Objective To evaluate the diastolic function and relationship between diastolic function and early diastolic synchrony in patients with dilated cardiomyopathy (DCM) by real-time three-dimensional echocardiography (RT-3DE) volume-time curves (VTC) after cardiac resynchronization therapy (CRT).Methods Thirty-nine patients with DCM were enrolled by RT-3DE VTC before and 1 week,6 months,12 months after CRT,draw the left ventricular (LV) 16,12,6 segments LV diastolic early volume standard deviation of the time (Tedv-SD),and with the R-R interval normalized as early diastolic unsynchronized index (DDI) ;draw end-systolic volume (LVESV),LV end-diastolic volume (LVEDV),LV ejection fraction (LVEF) ;and calculate the diastolic peak filling rate(PFR),the ratio of early diastolic volume and enddiastolic volume(EDVearly/EDV).Results LVEDV,LVESV had no significant improvement.Compared with the before and 1 week after CRT,but the improvement was statistically significant after 6 months and 12 months (P ＜0.05,P ＜0.01); LVEF after 1 week,6 months and 12 months were statistically significant (P ＜0.05) ;Compared with before,PFR after 6 months was significantly increased (P ＜0.05),EDVearly/EDV at 12 months after CRT was significantly reduced (P ＜ 0.01); There was a significantly shortened in each segment (Tedv-SD)/R-R 1 week after CRT (P ＜0.01),but the parameters had no obvious improvement later.Correlation analysis:△ DDI and △ EDVearly/EDV reduction was significant positive correlation (r =0.52,P ＜0.01),△DDI and PFR has negative correlation (r =-0.40,P ＜ 0.05),△ EDVearly/EDV and △PFR also had a good relationship (r =-0.56,P ＜0.01).Conclusions The LV synchrony and diastolic function were improved after CRT in patients with DCM; PFR,EDVearly/EDV can be used as evaluation of left ventricular diastolic function effectively targets.

AIM:To investigate the impact of excessive endoplasmic reticulum stress on apoptotic cell death in a rat model of chronic cyclosporine A ( CsA ) nephrotoxicity .METHODS: Male Sprague-Dawley rats on a low-salt diet were subcutaneously injected with vehicle (olive oil, 1 mL· kg-1· d-1) or CsA (15 mg/kg) daily for 1 or 4 weeks.Tu-bulointerstitial fibrosis and apoptotic cell death were estimated by trichrome staining and TUNEL staining .In addition , im-munohistochemistry and immunoblotting were used to evaluate the expression of immunoglobulin -binding protein ( BiP) , eu-karyotic initiation factor 2α(eIF2α), growth arrest and DNA damage-inducible protein 153 (GADD153), caspase-12 and caspase-3.RESULTS:The rats treated with CsA for 1 week did not develop tubulointerstitial fibrosis and TUNEL-positive cells, whereas 4-week treatment with CsA induced typical tubulointerstitial fibrosis and increased TUNEL-positive cells. CsA induced a significant increase in BiP and caspase-12 expression peaked at 1 week, and then returned to normal levels at 4 weeks.In contrast, the expression of eIF2α, GADD153 and caspase-3 in CsA-treated rat kidneys were significantly in-creased in a time-dependent manner .CONCLUSION:Excessive endoplasmic reticulum stress causes apoptotic cell death by depleting molecular chaperones and stimulating the proapoptotic pathway in chronic CsA nephrotoxicity .

