摘要:目的:探討卡配因抑制劑3（MDL28170）對新生大鼠缺氧缺血性腦損傷(HIBD)神經細胞凋亡的影響。方法:建立新生SD大鼠HIBD模型,治療組于缺養缺血后即刻、2 h、4 h腹腔內注射MDL28170,對照組及手術組同時予生理鹽水。缺氧缺血后24 h用免疫組化方法觀察大腦皮質及海馬CA1區Caspase3 蛋白表達、TUNEL法檢測細胞凋亡,觀察組織病理改變并計算海馬神經元死亡數,透射電鏡觀察細胞超微結構。結果:缺氧缺血后24 h缺血側大腦皮質及海馬CA1區Caspase3和TUNEL陽性細胞數較對照組明顯增加,透射電鏡證實有凋亡細胞;MDL28170可減少陽性細胞數量,抑制神經元死亡,差異有顯著性(Plt;0.05)。結論:MDL28170可通過抑制神經凋亡而對新生大鼠HIBD具有一定保護作用。Abstract: Objective: To investigate the effect of (Calpain inhibitor3) MDL28170 on neural apoptosis in a neonatal model of hypoxicischemic brain damage (HIBD). Methods: A neonatal model of HIBD was established, 7dayold SD rats were divided into three groups. The treatment group received MDL28170(ip) at 0 h,2 h,4 h after HI, whereas the other two groups were administered normal saline simultaneously. The expression of caspase3 (by immunohistochemistry), neural apoptosis (by TUNEL) in cortex and hippocampus ipsilateral to the insult were observed 24 h after HI; hippocampal CA1 neural loss and electromicroscopic changes were assessed at the same time. Results: Apoptotic body was observed by electromicroscopy. Caspase3 positive cells and apoptotic cells increased significantly in the ipsilateral cortex and hippocampal CA1 region compared to the control, and MDL28170 reduced the number of positive cells, attenuated CA1 neural loss with significance (Plt;0.05). Conclusion: It is suggested that MDL28170 may protect the brain of neonatal rats after HIBD by suppressing neural apoptosis.
To investigate the function of nitric oxide (NO) and nitric oxide synthetase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME), the skin avulsion model was made in the lower extremity of pig. The methods of measurement of size of the survived flap, weighing, immunocytochemistry and hybridization in situ were employed, so that the survival surface area of flaps, tissue wet/dry weight ratio, NO content in the serum, gene expression of NO and NOS content in the flap tissue were determined, respectively. The results showed that the early gene expression of NOS was increased as well as the NO content and tissue wet/dry weight ratio (P lt; 0.01). After L-NAME was applied introvenously, the NO content and tissue wet/dry weight ratio were decreased (P lt; 0.01), and the survival surface area of flaps was enlarged (P lt; 0.01). It could be concluded that the NO might play a role in the development of the pathological changes as early congestion, edema and secondary necrosis in the avulsed skin flaps. The early application of L-NAME could do some good to the avulsed skin flap and protect it from further necrosis owing to the presence of NO.
【Abstract】 Objective To reduce restenosis in vein grafts after coronary artery bypass grafting, to investigate theeffect of human tissue factor pathway inhibitor(TFPI) gene del ivery on neointima formation. Methods The eukaryotic expressed plasmid vector pCMV-(Kozak) TFPI was constructed. Forty-eight Japanese white rabbits were randomly divided into 3 groups with 16 rabbits in each group: TFPI group, empty plasmid control group and empty control group. Animal model of common carotid artery bypass grafting was constructed. Before anastomosis, vein endothel iocytes were transfected with cationic l iposome containing the plasmid pCMV- (Kozak) TFPI (400 μg) by pressurizing infusion (30 min) in TFPI group. In empty plasmid control group, vector pCMV- (Kozak) TFPI was replaced by empty plasmid pCMV (400 μg). In empty control group, those endothel iocytes were not interfered. After operation, vein grafts were harvested at 3 days for immunohistochemical, RTPCR and Western-blot analyses of exogenous gene expression and at 30 days for histopathology measurement of intimal areas, media areas and calculation of intimal/media areas ratio. Luminal diameter and vessel wall thickness were also measured byvessel Doppler ultrasonography and cellular category of neointima was analyzed by transmission electron microscope at 30 days after operation. Results Human TFPI mRNA and protein were detected in TFPI group. The mean luminal diameter of the TFPI group, empty plasmid control group and empty control group was (2.68 ± 0.32) mm, (2.41 ± 0.23) mm and (2.38 ± 0.21) mm respectively. There were statistically significant differences between TFPI group and control groups (P lt; 0.05). The vessel wall thickness of the TFPI group, empty plasmid control group and empty control group was (1.09 ± 0.11) mm, (1.28 ± 0.16) mm and (1.34 ± 0.14) mm respectively. There were statistically significant differences between TFPI group and other control groups (P lt; 0.01). The mean intimal areas, the ratio of the intimal/media areas of the TFPI group were (0.62 ± 0.05) mm2and 0.51 ± 0.08 respectively, which were reduced compared with those of the two control groups(P lt; 0.05). The mean media areas had no significant differences among three groups (P gt; 0.05). Through transmission electron microscope analyses, no smoothmuscle cells were seen in neointima of TFPI group in many visual fields, but smooth muscle cells were found in neointima of two control groups. Conclusion Human TFPI gene transfection reduced intimal thickness in vein grafts.
