Objective To explore the mechanism by which gentiopicroside (GPS) prevents macrophage-mediated hepatic fibrosis by regulating the macrophage migration inhibitory factor (MIF)-secreted phosphoprotein 1 (SPP1) signaling pathway in hepatic stellate cells. Methods LX-2 cells were divided into control group, transforming growth factor β(TGF-β) group, and TGF-β combined with GPS (25, 50, 100, 150 μmol/mL) groups. Cell proliferation was detected by EDU assay, cell invasion was assessed by Transwell^TM assay, and the protein expressions of α-smooth muscle actin (α-SMA) and type I collagen (COL1A1) were measured by Western blot. M1-type macrophage-conditioned medium (M1-CM) was used to treat LX-2 cells in the TGF-β group and TGF-β combined with GPS group. The concentrations of inducible nitric oxide synthase (iNOS) and arginase 1 (Arg1) in the cell supernatant, as well as cell proliferation, invasion ability, and the expressions of α-SMA and COL1A1 were detected. Bioinformatics analysis was performed to identify the target intersections of GPS, hepatic fibrosis, and macrophage-related genes. Drug affinity responsive target stability (DARTS) experiments and Western blot were used to verify the regulatory effect of GPS on MIF. Furthermore, LX-2 cells were divided into control group, TGF-β group, TGF-β combined with M2-CM group, TGF-β and oe-NC combined with M2-CM group, and TGF-β and oe-MIF combined with M2-CM group to analyze the concentrations of iNOS and Arg1 in the cell supernatant, as well as changes in cell proliferation, invasion, and the expressions of α-SMA and COL1A1. LX-2 cells were also divided into control group, TGF-β group, TGF-β combined with oe-NC group, TGF-β combined with oe-MIF group, and TGF-β and oe-MIF combined with GPS group to determine the protein expressions of MIF and SPP1 by Western blot. A rat model of hepatic fibrosis was constructed to explore the potential therapeutic effects of GPS on hepatic fibrosis in vivo. Results Compared with the control group, the proliferation and invasion abilities of LX-2 cells in the TGF-β group were increased, and the protein expressions of α-SMA and COL1A1 were enhanced. GPS intervention inhibited the proliferation and invasion of LX-2 cells under TGF-β conditions and reduced the expressions of α-SMA and COL1A1. Compared with the control group, the concentration of iNOS in the cell supernatant of the TGF-β group was upregulated, while the concentration of Arg1 was decreased. M1-CM treatment further increased the concentration of iNOS, decreased the concentration of Arg1, and promoted cell proliferation and invasion, as well as upregulated the expressions of α-SMA and COL1A1 on the basis of TGF-β intervention. However, GPS could reverse the effects of M1-CM intervention. Bioinformatics analysis revealed that MIF was one of the target intersections of GPS, hepatic fibrosis, and macrophage-related genes, and GPS could target and inhibit its expression. Compared with the TGF-β group, after M2-CM intervention, the concentration of iNOS in the cell supernatant decreased, the concentration of Arg1 increased, the proliferation and invasion abilities of LX-2 cells were reduced, and the expressions of α-SMA and COL1A1 were weakened. However, overexpression of MIF reversed the effects of M2-CM intervention. Western blot results showed that compared with the control group, the protein expressions of MIF and SPP1 were enhanced in the TGF-β group. Overexpression of MIF further enhanced the expressions of MIF and SPP1, while GPS intervention inhibited the expressions of MIF and SPP1. In the animal experiment, GPS intervention treatment alleviated liver injury in rats with hepatic fibrosis and inhibited the expressions of MIF and SPP1, as well as α-SMA and COL1A1 in liver tissue. Conclusion GPS may prevent macrophage-mediated hepatic fibrosis by inhibiting the MIF-SPP1 signaling pathway in hepatic stellate cells.
