ObjectiveTo investigate the effect of folic acid-modified crebanine polyethylene glycol-polylactic acid hydroxyacetic acid copolymer（PEG-PLGA） nanoparticles（FA-Cre@PEG-PLGA NPs， hereinafter referred to as NPs） combined with ultrasonic irradiation on subcutaneous tumor of liver cancer in Kunming（KM） mice. MethodsEighty-four healthy male KM mice were utilized to establish a subcutaneous tumor model of mouse hepatocellular carcinoma with H22 cells， then mice were randomly divided into model group， placebo group， hydroxycamptothecin group（8 mg∙kg^-1）， low， medium and high dose crebanine raw material groups（2， 2.5， 3 mg∙kg^-1， hereinafter referred to as the low， medium and high dose crebanine groups， respectively）， low， medium and high dose NPs groups（2， 2.5， 3 mg∙kg^-1）， and low， medium and high dose NPs combined with ultrasonic irradiation groups（2， 2.5， 3 mg∙kg^-1， hereinafter referred to as the low， medium and high dose combination groups， respectively）. The corresponding doses of drugs were administered via tail vein injection， the model group received no treatment， while the placebo group was injected with an equivalent amount of normal saline. Dosing was conducted for a total of 10 times on alternate days. The body mass of the mice was monitored， and parameters such as body mass change rate， thymus index， spleen index， tumor volume， tumor weight， relative tumor growth rate（T/C）， and tumor inhibition rate（TGI） were calculated. Pathological changes in liver and kidney tissues as well as the tumor were observed by hematoxylin-eosin（HE） staining. Additionally， the levels of aspartate aminotransferase（AST）， alanine aminotransferase（ALT）， blood urea nitrogen（BUN） and creatinine（CREA） in serum of mice were detected by biochemical method. Furthermore， the effect of ultrasound on the distribution of NPs in subcutaneous tumors of mouse hepatocellular carcinoma was observed by in vivo imaging technique. ResultsAmong different treatment methods， the combination of NPs and ultrasound irradiation had the best therapeutic effect. Compared with the model group， the body mass growth rates of mice in the medium and high combination groups decreased， while the thymus index and spleen index increased， but there was no statistically significant difference in serum AST， ALT， BUN and CREA levels， indicating that NPs combined with ultrasound irradiation had little effect on the normal physiological state of the body， oth groups had TGI>40% and T/C<60%， indicating a clear anti-tumor effect. Pathological analysis showed that compared with the NPs groups， the combination groups exhibited varying degrees of necrosis in tumor cells， accompanied by less damage to the liver and kidneys. In vivo imaging of small animals showed that compared with the high dose NPs group， the high dose combination group had stronger tumor targeting ability（P<0.01）. ConclusionNPs combined with ultrasonic irradiation can not only effectively targeted the drug to the tumor site， inhibit the subcutaneous tumor growth of mouse liver cancer， but also decrease damage to liver and kidney tissues.

OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.

A system for achieving two-dimensional(2D)visualization and three-dimensional(3D)reconstruction of lung images using CT data is designed.After DICOM image processing,and lung nodule segmentation and labeling,the multi-view and multi-resolution 3D display of lung parenchyma and nodules is realized using techniques such as resampling of CT sequences,3D reconstruction based on surface rendering,and morphological processing.Finally,the interactive interface is designed for implementing the functions of image enhancement,2D visualization,nodule delineation,3D reconstructions of lung parenchyma and nodules,rotation,zooming and switching the viewpoint.Experimental results show that the system provides clear and accurate 2D image visualization and lesion delineation,while reconstructing nodules in the generated 3D images completely and smoothly.Compared with the existing similar medical processing software,the developed system substantially improves the reconstruction and visualization efficiencies,enabling doctors to observe 3D images more quickly and accurately,and assisting in disease diagnosis and surgical planning.

