Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Objective To construct a prognosis prediction model of primary liver cancer after surgical treatment based on synthetic minority over-sampling technique(SMOTE)algorithm and machine learning model.Methods A retrospective cohort study was conducted on 4 297 patients with primary liver cancer from the surveillance,epidemiology,and end results(SEER)database.One-Hot Encoding and Multiple Imputation were used to preprocess the collect data,and SMOTE algorithm was employed to solve the imbalance of data categories.The obtained clinical variables were included in the machine learning model.Based on decision tree(DT),random forest(RF),gradient boosting decision tree(GBDT)and eXtreme Gradient Boosting(XGBoost),a prognostic prediction model(SMOTE+DT/RF/GBDT/XGBoost)was build,and then the best prediction model was determined by comparing the performance of various models.Finally,a prognostic analysis system for primary liver cancer was developed based on the optimal model,which was then visualized.Results The combination model SMOTE+RF showed the best predictive performance,with higher area under the curve(0.895),accuracy(0.811)and precision(0.806)than those of other models in receiver operating characteristic curve(ROC)analysis.Conclusion The SMOTE+RF prognostic prediction model can effectively predict the survival outcome of patients with primary liver cancer.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Pyroptosis is a programmed death of inflammatory cells triggered by pathogen invasion,dependent on caspase activation,through both classical and non-classical pyroptosis pathways.Cell pyroptosis is related to the occurrence and development of a variety of animal infectious diseases caused by microbial infection.After microorganisms invading,cells are stimulated by pathology-re-lated molecular patterns,causing strong immune response,stimulating inflammatory signaling pathways,and then activating inflammasome,leading to pyroptosis.The immune system has e-volved multiple mechanisms to fight microbial infections and regulate inflammatory responses.The innate immune system,by recognizing microbial molecules in pathogens and responding quickly by producing inflammasome and activating pyroptosis,helps clear pathogens to prevent infection and maintain the normal functioning of the body.A thorough study of the pathogenesis and immune es-cape mechanism of cell pyroptosis in animal infectious diseases will provide a new direction for the treatment of animal infectious diseases.

The meridian theory is the pioneer of clinical diagnosis and treatment of diseases in Traditional Chinese Medicine (TCM). From Shang Han Lun to Pi Wei Lun, the meridian theory has contributed important theoretical organization materials and clinical practice experience to the establishment of the diagnosis system of external and internal injuries. The acupoints contained in its clinical acupuncture and moxibustion record symptoms, and some laws summarized have been absorbed and used for reference. It shows the positive significance of its exploration in clinical diagnosis and treatment. A system of differentiation and treatment of external and internal injuries with acupuncture has not been formed, even though the meridian theory of TCM has a long history with many areas being explored, such as diseases, acupoints, acupuncture methods and stimulation amount. Therefore, this paper starts from the academic development history of meridians, reviews and analyzes the contribution and limitations of TCM acupuncture and moxibustion in the diagnosis and treatment of internal injury, in order to enlighten the current study and understanding of TCM.