Hepatic Stellate Cells/metabolism* ; Signal Transduction/drug effects* ; Macrophage Migration-Inhibitory Factors/genetics* ; Liver Cirrhosis/prevention & control* ; Macrophages/drug effects* ; Iridoid Glucosides/pharmacology* ; Humans ; Cell Proliferation/drug effects* ; Animals ; Cell Line ; Collagen Type I/metabolism* ; Collagen Type I, alpha 1 Chain ; Intramolecular Oxidoreductases/genetics* ; Rats ; Transforming Growth Factor beta/pharmacology* ; Actins/metabolism*

Objective:To investigate the value of nomogram model based on CT features in differentiating ectopic pancreas (EP) from gastrointestinal stromal tumors (GIST) with a long diameter less than 3 cm.Methods:This study was a case-control study. The clinical and imaging data of 43 patients with EP and 90 patients with GIST confirmed by pathology in the Affiliated Hospital of Guizhou Medical University from August 2013 to March 2024 were retrospectively analyzed. Preoperative CT images were analyzed to obtain qualitative features (number of lesions, location, morphology, growth pattern, borders, cystic degeneration, calcification, ulceration, catheter sign, central umbilication) and quantitative features (lesion long diameter, short diameter, long/short diameter, lesion and normal pancreas arterial-phase and venous-phase CT values, and enhancement ratio). Statistical analyses, including independent sample t-tests, Mann-Whitney U tests, χ2 tests, and Fisher exact tests, were performed to compare CT characteristics between the two groups. Binary logistic regression analysis was used to obtain independent predictors to identify the two groups, to establish a joint model, and to draw a nomogram. The discriminative performance of the independent predictors and the combined model was assessed using receiver operating characteristic (ROC) curves, while calibration curves were used to evaluate model fit. Results:The differences in age, location, morphology, border, catheter sign, central umbilication, short diameter, long/short diameter, arteriovenous phase enhancement CT value and arteriovenous phase enhancement ratio were statistically significant between the EP group and the GIST group (all P<0.05). The logistic analysis showed that the differences in age ( OR=0.920, 95% CI 0.885-0.956, P<0.001), border ( OR=5.994, 95% CI 2.111-17.022, P=0.001), long/short diameter ( OR=7.820, 95% CI 1.841-33.224, P=0.005), and venous phase enhancement ratio ( OR=8.847, 95% CI 1.103-70.972, P=0.040) were the independent predictors for distinguishing EP from GIST, and the area under the ROC curve (AUC) were 0.782 (95% CI 0.698-0.866), 0.684 (95% CI 0.600-0.767), 0.705 (95% CI 0.607-0.803), and 0.693 (95% CI 0.605-0.781), respectively. Combined age, border, long diameter/short diameter and venous phase enhancement ratio were plotted in a nomogram with an AUC of 0.881 (95% CI 0.817-0.945), sensitivity and specificity of 74.4% and 93.3%, respectively. The calibration curve demonstrated a strong agreement between predicted and actual probabilities (Hosmer-Lemeschow test, P=0.267). Conclusions:CT imaging reveals significant differences between EP and small GISTs (<3 cm). EP is more likely when patients are younger and lesions exhibit indistinct borders, a higher long-to-short diameter ratio, and greater venous-phase enhancement. The nomogram derived from CT features provides a valuable tool for differentiating EP from GIST.

