ObjectiveTo further evaluate the relation between usage of proton pump inhibitor (PPI) and the risk of pancreatic cancer. MethodThe observational studies were systematically searched in the databases of PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov, CNKI, Wanfang, and VIP. The combined odds ratio (OR) and 95% confidence interval (CI) of pancreatic cancer risk were estimated by the corresponding effect model according to the heterogeneous results, and the subgroup analysis, meta-regression, and sensitivity analysis were performed. In addition, the relation between the defined daily dose (DDD) and usage time of PPI and the pancreatic cancer risk were studied by using restricted cubic spline. ResultsA total of 14 studies were included, including 1 601 430 subjects. The meta-analysis result showed that usage of PPI was positively correlated with the risk of pancreatic cancer [I2=98.9%, OR (95%CI)=1.60 (1.21, 2.11), P<0.001]. The subgroup analysis results showed that usage of PPI would increase the risk of pancreatic cancer in the subgroups of literature published before 2018 [OR (95%CI)=1.88 (1.05, 3.38), P=0.034], non-Asian regions [OR (95%CI)=1.37 (1.04, 1.82), P=0.028], case-control studies [OR (95%CI)=1.59 (1.16, 2.18), P=0.004], cohort studies [OR (95%CI)=1.65 (1.13, 2.39), P=0.009], and high-quality studies [OR (95%CI)=1.62 (1.19, 2.20), P=0.002]. The dose-response curve showed that there was a nonlinear relation between the usage of PPI and the risk of pancreatic cancer (χ2linear=2.27, P=0.132; Pnonlinear=0.039). When the usage of PPI was 800 DDD or less, usage of PPI would increase the risk of pancreatic cancer, but there was no statistical significance when the usage of PPI was more than 800 DDD. The time-effect curve showed that there was a linear relation between the usage time of PPI and the risk of pancreatic cancer (χ2linear=6.92, P=0.009), and the risk of pancreatic cancer would increase by 2.3% if the usage of PPI increased by one month [OR=1.02, 95%CI (1.01, 1.04), P=0.009]. The sensitivity analysis confirmed that the results were stable by gradually eliminating each study, the OR (95%CI) of the risk of pancreatic cancer was 1.37 (1.08, 1.74) to 1.66 (1.22, 2.27), and the publication bias was not found by Egger test (P=0.594).ConclusionsFrom the results of this meta-analysis, usage of PPI will increase the risk of pancreatic cancer, and the dosage of PPI and usage time of PPI may be related to the risk of pancreatic cancer. The clinical usage of PPI should be strictly controlled, and the dosage and usage time should also be carefully considered.
【Abstract】Objective To introduce the possible effect of endogenous angiogenesis inhibitive factors in the therapy of hepatocarcinoma. Methods Recent relevant literatures were reviewed. ResultsEndogenous angiogenesis inhibitive factors can suppress the growth of tumor blood vessels, which might head off the development and metastasis of hepatocarcinoma effectively. This might provide a new approach to the therapy of hepatocarcinoma. ConclusionRecent studies on endogenous angiogenesis inhibitive factors will be helpful in the prevention and treatment of hepatocarcinoma.
