ObjectiveTo investigate the in vivo degradation and histocompatibility of modified chitosan based on conductive composite nerve conduit, so as to provide a new scaffold material for the construction of tissue engineered nerve.MethodsThe nano polypyrrole (PPy) was synthesized by microemulsion polymerization, blended with chitosan, and then formed conduit by injecting the mixed solution into a customized conduit formation model. After freeze-drying and deacidification, the nano PPy/chitosan composite conduit (CP conduit) was prepared. Then the CP conduits with different acetyl degree were resulted undergoing varying acetylation for 30, 60, and 90 minutes (CAP1, CAP2, CAP3 conduits). Fourier infrared absorption spectrum and scanning electron microscopy (SEM) were used to identify the conduits. And the conductivity was measured by four-probe conductometer. The above conduits were implanted after the subcutaneous fascial tunnels were made symmetrically on both sides of the back of 30 female Sprague Dawley rats. At 2, 4, 6, 8, 10, and 12 weeks after operation, the morphology, the microstructure, and the degradation rate were observed and measured to assess the in vivo degradation of conduits. HE staining and anti-macrophage immunofluorescence staining were performed to observe the histocompatibility in vivo.ResultsThe characteristic peaks of the amide Ⅱ band around 1 562 cm−1 appeared after being acetylated, indicating that the acetylation modification of chitosan was successful. There was no significant difference in conductivity between conduits (P>0.05). SEM observation showed that the surfaces of the conduits in all groups were similar with relatively smooth surface and compact structure. After the conduits were implanted into the rats, with the extension of time, all conduits were collapsed, especially on the CAP3 conduit. All conduits had different degrees of mass loss, and the higher the degree of acetylation, the greater the mass change (P<0.05). SEM observation showed that there were more pores at 12 weeks after implantation, and the pores showed an increasing trend as the degree of acetylation increased. Histological observation showed that there were more macrophages and lymphocytes infiltration in each group at the early stage. With the extension of implantation time, lymphocytes decreased, fibroblasts increased, and collagen fibers proliferated significantly. ConclusionThe modified chitosan basedon conductive composite nerve conduit made of nano-PPy/chitosan composite with different acetylation degrees has good biocompatibility, conductivity, and biodegradability correlated with acetylation degree in vivo, which provide a new scaffold material for the construction of tissue engineered nerve.
Objective To explore the proper dosage of establishment of stable hepatic oval cells （HOC） prolif-eration model by using 2-acetaminofluorene （2-AAF） combined with two-third partial hepatectomy （2/3 PH） surgery， and to explore isolated and cultured method of HOC in vitro. Methods The 174 Wistar rats were randomly divided into 4 experimental groups （each group enrolled 30 rats）， saline group （n=30）， and untreated group （n=24）. Rats of 4 experi-mental groups were underwent gavage of 5， 10， 15， and 20 mg/（kg ? d） 2-AAF， corresponding to the groups from No.1 to No.4 group. Rats of saline group received saline gavage and rats of untreated group didn’t received any treatment. A standard 2/3 PH surgery was performed on the 5th day after gavage， then the same gavage method was still administrated as preoperation untill rats were sacrificed. The liver tissues of 6 selected rats were adopted and identified by HE staining and immunohistochemical staining on 4， 8， 12， and 16 days after PH for observation of the proliferation of HOC in every group， on 4 days， levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were tested in addition. HOC were isolated and purified by collagenase perfusion method and percoll gradient centrifugation. Results The surv-ival rates of untreated group，saline group，No.1 group，No.2 group，No.3 group，and No.4 group were 100% （24/24），93% （28/30），93% （28/30），90% （27/30），90% （27/30），and 80% （24/30） respectively. Compared with the saline group and untreated group， the levels of serum ALT and AST increased significantly in No.2， No.3， and No.4 group on the 4th day after PH （P＜0.05）. The results of HE staining showed that No.2， No.3， and No.4 group were observed visibly different level of damage at liver tissue， and the proliferation level of HOC were most obviously in No.3 and No.4 group. The results of immunohistochemical staining revealed that proliferation cells were positively expressed oval cell marker-6 （OV-6）. The number of OV-6 positive cells were increased significantly with the increase of dosage of 2-AAF between 4 days and 12 days after operation， and proliferation levels were related with dosages of 2-AAF （P＜0.05）. In all cultured cells， 80% of cells were OV-6 positive cells after isolation and culture by using collagenase perfusion method and percoll gradient centrifugation. Conclusions The methods of gavage of 2-AAF at 15 mg/（kg ? d） combined with 2/3 PH surgery can establish the HOC proliferation model on the 12th day， as well as the rats have lower mortality and better tolerance， especially. The collagenase perfusion method and percoll gradient centrifugation can be used to isolate HOC effectively.
