With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

OBJECTIVES: To investigate YEATS2 expression in gastric cancer (GC), its prognostic value, and its regulatory role in epithelial-mesenchymal transition (EMT) of GC cells. METHODS: YEATS2 expression in GC was analyzed using publicly available databases. Paired GC and adjacent tissues were collected from 100 patients undergoing radical surgery for immunohistochemical detection of YEATS2 expression, and its correlations with the patients' clinicopathological parameters and Ki67 expression were analyzed. The prognostic value of YEATS2 was assessed using Kaplan-Meier analysis, Cox regression and ROC curves, and its regulatory mechanisms were analyzed using KEGG enrichment analysis. In cultured GC cell lines (HGC-27 and AGS), the effect of YEATS2 knockdown and overexpression on migration, invasion and EMT of the cells were examined with scratching assay, Transwell assay and Western blotting. RESULTS: YEATS2 was significantly overexpressed in GC tissues with a positive correlation with Ki67 (P<0.05). High YEATS2 expression was associated with elevated CEA (≥5 μg/L), CA19-9 (≥37 kU/L), T3-4 stage, and N2-3 stage (all P<0.05). Patients with high YEATS2 expression had significantly reduced 5-year survival (P<0.001); ROC analysis showed that YEATS2 expression levels had a sensitivity of 80.00% and a specificity of 66.67% for predicting patient survival (P<0.05). Cox regression identified high YEATS2 as an independent risk factor for poor postoperative 5-year survival outcome of GC patients (HR: 1.675, 95%CI: 1.013-2.771; P=0.045). KEGG enrichment analysis suggested involvement of YEATS2 in EMT in GC and Wnt/β-catenin signaling. In cultured GC cells, YEATS2 overexpression significantly promoted cell migration and invasion, upregulated the expressions of vimentin, N-cadherin, Wnt and active β-catenin, and downregulated E-cadherin expression, and these changes were obviously suppressed by treatment with XAV-939 (a Wnt/β-catenin inhibitor). CONCLUSIONS High YEATS2 expression activates Wnt/β-catenin signaling to promote EMT in GC and is correlated with poor prognosis of GC patients.
Humans ; Stomach Neoplasms/pathology* ; Epithelial-Mesenchymal Transition ; Wnt Signaling Pathway ; Cell Line, Tumor ; Prognosis ; Cell Movement ; Male ; Female ; beta Catenin/metabolism*

OBJECTIVES: To investigate the effect of hypaphorine (HYP) on Crohn's disease (CD)‑like colitis in mice and its molecular mechanism. METHODS: Thirty male C57BL/6J mice were equally randomized into WT, TNBS, and HYP groups, and in the latter two groups, mouse models of CD-like colitis were established using TNBS with daily gavage of 15 mg/kg HYP or an equivalent volume of saline. The treatment efficacy was evaluated by assessing the disease activity index (DAI), body weight changes, colon length and histopathology. The effect of HYP was also tested in a LPS-stimulated Caco-2 cell model mimicking intestinal inflammation by evaluating inflammatory responses and barrier function of the cells using qRT-PCR and immunofluorescence staining. GO and KEGG analyses were conducted to explore the therapeutic mechanism of HYP, which was validated in both the cell and mouse models using Western blotting. RESULTS: In the mouse models of CD-like colitis, HYP intervention obviously alleviated colitis as shown by significantly reduced body weight loss, colon shortening, DAI and inflammation scores, and expressions of pro-inflammatory factors in the colon tissues. HYP treatment also significantly increased the TEER values, reduced bacterial translocation to the mesenteric lymph nodes, liver, and spleen, lowered serum levels of I-FABP and FITC-dextran, increased the number of colonic tissue cup cells, and upregulated colonic expressions of MUC2 and tight junction proteins (claudin-1 and ZO-1) in the mouse models. In LPS-stimulated Caco-2 cells, HYP treatment significantly inhibited the expressions of pro-inflammatory factors and increased the expressions of tight junction proteins. Western blotting showed that HYP downregulated the expressions of the key proteins in the TLR4/MyD88 signaling pathway in both the in vitro and in vivo models. CONCLUSIONS HYP alleviates CD-like colitis in mice possibly by suppressing intestinal epithelial inflammation and improving gut barrier function.
Animals ; Male ; Mice, Inbred C57BL ; Crohn Disease/drug therapy* ; Mice ; Humans ; Caco-2 Cells ; Intestinal Mucosa/metabolism* ; Colitis/drug therapy* ; Disease Models, Animal ; Inflammation ; Toll-Like Receptor 4/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Intestinal Barrier Function

