Platelets are indispensable for physiological hemostasis and pathological thrombus formation, and platelet adhesion to endothelial collagen is a critical initial step in thrombus formation, often overlooked in current antiplatelet therapies. This study aims to elucidate how ginsenoside CK enhances hemodynamic circulation, alleviates stasis, and proposes therapeutic mechanisms. Inspired by the effects on improving microcirculatory disturbances in an acute soft tissue injury model, CK was identified as a PHD2 inhibitor, effectively suppressing platelet adhesion to collagen. It was proposed that targeting PHD2 regulates collagen hydroxylation modification, thereby influencing the formation of its three-dimensional structure, reducing the binding affinity between VWF and collagen, and ultimately suppressing thrombotic events. The efficacy of this mechanism was subsequently confirmed through a mouse DIC model, demonstrating the feasibility of CK in alleviating circulatory disorders. It is worth noting that when Phd2 was knocked down in mice's lungs, pulmonary embolism was significantly reduced. Additionally, PHD2 inhibitors approved for other diseases have exhibited similar anti-thrombotic effects. Moreover, when PHD2 inhibitors were combined with aspirin, they more effectively inhibited arterial thrombosis in rats. The findings offer valuable insights into potential targets for developing antiplatelet drugs or expanding therapeutic applications for existing PHD2 inhibitors in treating thrombotic diseases.

Quality marker (Q-Marker) of traditional Chinese medicine (TCM) is a new concept of TCM quality research. Since it was proposed in 2016, it has aroused wide response from the industry and has become an innovative theory and technical method leading the quality research and quality control of TCM. This paper summarized the core connotation, theoretical basis and innovative value of Q-Marker, proposed the technical strategies and paths of the Q-Marker research, and showed the prospect of its application in the TCM industry. The paper provides references for TCM quality research, quality evaluation, quality control and scientific supervision and has important significance for promoting the quality standard and quality control level of TCM.

As the field of oral pathology has evolved, the nomenclature and classification of oral mucosal diseases with a remarkable risk of malignant transformation have undergone several modifications. In 2005, the World Health Organization (WHO) introduced the concept of oral potentially malignant disorders (OPMDs) as an alternative to the terms for oral precancerous lesions and precancerous conditions. In the consensus report by the WHO Collaborating Center for Oral Cancer of 2021, OPMD is defined as "any oral mucosal abnormality that is associated with a statistically increased risk of developing oral cancer."This definition encompasses a range of conditions, in-cluding oral leukoplakia, oral submucous fibrosis, proliferative verrucous leukoplakia, oral lichen planus, and other lesions. In light of the complex etiology, unclear pathogenesis, and carcinogenesis of OPMDs, early and precise diagnosis and treatment can contribute to the secondary prevention of oral cancer. For this reason, this review, which aims to provide a basis for the precise clinical diagnosis of OPMDs, was performed. Its aim was achieved by reviewing the historical evolution and research progress of the nomenclature, classification, and histopathological diagnostic criteria of OPMDs.
Humans ; Mouth Neoplasms/diagnosis* ; Precancerous Conditions/diagnosis* ; Leukoplakia, Oral/diagnosis* ; Lichen Planus, Oral/pathology* ; Oral Submucous Fibrosis/pathology* ; Mouth Mucosa/pathology* ; World Health Organization

OBJECTIVES: This study aimed to explore the expression of lysosomal-associated membrane protein 5 (LAMP5) and microRNA (miR)-302a-3p in oral squamous cell carcinoma (OSCC) and their functional mechanism on the invasion and metastasis of OSCC. METHODS: The expression of LAMP5 in OSCC and its sensitivity as a prognostic indicator were analyzed on the basis of The Cancer Genome Atlas database. Western blot, quantitative reverse transcription polymerase chain reaction, and cell immunocytochemistry were used to detect the expression of LAMP5 in OSCC tissues and cells. The effect of LAMP5 on the proliferation, migration, and invasion of OSCC cells was evaluated through cell counting kit-8, immunocytochemistry, migration, and invasion assays, respectively. The miRNA targeting prediction websites were used to predict the miR that regulates LAMP5 and verify the targeted regulatory effect of miR-302a-3p on LAMP5. The effect of LAMP5 knockdown on OSCC tumor growth was evaluated in a nude mouse tumorigenesis model. RESULTS: LAMP5 was highly expressed in OSCC tissues and cells. It showed high sensitivity in the early diagnosis of OSCC. LAMP5 knockdown significantly inhibited the proliferation, migration, and invasion of OSCC cells, whereas LAMP5 overexpression increased these cell activities. The expression of LAMP5 was regulated by miR-302a-3p. In vivo, LAMP5 knockdown significantly inhibited the growth of OSCC tumor. CONCLUSIONS LAMP5 promotes the malignant progression of OSCC by enhancing the proliferation, migration, and invasion of OSCC cells. The expression of LAMP5 is negatively regulated by miR-302a-3p.
MicroRNAs/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Animals ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness ; Cell Proliferation ; Mice, Nude ; Cell Movement ; Lysosomal Membrane Proteins/genetics* ; Mice ; Cell Line, Tumor ; Neoplasm Metastasis