ObjectiveTo explore the effects and molecular mechanisms of histone methylase G9a inhibitor BIX-01294 on apoptosis in esophageal squamous cell carcinoma (ESCC).MethodsMTT assay and Colony-forming Units were adopted to determine the effects of BIX-01294 on the growth and proliferation of ESCC cell lines EC109 and KYSE150. Flow cytometry was used to analyze the apoptosis status of ESCC cells after the treatment of BIX-01294. The effects of BIX-01294 treatment on the expressions of G9a catalytic product H3K9me2, DNA double-strand break (DSB) markers, and apoptosis-related proteins were detected by Western blotting.ResultsBIX-01294 inhibited the growth of EC109 and KYSE150 cells in a dose-dependent manner (P<0.05), and BIX-01294 with the inhibitory concentration 50% (IC50) significantly inhibited the formation of colony (P<0.05). After 24 hours treatment of BIX-01294 (IC50), the apoptosis rate of EC109 cells increased from 11.5%±2.1% to 42.5%±5.4%, and KYSE150 cells from 7.5%±0.9% to 49.2%±5.2% (P<0.05). The expression level of the G9a catalytic product, H3K9me2, significantly decreased (P<0.05); while the expression of the DSB marker γH2AX was dramatically enhanced (P<0.05). We also found that the mitochondrial apoptosis pathway was activated and the expression levels of cleaved caspase3 and cleaved PARP were significantly elevated (P<0.05).ConclusionBIX-01294, the inhibitor of methyltransferase G9a, prompted apoptosis in ESCC cells by inducing DSB damage and activating mitochondrial apoptosis pathway.
[Abstract]In China, more than half of heart failure patients are ischemic heart failure patients. And a large proportion of left ventricular assist device implantation patients are also ischemic heart failure patients. However, left ventricular assist device implantation in ischemic heart failure patients is facing with problems such as patient screening, coronary artery disease, smaller left ventricle, mitral insufficiency, and ventricular aneurysm. There are only a few retrospective studies with small sample sizes abroad try to provide solutions to these problems. While there is a lack of systematic understanding of this issue in China. Therefore, we provide an overview of the application and progress of left ventricular assist devices in ischemic heart failure patients, aiming to help clinicians have a comprehensive understanding of this issue and provide some guidance.
Objective To assess the therapeutic effect of sulodexide for diabetic patients with early nephropathy. Methods A total of 60 patients with early diabetic nephropathy (albuminuria: 30 to 300 mg/24 h, male/female: 30/30, mean age: 51.23 years, mean course of disease: 12.9 years) were randomized equally into three groups: the routine treatment group, cozaar group (50 mg qd, po for 12 weeks) and sulodexid group (600 LSU qd, iv or im for 4 weeks, 250 LSU bid, po for 8 weeks). The levels of urinary albumin excretion rate (UAER), urea nitrogen and creatinine were determined. Results After three months of treatment, the level of UAER was decreased significantly in both the sulodexide group and cozaar group (Plt;0.01), but not in the routine treatment group (Pgt;0.05). The level of UAER was reduced by 34.04% and 33.62% in the cozaar group and the sulodexide group, respectively. Significant difference was noted in the level of UAER between the cozaar/sulodexide groups and the routine treatment group (Plt;0.01), but no significant difference was observed between cozaar group and sulodexide group (Pgt;0.05). Conclusion Sulodexide could decrease the level of UAER in patients with early diabetic nephropathy. It has similar efficacy to cozaar.
