OBJECTIVE To study the inhibitory effect and mechanism of curcumin and its derivatives A and B on TGF-β induced LX-2 cell fibrosis. METHODS Established the liver fibrosis model of LX-2 cells induced by TGF-β(10 ng·mL−1).The effects on cell proliferation were detected by CCK-8. The effects on cell apoptosis was detected by flow cytometry. The effects on fibrosis related factors(Collagen I, Collagen Ⅳ, Fibronectin, Vimentin, α-SMA, PDGFRβ, TGFβR1, TGFβR2, MMP2, MMP9, TIMP1 and TIMP2) protein expression and gene transcription levels were detected by Western blotting and q-PCR. RESULTS The curcumin and its derivative A and B had the inhibition effects on normal LX-2 cells, and the IC25 values were 15.7, 2.6, 10.2 μmol·L−1, respectively. Compared to the model group, the curcumin(15.7 μmol·L−1) and its derivative A(2.6 μmol·L−1) and B(10.2 μmol·L−1) had the significant inhibition effects on cell proliferation of the TGF-β induced LX-2 cells(P<0.05). The cell apoptosis rate of curcumin derivative B group was higher than the model group(P<0.05). Collagen I, Fibronectin, Vimentin, α-SMA, TGFβR1 and TIMP-1 protein expression levels in curcumin group were lower, while the protein expression level of MMP-9 was higher(P<0.05). The protein expression levels of Collagen I, Collagen IV, Fibronectin, Vimentin, α-SMA, TIMP-1 and TIMP-2 in curcumin derivative A group were lower, while the protein expression level of MMP-2 was higher(P<0.05). The protein expression levels of Collagen I, Collagen IV, Fibronectin, Vimentin, α-SMA, PDGFRβ, TGFβR1, TGFβR2, TIMP-1 and TIMP-2 in curcumin derivative B group were lower, while the protein expression level of MMP-2 was higher(P<0.05). The gene transcription levels of Collagen I, Fibronectin, α-SMA and TIMP-1 in curcumin group were lower(P<0.05). The gene transcription levels of Collagen I, Fibronectin and α-SMA in curcumin derivative A and B groups were lower(P<0.05). CONCLUSION Curcumin and its derivatives A and B inhibit the abnormal activation and proliferation of TGF-β-induced LX-2 cells, inhibit the excessive secretion and accumulation of its extracellular matrix components, and promote its degradation, thus playing an anti-fibrotic effect in vitro, especially the curcumin derivative B.

The technology of three-dimensional(3D)printing emerged in the late 1970s and has since undergone considerable development to find numerous applications in mechanical engineering,industrial design,and biomedicine.In biomedical science,several studies have initially found that 3D printing technology can play an important role in the treatment of diseases in hepatopancreatobiliary surgery.For example,3D printing technology has been applied to create detailed anatomical models of disease organs for preoperative personalized surgical strategies,surgical simulation,intraoperative navigation,medical training,and patient education.Moreover,cancer models have been created using 3D printing technology for the research and selection of chemotherapy drugs.With the aim to clarify the development and application of 3D printing technology in hepatopancreatobiliary surgery,we introduce seven common types of 3D printing technology and review the status of research and application of 3D printing technology in the field of hepatopancreatobiliary surgery.

Acute ischemic stroke is a major disease threatening the life and health of middle-aged and elderly people, and intravascular therapy is the most rapid and effective treatment for acute ischemic stroke. However, clinical findings showed that patients who were often treated intravascular within the time window or beyond the time window could not achieve functional independence for 90 days after vascular recanalization, that is, ineffective recanalization. Ineffective recanalization seriously affects the efficacy of intravascular therapy and has become the focus of clinical research by neurologists. In this paper, the mechanism and influencing factors of ineffective recanalization in acute large vascular occlusive ischemic stroke in recent years, as well as possible ways to reduce its occurrence, are comprehensively reviewed, providing references for clinicians to develop more reasonable and perfect programs.