ObjectiveTo investigate the effect and potential mechanism of Dihuangyin on 2， 4-dinitrochlorobenzene （DNCB） -induced model mice with atopic dermatitis （AD）. MethodA mouse model with AD was established by repeatedly stimulating the back skin of mice with DNCB. After successful modeling， the mice were randomly divided into model group， Runzao group （0.78 g·kg^-1）， and high， medium， and low dose （40.30， 20.15， and 10.08 g·kg^-1） groups of Dihuangyin， with 12 mice in each group， and the blank group consisted of 12 mice， 72 in total. The administration groups were given the corresponding liquid by dose， and the blank group and model group were given the same dose of pure water by intragastric administration， once a day. The skin lesions and scratching times of mice were observed after continuous administration for two weeks. The back skin lesions of mice were stained with hematoxylin-eosin （HE） and toluidine blue to observe the pathology. The contents of serum immunoglobulin E （IgE）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， and interferon-γ （IFN-γ） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of IFN-γ， IL-4， IL-6， Janus kinase 1 （JAK1）， and transcriptional activator 3 （STAT3） in skin lesion tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of JAK1， phosphorylation（p）-JAK1， STAT3， and p-STAT3 proteins in skin lesion tissue were detected by Western blot. ResultCompared with the blank group， the back skin of the model group showed large-scale scab， dryness， erosion， hypertrophy with scratching， epidermal hyperplasia with hyperkeratosis and parakeratosis， hyperacanthosis with edema， and a large number of mast cell infiltration in the dermis， some of which were degranulated. The contents of IgE， IL-4， IL-6， and IFN-γ in the serum of mice were significantly increased （P<0.01）， and the protein expression levels of p-JAK1， STAT3， and p-STAT3 and mRNA expressions of IL-4， IL-6， IFN-γ， JAK1， and STAT3 in skin lesion tissue were significantly increased （P<0.01）. Compared with the model group， only a small amount of dryness and desquamation were observed in the back skin of mice in each administration group， and cell edema was reduced. The inflammatory infiltration was significantly reduced， and the number of mast cell infiltration was significantly decreased. The serum IgE， IL-4， IL-6， and IFN-γ of mice were decreased to varying degrees （P<0.05， P<0.01）. The protein expression levels of p-JAK1， STAT3， and p-STAT3 and mRNA expressions of IL-4， IL-6， IFN-γ， JAK1， and STAT3 in skin lesion tissue were significantly decreased， and the effect of high dose group of Dihuangyin was the best （P<0.01）. ConclusionDihuangyin can improve skin lesions and pruritus in mice with AD， and its mechanism may be related to the effective regulation of cytokines on the helper T cells （Th1）/Th2 axis by interfering with the JAK1/STAT3 signaling pathway and affecting skin barrier function.