OBJECTIVE: To investigate the interventional effect of the Chinese herbal preparation Xi Fu Pai Chen(XFPC) on pulmonary inflammation and fibrosis in rats with silicosis. METHODS: A total of 144 adult specific pathogen free male SD rats were randomly divided into 6 groups: blank control group, silicosis model group, drug administration control group and groups of low-dose,medium-dose and high-dose XFPC, with 24 rats in each group. Lung silicosis model was established by single inhalation tracheal instillation method, which was treated with 50.0 g/L silica suspension, in groups except in the blank control group. On the 7 th day of modeling, the rats in the drug administration control group were orally given tetrandrine(5 mg/kg body weight), while those in the low-, medium-and high-dose groups were given 43, 86 and 192 g/L of XFPC by atomization inhalation once a day for 20 minutes, 5 days a week for 4 weeks. At the end of drug administration, the histopathological changes of the lung were observed. The number and classification of cells in bronchoalveolar lavage fluid(BALF)were examined, and the levels of malondialdehyde(MDA) and interferon-gamma(IFN-γ) in BALF were measured by enzyme-linked immunosorbent assay. RESULTS: On the 7 th day after modeling, the body weight in the drug administration control group and XFPC high-dose group decreased compared with the blank control group(P<0.05). On the 35 th day after modeling, the body weights of rats in the other 5 groups were lower than that in the blank control group(P<0.05). The pathological changes of lung tissue(infiltration of inflammatory cells, fibrosis and size of silicon nodule) in drug administration control group and XFPC low-dose group were better than those in silicosis model group by naked eyes and under light microscope. The lung coefficient, the proportion of neutrophils and the level of MDA and IFN-γ in BALF of the drug administration control group and XFPC low-dose group decreased(P<0.05), and the proportion of macrophages in BALF increased(P<0.05) compared with the silicosis model group. There was no significant difference in lung coefficients and the relevant indices of BALF between XFPC medium-, high-dose groups and silicosis model group(P>0.05). CONCLUSION: Low dosage XFPC can improve pulmonary fibrosis and inflammation in rats with silicosis, and its mechanism of action may be related to reducing the levels of IFN-γ and MDA in BALF.

Objective: To evaluate the feasibility of intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI MRI) in the evaluation of tumor vascular normalization in a mouse model of colorectal cancer induced by recombinant human endostatin (rhES). Methods: The CT26 colorectal cancer xenograft model of BALB/c mice were established and divided into rhES group and control group, with 20 mice in each group. The mice of rhES group were intravenously injected with rhES 5 mg·kg^-1·d^-1 once daily for 12 days, while the mice of the control group were intravenously injected with the same volume of 0.9% saline. 5 mice of rhES group and control group were randomly selected to perform IVIM-DWI MRI as following times: before treatment and four, eight, twelve days after treatment. The parameters of IVIM-DWI were recorded, including true diffusion coefficient(D), pseudo-diffusion coefficient (D^*) and perfusion fraction (f). Meanwhile, microvessel density (MVD), pericyte coverage and tumor perfusion in tumor tissues were detected by immunofluorescence, respectively. Results: The tumor volumes of control group and rhES group before treatment were (154.42±24.65) mm³ and (174.24±28.27)mm^3, respectively, without statistically significant difference (P=0.440). From day 2 to day 12 after treatment, the tumor volume of rhES group was significantly smaller than that of control group (all P<0.05). There were no statistical significances of D value between the rhES group and control group before and after treatment (all P>0.05). The D^* values of the rhES group were (10.940±2.834)×10^-3mm²/s and (12.940±2.801)×10^-3mm²/s in day 4 and 8 after treatment respectively, significantly higher than (6.980±1.554)×10^-3mm²/s and (7.898±1.603)×10^-3mm²/s of control group (P<0.05). Moreover, compared with control group, the D^* value of rhES group was significantly lower in day 12 (6.848±1.460)×10^-3mm²/s vs (9.950±2.596)×10^-3mm²/s, (P<0.05). The f value of rhES group in day 8 was (0.226±0.021)%, significantly higher than (0.178±0.016)% of control group (P<0.01). The MVD of rhES group was significantly lower than that of control group (P<0.05), while the pericyte coverage and tumor perfusion of rhES group were significantly higher than those of control group in day 4 and 8 after treatment (all P<0.05). In addition, we found D^* value of IVIM-DWI in rhES group was significantly related with MVD, pericyte coverage and tumor perfusion (r=-0.354, r=0.555, r=0.559, all P<0.05). Meanwhile, the f value in rhES group was also significantly related with MVD, pericyte coverage and tumor perfusion (r=-0.391, r=0.538, r=0.315, all P<0.05). Conclusions IVIM-DWI MRI can effectively evaluate the vascular normalization in rhES-induced CT26 colorectal tumor.The parameters D^* and f are closely related to intratumorally microvessel density, pericyte coverage and perfusion, which can effectively monitor the occurrence of tumor vascular normalization time.