Objective:To screen the differential metabolites and metabolic pathways in silicosis model by analyzing plasma metabolomics of silicosis rats.Methods:In May 2021, twenty male SD rats were randomly divided into control group (C), 1-week silicosis group (S1W), 2-week silicosis group (S2W) and 4-week silicosis group (S4W), with 5 rats in each group. Rats were intratracheally instillated with 1ml crystalline SiO 2 suspension (50 mg/ml) or normal saline and were sacrificed after 1 week, 2 weeks and 4 weeks, HE staining was used to observe the lung pathology of rats. The plasma samples were analyzed by UPLC-IMS-QTOF mass spectrometer to screen out potential differential metabolites in silicosis models and analyze their lipid enrichment. Results:HE results showed that nodules formed in the silicosis model group, and with the extension of time, nodules gradually increased and alveolar structure was gradually destroyed. Metabolomics screened out 14 differential metabolites in S1W, 24 in S2W, and 28 in S4W, and found that the differential metabolites were mainly enriched in the metabolism of glycerophospholipid metabolism, fatty acid degradation, Glycosylphosphatidylinositol (GPI) -anchor biosynthesis, fatty acid elongation and other metabolic pathways.Conclusion:There are significant changes in plasma lipid metabolites in silicosis rat models.

Objective:To screen the differential metabolites and metabolic pathways in silicosis model by analyzing plasma metabolomics of silicosis rats.Methods:In May 2021, twenty male SD rats were randomly divided into control group (C), 1-week silicosis group (S1W), 2-week silicosis group (S2W) and 4-week silicosis group (S4W), with 5 rats in each group. Rats were intratracheally instillated with 1ml crystalline SiO 2 suspension (50 mg/ml) or normal saline and were sacrificed after 1 week, 2 weeks and 4 weeks, HE staining was used to observe the lung pathology of rats. The plasma samples were analyzed by UPLC-IMS-QTOF mass spectrometer to screen out potential differential metabolites in silicosis models and analyze their lipid enrichment. Results:HE results showed that nodules formed in the silicosis model group, and with the extension of time, nodules gradually increased and alveolar structure was gradually destroyed. Metabolomics screened out 14 differential metabolites in S1W, 24 in S2W, and 28 in S4W, and found that the differential metabolites were mainly enriched in the metabolism of glycerophospholipid metabolism, fatty acid degradation, Glycosylphosphatidylinositol (GPI) -anchor biosynthesis, fatty acid elongation and other metabolic pathways.Conclusion:There are significant changes in plasma lipid metabolites in silicosis rat models.