Objective:To investigate impact of atractylolidⅠ(ATR-Ⅰ)on liver function of hepatitis B virus(HBV)infection rats by regulating cGAS-STING pathway.Methods:Ten rats were randomly selected as control group(NC),rest rats were injected with HBV antigen via tail vein to construct HBV model.Rats successfully modeled were randomly grouped into HBV group,ATR-Ⅰgroup(50 μg/kg),inhibitor of cGAS-STING pathway(RU.521)group(450 μg/kg),ATR-Ⅰ+RU.521 group(50 μg/kg ATR-Ⅰ+450 μg/kg RU.521),with 10 rats in each group.NC group and HBV group were injected with same amount of normal saline once a day for 1 week.Serum aspartate aminotransferase(AST),alanine aminotransferase(ALT),hyaluronic acid(HA),laminin(LN),procolla-gen type Ⅲ(PC Ⅲ),IFN-γ,IL-2,TNF-α,hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg)were detected by ELISA;HE staining was applied to detect liver histopathology;Masson staining was applied to detect degree of liver fibrosis;Western blot was applied to detect expressions of cGAS-STING pathway proteins in liver tissue.Results:Collagen volume fraction,ALT,AST,HBsAg,HBeAg contents,HA,LN and PC Ⅲ,IFN-γ,TNF-α and IL-2 levels in HBV group were higher than NC group,levels of cGAS,STING,p-TBK1/TBK1,p-IRF3/IRF3 and IFN-β were decreased(P<0.05);compared with HBV group,degree of liver injury and liver fibrosis in ATR-Ⅰ group were improved,collagen volume fraction,ALT,AST,HBsAg,HBeAg contents,HA,LN,PC Ⅲ,IFN-γ,TNF-α and IL-2 levels were decreased,levels of cGAS,STING,p-TBK1/TBK1,p-IRF3/IRF3 and IFN-β were in-creased(P<0.05),RU.521 group showed opposite trend,RU.521 eliminated improvement effect of ATR-Ⅰ on liver function of HBV rats.Conclusion:ATR-Ⅰmay improve liver function of HBV rats by activating cGAS-STING pathway.

Objective:To investigate impact of atractylolidⅠ(ATR-Ⅰ)on liver function of hepatitis B virus(HBV)infection rats by regulating cGAS-STING pathway.Methods:Ten rats were randomly selected as control group(NC),rest rats were injected with HBV antigen via tail vein to construct HBV model.Rats successfully modeled were randomly grouped into HBV group,ATR-Ⅰgroup(50 μg/kg),inhibitor of cGAS-STING pathway(RU.521)group(450 μg/kg),ATR-Ⅰ+RU.521 group(50 μg/kg ATR-Ⅰ+450 μg/kg RU.521),with 10 rats in each group.NC group and HBV group were injected with same amount of normal saline once a day for 1 week.Serum aspartate aminotransferase(AST),alanine aminotransferase(ALT),hyaluronic acid(HA),laminin(LN),procolla-gen type Ⅲ(PC Ⅲ),IFN-γ,IL-2,TNF-α,hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg)were detected by ELISA;HE staining was applied to detect liver histopathology;Masson staining was applied to detect degree of liver fibrosis;Western blot was applied to detect expressions of cGAS-STING pathway proteins in liver tissue.Results:Collagen volume fraction,ALT,AST,HBsAg,HBeAg contents,HA,LN and PC Ⅲ,IFN-γ,TNF-α and IL-2 levels in HBV group were higher than NC group,levels of cGAS,STING,p-TBK1/TBK1,p-IRF3/IRF3 and IFN-β were decreased(P<0.05);compared with HBV group,degree of liver injury and liver fibrosis in ATR-Ⅰ group were improved,collagen volume fraction,ALT,AST,HBsAg,HBeAg contents,HA,LN,PC Ⅲ,IFN-γ,TNF-α and IL-2 levels were decreased,levels of cGAS,STING,p-TBK1/TBK1,p-IRF3/IRF3 and IFN-β were in-creased(P<0.05),RU.521 group showed opposite trend,RU.521 eliminated improvement effect of ATR-Ⅰ on liver function of HBV rats.Conclusion:ATR-Ⅰmay improve liver function of HBV rats by activating cGAS-STING pathway.

