ObjectiveTo investigate the antitumor effects of triptolide against CT26 colon cancer and its impact on the expression of Polo-like kinase-1 (PLK-1) protein.  Methods  Forty clean grade BALB/c mice, each mouse was implanted with 1×10⁶ CT26 cells into the dorsal side of the right forelimb to establish a tumor-bearing mouse model. Experimental animals were randomly divided into four groups, the tumor model group (saline control), the positive drug group ［oxaliplatin, 5mg/(kg·d)］, the low-dose triptolide group ［50μg/(kg·/d)］, and the high-dose triptolide group ［100μg/(kg·d)］. The drugs were administered through intraperitoneal injection (10 times in total, once every other day). The in vitro effects of the drugs on the proliferation, migration, invasion, and mitosis of CT26 cells were also assessed.   Results  Triptolide significantly inhibited the proliferation, migration, and invasion of CT26 colon cancer cells, and disrupted the separation of centrosomes and the correct arrangement of chromosomes during the prophase of mitosis in tumor cells. The binding energy of triptolide and PLK-1 protein was -7.1 kcal/mol, and it could down-regulate the expression of PLK-1 in CT26 cells.  Conclusion  Triptolide exerts its antitumor effects against CT26 colon cancer by downregulating the expression of PLK-1.

Objective To investigate the related mechanism which metformin inhibited the proliferation of HCT116 colorectal cancer cells via down-regulating the expression of up-frameshift protein 1 (UPF1).     Methods TCGA and UALCAN databases were utilized to analyze the expression level of UPF1, while Western blotting and Real-time PCR were performed to validate the differences of UPF1 expressions in colon cancer tissues and adjacent normal tissues. Clone formation assay, CCK-8 assay, wound healing assay and Transwell invasion assay were used to examine the effects of knockdown UPF1 on the proliferation, migration and invasion of HCT116 cells respectively. The HCT116 cell dataset with UPF1 knockdown was screened from GEO database for Kyoto Encydopedia of Genes and Genomes(KEGG) pathway analysis, the expression level of differential genes that enriched in Hippo pathway were verified by Real-time PCR. The HCT116 cells were treated with metformin, Western blotting and Real-time PCR were employed to detect the UPF1 expression. Mendelian randomization analysis was performed to explore the causal association between metformin treatment and colorectal cancer.     Results Analysis of TCGA and UALCAN databases showed that both UPF1 mRNA and protein were highly expressed in colon cancer tissues and the expression level of UPF1 was closely correlated with clinicopathologic stage and lymph node metastasis. Compared with adjacent normal tissues, the UPF1 protein and mRNA were highly expressed in colon cancer tissues. Knockdown UPF1 expression could inhibit the proliferation, migration and invasive ability of HCT116 cells. There were 8 differential genes affect the Hippo pathway by KEGG enrichment analysis, Real-time PCR experiments confirmed that CTNNB1, BMP4, TEAD2, PARD6G and FZD1 mRNA decreased in HCT116 cells with UPF1 knockdown. Both UPF1 protein and mRNA expressions decreased after metformin treatment in HCT116 cells. Mendelian randomization analysis showed a negative causal association between metformin treatment and colorectal cancer.      Conclusion Knockdown of UPF1 expression inhibits the proliferation of HCT116 cells through regulating Hippo pathway. Metformin can reduce the UPF1 expression for further inhibiting the proliferation of colorectal cancer cells.

Objective To develop a melanoma diagnosis framework based on large-scale vision-language models, and to explore the feasibility and accuracy of the framework for melanoma diagnosis.   Methods The publicly available Derm7pt dataset, which was divided into a training set (346 cases), a validation set (161 cases), and a test set (320 cases) was utilized. A melanoma diagnosis framework based on large-scale vision-language models was proposed, comprising two text branches and one visual branch. In the text branches, one branch processed fixed clinical prompts, while the other handled learnable prompts. This design aimed to optimize the effectiveness of learnable prompts through guidance from fixed clinical prompts. The visual branch processed dermoscopic images and enhanced melanoma feature recognition through fine-tuning the image encoder.   Results On the Derm7pt dataset, our method  outperformd other existing method. It achieved an area under the receiver operating characteristic curve (AUC) of 87.35%, an accuracy of 84.17%, and an F1-score of 84.01%.   Conclusion The study demonstrates that with appropriate fine-tuning strategies, methods based on large-scale vision-language pre-trained models can effectively adapt to melanoma diagnosis tasks. This approach can serve as a powerful auxiliary tool for doctors, helping them make more accurate diagnostic decisions.