Objective:To explore the influencing factors for falls in inpatients during the rehabilitation period of stroke and research humanistic care strategies.Methods:Using a retrospective case-control study design,32 stroke patients who experienced falls in the rehabilitation department of the Second Affiliated Hospital of Xi'an Jiaotong University from January 2019 to December 2022 were selected as the observation group,and 64 stroke patients who were hospitalized in the same department during the same period and did not suffer from falls were matched 1:2 by age and gender as the control group.Logistic regression analysis was used to determine the influencing factors for falls in inpatients during the rehabilitation period of stroke.Results:The results of multivariate analysis showed that a history of falls(OR=8.688,P=0.036),a fall risk score(OR=1.615,P=0.018),sleep disorders(OR=5.378,P=0.031),malnutrition(OR=11.071,P=0.035),and osteoporosis(OR=15.831,P=0.006)were the independent risk factors for falls in inpatients during the rehabilitation period of stroke.Conclusion:There are many influencing factors for falls in inpatients during the rehabilitation period of stroke.Medical staff should take effective intervention measures based on different risk factors and implement humanistic care to reduce the incidence of falls in inpatients during the rehabilitation period of stroke.

Objective To explore the role of miR-199a-3p in osteoblast proliferation induced by fluid shear stress (FSS) and the potential molecular mechanism. Methods Osteoblast MC3T3-E1 was treated with 1. 2 Pa FSS with time gradients of 0, 15, 30, 45, 60, 75 and 90 min, respectively. MC3T3-E1 cells were transfected with miR-199a-3p mimic or miR-199a-3p inhibitor. MC3T3-E1 cells were transfected with miR-199a-3p mimic and itsnegative control and then treated with 1. 2 Pa FSS for 45 min. The pc DNA NC, pc DNA-CABLES -1, si RNA NC and si RNA CABLES-1 were transfected into MC3T3-E1 cells. The pc DNA-CABLES-1 and mir-199a-3p mimic and SI NA-cables-1 and miR-199a-3p inhibitor were co-transfected, respectively. Cell activity was detected by CCK-8 assay. Real-time quantitative PCR (RT-qPCR) was used to detect expression levels of CABLES-1, miR-199a-3p, CDK 6, Cyclin D1 and PCNA. Luciferase reporting assay was used to detect targeting relationship between CABLES-1 and miR-199a-3p. Immunofluorescence was used to detect protein expression of CABLES-1.Western blot was used to detect protein expression of CABLES-1, CDK 6, PCNA and Cyclin D1. Results Mir- 199a-3p in MC3T3-E1 cells was significantly down-regulated by FSS. Over-expressed miR-199a-3p inhibitedosteoblast proliferation, and down-regulated miR-199a-3p expression promoted osteoblast proliferation. miR-199a- 3p could reverse the FSS-induced proliferation in osteoblasts. Dual luciferase assay showed that miR-199a-3p targeted to CABLES-1 and over-expressed miR-199a-3p inhibited expression of CBALES-1 protein. CABLES-1 could promote proliferation of osteoblasts. miR-199a-3p inhibited osteoblast proliferation induced by FSS through CABLES-1. Conclusions FSS-induced osteoblast proliferation can be realized by down-regulated miR-199a-3p expression via targeting CABLES-1. The findings in this study provide new direction for researches on mechanism of FSS-induced osteoblast proliferation, as well as new ideas for future research on clinical application of mechanical loading in the treatment of bone and joint diseases.

The development of multifunctional nanocontrast agents with high sensitivity, high specificity, and low toxicity so that they can precisely localize tumors and reflect tumor biological information in real time is the core of promoting the development of tumor molecular imaging technology and realizing early and precise tumor diagnosis. Polydopamine (PDA) nanomaterials are bionanomaterials with a structure extremely similar to that of natural melanin. They can be easily fabricated and functionalized, and can achieve controlled assembly of functional molecules such as contrast components and targeting ligands via metal coordination, π-π stacking, electrostatic adsorption, and other methods. They have good biocompatibility and biodegradability, show great potential for clinical translation, and have been widely used in molecular imaging of tumors. In this review paper, the preclinical studies of PDA nanoparticles are reviewed as well as the synthesis methods, functionalized modification, and assembly strategies of PDA nanoparticles and their applications in tumor molecular imaging. The development trends of PDA are also presented to promote their application in the field of tumor molecular imaging.

