Objectives To assess the effects of alpha-glucosidase inhibitors in patients with type 2 diabetes mellitus. Method We searched The Cochrane Library, MEDLINE, EMBASE, Current Contents, LILACS, databases of ongoing trials, reference lists of reviews on the topic of alpha-glucosidase inhibitors and we contacted experts and manufacturers for additional trials. Date of most recent search: December 2003 (Current Contents) and April 2003 (other databases). Randomised controlled trials of at least 12 weeks duration comparing alpha-glucosidase inhibitor monotherapy in patients with type 2 diabetes with any other intervention and that included at least one of the following outcomes: mortality, morbidity, quality of life, glycemic control, lipids, insulin levels, body weight, adverse events. Two reviewers read all abstracts, assessed quality and extracted data independently. Discrepancies were resolved by consensus or by the judgement of a third reviewer. A statistician checked all extracted data entrance in the database. We attempted to contact all authors for data clarification. Results We included 41 trials (8130 participants), 30 investigated acarbose, seven miglitol, one trial voglibose and three trials compared different alpha-glucosidase inhibitors. Study duration was 24 weeks in most cases and only two studies lasted amply longer than one year. We found only few data on mortality, morbidity and quality of life. Acarbose had a clear effect on glycemic control compared to placebo: glycated haemoglobin –0.77% (95% confidence interval –0.90 to –0.64), fasting blood glucose –1.1 mmol/L (95% confidence interval –1.4 to –0.9), post-load blood glucose –2.32 mmol/L (95% confidence interval –2.73 to –1.92). The effect on glycated haemoglobin by acarbose was not dose-dependent. We found a decreasing effect on post-load insulin and no clinically relevant effects on lipids or body weight. Adverse effects were mostly of gastro-intestinal origin and dose dependent. Compared to sulphonylurea, acarbose decreased fasting and post-load insulin levels by –24.8 pmol/L (95% confidence interval –43.3 to –6.3) and –133.2 pmol/L (95% confidence interval –184.5 to –81.8) respectively and acarbose caused more adverse effects. Conclusions It remains unclear whether alpha-glucosidase inhibitors influence mortality or morbidity in patients with type 2 diabetes. Conversely, they have a significant effect on glycemic control and insulin levels, but no statistically significant effect on lipids and body weight. These effects are less sure when alpha-glucosidase inhibitors are used for a longer duration. Acarbose dosages higher than 50 mg TID offer no additional effect on glycated haemoglobin but more adverse effects instead. Compared to sulphonylurea, alpha-glucosidase inhibitors lower fasting and post-load insulin levels and have an inferior profile regarding glycemic control and adverse effects.
Objective Risk factors for real-word immune checkpoint inhibitor-related pneumonitis in patients with lung cancer were analyzed by systematic analysis. Methods Computerized retrieval of PubMed, EMbase, Web of Science, the Cochrane Library , WanFang Data, CNKI and VIP databases was carried out. Studies were collected from the database establishment to March 2023. Three researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Meta-analysis was performed using RevMan5.4.1software. Results A total of 18 studies were included with a total of 4 990 patients. The results of meta-analysis showed that, interstitial pneumonia [odds ratio (OR)=9.32, 95% confidence interval (CI) 4.66 - 18.67, P<0.01], smoking history (OR=2.39, 95%CI 1.29 - 4.45, P<0.01), chronic obstructive pulmonary disease (COPD) (OR=5.54, 95%CI 2.96 - 10.36, P<0.01), chest radiotherapy (OR=2.74, 95%CI 1.80 - 4.19, P<0.01), pulmonary fibrosis (OR=7.46, 95%CI 4.25 - 13.09, P<0.01), high programmed death ligand 1 (PD-L1) expression (OR=2.98, 95%CI 1.71 - 5.22, P<0.01), high absolute eosinophil count (AEC) (OR=3.92, 95%CI 2.17 - 7.08, P<0.01) and pembrolizumab (OR=2.90, 95%CI 1.56 - 5.37, P<0.01) were independent risk factors for immune checkpoint inhibitor-related pneumonitis in lung cancer patients. Conclusions Interstitial pneumonia, smoking history, COPD, Chest radiotherapy, pulmonary fibrosis, high PD-L1expression, high AEC and pembrolizumab are independent risk factors for immune checkpoint inhibitor-related pneumonitis in lung cancer patients. Due to insufficient evidence on the risk factors of low albumin, more studies are needed to further identify it.