Objective To propose a high-precision deep learning-based image assessment method  of osteosarcoma chemotherapy efficacy for clinical treatment, as existing methos have low accuracy of osteosarcoma assessment.   Methods The low incidence of osteosarcoma led to the small scale of its imaging data and the problem of imbalance in data categories. This study combined deep learning with clinical medical information, combined the bone sarcoma generation module of BoneGAN and the scale lesion information capture module, and proposed OMLA-Net, a deep learning assessment network for chemotherapy effect of bone sarcoma based on multi-scale lesion attention network, which achieved computer-aided bone tumor assessment with integrated data augmentation and focused lesion information through pre-training and generalized loss training. Results  In this study, 40 cases of osteosarcoma MRI data were used as the basis for the comparison test on the generated dataset, and the OMLA-Net assessment outperformed the SOTA method  Conv-LSTM-GAN in terms of the assessment effects such as accuracy and F1 scores, and the difference was statistically significant (P<0.05); the subsequent K-fold cross-validation ablation experiments further demonstrated the effectiveness of each module proposed by OMLA-Net.   Conclusion   OMLA-Net can effectively perform the impact assessment of chemotherapy effect on osteosarcoma, which provides a new idea for subsequent clinical application.

Objective To explore the mechanism of action of jolkinolide B in the treatment of gastric cancer by network pharmacology combined with molecular docking technique.   Methods The SwissTargetPrediction database was used to obtain the targets of the active compounds. Search Genecards, OMIM, Drugbank, TTD, and PharmGKB databases to obtain targets for gastric cancer. The intersection between the targets of jolkinolide B and those of gastric cancer was identified pinpoint potential targets for jolkinolide B in treating gastric cancer. The String database was utilized construct a protein-protein interaction(PPI) network. Bioconductor bioinformatics packages with R software was employed conduct Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the shared targets. This process revealed significant regulatory pathways crucial for jolkinolide B’s efficacy in treating gastric cancer. Cytoscape 3.7.1 software was utilized create the core network of “Potential Targets of Triptolide B in Gastric Cancer Treatment”, and SYBYL-X2.1.1 software was employed conduct molecular docking validation of the selected main active ingredients and critical targets.   Results Jolkinolide B may target multiple proteins, including MAPK1, glycogen synthase kinae-3β(GSK-3β), and JUN, impacting the proliferation, invasion, and metastasis of gastric cancer, ultimately inhibiting its growth.     ConclusionWe predicted the possible molecular mechanism of jolkinolide B in the treatment of gastric cancer to provide guide information for the subsequent experimental research and clinical application.

Objective To  explore the mechanism of cinobufagin (CBG) in treating gastric cancer based on network pharmacology combined with bioinformatics and molecular docking technology.   Methods Active ingredients and potential targets of CBG in treating gastric cancer were collected from PubChem, TCMSP, and SwissTargetPrediction databases. Transcriptional data of gastric cancer samples were obtained from TGGA database, and gastric cancer-related targets were identified through differential gene analysis. Intersection of targets between CBG and gastric cancer diseases was subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Protein-protein interaction (PPI) network of common targets was constructed using STRING database, and core targets were selected using Cytoscape software. Molecular docking verification of core targets screened with SYBYL-X 2.1.1 software was conducted with CBG.       Results CBG treatment of gastric cancer involved 59 targets, with 19 key targets identified. Key targets such as aurora kinase A(AURKA), cyclin-dependent kinase 1(CDK1), enhancer of zeste homolog 2(EZH2), hepatocyte growth factor receptor (MET), matrix metallopeptidase 3(MMP-3), progesterone receptor (PGR), prostaglandin-endoperoxide synthase 1(PTGS1), and thymidylate synthase (TYMS) which exhibited good binding activity with CBG and were closely associated with gastric cancer prognosis.    Conclusion CBG may exert anti-gastric cancer effects through multiple targets and pathways.