Objective To explore the effects of overexpression of human tissue inhibitors of metalloproteinase-1 (hTIMP-1) on proliferation of human liver cancer cell line HepG2 in vitro. Methods A recombinant adenoviral vector containing full-length cDNA of hTIMP-1 was generated and transfected into HepG2. The viral titer was checked by measuring GFP, and the expression of hTIMP-1 in vitro was detected by the techniques of Western blot and semi-quantitative RT-PCR. The ultrastructure was observed by transmission electron microscope and the effects of overexpression of hTIMP-1 on proliferation of HepG2 in vitro was analyzed by MTT assay and growth curve. Results The resultant AdhTIMP-1 was successfully constructed and the expression of hTIMP-1 was detected by Western blot and RT-PCR. The growth and proliferation of HepG2, which had been transfected with AdhTIMP-1, was significantly inhibited. Conclusion The proliferation of HepG2 was markedly inhibited by recombinant adenovirus-mediated overexpression of hTIMP-1, which may pave the way for further application in liver gene therapy.
To observe the efficacy of intravitreal injection of conbercept (IVC) combined with panretinal laser photocoagulation (PRP) in the treatment of diabetic retinopathy (DR) combined with stage I and II neovascular glaucoma (NVG).MethodsA clinical case-control study. From October 2013 to March 2019, 50 eyes (50 patients) with DR and stage Ⅰ to Ⅱ NVG diagnosed in the Department of Ophthalmology, Peoples's Hospital of Xianghe were were included in the study. There were 27 eyes (27 males) and 23 eyes (23 females); all patients were monocular with the average age of 53.5±7.13 years old. Stage Ⅰ and Ⅱ NVG were 11 and 39 eyes, respectively. All patients underwent BCVA, intraocular pressure, and fundus angiography. The BCVA examination adopted the international standard visual acuity chart, which was converted to logMAR BCVA visual acuity in statistics. The patients were divided into the Conbercept+laser therapy (combination therapy) group and the laser therapy group by random number table, with 25 eyes. The age of the two groups of patients (t=0.058), gender composition ratio (χ2=0.081), logMAR BCVA (t=0.294), intraocular pressure (t=－0.070), the number of eyes with different grades of angle and iris neovascularization（χ2=1.683, 0.854）were compared, the difference was not statistically significant (P＞0.05). The changes of BCVA, intraocular pressure, iris neovascularization, and angular neovascularization were compared and observed between the two groups one week after the completion of PRP treatment, 1, 3, 6, and 9 months. Independent sample t test was used for continuous variables. Between the combination treatment group and the laser treatment group, at different time points within the two groups and the interaction of the two factors, a single-factor repeated analysis of variance was used.ResultsCompared with the results before treatment, the combined treatment group and laser treatment group had statistically significant differences in the number of angle and iris neovascularization, intraocular pressure and logMAR BCVA at different times after treatment in the combined treatment group and laser treatment group (F=124.211, 65.153, 69.249, 26.848; P＜0.001). After treatment, the combined treatment group was better than the laser treatment group in terms of the regression of eye angle and iris neovascularization, intraocular pressure and logMAR BCVA, and the difference was statistically significant (F=47.543, 25.051, 12.265, 9.994; P=0.001, 0.001, 0.001, 0.003). At different times after treatment, compared with the laser treatment group, the number of neovascularization in the iris and angle of the eye in the combined treatment group was less, the intraocular pressure was significantly decreased, and the BCVA was increased. The difference was statistically significant (P＜0.05).ConclusionThe efficacy of Kang IVC combined with PRP in the treatment of DR with stage Ⅰ and Ⅱ NVG is better than that of PRP alone.