Objective To evaluate the feasibility of intravoxel incoherent motion diffusion?weighted magnetic resonance imaging (IVIM?DWI MRI) in the evaluation of tumor vascular normalization in a mouse model of colorectal cancer induced by recombinant human endostatin (rhES).Methods The CT26 colorectal cancer xenograft model of BALB／c mice were established and divided into rhES group and control group, with 20 mice in each group.The mice of rhES group were intravenously injected with rhES 5 mg·kg－1·d－1 once daily for 12 days, while the mice of the control group were intravenously injected with the same volume of 0.9%saline. 5 mice of rhES group and control group were randomly selected to perform IVIM?DWI MRI as following times: before treatment and four, eight, twelve days after treatment. The parameters of IVIM?DWI were recorded, including true diffusion coefficient( D), pseudo?diffusion coefficient ( D?) and perfusion fraction ( f).Meanwhile, microvessel density ( MVD), pericyte coverage and tumor perfusion in tumor tissues were detected by immunofluorescence, respectively. Results The tumor volumes of control group and rhES group before treatment were (154.42 ± 24.65) mm3 and (174.24 ± 28.27) mm3, respectively, without statistically significant difference ( P＝0.440). From day 2 to day 12 after treatment, the tumor volume of rhES group was significantly smaller than that of control group ( all P＜0.05).There were no statistical significances of D value between the rhES group and control group before and after treatment ( all P＞0.05).The D? values of the rhES group were (10.940±2.834)×10－3mm2／s and (12.940±2.801)×10－3 mm2／s in day 4 and 8 after treatment respectively, significantly higher than (6.980±1.554)×10－3mm2／s and (7.898±1.603)×10－3mm2／s of control group (P＜0.05). Moreover, compared with control group, the D?value of rhES group was significantly lower in day 12 (6.848±1.460)×10－3mm2／s vs (9.950±2.596)×10－3 mm2／s, (P＜0.05). The f value of rhES group in day 8 was (0.226± 0.021)%, significantly higher than (0.178±0.016)% of control group (P＜0.01). The MVD of rhES group was significantly lower than that of control group (P＜0.05), while the pericyte coverage and tumor perfusion of rhES group were significantly higher than those of control group in day 4 and 8 after treatment ( all P＜0.05).In addition, we found D?value of IVIM?DWI in rhES group was significantly related with MVD, pericyte coverage and tumor perfusion ( r＝－0.354, r＝0.555, r＝0.559, all P＜0.05). Meanwhile, the f value in rhES group was also significantly related with MVD, pericyte coverage and tumor perfusion ( r＝－0.391, r＝0.538, r＝0.315, all P＜0.05). Conclusions IVIM?DWI MRI can effectively evaluate the vascular normalization in rhES?induced CT26 colorectal tumor.The parameters D? and f are closely related to intratumorally microvessel density, pericyte coverage and perfusion, which can effectively monitor the occurrence of tumor vascular normalization time.[Subject words] Colorectal neoplasms; Intravoxel incoherent motion; Diffusion magnetic resonance imaging; Vascular normalization; Recombinant human endostatin; Angiogenesis

Objective To evaluate the feasibility of intravoxel incoherent motion diffusion?weighted magnetic resonance imaging (IVIM?DWI MRI) in the evaluation of tumor vascular normalization in a mouse model of colorectal cancer induced by recombinant human endostatin (rhES).Methods The CT26 colorectal cancer xenograft model of BALB／c mice were established and divided into rhES group and control group, with 20 mice in each group.The mice of rhES group were intravenously injected with rhES 5 mg·kg－1·d－1 once daily for 12 days, while the mice of the control group were intravenously injected with the same volume of 0.9%saline. 