gyrus， and right inferior temporal gyrus （FWE-corrected， P<0.05 for all）. In the AD-A group， changes in the gray matter volume of the left caudate nucleus （r= -0.557， P=0.002） and right middle frontal gyrus （r=-0.620， P=0.001） were negatively correlated with the apathy evaluation scale （AES） scores. ConclusionPatients in the AD-A group exhibited significant atrophy in the frontal-temporal-basal ganglia circuit， and the degree of gray matter atrophy was correlated with the severity of apathy.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

ObjectiveThis study aimed to investigate the anti-Mycoplasma pneumoniae (MP) activity of luteolin and elucidate its underlying mechanisms. MethodsLuteolin was identified as the primary active compound from the polyphenol extract ofF. diotrys using network pharmacology. Its efficacy was evaluated against two MP strains: the standard strain M129 and the multidrug-resistant strain M19. A modified culture medium with visual characteristics was employed to determine the minimum inhibitory concentration (MIC) of luteolin. The expression of key proteins involved in MP growth and pathogenicity was assessed by qRT-PCR following luteolin treatment. Additionally, the viability of A549 cells infected with MP was compared between luteolin-treated and untreated groups. In vivo anti-MP activity was evaluated using a mouse model, and the expression of inflammatory cytokines in lung tissues was analyzed. ResultsLuteolin effectively inhibited both MP strains, with MIC₉₀ values of 100 mg/L for M19 and M129. Treatment with luteolin significantly downregulated the expression of adhesion proteins P1 and P30 in both strains. However, the expression of P65, HMW3, TrmB, and CARDS TX was reduced only in the M19 strain following luteolin intervention. Luteolin also enhanced the growth and viability of A549 cells infected with MP. In the mouse model, luteolin treatment resulted in steady weight gain and was well tolerated. The bacteriostatic rate of luteolin in lung tissues was 50.7%, significantly higher than the 25.2% observed in the roxithromycin group. Furthermore, luteolin reduced the expression of inflammatory factors, including IL-6, TNF-α, and HMGB1, in MP-infected mice. ConclusionLuteolin effectively and safely inhibits the proliferation and pathogenicity of MP, particularly the drug-resistant M19 strain, by downregulating the expression of toxicity-associated proteins (P1, P30, P65, HMW3, TrmB, CARDS TX) and modulating host inflammatory responses. These findings suggest that luteolin may offer a novel therapeutic strategy for treating MP infections, especially those caused by drug-resistant strains.

ObjectiveThis study aimed to investigate the anti-Mycoplasma pneumoniae (MP) activity of luteolin and elucidate its underlying mechanisms. MethodsLuteolin was identified as the primary active compound from the polyphenol extract ofF. diotrys using network pharmacology. Its efficacy was evaluated against two MP strains: the standard strain M129 and the multidrug-resistant strain M19. A modified culture medium with visual characteristics was employed to determine the minimum inhibitory concentration (MIC) of luteolin. The expression of key proteins involved in MP growth and pathogenicity was assessed by qRT-PCR following luteolin treatment. Additionally, the viability of A549 cells infected with MP was compared between luteolin-treated and untreated groups. In vivo anti-MP activity was evaluated using a mouse model, and the expression of inflammatory cytokines in lung tissues was analyzed. ResultsLuteolin effectively inhibited both MP strains, with MIC₉₀ values of 100 mg/L for M19 and M129. Treatment with luteolin significantly downregulated the expression of adhesion proteins P1 and P30 in both strains. However, the expression of P65, HMW3, TrmB, and CARDS TX was reduced only in the M19 strain following luteolin intervention. Luteolin also enhanced the growth and viability of A549 cells infected with MP. In the mouse model, luteolin treatment resulted in steady weight gain and was well tolerated. The bacteriostatic rate of luteolin in lung tissues was 50.7%, significantly higher than the 25.2% observed in the roxithromycin group. Furthermore, luteolin reduced the expression of inflammatory factors, including IL-6, TNF-α, and HMGB1, in MP-infected mice. ConclusionLuteolin effectively and safely inhibits the proliferation and pathogenicity of MP, particularly the drug-resistant M19 strain, by downregulating the expression of toxicity-associated proteins (P1, P30, P65, HMW3, TrmB, CARDS TX) and modulating host inflammatory responses. These findings suggest that luteolin may offer a novel therapeutic strategy for treating MP infections, especially those caused by drug-resistant strains.