ObjectiveTo systematically review the efficacy and safety of JAK inhibitor in the treatment of axial spondyloarthritis (axSpA). MethodsThe PubMed, Cochrane Library, Embase, CNKI, WanFang Data, and VIP databases were electronically searched to collect randomized controlled trials (RCTs) on the efficacy and safety of JAK inhibitors in patients with axSpA from inception to December, 2023. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies Meta-analysis was then performed using RevMan 5.3 software. ResultsA total of 7 RCTs involving 1 602 patients were included, including 852 patients in the experimental group and 750 patients in the placebo group. The results of meta-analysis showed that in terms of clinical efficacy, ASAS20 (RR=1.67, 95%CI 1.50 to 1.86, P<0.01), ASAS40 (RR=2.30, 95%CI 1.93 to 2.73, P<0.01), ΔBASFI (MD=?1.04, 95%CI ?1.21 to ?0.87, P<0.01), and ΔBASMI (MD=?0.30, 95%CI ?0.41 to ?0.19, P<0.01) of JAK inhibitors in the treatment of axSpA patients were significantly higher than those in the placebo group. In terms of safety, adverse event (RR=1.09, 95%CI 0.97 to 1.21, P=0.14) and major adverse events, such as diarrhea (RR=1.18, 95%CI 0.55 to 2.51, P=0.67), nasopharyngitis (RR=0.98, 95%CI 0.55 to 1.75, P=0.96), liver enzyme abnormalities (RR=1.83, 95%CI 0.84 to 3.99, P=0.13), and headache (RR=1.94, 95%CI 0.77 to 4.87, P=0.16) were statistically insignificant. ConclusionCurrent evidence shows that JAK inhibitors can improve the clinical efficacy in the axSpA patients, and the safety is high. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
ObjectiveTo observe the clinical efficiency of intravitreal Conbercept on exudative age-related macular degeneration (eAMD). MethodsThis is an open and prospective study without control trial. Twenty eyes from 20 patients (19 males and 1 female) with eAMD diagnosed by fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were enrolled in this study. Before the injection, best-corrected visual acuity (BCVA) of early treatment of diabetic retinopathy study (ETDRS), non-contact tonometer, ophthalmoscope, fundus photography, fundus fluorescein angiograph (FFA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT) were examined. The initial average letters of ETDRS acuity were 41.20±22.61, range from 8 to 80. The initial average central retina thickness (CRT) was (345.25±131.96) μm, range from 152 to 770 μm.All affected eyes were treated with intravitreal conbercept 0.05 ml (10 mg/ml). The patients were followed up for 6 to 9 months, with the mean time of (7.35±0.99) months.The BCVA, CRT after treatment were compared with baseline using paired t-test. ResultsDuring the 1, 3, 6, 12 months after treatment and the latest follow up, the mean BCVA were all improved with statistically significant difference (t=5.85, 7.09, 7.44, 7.25; P < 0.05). At 1 month ater treatment, the mean BCVA was obviously improved in 6 eyes (30%), improved in 8 eyes (40%), stable in 6 eyes (30%). At latest follow up, the mean BCVA was obviously improved in 6 eyes (30%), improved in 9 eyes (45%), stable in 5 eyes (25%). During the 1, 3, 6, 12 months after treatment and the latest follow up, the mean CRT were all decreased with statistically significant difference (t=3.34, 3.78, 3.47, 3.44; P < 0.05). At latest follow up, the leakage in macula lutea disappeared in 6 eyes (30%), decreased in 11 eyes (55%) and increased in 3 eyes (15%). No adverse events such as secondary retinal detachment or endoophthalmitis were found during the follow-up duration. ConclusionIntravitreal conbercept is a safe and effective approach for eAMD, may improve visual acuity, exudation and macular edema.