Objective:To fabricate tAu@glutathione(GSH)@Gd nanoprobe for tumor angiogenesis bimodal (MR/CT) imaging, and evaluate its characteristics and potential for MR/CT imaging in vivo. Methods:The tAu@GSH@Gd nanoprobes were constructed by encapsulating Au and Gd atoms into the GSH shell with cyclic asparagine-glycine-arginine (cNGR) peptide conjugation. EMT-6 BALB/c mice subcutaneous transplantation tumor models were established ( n=30) and divided into blank control group (saline), control group (Au@GSH@Gd nanoparticles) and experimental group (tAu@GSH@Gd nanoprobes) ( n=10 in each group). In vivo MR/CT imaging and distribution study were performed at different time points after tail intravenously injection. Relative MR signal value and relative CT value of tumor site and main organs in mice were used to evaluate MR/CT imaging property and biological distribution. After that, tumor tissues were collected for silver staining to study the accumulation of Au@GSH@Gd nanoparticles and tAu@GSH@Gd nanoprobes. Independent-sample t test was used for data analysis. Results:The tAu@GSH@Gd nanoprobes were (6.40±0.22) nm with high T 1 relaxation efficiency ((36.91±0.07) mmol·L -1·s -1). MR/CT imaging of tAu@GSH@Gd nanoprobes showed good performance in vitro. In vivo MR/CT imaging demonstrated MR/CT imaging of tumor was significantly enhanced by tAu@GSH@Gd nanoprobes after 2 h post injection. The strongest enhancement was observed at 24 h, with an increased relative MR signal value from 1.04±0.12 (before injection) to 1.84±0.26 ( t=12.61, P=0.006), and increased relative CT value from 1.01±0.04 (before injection) to 1.95±0.05 ( t=15.34, P=0.004). The highest MR/CT effect in control group appeared at 16 h, with the relative MR signal value of 1.50±0.06 and the relative CT value of 1.53±0.10, which were significantly lower than those in experimental group (1.84±0.26 and 1.95±0.05; t values: 5.35 and 16.46, both P<0.05). Distribution in normal tissues showed that most of tAu@GSH@Gd nanoprobes were metabolized through the kidneys. Tissue silver staining experiment verified the tumor angiogenesis targeting effect. Conclusion:The tAu@GSH@Gd nanoprobes exhibit favorable tumor angiogenesis target MR/CT imaging ability, providing a new design concept and basis for assessing tumor angiogenesis.

OBJECTIVE：To provide reference for constructing and improving the pharmacovigilance signal management sys - tem in China by comparing signal management system among the European Union （EU），the United States （U. S. ）and Japan. METHODS：Literature analysis method was used to systematically compare the similarities and differences on definitions ，sources， detection methods and management process of pharmacovigilance signals among EU ，U. S. and Japan. Some suggestions were put forward for pharmacovigilance management in China. RESULTS & CONCLUSIONS ：Regulatory authorities of the EU ，U. S. and Japan did not have a uniform definition on signals ；EU drug administration adopted the definition of the eighth working group of Council for International Organizations of Medical Sciences ，FDA adopted its own definition ，while the Japanese regulatory agency had no clear definition. Currently ，post-marketing surveillance still relied mainly on spontaneous reporting systems ；EU，U. S. and Japan had carried out the signal detection based on the spontaneous reporting system ；EU mainly adopted the proportional reporting ratio method ，U. S. mainly adopts the multiple gamma Poisson Shrinker ，and Japan mainly adopted the reporting ratio method. EU had special guidelines for signal management process ，while the U. S. and Japan did not. It is recommended to accelerate the deve- lopment of the legal and regulatory framework on pharmacovigilance in China ，draw up guidelines on pharmacovigilance practices ， strengthen the active ADR surveillance and promote the application of data mining techniques in signal detection field ，for accelerat - ing the standardization and internationalization of China ’s pharmacovigilance work.