PURPOSE:To investigale the influence of orally administered aldose reduetace inhibitor(ARI) and myo-inositol (MI)for contents of gluecose,sorbitol and myo-inositol in experimental diabetic retinal tissue in rat. METHODS :The STZ-induced diabetic rats were administered ARI or MI by oral. The glucose sorbitol and myo-inositol in retinal tissues were analysed by high performance liquid chromatography after experimental period of 6 montbs. RESULTS:It was found that the contents of glucose and sorhitol were increased and myo inosltol was decreased in diabetic group. In diabetes with ARI group.the content of sorbitol was increased although the glucose was in high level. In diabetes wilb MI group,the sorbitol accumulaled and coment of myo-inositol was close to the normal control group. CONCLUSIONS:The ARI can effectively obstruct sorbitol accumulation in retina. MI increase myo-inositol level but fail to reduce sorbitol contenl of retina. （Chin J Ocul Fundus Dis,1997,13: 75-77 ）
ObjectiveTo observe the effects of repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs on vitreous macular interface (VMI) in patients with exudative age-related macular degeneration (AMD).MethodsRetrospective study. Thirty-four exudative AMD patients who treated with intravitreal anti-VEGF drugs were included in this study. There were 26 males and 8 females. The age ranged from 50 to 80 years, with the average of (62.8±8.35) years. The eyes with at least 6 treatments during the 1-year follow-up were taken as the study eyes, and the eyes with no anti-VEGF drug treatment were the control eyes. Optical coherence tomography (OCT) examination was used to observe the VMI status of both eyes before treatment. Vitreous macular adhesion (VMA), macular epiretinal membrane (MEM), and complete vitreous detachment (C-PVD) were defined as abnormalities in VMI. The VMA was classified as focal (≤1500 μm) and broad (＞1500 μm) depending on the diameter of the vitreous and macular adhesions on the OCT images. Before treatment, there were 12 eyes with abnormal VMI in study eyes, including 8 eyes with broad VMA, 3 eyes with focal VMA, and 1 eye with MEM; 12 eyes with abnormal VMI in control eyes: broad VMA in 7 eyes, focal VMA in 2 eyes, C-PVD in 2 eyes, and MEM in 1 eye. The average follow-up time after treatment was 16.4 months. During the follow-up period, OCT was performed monthly in a follow-up mode. Comparing the changes on VMI between before and after treatment in both eyes of patients, respectively. The chi-square test was used to compare the difference on VMI. Because the number of samples was ＜40, Fisher's exact test was used for the analysis.ResultsAt the final follow-up, 12 eyes with abnormal VMI in the study eyes, including 5 eyes with broad VMA, 2 eyes with focal VMA, 3 eyes with C-PVD, and 2 eyes with MEM. There were 6 eyes altered comparing with baseline. In the control eyes, there were 13 eyes with abnormal VMI, including 5 eyes with broad VMA, 7 eyes with C-PVD, and 1 eye with MEM. A total of 6 eyes changed on VMI comparing with baseline. At the final follow-up, there was no significant difference on VMI changes between the study eyes and its corresponding control eyes (P=0.053). In all eyes, a total of 4 eyes changed from focal VMA to C-PVD at the final follow-up, accounting for 80.0% of the total focal VMA; 3 eyes changed from broad VMA to C-PVD, accounting for 21.4% of the total broad VMA.ConclusionsRepeated anti-VEGF treatment has little effect on VMI. Regardless of anti-VEGF therapy, eyes with focal VMA appears to be more prone to C-PVD than the broad one.