【Objective】 Dyslipidemia has shown to be associated with cardiovascular, metabolic and renal diseases. This study aimed to investigate the association between residual cholesterol and the risk of subclinical renal damage (SRD). 【Methods】 A total of 2 342 participants were recruited from the previously established Hanzhong Adolescent Hypertension Study cohort. According to estimated glomerular filtration rate(eGFR) and urinary albumin-to-creatine ratio(uACR), the subjects were divided into SRD group and non-SRD group. The associations of residual cholesterol with eGFR, uACR, and the risk of SRD were analyzed by multiple linear and Logistic regression analyses. 【Results】 Residual cholesterol was positively correlated with uACR(r=0.081, P<0.001) but negatively correlated with eGFR (r=-0.091, P<0.001). Multiple linear regression analysis revealed that residual cholesterol was an influencing factor of uACR (β=0.075, P<0.001) and eGFR (β=-0.027, P<0.001) after adjustment for gender, age, smoke, alcohol, exercise, BMI, hypertension, diabetes and serum uric acid. In addition, Logistic regression analysis revealed that residual cholesterol was significantly associated with the risk of SRD independently of potential confounders [OR(95% CI)=1.387 (1.113-1.728), P<0.001]. Further subgroup analysis showed that residual cholesterol was significantly associated with the risk of SRD in women but not in men. 【Conclusion】 Residual cholesterol is a contributing factor in the risk of subclinical renal damage with gender-specific association.

【Objective】 4-like protein with down-regulated expression and development in neural precursor cells (NEDD4L) plays an important role in blood pressure (BP) regulation and sodium homeostasis by regulating epithelial sodium channel protein. In this study, we aimed to explore the relationship of NEDD4L gene polymorphisms with BP responses to sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Meixian County, Shaanxi Province, were recruited to establish a salt-sensitive hypertension study cohort. All the subjects received a 3-day baseline survey, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Their BP was measured and peripheral blood samples were collected at different intervention periods. The 14 gene polymorphisms of NEDD4L gene were genotyped and analyzed by MassARRAY platform. 【Results】 BP decreased on a low-salt diet, and significantly increased on a high-salt diet, and decreased again after potassium supplementation. NEDD4L SNPs rs74408486 were significantly associated with systolic BP, diastolic BP and mean arterial pressure responses to the low-salt diet. SNPs rs292449 and rs2288775 were significantly associated with pulse pressure response to the high-salt diet. In addition, SNPs rs563283 and rs292449 were significantly associated with diastolic BP, mean arterial pressure, and pulse pressure responses to high-salt and potassium supplementation diet. 【Conclusion】 NEDD4L gene polymorphisms were significantly associated with BP responses to sodium and potassium intake, suggesting that NEDD4L gene may be involved in the development of salt sensitivity and potassium sensitivity.

【Objective】 Based on our previously established salt-sensitive hypertension cohort, we aimed to examine the association of genetic variants in uromodulin with blood pressure(BP) responses to dietary interventions of sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Mei County, Shaanxi Province, were recruited to establish the salt-sensitive hypertension study cohort. Among them, 333 non-parent subjects were selected and sequentially maintained on a normal-diet for 3 days, low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Thirteen single nucleotide polymorphisms(SNPs) in the uromodulin gene were genotyped on the MassARRAY platform. 【Results】 BP levels decreased from the baseline to low-salt diet, increased from low-salt to high-salt diet, and decreased again from the high-salt diet to the high-salt plus potassium supplementation intervention. SNPs rs77875418 and rs4997081 of the uromodulin gene were significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to high-salt diet. In addition, SNPs rs77875418, rs79245268, rs4293393, rs6497476, rs4997081, rs13333226, and rs12917707 were significantly associated with systolic BP(SBP), DBP, and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in uromodulin gene are significantly associated with BP responses to sodium and potassium supplementation, suggesting that uromodulin may be mechanistically involved in BP sodium-sensitivity and potassium-sensitivity.