Background The pathogenesis of silicosis is complex and treatment methods are limited. SiO₂-induced increase of transforming growth factor-β1 (TGF-β1) can activate fibroblasts to promote collagen deposition, ultimately leading to fibrosis. Previous studies have confirmed that lipid metabolism plays an important role in the progression of silicosis. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) mediates mitochondrial dysfunction and lipid metabolism pathways in diabetic models, but its role in silicosis has not been elucidated. Objective To investigate the effect of PGC1α on lipid metabolism disorder of macrophages induced by SiO₂ and its effect on the progression of silicosis fibrosis. Methods (1) Macrophages were divided into four groups by transfecting and silencing PGC1α and its control sequence in macrophages and followed by SiO₂ stimulation: negative control group (transfected with si-NC for 48 h), si-PGC1α group (transfected with si-PGC1α for 48 h), SiO₂ stimulation group (stimulated with 50 μg·mL⁻¹ SiO₂ for 36 h after transfection with si-NC for 48 h), and si-PGC1α+SiO₂ group (stimulated with 50 μg·mL⁻¹ SiO₂ for 36 h after transfection with si-PGC1α for 48 h). Western blot and cell immunofluorescence were used to test PGC1α expression, 4,4-difluoro-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene (BODIPY 493/503) and total cholesterol (TC) and free cholesterol (FC) kits were used to test lipid accumulation, and the Oroboros2k-Oxygraph respiratory test system (O2K) was used to assess the effects of PGC1α on mitochondrial respiratory chain. ELISA kits were used to test TGF-β1 expressed in the macrophage supernatant. (2) Lung fibroblasts were divided into the same four groups as above, and stimulated with the supernatant of macrophages in the above groups. The expression of collagen Ι (COL Ι), E-cadherin (Eca), and fibronectin (FN) were detected by cell immunofluorescence and Western blot to further evaluate the effect of silencing PGC1α on fibrosis. Results The protein expression level of PGC1α stimulated by SiO₂ was decreased, and the relative expression level of PGC1α was 0.78 times that of the control group (P<0.05). After transfection with si-PGC1α, the expression of PGC1α was decreased, and the relative protein expression level of the si-PGC1α group was 0.86 times that of the control group (P<0.05). Compared with the SiO₂ stimulation group, the staining area of BODIPY 493/503 in the si-PGC1α+SiO₂ group was enhanced, and the cholesterol-related indexes [TC, FC and cholesterol ester (CE)] were increased to 1.38, 1.10, and 2.26 times those in the SiO₂ stimulation group (P<0.05). The activity of mitochondrial complex Ι was decreased, and the level of complex Ι in the si-PGC1α+SiO₂ group was 0.63 times that in the SiO₂ stimulation group (P<0.05). The secretion of TGF-β1 by macrophages increased, and the level of TGF-β1 in the si-PGC1α+SiO₂ group was 1.15 times that of the SiO₂ stimulation group (P<0.05). In addition, after stimulation of primary lung fibroblasts with macrophage supernatant, silencing PGC1α increased the expression levels of COL Ι and FN, while decreased the expression of Eca. The protein levels of COL Ι, FN, and Eca in the si-PGC1α+SiO₂ group were 1.39, 1.18, and 0.82 times those in the SiO₂ stimulation group, respectively (P<0.05). Conclusion Silencing PGC1α exacerbates SiO₂-induced lipid metabolism disorder, inhibits mitochondrial respiratory chain, and aggravates the fibrosis induced by SiO₂, suggesting that PGC1α may participate silicosis fibrosis by regulating mitochondrial respiratory chain and lipid metabolic disorder induced by SiO₂.