Homeobox(HOX) genes encode a group of proteins that are highly conserved and closely related to the axial differentiation of embryos. The disorder of segmental development caused by HOX genes deficiency or abnormal expression has been observed in drosophila and mice. However, subsequent studies have found that proteins encoded by the HOX gene family are also involved in the regulation of tumor genesis and development. The roles of the whole HOX family had been reviewed by the author in the past, and through the in-depth researches, the author paid attention to the pivotal role of HOXB9 and made new progress in the study of post-translational modifications of this protein. Taking HOXB9 as a clue, this review summarizes the tumor-related signaling pathways and the modulating effects of post-translational modification of HOXB9 on tumor progression, as well as the possible research directions in the future.

 Integrins are transmembrane receptors that can coordinate signal transduction between cells and extracellular matrix or between cells. The abnormal function of integrins is one of the recognized mechanisms of tumor development. As an important regulatory mode, post-translational modification can change the conformation and physicochemical properties of proteins, thus affecting their activities, stability and functions. After the modification of the integrin, such as glycosylation and methylation, the corresponding signal transduction pathway changes, and then affects cell adhesion, migration, differentiation and other life activities, involving in diverse physiology and pathological processes. Post-translational modifications of integrins are abundant in tumor progression and play a key role in regulating the growth, metastasis and drug resistance of different tumor cells. In this review, the structure and function, post-translational modification of integrins, and their relationship with occurrence and development of tumors will be discussed, in order to provide more explorable targets for the treatment of cancer.

 Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor of the central nervous system in adults, with a median survival of less than 15 months. The tumor microenvironment (TME) of GBM includes extracellular matrix and a variety of immune cells, including tumor-associated macrophages, microglia and myeloid-derived suppressor cells. The interaction between these cells and tumor cells plays a key role in the occurrence and development of GBM. The heterogeneity of GBM microenvironment is one of the main reasons for the poor efficacy of many therapies. Therefore, understanding the interaction between GBM and its tumor microenvironment is helpful to explore new targeted therapeutic strategies, which is expected to provide better treatment options for patients, thereby improving patient prognosis.

Objective  To investigate the association of digit ratio with single nucleotide polymorphism (SNP) at three loci (rs17576, rs3918249, rs9509) of matrix metallopeptidase 9 (MMP-9) gene.   Methods  A total of 804 Ningxia Han youths (399 males and 405 females) were used as the study subjects. A digital camera was used to take frontal photographs of the hands, and image analysis software was used to mark the anatomical points and measure the lengths of each finger of both hands (2D, 3D, 4D, 5D); Multiplexed PCR was used to detect the three polymorphic sites of the MMP-9 gene, SPSS 25.0 and R Studio software were used for data analysis and plotting.   Results  The 2D/3D (P<0.05) and 2D/4D (left,  P<0.01, right,  P<0.05) of both hands, 2D/5D (P<0.01), 3D/5D, 4D/5D (P<0.05) of the right hand, and 3D/4D (P<0.05) of the left hand in female youths of Ningxia Han were significantly higher than those in males, Differences in genotypes and allele frequencies at all 3 loci of the MMP-9 gene were not statistically significant between genders (P>0.05). Right hand 2D/4D was significantly associated with genotypes at the rs17576 and rs3918249 loci in male youths (P<0.05).    Conclusion  MMP-9 gene SNPs (rs17576 and rs3918249) may be associated with the formation of 2D/4D of Ningxia Han male youths. 

Objective To identify differentially expressed genes (DEGs) during the early stage of differentiation of human embryonic stem cells (hESCs) into insulin-producing cells (IPCs) and construct the microRNA(miRNA)-mRNA regulatory network.   Methods The datasets GSE42094 from Gene Expression Omnibus (GEO) were employed in this study and included hESCs, Diff1, Diff2, Diff3, Diff4 and IPCs groups. DEGs in the Diff1 group were selected and gene ontology(GO) and Keyoto Encyclopedia of Genes and Genomes(KEGG) pathway were deciphered. The miRNAs associated with DEGs were predicted and the miRNAmRNA regulatory network was visualized. Then the predicted miRNA was validated by paper result.   Results GO result  demonstrated that the significant term of biological process were “cell migration involved in gastrulation” and “SMAD protein signal transduction”. The KEGG pathway analysis indicated that “transformating growth factor(TGF)-beta signaling pathway” and “Signaling pathways regulating pluripotency of stem cells” played essential roles for 28 DEGs in the Diff1 group. To predict miRNA associated with DEGs, we found that miR-335-5p may regulate expressions of CDA, IFITM1, FREM1, FGF17 and ROR2 genes. There were 26 miRNAs which were validated by result  of paper.    Conclusion The miRNA-mRNA regulatory network plays an essential role during the early stage of the induction of IPCs. 