【Objective】 M3 muscarinic acetylcholine receptor(M3 receptor), encoded by CHRM3 gene, is widely distributed in the cardiovascular system and plays an important role in cardiac regulation. The aim of this study was to assess the association of genetic variants in M3 receptor with blood pressure(BP) responses to controlled dietary sodium and potassium interventions. 【Methods】 A total of 333 subjects from 124 families were recruited from the rural areas of northern China. After a three-day baseline observation, they were sequentially on a seven-day low-salt diet, a seven-day high-salt diet, and a seven-day high-salt diet plus potassium supplementation. Thirteen CHRM3 single nucleotide polymorphisms(SNPs) were selected for analysis. 【Results】 SNP rs10802811 of the CHRM3 was significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to both low-salt and high-salt diets while SNPs rs6429147, rs373288072, rs114677844 and rs663148 showed significant associations with systolic BP(SBP) and MAP responses to high-salt diet. In addition, SNP rs6692904 was significantly associated with SBP, DBP and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in M3 receptor are significantly associated with BP responses to sodium and potassium intervention, suggesting that M3 receptor may be mechanistically involved in BP salt and potassium sensitivity.

Objective:To investigate the management of patients with intravenous misplacement of nephrostomy tube following percutaneous renal surgery.Methods:The data of 6 patients with intravenous misplacement of nephrostomy tube during percutaneous nephrolithotomy (PCNL) treated in the two hospitals of Chenzhou from January 2006 to December 2020 were retrospectively analyzed. The median age was 41.0(38.5, 53.0) years old. There were 4 males and 2 females. Three patients had undergone contralateral upper urinary tract operation. One patient had undergone ipsilateral upper urinary tract operation. Two patients had not undergone upper urinary tract operation. Two of the 6 patients had a solitary kidney. Two patients were diagnosed with staghorn calculi (combined with mild hydronephrosis in 1 patient, moderate hydronephrosis in 1 patient). Four patients were diagnosed with ureteral calculus (combined with mild hydronephrosis in 2 patients, moderate hydronephrosis in 1 patient, severe hydronephrosis in 1 patient). In all 6 patients, the tract was dilated with fascial dilators. Immediately after dilator removal, brisk venous bleeding was noted. A nephrostomy tube was inserted promptly through the sheath to tamponade the tract and was immediately closed. Five cases were diagnosed by CT after operation, and 1 case was early diagnosed by intraoperative injection of contrast medium through nephrostomy tube. The nephrostomy tube was misplaced in 5 patients with left upper urinary tract calculi, and in 1 patient with right upper urinary tract calculi. The tip of nephrostomy tube was located in ipsilateral renal vein in 3 patients with left upper urinary tract calculus, inferior vena cava in 2 patients with left upper urinary tract calculus, and contralateral renal vein in 1 patient with right upper urinary tract calculus. No venous thrombosis of renal vein or inferior vena cava was founded in the 6 patients. All 6 patients were managed with strict bed rest, intravenous antibiotics, and one-step or two-step tube withdrawal under close monitoring. One step method referred to total removal of nephrostomy tube under ultrasonic monitoring. Two step method referred to retracting the end of nephrostomy tube into the renal sinus under CT monitoring in the first step, then the nephrostomy tube was completely removed under ultrasound monitoring.Results:All 6 patients were successfully managed with strict bed rest, intravenous antibiotics, and one-step or two-step tube withdrawal under close monitoring. The tube was withdrew by one-step method in 1 patient, by two-step method in 5 patients. The original operations were performed successfully under close observation in 4 patients during the same hospitalization and in 1 patient during the next hospitalization. Other type of operation in 1 patient was performed during the next hospitalization. The all 6 patients were discharged uneventfully. The stone was cleared.Conclusions:Intravenous misplacement of a nephrostomy tube is mainly diagnosed by CT. The nephrostomy tube should be sealed immediately after diagnosis. The intravenously misplaced nephrostomy tube can be successfully removed by one-step or two-step withdrawing under close monitoring. Upper urinary tract stones can be successfully treated at the same time or by stages.