5 mice of rhES group and control group were randomly selected to perform IVIM?DWI MRI as following times: before treatment and four, eight, twelve days after treatment. The parameters of IVIM?DWI were recorded, including true diffusion coefficient( D), pseudo?diffusion coefficient ( D?) and perfusion fraction ( f).Meanwhile, microvessel density ( MVD), pericyte coverage and tumor perfusion in tumor tissues were detected by immunofluorescence, respectively. Results The tumor volumes of control group and rhES group before treatment were (154.42 ± 24.65) mm3 and (174.24 ± 28.27) mm3, respectively, without statistically significant difference ( P＝0.440). From day 2 to day 12 after treatment, the tumor volume of rhES group was significantly smaller than that of control group ( all P＜0.05).There were no statistical significances of D value between the rhES group and control group before and after treatment ( all P＞0.05).The D? values of the rhES group were (10.940±2.834)×10－3mm2／s and (12.940±2.801)×10－3 mm2／s in day 4 and 8 after treatment respectively, significantly higher than (6.980±1.554)×10－3mm2／s and (7.898±1.603)×10－3mm2／s of control group (P＜0.05). Moreover, compared with control group, the D?value of rhES group was significantly lower in day 12 (6.848±1.460)×10－3mm2／s vs (9.950±2.596)×10－3 mm2／s, (P＜0.05). The f value of rhES group in day 8 was (0.226± 0.021)%, significantly higher than (0.178±0.016)% of control group (P＜0.01). The MVD of rhES group was significantly lower than that of control group (P＜0.05), while the pericyte coverage and tumor perfusion of rhES group were significantly higher than those of control group in day 4 and 8 after treatment ( all P＜0.05).In addition, we found D?value of IVIM?DWI in rhES group was significantly related with MVD, pericyte coverage and tumor perfusion ( r＝－0.354, r＝0.555, r＝0.559, all P＜0.05). Meanwhile, the f value in rhES group was also significantly related with MVD, pericyte coverage and tumor perfusion ( r＝－0.391, r＝0.538, r＝0.315, all P＜0.05). Conclusions IVIM?DWI MRI can effectively evaluate the vascular normalization in rhES?induced CT26 colorectal tumor.The parameters D? and f are closely related to intratumorally microvessel density, pericyte coverage and perfusion, which can effectively monitor the occurrence of tumor vascular normalization time.[Subject words] Colorectal neoplasms; Intravoxel incoherent motion; Diffusion magnetic resonance imaging; Vascular normalization; Recombinant human endostatin; Angiogenesis

Objective To explore the clinical effect of two different connecting tubes in hemodialysis combined with hemoperfusion. Methods A total of 25 patients were selected and divided into observation group and control group by self- control method. In the observation group, the hemodialysis combined with hemoperfusion was used 8 times, and the control group was treated with hemodialysis combined with hemoperfusion 8 times using conventional connecting tube. The time of the unloading of the perfusate and the amount of physiological saline required were compared between the two groups. There was no blood spillover during the unloading of the perfusate, the number of cases of allergic reaction during the treatment, and the coagulation of the dialyzer and the pipeline after the treatment. Results There was no allergic reaction in both groups. There was no significant difference between the two groups in the amount of saline needed to return blood (t=46.412, P=0.307). In the control group, there was 15 cases of blood spillover, while the observation group did not show blood spillover. There was significant difference between the two groups in unloading perfusion time(4.43±0.14)min vs. (3.02±0.11) min (t=10.784, P=0.003). The level Ⅰ and Ⅱ blood coagulation of dialyzer and pipeline was 12, 2 cases in the control group after the treatment and 5, 0 case in the observation group, no level Ⅲ blood coagulation cases, and there was a significant difference between the two groups (χ2=10.667, P<0.01). Conclusion In the hemodialysis combined with hemoperfusion therapy, multi-function group of the application effect is superior to conventional piping, is worthy of clinical application.