Background The mental health status of prison officers is crucial to the efficiency, security, and stability of a prison, and it is essential to pay attention to the factors that influence their mental health. Objective To understand the mental health status of prison officers, and analyze how nature exposure affects their mental health problems and a potential mediating role of mental fatigue. Methods A cross-sectional survey was carried out from May to June 2022 among 1392 prison officers from eight prisons in a province, and a total of 1284 valid questionnaires were recovered. The Nature Exposure Scale, Mental Fatigue Scale, and Depression-Anxiety-Stress Scale were used to assess nature exposure, mental fatigue, and mental health indicators among prison officers, and to explore the effect of nature exposure on mental health problems and a potential mediating role of mental fatigue. Results The recruited prison officers showed high levels of depression, anxiety, and stress. The prevalence rates of depression, anxiety, and stress were 59.11% (759/1284), 60.67% (779/1284),and 43.93% (564/1284), respectively. The results of correlation analysis revealed that nature exposure was negatively related with mental fatigue and mental health indicators (depression, anxiety, and stress) (r_s=−0.242, −0.308, −0.235, −0.254, P<0.01), while mental fatigue was positively correlated with mental health indicators (depression, anxiety, and stress) (r_s=0.546, 0.533, 0.536, P<0.01). The PROCESS macro results showed that the level of nature exposure among prison officers negatively associated with depression, anxiety, and stress (β=−0.180, −0.104, −0.123), and mental fatigue played a mediating role, with indirect effects of −0.200, −0.192, and −0.199, respectively. Conclusion The levels of depression, anxiety, and stress of prison officers are higher than those of other occupations. Nature exposure negatively associates with depression, anxiety, and stress, that is, it may directly alleviate the mental health problems of prison officers; and it may also alleviate mental health problems by relieving mental fatigue.

Objective To explore the otherness of orthotopic injection of cell suspensions and transplantation of tumor tissue blocks to establish orthotopic implantation models of hepatocellular carcinoma in mice,and to provide a technical reference for the establishment of an orthotopic implantation model.Methods Healthy KM mice were divided into four groups:group A,direct injection of H22 cells;group B,direct injection of H22 ascitic cells;group C,transplantation of tissues;and group D,direct injection of saline.Activity and weight changes were observed regularly in each group and survival times were recorded.Liver tumor formation,tumor size,abdominal organ adhesion degree,and metastasis were observed in all groups.B-ultrasound imaging was performed,concentrations of alpha fetoprotein(AFP)and abnormal prothrombin(DCP)were detected,and liver histopathological changes were detected by hematoxylin and eosin staining.Results Mice molding operation time in groups A,B,and C were(3.36±0.44)min,(3.30±0.41)min,and(5.68±0.65)min,respectively.After modeling for 25 days,the rates of model formation in groups A,B,and C were all 100.0%.Severe abdominal adhesions occurred in 40.0%of mice in group A and 60.0%in group B,but in no mice in group C or D.Ascites occurred in 40.0%,100.0%,and 0.0%and abdominal wall tumors in 30.0%,60.0%,and 0.0%of mice in groups A,B,and C,respectively,while 40.0%of mice in group B also had liver metastasis.B-ultrasound imaging,detection of serum AFP and DCP levels,and histopathological result showed smooth liver margins,uneven echo and slightly lower echo mass,maintained high AFP and DCP secretion,and large numbers of inflammatory cells and tumor cells in mice in groups A,B,and C.Conclusions At day 25,all three methods can thus be used to establish orthotopic transplantation models of HCC.Among these,inj ection of cell suspensions demonstrated the advantage of simplicity in operation and the presence of multiple metastatic nodules within the liver,compared to transplantation of tumor tissue.Conversely,transplantation of tumor tissue showed the advantage of causing less impact on the abdomen and other organs when compared to inj ection of cell suspensions.

Plant diterpenoids are widely distributed and abundant natural products with diverse structures and functions in nature, which have been commonly used in pharmaceutical, agricultural and industrial production. In recent years, plant diterpenoids have attracted increasing attention, including their biosynthetic pathways, transcriptional regulatory networks, and biological functions. Herein, the biosynthetic pathways of diterpenoids are summarized in a modular fashion. Further, the regulatory network between diterpene biosynthesis and environmental factors is reviewed. Insights into diterpene metabolism may drive elucidation of complex active diterpene pathways and serve as a knowledge repository for metabolic engineering and cell factory construction.
Plants, Medicinal/metabolism* ; Diterpenes/chemistry* ; Metabolic Engineering ; Biosynthetic Pathways ; Biological Products/metabolism*