ObjectiveTo compare the perioperative renal function changes in patients undergoing heart transplantation (HT) and left ventricular assist device (LVAD) implantation. MethodsPatients with end-stage heart failure who underwent surgical treatment at Beijing Anzhen Hospital, Capital Medical University from January 2019 to April 2024 were included. According to the surgical method, patients were divided into a HT group and a LVAD group, and the estimated glomerular filtration rate (eGFR) of patients before surgery, postoperative 1 d, 7 d, 30 d, and 60 d was compared between the two groups. The patients with preoperative renal dysfunction were subdivided into subgroups for comparison of eGFR changes before surgery and 30 days after surgery between the two groups. ResultsA total of 112 patients were enrolled. There were 78 patients in the HT group, including 61 males and 17 females, aged 44.42±18.51 years. There were 34 patients in the LVAD group, including 30 males and 4 females, aged 54.94±11.37 years. Compared with the HT group, the average age of patients in the LVAD group was greater (P<0.001), body mass index was higher (P=0.008), preoperative eGFR was lower (P=0.009), and the proportions of smokers (P=0.017), alcohol drinkers (P=0.041), and diabetes mellitus (P=0.028) patients were higher. Among patients with preoperative renal dysfunction [eGFR<90 mL/(min·1.73 m2)], compared with the HT group, the postoperative eGFR of the LVAD group was significantly higher than that of the HT group, and it was significantly increased compared with that before surgery; the postoperative eGFR of the HT group was comparable to that before surgery, and more than half of the patients had a lower eGFR than before surgery. Among patients with preoperative renal dysfunction, 11 patients in the HT group received continuous renal replacement therapy, and 8 died early; 2 patients in the LVAD group received continuous renal replacement therapy, and 1 died early. ConclusionFor end-stage heart failure patients with combined renal dysfunction, compared with HT, LVAD implantation enables patients to obtain better renal function benefits.
ObjectiveTo analyze the clinical efficacy valve surgeries for infective endocarditis and the affecting factors, and compare the early- and long-term postoperative outcomes of different surgery approaches. MethodsThe patients with infective endocarditis who underwent valve replacement/valvuloplasty in our hospital from 2010 to 2022 were retrospectively collected. The clinical data of the patients were analyzed. ResultsA total of 343 patients were enrolled, including 197 patients with mechanical valve replacement, 62 patients with bioprosthetic valve replacement, and 84 patients with valvuloplasty. There were 238 males and 105 females with an average age of 44.2±14.8 years. Single-valve endocarditis was present in 200 (58.3%) patients, and multivalve involvement was present in 143 (41.7%) patients. Sixty (17.4%) patients had suffered thrombosis before surgery, including cerebral embolisms in 32 patients. The mean follow-up time was 60.6±43.8 months. Early mortality within one month after the surgery occurred in 17 (5.0%) patients, while later mortality occurred in 19 (5.5%) patients. Eight (2.3%) patients underwent postoperative dialysis, 13 (3.8%) patients suffered postoperative stroke, 6 patients underwent reoperation, and 3 patients suffered recurrence of infective endocarditis. Smoking (P=0.002), preoperative embolisms (P=0.001), duration of surgery (P=0.001), and postoperative dialysis (P=0.001) were risk factors for early mortality, and left ventricular ejection fraction≥60% (P=0.022)was protective factor for early mortality. New York Heart Association classification Ⅲ-Ⅳ (P=0.010) and ≥3 valve procedures (P=0.028) were risk factors for late mortality. The rate of composite endpoint events was significantly lower in the valvuloplasty than that in the valve replacement group. ConclusionFor patients with infective endocarditis, smoking and preoperative embolisms are associated with high postoperative mortality, multiple-valve surgery is associated with a poorer prognosis, and valvuloplasty has advantages over valve replacement and should be attempted in the surgical management of patients with infective endocarditis.