ObjectiveTo recognize the latest research progress of immunotherapy for advanced gastric cancer (AGC). MethodThe domestic and international literature on immunotherapy for AGC in recent years were retrieved and reviewed. ResultsThe immunotherapy for AGC mainly focused on immune checkpoint inhibitors (ICIs), cellular immunity, and antitumor vaccines. The most immunotherapy researched was ICIs, especially for programmed death protein-1 / programmed death protein ligand 1, cytotoxic T lymphocyte associated antigen 4, and lymphocyte activating gene 3. The cellular immunotherapy and tumor vaccine therapy were less relatively. Although immunotherapy alone did not have a particularly good effect, its therapeutic effect was not inferior to that of chemotherapy alone and the incidence of adverse reactions was lower. Moreover, most studies had concluded that the use of immunotherapy in combination with other therapy had shown a good clinical efficacy, especially in combination with anti-human epidermal growth factor receptor 2 antibody, and chimeric antigen receptor T cells targeting Claudin 18.2 site had promising results in the AGC. ConclusionsWith the development of immunotherapy research, the strategies of immunotherapy for AGC are also constantly improving. Precision medicine is important in the process of immunotherapy. Targeted screening suitable patients and adopting precise treatment can further benefit the survival of patients with AGC.
ObjectiveTo observe the efficacy of intravitreal injection of ranibizumab (IVR) and combined treatment for severe Coats disease. MethodsNineteen Coats disease patients (24 eyes) were enrolled in this retrospective non-comparative interventional clinical study. The patients included 17 males and 2 females. The age was ranged from 1 to 42 years old, with an average of (13.05±6.78) years. The patients included 15 children (age ≤14 years old) and 4 adults (age ≥18 years old). There were 13 patients with 3a stage and 6 patients with 3b stage. The treatment methods including IVR only, IVR combined with cryotherapy, IVR combined with cryotherapy and sclerotomy to drain subretinal fluid, IVR combined with vitrectomy. Treatments were repeated if it was necessary at the first day, the first week and the first month after injection. The interval between treatments was ≥1 month. Eleven patients (57.9%) underwent one treatment, 3 patients (15.8%) underwent 2 treatments, 3 patients (15.8%) underwent 3 treatments, 2 patients (10.5%) underwent 4 treatments. The treatment frequency including 22 times of IVR only, 6 times of IVR combined with cryotherapy, 5 times of IVR combined with cryotherapy and sclerotomy to drain subretinal fluid, 1 time of IVR combined with vitrectomy. The follow-up period was ranged from 6 to 36 months, with an average of (19.11±7.05) months. Visual acuity, retinal reattachment and ocular adverse events were observed. ResultsThree children (15.8%) were failing to test the visual acuity. Visual acuity was improved in 2 patients (10.5%), stable in 13 patients (68.4%) and decreased in 1 patient (5.3%). Three patients (15.8%) achieved totally retinal reattachment after treatment, while 16 patients (84.2%) achieved partially retinal reattachment. One patient had vitreous hemorrhage. One patient had neovascular glaucoma. ConclusionIVR and combined treatment were effective for severe Coats disease.
ObjectiveTo overview the systematic reviews/meta-analyses (SRs/MAs) of efficacy and safety of dipeptidyl peptidase-4 inhibitors (DPP-4) in treatment of type 2 diabetes mellitus (T2DM).MethodsDatabase including The Cochrane Library, PubMed, EMbase, CBM, WanFang Data and CNKI were searched from inception to December 2016 to collect SRs/MAs of randomized controlled trials (RCTs) of DPP-4 for the treatment of T2DM. Two reviewers independently screened literature, extracted data, and evaluated the reporting and methodological qualities using the PRISMA checklist and the AMSTAR tool.ResultsTwenty-seven SRs/MAs of DPP-4 for the treatment of T2DM were included in this overview. The average score of AMSTAR was 7.04. The worst score were the item 1 (26 studies didn't provide an ‘a priori’ design), item 4 (10 studies didn't provide whether the status of publication used as an inclusion criterion?), item 10 and item 11 (15 studies didn't assess the likelihood of publication bias and the potential conflicts of interest). The PRISMA score ranged from 17.0 to 24.5. The main problems of reporting were protocol and registration, search, additional analyses and funding.ConclusionThe evidence shows that the reporting and methodological quality of the SRs/MAs of DPP-4 inhibitors for type 2 diabetes are not high.