Objective:To investigate the value of nomogram model based on CT features in differentiating ectopic pancreas (EP) from gastrointestinal stromal tumors (GIST) with a long diameter less than 3 cm.Methods:This study was a case-control study. The clinical and imaging data of 43 patients with EP and 90 patients with GIST confirmed by pathology in the Affiliated Hospital of Guizhou Medical University from August 2013 to March 2024 were retrospectively analyzed. Preoperative CT images were analyzed to obtain qualitative features (number of lesions, location, morphology, growth pattern, borders, cystic degeneration, calcification, ulceration, catheter sign, central umbilication) and quantitative features (lesion long diameter, short diameter, long/short diameter, lesion and normal pancreas arterial-phase and venous-phase CT values, and enhancement ratio). Statistical analyses, including independent sample t-tests, Mann-Whitney U tests, χ2 tests, and Fisher exact tests, were performed to compare CT characteristics between the two groups. Binary logistic regression analysis was used to obtain independent predictors to identify the two groups, to establish a joint model, and to draw a nomogram. The discriminative performance of the independent predictors and the combined model was assessed using receiver operating characteristic (ROC) curves, while calibration curves were used to evaluate model fit. Results:The differences in age, location, morphology, border, catheter sign, central umbilication, short diameter, long/short diameter, arteriovenous phase enhancement CT value and arteriovenous phase enhancement ratio were statistically significant between the EP group and the GIST group (all P<0.05). The logistic analysis showed that the differences in age ( OR=0.920, 95% CI 0.885-0.956, P<0.001), border ( OR=5.994, 95% CI 2.111-17.022, P=0.001), long/short diameter ( OR=7.820, 95% CI 1.841-33.224, P=0.005), and venous phase enhancement ratio ( OR=8.847, 95% CI 1.103-70.972, P=0.040) were the independent predictors for distinguishing EP from GIST, and the area under the ROC curve (AUC) were 0.782 (95% CI 0.698-0.866), 0.684 (95% CI 0.600-0.767), 0.705 (95% CI 0.607-0.803), and 0.693 (95% CI 0.605-0.781), respectively. Combined age, border, long diameter/short diameter and venous phase enhancement ratio were plotted in a nomogram with an AUC of 0.881 (95% CI 0.817-0.945), sensitivity and specificity of 74.4% and 93.3%, respectively. The calibration curve demonstrated a strong agreement between predicted and actual probabilities (Hosmer-Lemeschow test, P=0.267). Conclusions:CT imaging reveals significant differences between EP and small GISTs (<3 cm). EP is more likely when patients are younger and lesions exhibit indistinct borders, a higher long-to-short diameter ratio, and greater venous-phase enhancement. The nomogram derived from CT features provides a valuable tool for differentiating EP from GIST.

Objective To investigate the serum microRNA(miR)-125a-5p,miR-127-3p expression and clinical significance in patients with hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC).Meth-ods A total of 90 HBV-associated HCC patients admitted to a hospital from January 2018 to October 2020 were selected as the HBV-associated HCC group.Another 90 healthy subjects from the same period were se-lected as the control group.Serum miR-125a-5p and miR-127-3p expressions were detected by real-time fluo-rescence quantitative polymerase chain reaction.To analyze the relationship between miR-125a-5p and miR-127-3p expression and pathological features of patients with HBV-associated HCC.Patients with HBV-associ-ated HCC were divided into high and low expression groups according to the mean values of serum miR-125a-5p and miR-127-3p expression,and the different survival curves of each groups were plotted by the Kaplan-Meier method.Factors affecting the prognosis of patients with HBV-associated HCC were analyzed by Cox re-gression,and the predictive value of serum miR-125a-5p and miR-127-3p expression on the death of patients with HBV-associated HCC was analyzed by receiver operating characteristic(ROC)curve.Results The rela-tive expression levels of miR-125a-5p and miR-127-3p in HBV-associated HCC group were lower than those in control group,with statistical significance(P＜0.05).There were significant differences in the expression of miR-125a-5p and miR-127-3p in serum of HBV-associated HCC patients with different tumor size,differentia-tion degree,vascular invasion,TNM stage and lymph node metastasis(P＜0.05).Kaplan-Meier survival curve analysis showed that the 3-year overall survival rate(64.58％)of the group with high expression of miR-125a-5p was higher than that of the group with low expression of miR-125a-5p(38.10％).The 3-year overall survival rate of miR-127-3p high expression group(66.00％)was higher than that of miR-127-3p low expres-sion group(35.00％),and the difference was statistically significant(x2=7.770,9.507,P=0.005,0.002).The independent risk factors for death in HBV-associated HCC patients were maximum tumor diameter ≥5 cm,low differentiation,vascular invasion,TNM stage Ⅲ-Ⅳ,and lymph node metastasis,and the independent protective factors were elevated miR-125a-5p and miR-127-3p.ROC curve analysis results showed that the are-a under the curve(AUC)for the combined prediction of serum miR-125a-5p and miR-127-3p expression was 0.907,which was significantly higher than the AUC for the individual prediction of serum miR-125a-5p and miR-127-3p expression(0.790,0.787),with a statistically significant difference(Z=2.691,3.152,P=0.007,0.002).Conclusion The low expression of serum miR-125a-5p and miR-127-3p in HBV-associated HCC pa-tients is related to tumor maximum diameter,differentiation degree,vascular invasion,TNM stage and prog-nosis.The combined expression of serum miR-125a-5p and miR-127-3p has a high predictive value for the prognosis of HBV-associated HCC patients.