This paper summarizes Professor SHI Zaixiang's clinical experience in treating high fever caused by sepsis using Chaihu Guizhi Ganjiang Decoction （柴胡桂枝干姜汤）. He holds that the key pathogenesis of sepsis involves constrained heat in the shaoyang and internal accumulation of water and fluids. The clinical manifestations such as high fever， chills， and alternating sensations of cold and heat are attributed to pathogenic heat constrained in the shaoyang. Meanwhile， soft tissue edema and serous cavity effusions are due to shaoyang dysfunction and internal water retention. In clinical practice， treating sepsis-related high fever requires addressing both the shaoyang-constrained heat and the associated edema and effusions. The therapeutic approach focuses on harmonizing the shaoyang and resolving internal fluids， using Chaihu Guizhi Ganjiang Decoction as the base formula with flexible modifications. Professor SHI emphasizes that this formula shows a rapid antipyretic effect， particularly in cases where multiple anti-infective treatments have failed.

OBJECTIVE: To explore the prognostic factors of patients with unresectable liver metastasis colorectal cancer after failed conversion chemotherapy. METHODS: A retrospective, case-controlled study was performed. Study subjects were 105 patients who were diagnosed with synchronous liver metastasis colorectal cancer after failed chemotherapy (metastasis evaluated as unresectable after the conversion chemotherapy) at Xinhua Hospital, Shanghai Jiaotong University from January 2012 to December 2015. Overall survival(OS) was retrospectively analyzed using Kaplan-Meier method. Log-rank test was used to compare survival among groups. Univariate and multivariate analysis was conducted for prognosis using Cox regression model. RESULTS: Of 105 cases,70 were male and 35 were female with median age of 60 years old. Twenty-one patients had right colon cancer, 41 had left colon cancer, 42 had rectal cancer and 1 had synchronous cancers(sigmoid colon and rectum). One hundred and two (97.1%) patients were cT3-4 and 90 patients were cN+ (imaging diagnosis). Eighty-nine (84.8%) patients were loaded with 2 or more liver metastases with the median maximum diameter of 48.3 mm. The patients were followed up for 3 to 43 months from the day of diagnosis. The median OS was 11 months (interquartile range, 8-18). The median OS of patients with cN0, cN1 and cN2 stage was 17, 13 and 10 months, respectively(P=0.026). The median OS of patients with single lesion, 2-3 lesions, 4-10 lesions and more than 10 lesions was 15, 15, 17 and 9 months, respectively (P=0.002). OS of patients with maximum diameter of liver metastatic lesion ≤ 50 mm, 51-100 mm and >100 mm was 15, 10 and 8 months, respectively(P=0.003). The median OS of patients with chemotherapy response of partial response (PR), stable disease (SD) and progressive disease (PD) was 17, 14 and 8 months, respectively(P<0.001). OS was 17 months in patients receiving second line chemotherapy and was 10 months in those without second line chemotherapy (P<0.001). OS in patients undergoing primary tumor resection was 13 month and in those without primary tumor resection was 9 months; the difference was not significant (P=0.060). Multivariate analysis showed that cN2(HR=2.115, 95%CI:1.089-4.109, P=0.027), the maximum diameter of liver metastatic lesion more than 100 mm (HR=3.112, 95%CI:1.455-6.657, P=0.003), chemotherapy response of PD (HR=4.435, 95%CI:2.506-7.533,P<0.001) and without second line chemotherapy(HR=4.432,95%CI:2.186-8.986, P=0.010) were independent prognostic factors. CONCLUSIONS For patients with unresectable liver metastasis from colorectal cancer after failed conversion chemotherapy, prognostic factors include cN2, the maximum diameter of liver metastatic lesion, chemotherapy response and second line chemotherapy. Whether the resection of primary tumor can prolong OS further study.
Antineoplastic Agents ; therapeutic use ; China ; Colorectal Neoplasms ; drug therapy ; pathology ; Female ; Humans ; Liver Neoplasms ; diagnosis ; secondary ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Treatment Failure

Objective : To explore the regulatory role of microRNA⁃455 ⁃3p ( miR⁃455 ⁃3p) in lymphangiogenesis of rat silicosis model , and to investigate the effect of miR⁃455 ⁃3p targeted regulation of vascular endothelial growth factor C (VEGF⁃C) on the tubular structure formation of human lymphatic endothelial cells ( HLECs) . Methods: The rats were randomly divided into the silicosis model group and the normal control group. The silicosis model group were injected with silicon dioxide (SiO2 )dust suspension , and the control group was injected with the same amount of normal saline. HE , Masson and immunohistochemistry staining were used to observe the pathological changes and lymphangiogenesis of lung tissue. The expression levels of miR⁃455 ⁃3p and VEGF⁃C in lung tissues of rats were detected by Quantitative real⁃time PCR ( RT⁃qPCR) and Western blot; The miR⁃455 ⁃3p inhibitors and negative controls ( NC) were transfected into HLECs , and the expression levels of miR⁃455 ⁃3p and VEGF⁃C in cells were detected by RT⁃qPCR and Western blot. The migration ability of HLECs was detected by scratch test , the ability of tubular structure formation was detected by matrigel tube formation test , and dual luciferase experiments were used to verify the targeting relationship between miR⁃455 ⁃3p and VEGF⁃C. Results : Compared with the normal control group , in the silicosis model group , a large number of inflammatory cells gathered and collagen gradually deposited in the pulmonary interstitium , and there was lymphatic hyperplasia in the lung. The expression of miR⁃455 ⁃3p in the lung tissue was lower than that in the control group , and the expression of VEGF⁃C was higher than that in the control group ; After transfection with HLECs , compared with the NC group , the expression of miR⁃455 ⁃3p in the cells of the Inhibitors group decreased , the expression of VEGF⁃C increased , and the ability of cell migration and tubular structure formation increased(P < 0. 05) ; VEGF⁃C was confirmed as a target gene of miR⁃455 ⁃3p by the dual luciferase experiments. Conclusion miR⁃455 ⁃3p can affect the tubular structure formation ability of HLECs and regulate lymphangiogenesis by targeting the expression of VEGF⁃C.