Breast cancer (BC) is one of the most prevalent malignant tumors affecting women worldwide, with its incidence rate continuously increasing. As a result, treatment strategies for this disease have received considerable attention. Research has highlighted the crucial role of the Hedgehog (Hh) signaling pathway in the initiation and progression of BC, particularly in promoting tumor growth and metastasis. Therefore, molecular targets within this pathway represent promising opportunities for the development of novel BC therapies. This study aims to elucidate the therapeutic mechanisms by which natural compounds modulate the Hh signaling pathway in BC. By conducting a comprehensive review of various natural compounds, including polyphenols, terpenes, and alkaloids, we reveal both common and unique regulatory mechanisms that influence this pathway. This investigation represents the first comprehensive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC. Furthermore, by exploring the structure-activity relationships between these compounds and their molecular targets, we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway. These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics. Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.

As the foremost among the four examinations in traditional Chinese medicine （TCM）， inspection and related equipment research face challenges in landing and transformation due to variations in evidence quality， lack of standardization， insufficient algorithm transparency， and poor reliability and stability of decision-making. Against the backdrop of rapid development of emerging technologies such as big data， the internet of things， and artificial intelligence， coupled with macro policy support from the government， digital and intelligent generalized inspection in TCM has emerged， with the aim of utilizing digital technologies to overcome the limitations of naked-eye inspection and comprehensively perceive and analyze facial and bodily expressions. The research in this field intelligently correlates Zang-fu organ functions with health conditions and disease progression and establishes a technical system for digital and intelligent inspection， multi-dimensional and multimodal perception， fusion analysis， and decision-making. This system aims to enhance the accuracy of disease risk warning and diagnosis， bridging the gap between inspection equipment and assistance in clinical decision-making. From an evidence-based perspective， this paper systematically examines the research ideas of digital and intelligent inspection and the development of related equipment， deeply explores how to propose clinical practice-oriented key scientific issues， comprehensively acquire and co-apply multi-dimensional data， establish precise inspection models driven by digital intelligence， optimize standards to enhance equipment interoperability and reliability， construct post-effect evaluation mechanisms to promote improvement， and actively address potential risks such as the black box nature and information security in the application of intelligent technology. This paper not only demonstrates the tremendous potential of digital technologies in improving the accuracy and clinical application efficiency of inspection but also provides new perspectives and ideas for the modernization of inspection in TCM， paving the way for the application of inspection in the global medical and health field.

Objective　To investigate the relationship between exosomal microRNA (miR)-335-5p and the severity of cirrhosis in patients with chronic hepatitis B (CHB), in order to provide more clinical information for early intervention and treatment. Methods From February to August 2019, 6 healthy controls, 8 cases of compensated cirrhosis (CLC), and 8 cases of decompensated cirrhosis (DLC) were recruited from the physical examination outpatient department and the hepatology department of Peking University Third Hospital Qinhuangdao Hospital as a discovery cohort, and serum samples were collected for exosome extraction and miRNA microarray analysis. A validation cohort of 229 CHB patients with cirrhosis, including 94 CLC and 135 DLC patients, was selected from those diagnosed and treated in the hepatology department of the hospital from December 2019 to May 2022. Exosomes were extracted and identified, and the expression level of serum exosomal miR-335-5p was detected by real-time fluorescence quantitative PCR. The model for end-stage liver disease (MELD) score and the combined formula of serum sodium with MELD (MELD-Na) score were used to evaluate the severity of cirrhosis. Results In the discovery cohort, the expression of miR-335-5p in the DLC group was significantly down-regulated compared to the control group and CLC group (P<0.05). In the validation cohort, the level of exosomal miR-335-5p in the DLC group was significantly lower than that in the CLC group (P<0.001). Spearman correlation analysis showed a negative correlation between the expression of exosomal miR-335-5p and both MELD and MELD-Na scores in patients with cirrhosis (P<0.05). After adjusting for other confounding factors in the multiple linear regression model, the expression of exosomal miR-335-5p was still negatively correlated with MELD score (β=-0.103, 95%CI:-3.692 to -1.149, P<0.001) and MELD-NA score (β=-0.109, 95%CI:-4.007 to -1.270, P<0.001). ROC curve analysis indicated that serum exosomal miR-335-5p could differentiate DLC with an area under the ROC curve of 0.905 (95%CI: 0.867 to 0.944), corresponding to a cutoff value of 0.158, with a specificity of 87.2%, and a sensitivity of 83.7%. Conclusions The low expression of exosomal miR-335-5p is associated with the aggravation of cirrhosis in CHB patients, and may serve as a useful biomarker for the early diagnosis of DLC.