INTRODUCTION: Takayasu arteritis is the most common large-vessel vasculitis in childhood, but there is a lack of literature regarding childhood-onset Takayasu arteritis (c-TAK) in Southeast Asia. We aim to describe a c-TAK cohort in Singapore and highlight a unique subset that first presents with Kawasaki-like disease (KD). METHOD: A single-centre cohort study in Singapore of consecutive children diagnosed with c-TAK between 2002 and 2023 was performed. Demographic and clinical features, laboratory and angiographic findings, treatment, and outcomes were summarised. Disease activity was evaluated using the Paediatric Vasculitis Disease Activity Score and inflammatory markers. RESULTS: Twenty-three patients, fulfilling both the EULAR/ PRINTO/PReS and ACR/EULAR 2022 criteria, were recruited. The most common clinical features at diagnosis were fever (15, 65%) and neurological symptoms (11, 48%, half of which presented with stroke), while the most prevalent angiographic pattern by Hata's classification was Type V (21, 91%). Eight children (35%) initially presented with refractory KD, and these patients were significantly younger, more male-predominant, and had higher inflammatory markers at diagnosis; all of them had coronary artery involvement, but none had intracranial vascular findings. Of the entire cohort, 16 (70%) achieved inactive disease on medications with a median duration of 6 months (interquartile range [IQR]: 4-11), and 8 (35%) achieved remission off medications with a median duration of 43 months (IQR 35-60). CONCLUSION Our c-TAK cohort has high proportions of neurological involvement and stroke. This is also the first cohort study to describe a distinct group of patients who first presented with refractory KD.
Humans ; Takayasu Arteritis/complications* ; Singapore/epidemiology* ; Male ; Female ; Child ; Adolescent ; Age of Onset ; Mucocutaneous Lymph Node Syndrome/diagnosis* ; Cohort Studies ; Child, Preschool ; Fever/etiology* ; Stroke/epidemiology* ; Retrospective Studies

This study aims to explore the effects and mechanisms of the traditional Chinese medicine Cordyceps sinensis(CS) in ameliorating heart aging and injury in mice based on animal experiments and network pharmacology. A mouse model of heart aging was established by continuously subcutaneous injection of D-galactose(D-gal). Thirty mice were randomly assigned into a normal group, a model group, a low-dose CS(CS-L) group, a high-dose CS(CS-H) group, and a vitamin E(VE) group. Mice in these groups were administrated with normal saline, different doses of CS suspension, or VE suspension via gavage daily. After 60 days of treatment with D-gal and various drugs, all mice were euthanized, and blood and heart tissue samples were collected for determination of the indicators related to heart aging and injury in mice. Experimental results showed that both high and low doses of CS and VE ameliorated the aging phenotype, improved the heart index and myocardial enzyme spectrum, restored the expression levels of proteins associated with cell cycle arrest and senescence-associated secretory phenotypes(SASP), and alleviated the fibrosis and histopathological changes of the heart tissue in model mice. From the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),259 active ingredients of CS were retrieved. From Gene Cards and OMIM, 2 568 targets related to heart aging were identified, and 133common targets shared by CS and heart aging were obtained. The Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment revealed that the pathways related to heart aging involved oxidative stress,apoptosis, inflammation-related signaling pathways, etc. The animal experiment results showed that both high and low doses of CS and VE ameliorated oxidative stress and apoptosis in the heart tissue to varying degrees in model mice. Additionally, CS-H and VE activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway and inhibited the expression of key proteins in the nuclear factor-κB(NF-κB) pathway in the heart tissue of model mice. In conclusion, this study demonstrated based on network pharmacology and animal experiments that CS may alleviate heart aging and injury in aging mice by reducing oxidative stress,apoptosis, and inflammation in the heart via the Nrf2/HO-1/NF-κB pathway.
Animals ; Cordyceps/chemistry* ; Mice ; NF-E2-Related Factor 2/genetics* ; NF-kappa B/genetics* ; Aging/genetics* ; Male ; Signal Transduction/drug effects* ; Network Pharmacology ; Drugs, Chinese Herbal/pharmacology* ; Heme Oxygenase-1/genetics* ; Heart/drug effects* ; Humans ; Myocardium/metabolism* ; Membrane Proteins/genetics*

Facing the requirements of promoting the healthy China initiative and improving people's health, the "bone health program" was proposed in 2024. In-depth development of a traditional Chinese medicine(TCM) prevention and control system is of strategic significance to the implementation of the "bone health program". Focusing on osteoporosis(OP), a representative disease affecting people's bone health, this paper concludes that accelerating the research on the prevention and control of OP by TCM is conducive to enhancing the knowledge and awareness of OP among the public, and it is beneficial to revealing the evolutionary pattern of OP and improving the understanding and management of this disease. Additionally, it can provide an overall framework for and strengthen the systematicity and completeness of the research on the prevention and treatment of OP by TCM. Meanwhile, it can help to explore new research paradigms and optimize the existing research model, so as to promote innovative breakthroughs in the prevention and treatment of bone health-related diseases by TCM. Under the overall layout of the "bone health program", importance should be attached to the early prevention and the innovation of very early diagnosis and intervention of OP. Emphasis should be put on the discovery of the target network of disease and treatment mechanism for revealing the core pathogenesis of OP and the therapeutic mechanism of TCM. In addition to local lesions of the bone and its clinical outcomes, attention should be paid to the development of multiple metabolic complications. The fusion of advanced interdisciplinary technologies should be promoted for OP and its complications, and thus a research and development system based on clinical application scenarios and driven by big data can be built. The measures above will facilitate the progress in the prevention and treatment of OP and other bone diseases by TCM and provide new momentum for enriching and deepening the research connotation of the "bone health program".
Osteoporosis/therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; China ; Bone and Bones/drug effects*