Objective To observe the difference of bone micro-structure in different regions of proximal femur, micro-CT scanning was performed on 30 proximal femur specimens to explain the mechanism of proximal femur fracture and to provide anatomical basis for prosthesis design.     Methods Totally 30 intact proximal femur specimens were obtained from 60-80 year-old cadavers. Micro-CT scanning was used to measure the trabecular thickness(Tb.Th), trabecular number(Tb.N), trabecular space(Tb.Sp), connectivity(Conn) and bone mineral density(BMD) and other parameters in 7 regions of proximal femur, including proximal pressure trabecular(PPT), distal pressure trabecular(DPT), femoral head-neck junction(FHNJ), head and neck of femoral neck(HNFN), the base of femoral neck(BPFN), intertrochanteric line(IL) and greater trochanter(GT).    Results The bone mineral density of IL and GT were higher than those of BPFN, FHNJ, DPT and PPT. The trabecular thickness of GT was the largest, followed by IL, BPFN and HNFN, and the smallest was FHNJ, DPT and PPT. The trabecular space of IL was larger than that of GT, and the data of both were larger than those of other parts, among which DPT and PPT were the smallest. The trabecular number of IL and GT were the smallest, BPFN, HNFN and FHNJ were larger, and DPT was the largest. The volume fraction of IL was the smallest, BPFN and HNFN were larger, DPT and PPT were the largest.     Conclusion The bone density, trabecular thickness, bone volume, and total volume of GT and IL in the proximal femur of elderly patients are all relatively large, so the reason for the high incidence of fractures is not due to weak internal bone microstructure; The bone density, trabecular thickness, and trabecular gap at the proximal and distal ends of the vertical trabecular bone are relatively small. If it is necessary to perform core decompression for prosthesis filling at this location, the design should be conducive to the mechanical conduction of the prosthesis and the regeneration of surrounding bone tissue.

Objective To investigate the effect and mechanism of edaravone (Eda) on myocardial injury in chronic heart failure (CHF) rats by regulating Notch/Hes-1 signaling pathway.   Methods The CHF rat model was established and the rats were separated into sham surgery (S) group, model(M) group, low dose Eda (Eda-L) group, medium dose Eda (Eda-M) group, high dose Eda (Eda-H) group, and Eda-H + Notch signal pathway inhibitor DAPT (Eda-H + DAPT) group, with 25 rats in each group. Echocardiography was applied to detect the levels of left ventricular end diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVEDs), and left ventricular ejection fraction (LVEF) in rats. ELISA was applied to detect levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, malondialdehyde (MDA), superoxide dismutase (SOD), and angiotensin Ⅱ (Ang Ⅱ) in serum. Myocardial infarction was observed by 2,3,5-triphenyl tetrazolium chloride(TTC) staining. HE staining, TUNEL staining and Masson staining were applied to observe the morphological changes of myocardial tissue, myocardial cell apoptosis and myocardial fibrosis respectively. immunohistochemistry was applied to detect the expression of collagen Ⅰ and angiotensin converting enzyme 2 (ACE2) proteins in myocardial tissue. Western blotting was applied to detect the expression of Notch 1, Hes-1, transforming growth factor-β1 (TGF-β1), Bcl-2, Bax, and Caspase-3 proteins in myocardial tissue.   Results Compared with the sham group, the distribution of cardiomyocytes in model group was disordered, and severe inflammatory symptoms. There was a large amount of blue collagen deposition between the perivascular area and the myocardium. The LVEDd, LVEDs, TNF-α, IL-1β, IL-6, MDA and Ang Ⅱ levels, myocardial infarction size, cardiomyocyte apoptosis rate, Collagen Ⅰ, Bax, Caspase-3 and TGF-β1 protein expressions increased obviously (P<0.05), the LVEF, SOD levels, ACE2, Bcl-2, Notch 1, and Hes-1 protein expressions were obviously reduced (P<0.05). Compared with the model group, the myocardial tissue damage was reduced in the Eda-L, Eda-M, and Eda-H groups, with reduced inflammatory cell infiltration and collagen deposition; The LVEDd, LVEDs, TNF-α, IL-1β, IL-6, MDA and Ang Ⅱ levels, myocardial infarction size, cardiomyocyte apoptosis rate, collagen Ⅰ, Bax, Caspase-3 and TG-β1 protein expressions reduced obviously(P<0.05), the LVEF, SOD levels, ACE2, Bcl-2, Notch 1, and Hes-1 protein expressions increased obviously (P<0.05). Notch signaling pathway inhibitor DAPT reversed the protective effect of edaravone on myocardial injury in rats with CHF (P<0.05).   Conclusion Edaravone may improve myocardial injury in CHF rats by activating Notch/Hes- 1 signaling pathway.