As a new strategy for the application of sacubitril/valsartan (LCZ696) in patients with CKD, much evidence showed that it improved the prognosis of patients with CKD. This review summarizes the efficacy and safety of sacubitril/valsartan in physiology, pathology, pharmacology and clinical application by searching Wanfang, CNKI, PubMed and other databases for related articles on the application of sacubitril/valsartan in CKD patients. Although LBQ657, the active product of sacubitril, has a high drug accumulation in patients with moderate, severe renal injury, and ESRD, it is not cleared in hemodialysis, and has very little eliminated in peritoneal dialysis, which does not affect its safety. Compared with angiotensin converting enzyme inhibitor and angiotensin receptor blocker drugs, LCZ696 could increase the blood pressure control rate, improve cardiac function, slow down the decline of glomerular filtration rate, and significantly improve cardiovascular outcomes without more adverse events. Sacubitril/valsartan can be used in all levels of CKD patients complicated with hypertension and/or heart failure, with reliable safety and tolerance.

Objective To evaluate the prognostic significance of lymph node ratio (LNR) in axillary lymph node positive breast cancer.Methods Eight hundred and three cases axillary lymph node positive breast cancer patients without distant metastasis were systematically treated in the Obstetrics and Gynecology Hospital of Fudan University from 2006 to 2014,at least 10 lymph node removed in each case.Clinicopathological data including 5-year disease-free survival rate (5y-DFSR) and 5-year overall survival rate (5y-OSR) were described.Factors related with prognosis were analyzed by univariate analysis.Prognostic difference was compared among different LNR stage in each axillary lymph node pathological stage(pN).Prognostic significance of pN and LNR was compared by multivariate analysis.Results Mean lymph nodes removed were 15.47±4.70 lymph,and median positive lymph nodes were 4 lymph in 803 cases axillary lymph node positive breast cancer patients.Altogether 159 cases of local recurrence and distant metastasis and 99 cases of breast cancer-related death occurred during median follow-up of 61 months.Five-year DFSR was 77％ and 5y-OSR was 83％.Log-rank univariate analysis showen that pT,pN,LNR,lymphovascular invasion and ER status were related to DFS and OS.Five-year DFSR and OSR for pN1,pN2,pN3 were 89％,68％,59％ and 93％,78％,63％,respectively,whereas 5y-DFSR and 5y-OSR for LNR1,LNR2,LNR3 were 90％,69％,56％ and 94％,80％,57％,respectively.There was statistically significant difference among different LNR in pN1 and pN2 (pN1:DFS:P=0.005,0S:P=0.024;pN2:DFS:P=0.017,0S:P=0.000),but not in pN3,inspite of difference tendency (DFS:P =0.165,OS:P =0.075).In multivariate analysis,when pN or LNR were entered into the Cox regression mode respectively,both were the independent prognostic factors of DFS(P＜0.001) and OS(P＜0.001).When pN and LNR were entered into the Cox hazard regression model at the same time,LNR remained as the independent prognostic factor of DFS and OS (P ＜ 0.001),but pN lost significance (DFS:P =0.461,OS:P=0.162).Conclusion LNR is independent prognostic factor for positive axillary lymph node breast cancer.