ObjectiveTo review the present situation of immune checkpoint inhibitors in treatment of advanced hepatocellular carcinoma (HCC), and discuss the advance of combined immunotherapy.MethodsThe relevant literatures on researches of immune checkpoint inhibitors in the treatment of advanced HCC were retrieved to make an review.ResultsImmunotherapy intervention had been becoming a novel and promising therapeutic approach for HCC, which could suppress the progression of aggressive tumor and could inhibit tumor recurrence and metastasis shown in some pre-clinical trials. Other studies had found that the combined strategy of specific immunotherapy and conventional therapies could significantly improve the clinical outcomes of HCC patients.ConclusionCombined immunotherapy can significantly improve the clinical outcomes of HCC and benefit more patients with advanced HCC.
Objective To analyze the clinical features of immune checkpoint inhibitor-related pneumonia (CIP) in patients with lung cancer. Methods The case data of patients with CIP admitted to Zhongshan Hospital of Fudan University from January 2017 to December 2020 were retrospectively collected, and the basic data, clinical manifestations, imaging data, laboratory examination results, treatment and prognosis of the patients were analyzed. Results The ratio of male to female was 18:1, and the median age was 65 years (from 41 to 74 years). Fourteen patients received a programmed death protein-1 (PD-1) inhibitor and five patients received a programmed death protein-ligand-1 (PD-L1) inhibitor. The median time to CIP was 3.5 months. The respiratory symptoms of 15 patients were dyspnea in 11 cases, cough in 9 cases, chest tightness in 8 cases, fever in 4 cases, expectoration in 4 cases and hemoptysis in 2 cases. Chest CT findings mainly showed interstitial pneumonia, including 8 cases of implicit organizational pneumonia (COP), 7 cases of non-specific interstitial pneumonia (NSIP), 2 cases of acute interstitial pneumonia, and 2 cases of allergic pneumonia. C-reactive protein, erythrocyte sedimentation rate and lactate dehydrogenase were higher in CIP than before, and the difference was statistically significant. Follow-up observation was performed in 3 patients alone, 14 patients were treated with glucocorticoid alone, 2 patients were treated with immunosuppressant therapy, 19 patients had stable or more absorption of pneumonia lesions, and 5 patients had restarted immunotherapy. There were no deaths from CIP. Conclusions CIP mainly occurs in men, with slow onset, lack of specificity in clinical manifestations, and increased inflammatory indicators. Imaging findings are mainly NSIP and COP changes. Early identification, diagnosis and rational application of glucocorticoid therapy have good effects.
Objective To investigate the intervention effect of 3-phosphoinositede dependent protein kinase-1 (PDK1) inhibitor on prostaglandin E2 (PGE2) in smoking-induced chronic obstructive pulmonary disease (COPD) mice. Methods Fifty C57BL/6 male mice were randomly divided into normal control group, smoking group, smoking +low dose PDK1 inhibitor group, smoking + medium dose PDK1 inhibitor group and high dose PDK1 inhibitor group with 10 mice in each group. The mice in the normal control group inhaled phosphate-buffered saline twice a day for 12 weeks, and the mice in the smoking group were fumigated twice a day, 5 days per week for 12 weeks, and the other three groups were given intraperitoneal injection of low-dose PDK1 inhibitor OSU-03012 (0.25 mg/kg), medium-dose PDK1 inhibitor (0.5 mg/kg) and high-dose PDK1 inhibitor (1.0 mg/kg) respectively before smoking. After smoking, lung function was tested, the bronchoalveolar lavage fluid (BALF) of each mouse was taken for cell count, the PGE2 in serum and BALF of mice was determined by enzyme linked immunosorbent assay, and the lung tissue of mice was sectioned with paraffin and stained by hematoxylin-eosin (HE), and pathological changes were observed under microscope. Results Compared with the control group, FEV100/FVC and FEV200/FVC of the mice in each smoking group were significantly decreased (P<0.05); The number of cells in BALF of smoking group was significantly higher than that of normal control group (P<0.05). There was no significant difference in the total number of BALF cells, the proportion of neutrophils and macrophages between the smoking + low-dose PDK1 inhibitor group and the smoking group. However, the