The PRR11 gene (Proline Rich 11) has been implicated in lung cancer; however, relationship between PRR11 and immune infiltration is not clearly understood. In this study, we used The Cancer Genome Atlas (TCGA) data to analyze the lung adenocarcinoma patients; PRR11 gene expression, clinicopathological findings, enrichment, and immune infiltration were also studied. PRR11 immune response expression assays in lung adenocarcinoma (LUAD) were performed using TIMER, and statistical analysis and visualization were conducted using R software. All data were verified using Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA). We found that PRR11 was an important prognostic factor in patients with LUAD. PRR11 expression was correlated with tumor stage and progression. Gene Set Enrichment Analysis (GSEA) showed that PRR11 was enriched in the cell cycle regulatory pathways. Immune infiltration analysis revealed that the number of T helper 2 (Th2) cells increased when PRR11 was overexpressed. These results confirm the role of PRR11 as a prognostic marker of lung adenocarcinoma by controlling the cell cycle and influencing the immune system to facilitate lung cancer progression.
Humans ; Prognosis ; Adenocarcinoma of Lung/genetics* ; Lung Neoplasms/genetics* ; Biological Assay ; Cell Cycle

AIM: To compare the accuracy of different intraocular lens(IOL)calculation formulas in cataract patients with axial length longer than 28mm and a history of radial keratotomy(RK).METHODS: Retrospective study. The medical records of 19 cataract patients(29 eyes)after RK and with axial length longer than 28mm who underwent cataract surgery from January 2011 to July 2020 in Beijing Tongren Hospital were analyzed. The absolute error(AE)of the difference among three different formulas was calculated. AE refers to the absolute value between the actual spherical equivalent after cataract surgery and the spherical equivalent predicted by the IOL formula. The AE values of the three formulas and the percentages of eyes with AE≤0.5, 0.75, 1.0, and 2.0D were calculated and compared.RESULTS: The AE values of the three formulas were significantly different(χ2=8.759, P=0.013). The Barrett True-K formula had the smallest median AE, which was only 0.62(0.20, 1.15)D, followed by the Haigis formula 0.76(0.34, 1.26)D, and the Holladay 1(D-K)formula had the largest 1.01(0.49, 1.62)D. The percentages of affected eyes with AE ≤0.5, 0.75, 1.0, and 2.0D for the Barrett True-K formula were 48%, 59%, 69%, and 93%, which were equal to or higher than the other two formulas.CONCLUSION: The Barrett True-K formula is more recommended among the three formulas for cataract patients after RK and with axial length longer than 28 mm.

Objective: To investigate the regulatory relationship of Protein Phosphatase 2 Regulatory Subunit B"Alpha ( PPP2R3A) and hexokinase 1 ( HK1) in glycolysis of hepatocellular carcinoma (HCC). Methods: In HepG2 and Huh7 cells, PPP2R3A expression was silenced by small interfering RNA (siRNA) and overexpression by plasmid transfection. The PPP2R3A-related genes were searched by RNA sequencing. Glycolysis levels were measured by glucose uptake and lactate production. QRT-PCR, ELISA, western blot and immunofluorescence assay were performed to detect the changes of PPP2R3A and HK1. Cell proliferation, migration and invasion assay were used to study the roles of HK1 regulation by PPP2R3A. Results: RNA sequencing data revealed that PPP2R3A siRNA significantly downregulated the expression of HK1. PPP2R3A gene overexpression promotes, while gene silencing suppresses, the level of HK1 and glycolysis in HCC cells. In HCC tissue samples, PPP2R3A and HK1 were colocalized in the cytoplasm, and their expression showed a positive correlation. HK1 inhibition abrogated the promotion of glycolysis, proliferation, migration and invasion by PPP2R3A overexpression in liver cancer cells. Conclusion Our findings showed the correlation of PPP2R3A and HK1 in the glycolysis of HCC, which reveals a new mechanism for the oncogenic roles of PPP2R3A in cancer.
Carcinoma, Hepatocellular/pathology* ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glycolysis ; Hexokinase/metabolism* ; Humans ; Liver Neoplasms/pathology* ; Protein Phosphatase 2/metabolism* ; RNA, Small Interfering/metabolism*