ObjectiveTo investigate the association of particulate matter and ozone with the prevalence of non-alcoholic fatty liver disease (NAFLD) in a district of Shanghai, and to provide epidemiological evidence for the further identification of early health hazards of air pollution and for the prevention and control of NAFLD. MethodsBased on Songjiang Sub-cohort of Shanghai Natural Population Cohort, a cross-sectional survey design was used to recruit participants from 2016 to 2017. Annual average exposure levels to air pollution from 2009 to 2017 were matched to the participant’s residential address using a high-resolution and high-quality ambient air pollutants dataset in China. NAFLD was diagnosed according to the “Guidelines for the prevention and treatment of metabolism⁃associated (non⁃alcoholic) fatty liver disease” by the Chinese Medical Association. Multivariate logistic regression models were employed to analyze the association between air pollution and the prevalence of NAFLD, and stratified analyses were used to compare differences by age, gender, obesity, and lifestyle habits within subgroups. ResultsA total of 32 791 individuals were included in the study. The prevalence of NAFLD among community residents in suburban Shanghai was 38.88%. For every 1 μg·m^-3 increase in PM₁, PM_2.5, PM₁₀, or O₃, the risk of NAFLD increased correspongdinglt, with the odds ratios (95%CI) of 1.071 (1.043‒1.099), 1.065 (1.042‒1.089), 1.041 (1.027‒1.055), or 1.061 (1.032‒1.091), respectively. There were differences in effects across different gender, age, and obesity status subgroups. ConclusionPM₁, PM_2.5, PM₁₀, and O₃ are positively associated with an increased risk of NAFLD. Stratified analyses reveal that individuals aged 65 years old or above exhibited greater susceptibility to PM₁, PM_2.5, and O₃, whereas those aged less than 65 years old are more vulnerable to PM₁₀. Males are more sensitive to PM₁ and O₃, and females are more susceptible to PM_2.5 and PM₁₀. The association between air pollutant exposure and NAFLD risk is more pronounced among obese participants compared to that in non-obese counterparts.

Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.

ObjectiveTo investigate the risk factors for liver cancer in patients with chronic hepatitis B （CHB） in the Qidong Chronic Hepatitis B cohort， and to construct a nomogram model for predicting the risk of liver cancer in CHB patients. MethodsA structured questionnaire survey was conducted among the CHB patients， aged ≥18 years， who attended the outpatient service of Qidong Third People’s Hospital from January 1 to December 31， 2016. The onset of liver cancer was defined as the primary outcome， and the outcomes of the cohort were obtained from Qidong Cancer Registry. Baseline clinical features were compared ；between the liver cancer group and the non-liver cancer group. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The Cox regression model was used to analyze the risk factors for liver cancer in CHB patients and calculate their hazard ratio （HR） and 95% confidence interval （CI）； the variables with statistical significance in the univariate Cox regression analysis were included in the LASSO regression analysis， and then the variables obtained were included in the multivariate Cox regression analysis to establish a predictive model. The nomogram was used to visualize the complex model. The receiver operating characteristic （ROC） curve， index of concordance （C-index）， and the calibration curve were used to assess the predictive efficacy of the model， and the decision curve was used to evaluate the clinical practicability of the nomogram. ResultsA total of 1 479 CHB patients were selected， among whom 58 patients with a confirmed diagnosis of liver cancer， 15 with missing data on testing indicators， and 164 with missing data on important information in the questionnaire were excluded， and finally 1 242 subjects were included in the study. Up to December 31， 2023， there were 67 new cases of liver cancer after a median follow-up time of 7.71 years， and the incidence density of liver cancer was 729.78/100，000 person-years. There were significant differences between the liver cancer group and the non-liver cancer group in age， sex， educational level， liver cirrhosis， duration of liver cirrhosis， history of diabetes mellitus， albumin， total bilirubin （TBil）， direct bilirubin， aspartate aminotransferase， aspartate aminotransferase， gamma-glutamyl transpeptidase （GGT）， and alkaline phosphatase （all P<0.05）. The multivariate Cox regression analysis showed that the increase in age （HR=1.07， 95%CI： 1.05‍ ‍—‍ ‍1.10， P<0.001）， a relatively high level of TBil （HR=1.98， 95%CI： 1.15‍ ‍—‍ ‍3.42， P=0.014）， a relatively high level of GGT （HR=2.41， 95%CI： 1.43‍ ‍—‍ ‍4.08， P=0.001）， and a long duration of liver cirrhosis （HR=1.09， 95%CI： 1.02‍ ‍—‍ ‍1.15， P=0.009） were independent risk factors for liver cancer in CHB patients. A nomogram prediction model was constructed based on the above four indicators， with an area under the ROC curve of 0.790， 0.845， and 0.829， respectively， in predicting the risk of liver cancer in CHB patients at 1， 3， and 5 years， and the bootstrap resampling method was used for internal validation and showed a C-index of 0. 778. The calibration curve showed that the prediction model had good stability， and the decision curve showed that it had certain clinical practicability. ConclusionThe increase in age， relatively high levels of TBil and GGT， and a long duration of liver cirrhosis are independent risk factors for liver cancer in CHB patients， and the nomogram model constructed based on these factors has a good predictive value and can be used in clinical practice to help develop strategies for the long-term monitoring of liver cancer.