total number of BALF cells and the proportion of neutrophils in the smoking + medium dose PDK1 inhibitor group and the high dose PDK1 inhibitor group gradually decreased, while the proportion of macrophages gradually increased, compared with the normal control group, the PGE2 concentrations of serum and BALF in the smoking group and the smoking + PDK1 inhibitor group were significantly higher than those in the control group. Compared with the smoking group, the PGE2 concentrations of serum and BALF in the middle and high dose PDK1 inhibitor groups were significantly lower than those in the smoking group. HE staining of lung tissue showed that there were a large number of inflammatory cell infiltration, alveolar cavity dilatation, alveolar wall rupture and fusion, alveolar formation, significant decrease in the number of alveoli and other pathological changes in the smoking group, which were consistent with the pathological changes of COPD. The inflammatory cell infiltration, mucus obstruction and alveolar dilatation were slightly alleviated in the smoking + low-dose PDK1 inhibitor group, while the inflammatory cell infiltration, alveolar wall thinning and alveolar dilatation were improved in both the medium-dose inhibitor group and the high-dose inhibitor group, and the improvement was more obvious in the high-dose inhibitor group. Conclusion The lung function of the smoked COPD mouse decreases, the airway inflammation is obvious, and the secretion of PGE2 is also increased, while the use of PDK1 inhibitor could reduce the secretion of PGE2, reduce airway inflammation and pathological changes, and improve lung function in a dose-dependent manner.
The therapeutic effect of anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) was determined by a number of factors. Comprehensive thorough analysis of clinical features, imaging results and treatment response can predict the potential efficacy and possible vision recovery for the patient, and also can optimize the treatment regime to make a personalized therapy plan. Precise medicine with data from genomics, proteomics and metabolomics study will provide more objective and accurate biology basis for individual precise treatment. The future research should focus on comprehensive assessment of factors affecting the efficacy of anti-VEGF therapy, to achieve individualized precise diagnosis and treatment, to improve the therapeutic outcome of nAMD.
Objective To evaluate the correlation between antiphospholipid (APLA) antibodies and retinal vein occlusion (RVO). Methods A computerized search was conducted in the Pubmed, Chinese Biological Medicine Database, China National Knowledge Infrastructure, VIP database, Wanfang Database combined with manually searching of literature reference proceedings. The search time was ranged from establishment of each database to August 1st, 2012. After the data extraction, quality of RCT was assessed. The meta analysis was performed by Stata 11.0. Results In total, 12 case-control studies (1324 subjects) that fulfilled the eligibility criteria were included in the meta-analysis involving 505 patients in RVO group and 819 subjects in control group. The odds ratio (OR) and 95% confidence interval (CI) of APLA, anticardiolipin antibodies (ACA), lupus coagulation inhibitor and RVO were 5.01 and 3.33 - 7.53,4.38 and 2.38 - 8.05, 1.72 and 0.73 - .88, 6.02 and 2.06 - 17.63, respectively. The OR and 95% CI of APLA, ACA, lupus coagulation inhibitor and branch RVO were 4.22 and 1.67 - 10.63, 3.69 and 1.32 - 10.32, 2.07 and 0.79 - 5.41, respectively. Conclusions APLA may increase the rick of RVO, especially ACA has a prediction function to RVO. It is necessary to screening for APLA in RVO patients.
The ‘glial scar’ has been widely studied in the regeneration of spinal cord injury (SCI). For decades, mainstream scientific concept considers glial scar as a ‘physical barrier’ to impede axonal regeneration after SCI. Moreover, some extracellular molecules produced by glial scar are also regarded as axonal growth inhibitors. With the development of technology and the progress of research, multiple lines of new evidence challenge the pre-existing traditional notions in SCI repair, including the role of glial scar. This review briefly reviewed the history, advance, and controversy of glial scar research in SCI repair since 1930s, hoping to recognize the roles of glial scar and crack the international problem of SCI regeneration.