Background: The risk of opportunistic infection in ulcerative colitis (UC) is significantly higher than that in healthy subjects, and has adverse impact on clinical outcome. Aims: To analyze the prevalence of opportunistic intestinal infection in UC patients and explore the risk factors of UC complicated with opportunistic infection. Methods: Clinical data of patients with UC hospitalized in Peking University Third Hospital from January 2012 to December 2020 were collected retrospectively. Information on demography, clinical characteristics, laboratory, endoscopic and pathological findings, as well as the medication histories were recorded; the factors associated with opportunistic intestinal infection were analyzed using univariate and multivariate analyses. Results: A total of 275 UC patients were included, with an opportunistic intestinal infection rate of 26.2%; among which, rates of cytomegalovirus (CMV), Epstein ‑ Barr virus (EBV), fungi, Clostridium difficile, amoeba, and multiple infection were 13.5%, 14.5%, 5.1%, 1.5%, 1.1%, and 9.1%, respectively. Multivariate Logistic analysis demonstrated that severe disease activity (OR=6.517, 95% CI: 1.487‑28.552, P=0.013) and albumin <30 g/L (OR=3.895, 95% CI: 1.590 ‑ 9.544, P=0.003) were independent risk factors for CMV infection. The independent risk factors for EBV infection included severe disease activity (OR=11.260, 95% CI: 2.249‑56.382, P=0.003), albumin <30 g/L (OR=2.548, 95% CI: 1.096‑5.927, P=0.030) and C‑reactive protein (CRP) elevation (OR=1.046, 95% CI: 1.007‑1.086, P=0.019). While for intestinal fungal infection, the risk in patients with chronic relapsing type UC was lower (OR=0.278, 95% CI: 0.087‑0.886, P=0.030). Intestinal multiple infection was mainly composed of viral infection, and the independent risk factors were similar to those of CMV and EBV infection. Conclusions: Most of the opportunistic intestinal infection in UC patients is viral infection. Disease activity, inflammatory response and reduced albumin are risk factors for intestinal viral infection in UC patients, while the risk of fungal infection is only related to clinical subtyping.

The incidence of inflammatory bowel disease (IBD) is increasing year by year, yet lacking specific treatment, which seriously affects patients' health and quality of life. The pathogenesis of IBD has not been fully clarified, the psycho-neuro-endocrine-immune regulation through gut-brain axis may play an important role in the pathogenesis of IBD. Studies have shown that IBD patient has an increased risk of depression. More than 20% of IBD patients have depression, the incidence is about 2-4 times that of general population. Antidepressant therapy has good efficacy in some IBD patients. The possible mechanism includes affecting the gut-brain axis, inhibiting inflammation, improving mood, etc. However, there are few relevant studies, and the value of antidepressant therapy in the treatment of IBD needs to be further confirmed by large-sample randomized controlled studies. This article reviewed the application of antidepressant therapy in IBD.

Adenocarcinoma ; complications ; drug therapy ; metabolism ; Aged ; Antineoplastic Agents ; therapeutic use ; Fusion Proteins, bcr-abl ; metabolism ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnosis ; etiology ; metabolism ; Male ; Organoplatinum Compounds ; therapeutic use ; Stomach Neoplasms ; drug therapy ; metabolism

Objective: To explore the value of dual energy CT lung perfusion imaging (DEPI) for diagnosing pulmonary embolism (PE) in comparison with CT pulmonary angiography (CTPA). Methods: There were 49 patients with suspected PE received DEPI scanning and 19 with CTPA conifrmed diagnosis were enrolled in this study. CTPA image was obtained by 80 kv data, and DEPI image was obtained by PBV software. The location, type of PE in CTPA image, and the location, shape of perfusion defect in DEPI were observed and compared by segment basis. The correlation and agreement of CTPA and DEPI for diagnosing PE were calculated and the un-agreement was analyzed. Results: A total of 380 segments were included for analysis. CTPA detected 162 segments of PE and DEPI detected 155 segments of perfusion defect or reduction, partial PE were mainly presented by perfusion defects as speckles, patches or without perfusion defect, and complete PE were mainly showed segmental or sub-segmental perfusion defects. CTPA and DEPI were correlated for PE diagnosis (χ2=305.5,P=0.000), the diagnostic agreement was 83.42% and KAPPA value was 0.659. Conclusion: The perfusion defect in DEPI is related to the degree and type of PE presented in CTPA, their combination is helpful for diagnosing PE.