Objective To evaluate the clinicopathological characteristics of mucinous breast carcinoma (MBC) and its prognosis.Methods 112 cases of MBC treated in Obstetrics and Gynecology Hospital of Fudan University between Jan 2005 and Dec 2014 were enrolled retrospectively together with 1 157cases of invasive ductal carcinoma (IDC) for comparison.There were 71 cases of pure MBC (PMBC) and 41cases of mixed MBC (MMBC).PMBC and MMBC were compared with each other,and were also compared with IDC respectively.Results PMBC had smaller tumor mass,higher expression rate of hormone receptors (all P＜0.05),lower rate of lymph node metastasis (7.0％ vs.40.6％,x2 =32.663,P ＜0.001) when compared with IDC.The 5 year disease free survival (DFS) and overall survival (OS) of PMBC were both better than those of IDC (DFS:94.6％ ±3.0％ vs.81.3％ ± 1.1％,x2 =7.265,P =0.007;OS:92.4％ ±5.3％ vs.88.5％ ± 1.0％,x2 =4.059,P =0.044).MMBC had relatively larger tumor mass,higher expression rate of hormone receptor,but had no difference in the rate of lymph node metastasis (48.8％ vs.40.6％,x2 =3.417,P =0.332) when compared with IDC.There was no statistically significant difference in 5 yearDFSandOSbetweenMMBCandIDC (DFS:79.1％ ±7.1％ vs.81.3％±1.1％,x2 =0.167,P=0.683;OS:84.5％ ±7.2％ vs.88.5％ ± 1.0％,x2 =0.123,P =0.726).PMBC had relatively smaller tumor mass,lower rate of lymph node metastasis,but had no difference in the expression rate of hormone receptors.The 5 year DFS and OS of MMBC were both better than those of MMBC (DFS:94.6％ ± 3.0％ vs.79.1％±7.1％,x2 =6.772,P =0.009;OS:92.4％ ±5.3％ vs.84.5％ ±7.2％,x2 =6.401,P=0.036).Lymph node status was the only statistically significant prognostic factor of MBC by COX multivariate analysis.Conclusions PMBC has better prognosis than MMBC and IDC owing to its lower rate of lymph node metastasis.MMBC has higher rate of node metastasis than PMBC,hence similar prognosis with IDC.

Objective To evaluate the effect of ultrasound-guided vacuum-assisted minimal invasive resection(Mammotome procedure)of breast lumps through the retromammary space. Methods Seven hundred and eighty-seven patients in Obstetrics and Gynecology Hospital Affiliated to Fudan University from Jan. 2011 to May 2012 were underwent ultrasound-guided Mammotome operation through the retromammary space (retromammary space group,385 cases),or adjacent the lumps,and followed by post-operation visits regularly (Mammotome operation adjacent the lumps group,402 cases). The operation effects were compared between the two groups. Results All cases were followed up for 12 months. The period of Mmmotome operation through the retromam mary space and the rate of resection were(48 ± 6)min and(52 ± 4)min,99. 48%(383 / 385), 99. 25%(399 / 402),perspectively,in group of Mammotome operation through the retromammary space and Mammotome operation adjacent lumpsand. There was no significant difference between the two groups( P> 0. 05). The amount of procedural bleeding,the incidence of ecchymosis,local hematoma and the number of incision in group of Mammotome operation through the retromammary space were(8 ± 3)ml,2. 34%(9 / 385), 0. 52%(2 / 385),(1. 3 ± 0. 6)respectively,which were significantly lower than those in Mammotome operation adjacent the lumps group((14 ± 6)ml,8. 71%(35 / 402),2. 74%(11 / 402),(2. 4 ± 0. 3)respectively). There were statistical difference between two groups( P = 0. 003,P < 0. 001,P = 0. 001,P = 0. 006). The rate of satisfaction in group of Mammotome operation through the retro-mammary space was 98. 70%(380 / 385),which is significantly higher than in group of Mammotome operation adjacent the lumps(89. 30%(359 / 402),P< 0. 01). Conclusion The therapy approach of ultrasound-guided Mammotome operation through the retromammary space has lower hemorrhagic complication,as well as the better effect with special advantages. Therefore it has prospective clinical application.