Objective: To explore the effect of miR-3188 on the proliferation, apoptosis, invasion and migration of gastric cancer cells and the underlying molecular mechanism. Methods: The expression level of miR-3188 was examined in normal human gastric mucosal cells(GES-1) and human gastric cancer cell lines(HGC-27,MGC-803,BGC-823,MKN-45) by qRT-PCR. It was determined by bioinformatic analysis and dual luciferase reporter assay whether NRAGE was the target gene of miR-3188.miR-3188 mimic, miR-3188 inhibitor and negative control miR-NC were transfected into gastric cancer cell line HGC-27 respectively, and the expression of NRAGE on protein and mRNA levels was detected by Western blot and qRT-PCR. miR-3188 mimic, NRAGE overexpression plasmid(pc-NRAGE) and its negative control(miR-NC,pc-control) were separately or co-transfected into gastric cancer cell line HGC-27. CCK-8, flow cytometry and Transwell experiment were used to detect cell proliferation, apoptosis, invasion and migration in each group. The expressions of epithelial-mesenchymal transition(EMT), proliferation, apoptosis, invasion and migration related proteins [CyclinD 1,matrix metalloproteinase 9(MMP 9),Bcl-2,N-cadherin, Vimentin, E-cadherin] in each group were detected by Western blot. Results: The expression of miR-3188 in human gastric cancer cell lines was lower than that of human normal gastric mucosal cells. Bioinformatics analysis and dual luciferase reporter assay confirmed that miR-3188 could target and bind to NRAGE 3′UTR.Western blot and qRT-PCR confirmed that miR-3188 negatively regulated the expression of NRAGE on the protein level in HGC-27 cells, but not on the mRNA level. Compared with the miR-NC group, Transfected miR-3188 mimic reduced the proliferation, invasion and migration ability of HGC-27 cells, and increased the apoptosis rate, and the co-transfection of pc-NRAGE could reverse the above effects. Compared with the miR-NC group, when miR-3188 was overexpressed in HGC-27 cell, the expression of cyclinD 1, MMP 9, Bcl-2, N-cadherin, and Vimentin was down regulated, while E-cadherin expression was up-regulated, and the above effects could be reversed by co-transfection with pc-NRAGE. Conclusion The miR-3188/NRAGE axis may play important roles in the progression of gastric cancer, and miR-3188 may be a potential therapeutic target for gastric cancer.

Objective To explore the effect of carbon nanoparticles-epirubicin suspension on proliferation and apoptosis in human breast cancer MCF-7 cells.Methods MCF-7 cells were cultured with different concentrations of CNP-EPI in vitro.CCK-8 assay was used for determinate inhibition effect of CNP-EPI on the proliferation of MCF-7 cells at different concentration and different time.According to the determination of IC90,5 μg/ml CNP-EPI was selected,and cell morphology and cell apoptosis rates were observed after 24 h.Results The inhibition effect of the CNP-EPI was stronger significantly in CNP-EPI group than in normal control group within 24 h,48 h,72 h when the concentration was from 1 μg/ml to 200 μg/ml (P＜0.01).The inhibition of CNP-EPI on the proliferation of MCF-7 cells was gradually strengthened in a dose-dependent relation within the same time,and the inhibition effect is reduced in the same concentration of drugs with the time extension,but it still has a strong inhibitory effect in 72 h,and the inhibition effect of different concentration of CNP was not obvious on MCF-7 cells.Obvious changes of cell morphology were observed under inverted microscope such as:a lot of dead cells,cell adherent growth poor,cell morphology became round and karyopycnosis etc,in 5 μg/ml CNP-EPI group after 24 h.However,no obvious abnormity of cell norphology was observed in normal control group and corresponding CNP group.Late apoptosis rate was (14.57±2.41) ％,the mortality rate could reach (78.63±-20.55)％ in 5 μg/ml CNP-EPI group after 24 h.The mortality rate and apoptosis rate of cells was higher significantly in CNP-EPI group than in CNP group and normal control group (P＜0.05).Conclusion CNP-EPI can obviously inhibit the proliferation or kill human breast cancer MCF-7cells,and the inhibition effect of CNP-EPI on proliferation of breast cancer cells might be the result of delayed releasing of EPI.

Proceeding from the requirements of teaching target for postgraduate students,the course of progress in pathophysiology was constructed and administrated.The course objective was defined which combined teaching knowledge with fostering students' ability together,especially the ability to think new ideas and to do scientific research.Aiming at this teaching target,the teaching contents which combined with the direction of scientific research of the department was growing together with scientific development,especially in new knowledge and new technique.Multiple teaching means and several mode of examine were adopted during the process of teaching practice.

ial of cells. It may serve as an index for monitoring and prognostic diagnosis of breast cancer.