BACKGROUND: Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) are the main causes of restenosis (RS) in diabetic lower extremity arterial disease (LEAD). However, the relevant pathogenic mechanisms are poorly understood. METHODS: In this study, we introduced a "two-step injury protocol" rat RS model, which started with the induction of atherosclerosis (AS) and was followed by percutaneous transluminal angioplasty (PTA). Hematoxylin-eosin (HE) staining and immunohistochemistry staining were used to verify the form of RS. Two-step transfection was performed, with the first transfection of Lin28a followed by a second transfection of let-7c and let-7g, to explore the possible mechanism by which Lin28a exerted effects. 5-ethynyl-2΄-deoxyuridine (EdU) and Transwell assay were performed to evaluate the ability of proliferation and migration of VSMCs. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect the expression of Lin28a protein and let-7 family members. RESULTS: Using a combination of in vitro and in vivo experiments, we discovered that let-7c, let-7g, and microRNA98 (miR98) were downstream targets of Lin28a. More importantly, decreased expression of let-7c/let-7g increased Lin28a, leading to further inhibition of let-7c/let-7g. We also found an increased level of let-7d in the RS pathological condition, suggesting that it may function as a protective regulator of the Lin28a/let-7 loop by inhibiting the proliferation and migration of VSMCs. CONCLUSION These findings indicated the presence of a double-negative feedback loop consisting of Lin28a and let-7c/let-7g, which may be responsible for the vicious behavior of VSMCs in RS.
Rats ; Animals ; Down-Regulation ; MicroRNAs/metabolism* ; Feedback ; Cell Proliferation/genetics* ; Atherosclerosis

Abstract OBJECTIVE To study the mechanism of NLRP3 gene’s regulation on inflammatory response in non-alcoholic fatty liver disease(NAFLD) mice induced by high-fat and high-fructose diet using NLRP3 gene knockout mice. METHODS Use male homozygous(NLRP3-/-) mice, and the high-fat and high-fructose diet was used to establish NAFLD model in NLRP3 knockout(KO) mice and wild-type(WT) mice, divided into KO high-fat and high-fructose diet(KO-HFD) group and WT high-fat and high-fructose diet(WT-HFD) group, while the WT and KO groups were also established. The body weight of mice in each group were observed. The changes of ALT, AST, TG, TC, MDA, SOD, lipidosis, apoptosis rate, IL-1β, IL-18, TNF-α, NF-κB, NLRP3, Caspase-1 and ASC in serum and tissue samples were tested to study the mechanism of the NLRP3 gene regulating the inflammatory response in NAFLD mice. RESULTS As time goes on, the mice weight of each group increased gradually, but the KO-HFD group increased less than the WT-HFD group. Each group’s level of ALT, AST, TG, TC in serum increased gradually, but the KO-HFD group increased less than the WT-HFD group. The level of MDA in liver tissues of each group was gradually increased and the level of SOD was gradually decreased, but the change range of KO-HFD group was smaller than that of WT-HFD group. The results of oil red O staining and Tunel section showed that the degree of lipid deposition and apoptosis in hepatocytes increased gradually in all groups, but the changes in KO-HFD group were less than that in WT-HFD group. The levels of serum and liver inflammatory factors IL-1β, IL-18, TNF-α and NF-κB increased in all groups, but the changes of KO-HFD group 20 weeks were less than those of WT-HFD group 20 weeks, and the difference was statistically significant. The expression levels of NLRP3 inflammasomes and related inflammatory cytokines NLRP3, Caspase-1, ASC, IL-1β and IL-18 in liver tissues of WT-HFD group were higher than those of KO-HFD group. The mRNA transcription levels of NLRP3, ASC, Caspase-1, IL-1β and IL-18 in WT-HFD group were gradually increased, while there was no change in KO-HFD group. CONCLUSION The NLRP3 gene may be activated in NAFLD mice model, resulting in increased expression of NLRP3 inflammasome-associated protein, promoting the synthesis and secretion of downstream inflammatory factors, resulting in significant inflammatory response and liver damage, and promoting the progression of NAFLD disease.