Objective To reveal the development characteristics of fat percentage and muscle mass in three nomadic populations in the Hexi Corridor of Gansu.   Methods Bioelectrical impedance analysis was used to determine the values of 13 indexes of fat percentage and muscle mass in 263 cases of Gansu Kazakhs, 400 cases of Gansu Mongols, and 362 cases of Yugu adults.     Results In the three nomadic populations of the Hexi Corridor, visceral fat level of males was significantly positively correlated with age, while total body muscle mass and estimated bone mass were significantly negatively correlated with age. In females, percent body fat, visceral fat grade, percent left and right upper limb fat, percent right lower limb fat and percent trunk fat were all significantly positively correlated with age, while trunk muscle mass was significantly negatively correlated with age. The result  of principal component analysis showed that the three nomadic populations in the Hexi Corridor were close to each other in terms of fat percentage and muscle mass characteristics, with high visceral fat grades in males and normal visceral fat grade in females. Among the 13 populations, three nomadic groups in the Hexi Corridor had high fat percentage and muscle mass. Overall, the nomadic population had greater fat percentage and muscle mass than the semi-agricultural and semi-pastoral population, and even more significantly greater than the agrarian population. The long-term integration of the historical Hexi Corridor populations result ed in the relative proximity of the genetic structure of three nomadic populations, which was a genetic factor for the proximity of their fat percentage and muscle mass. Higher per capita disposable income was a socio-economic factor for high fat percentage and muscle mass among Gansu Kazakhs and Gansu Mongolians. Low average annual temperature was an environmental factor for high muscle mass among Gansu Kazakhs and Yugus.    Conclusion Gansu Kazakhs, Gansu Mongols, and Yugus have the fat percentage and muscle mass characteristic of northern Chinese populations.

Objective To initially explore the possibility of applying the fluorescence micro-optical sectioning tomography (fMOST) high-resolution 3D reconstruction system to the morphological study of the intestinal nervous system and to preliminarily establish a method  for studying the morphology of the intestinal nervous system using this system.    Methods fMOST high-resolution 3D reconstruction system was used to study the intestinal nervous system of C57BL/6 mice in detail. Based on this method, a new morphological method  of the visceral nervous system of small animal models was explored at the single-cell level.   Results Compared with the large intestine, the small intestine lacked the typical myenteric plexus (Auerbach), deep mucosal plexus (Henley), and submucosal superficial plexus (Meissner).   Conclusion The result  of this paper provide a clearer and systematic display of the anatomical structure of the enteric nervous system in C57BL/6 mice, and further clarify the similarities and differences between the enteric nervous system of mice and human, and provide a theoretical basis for its rational application in the study of digestive system diseases. The morphological study of fMOST high-resolution 3D reconstruction system is not limited to the central nervous system, but can be extended to the morphological study of multiple visceral nervous systems.

There are a variety of mechanical signals in the microenvironment of cells, which have temporal and spatial variability, which jointly regulate the histological processes such as cell proliferation, differentiation and migration. Piezo1 is a mechanically sensitive cationic channel. As a force sensor, it transmits signals to downstream pathways and participates in a variety of life activities in response to changes in the cell microenvironment. In this paper, the common signal pathways of Piezo1 were reviewed in order to identify the downstream signaling pathways regulated by Piezo1, thereby providing theoretical basis for inhibiting or delaying related diseases.