Background and purpose:Human epidermal growth factor receptor 2(HER2)is closely associated with drug efficacy and prognosis in urothelial carcinoma(UC).HER2 is a significant biomarker and therapeutic target in various tumors.In recent years,anti-HER2 antibody-drug conjugates have shown significant clinical efficacy in UC patients with HER2 overexpression.Therefore,an in-depth understanding of HER2 expression and its characteristics in Chinese UC patients is crucial to guide treatment decision-making,optimize treatment strategies and achieve personalized therapy.This study aimed to thoroughly investigate correlation of HER2 expression and clinicopathological characteristics in Chinese patients with UC.Methods:This study was a multicenter study that retrospectively included UC patients from urology departments of 8 tertiary hospitals in 5 geographical regions of China(North China,East China,South China,Central China and Northwest)whose tissue samples were collected from January 2023 to March 2024.Inclusion criteria:① age above 18 years;② UC diagnosed by histopathological or cytological examination;③ complete results of HER2 expression detection using immunohistochemistry(IHC)in the primary tumor site were required.Exclusion criteria:① diagnosed patients with tumors in other parts of the body;② physicians evaluated other situations that were not suitable for inclusion in this study.IHC results for HER2 expression and clinicopathological data were collected.HER2 expression was determined according to the criteria outlined in"Clinical pathological expert consensus on HER2 testing in urothelial carcinoma in China",with HER2 2+and 3+defined as HER2 overexpression.The HER2 expression and clinicopathological features were analyzed.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethical number:2301268-12)and was registered at China Clinical Trial Registry(registration number:ChiCTR2300069746).Results:A total of 1054 patients with UC were included.Most of the tumors were bladder UC(n=807,76.6%).The mean age of patients was(66.8±10.5)years,and the majority were male(78.5%).The HER2 overexpression rate was 58.4%(n=616),with an additional 23%of patients having HER2 1+expression(n=242),and a small proportion exhibiting negative HER2 expression(n=196,18.6%).HER2 expression was significantly associated with various clinical and pathological characteristics such as Eastern Cooperative Oncology Group(ECOG)performance status,history of cardiovascular disease,history of metabolic disorders,smoking,UC disease location,differentiation grade,pathological type,and tumor stage.Conclusion:Retrospective analysis of multi-center data shows that HER2 expression is frequently observed in Chinese UC patients,with an overexpression rate of up to 58.4%.Furthermore,HER2 expression is closely associated with various clinical and pathological features of UC patients.This study underscores the critical importance of accurately assessing HER2 expression in UC patient to guide personalized therapies.

Oral squamous cell carcinoma(OSCC)is the predominant type of oral cancer,while some patients may develop oral multiple primary cancers(MPCs)with unclear etiology.This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs.Clinicopathological data from patients with oral single primary carcinoma(SPC,n=202)and oral MPCs(n=34)were collected and compared.Copy number alteration(CNA)analysis was conducted to identify chromosomal-instability differences among oral MPCs,recurrent OSCC cases,and OSCC patients with lymph node metastasis.Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients.Additionally,CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients.Our findings revealed that,in contrast to oral SPC,females predominated the oral MPCs(70.59%),while smoking and alcohol use were not frequent in MPCs.Moreover,long-term survival outcomes were poorer in oral MPCs.From a CNA perspective,no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis.In addition to commonly mutated genes such as CASP8,TP53 and MUC16,in oral MPCs we also detected relatively rare mutations,such as HS3ST6 and RFPL4A.Furthermore,this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals,and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

Odontogenic keratocyst(OKC)is a common jaw cyst with a high recurrence rate.OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome.Moreover,OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts.Because of the different prognosis,differential diagnosis of several cysts can contribute to clinical management.We collected 519 cases,comprising a total of 2157 hematoxylin and eosin-stained images,to develop digital pathology-based artificial intelligence(AI)models for the diagnosis and prognosis of OKC.The Inception_v3 neural network was utilized to train and test models developed from patch-level images.Finally,whole slide image-level AI models were developed by integrating deep learning-generated pathology features with several machine learning algorithms.The AI models showed great performance in the diagnosis(AUC=0.935,95%CI:0.898-0.973)and prognosis(AUC=0.840,95%CI:0.751-0.930)of OKC.The advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide model.Furthermore,the study investigates the correlation between AI features generated by deep learning and pathological findings,highlighting the interpretative potential of AI models in the pathology.Here,we have developed the robust diagnostic and prognostic models for OKC.The AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.