ObjectiveTo evaluate the macular visual function of patients with myopic choroidal neovascularization (MCNV) before and after intravitreal injection of conbercept.MethodsA prospective, uncontrolled and non-randomized study. From April 2017 to April 2018, 21 eyes of 21 patients diagnosed as MCNV in Shanxi Eye Hospital and treated with intravitreal injection of conbercept were included in this study. There were 9 males (9 eyes, 42.86%) and 12 females (12 eyes, 57.14%), with the mean age of 35.1±13.2 years. The mean diopter was −11.30±2.35 D and the mean axial length was 28.93±5.68 mm. All patients were treated with intravitreal injection of conbercept 0.05 ml (1+PRN). Regular follow-up was performed before and after treatment, and BCVA and MAIA micro-field examination were performed at each follow-up. BCVA, macular integrity index (MI), mean sensitivity (MS) and fixation status changes before and after treatment were comparatively analyzed. The fixation status was divided into three types: stable fixation, relatively unstable fixation, and unstable fixation. The paired-sample t-test was used to compare BCVA, MI and MS before and after treatment. The x2 test was used to compare the fixation status before and after treatment.ResultsDuring the observation period, the average number of injections was 3.5. The logMAR BCVA of the eyes before treatment and at 1, 3, and 6 months after treatment were 0.87±0.32, 0.68±0.23, 0.52±0.17, and 0.61±0.57, respectively; MI were 89.38±21.34, 88.87±17.91, 70.59±30.02, and 86.76±15.09, respectively; MS were 15.32±7.19, 21.35±8.89, 23.98±11.12, 22.32±9.04 dB, respectively. Compared with before treatment, BCVA (t=15.32, 18.65, 17.38; P＜0.01) and MS (t=4.08, 3.50, 4.26; P＜0.01) were significantly increased in the eyes 1, 3, and 6 months after treatment. There was no significant difference in the MI of the eyes before treatment and at 1, 3, and 6 months after treatment (t=0.60, 2.42, 2.58; P＞0.05). Before treatment and at 1, 3, and 6 months after treatment, the proportion of stable fixation were 28.57%, 38.10%, 38.10%, 33.33%;the proportion of relatively unstable fixation were 47.62%, 47.62%, 52.38%, 57.14% and the proportion of unstable fixation were 23.81%, 14.28%, 9.52%, 9.52%, respectively. The proportion of stable fixation and relatively unstable fixation at 1, 3 and 6 months after treatment were higher than that before treatment, but the difference was not statistically significant (x2=1.82, 1.24, 1.69; P＞0.05).ConclusionBCVA and MS are significantly increased in patients with MCNV after intravitreal injection of conbercept.
Objective To explore the inhibitory effects of r-k4k5 on retinal neovascularization. Methods Eighty-eight one-week-old C57BL/6J mice were put into the environment with 75% oxygen for 5 days to establish models of vascular proliferation retinopathy. One eye of each mouse received an intravitreal injection of 500 ng of r-k4k5 (large-dosage group) and of 250 ng of r-k4k5(small-dosage group), and the same volume of BSS was injected into the other eye of the mice both in these two groups as a control. The ADPase histochemical staining was used for retinal flatmount to observe changes of retinal vessels. The inhibitory effects of r-k4k5 on retinal neovascularization were evaluated by counting the endotheliocyte nuclei of new vessels extending from retina to vitreous in the tissue-slice. Results Regular distributions and reduced density of retinal blood vessels in eyes in the treatment group were found in retinal flatmount. The number of the endotheliocyte nuclei of new vessels extending from retina to vitreous was less in the eyes in the treatment group than which in control group (Plt;0.001). The nuclei of new blood vessels in the large-dosage group were less than which in small-dosage group (Plt;0.001). No histologic evidence of retinal toxicity or inflammatory response was found in the tissue-slice after the injection of r-k4k5. Conclusions Retinal neovascularization can be inhibited by intravitreal injection of r-k4k5,which suggests that intravitreal injection of r-k4k5 may have potential therapeutic benifits in retinal vascular disease. (Chin J Ocul Fundus Dis，2003，19：121-124)
In the expert consensus published by the Pediatrics in 2013, it was first proposed that anti-VEGF drugs can be considered for retinopathy of prematurity (ROP) with stage 3, zone Ⅰ with plus disease. However, there are many problems worth the attention of ophthalmologists, including the advantages and disadvantages of anti-VEGF therapy compared with traditional laser therapy, systemic and ocular complications after anti-VEGF therapy, and what indicators are the end points of anti-VEGF therapy. Combined with this consensus and numerous research findings, we recommend that the first treatment for anti-VEGF or laser therapy should be considered from disease control effects. For the threshold and pre-threshold lesions, the effect of anti-VEGF therapy for zoneⅡ lesions is better than that for zone Ⅰ lesions and the single-time effective rate is high. So, it is suggested that anti-VEGF therapy should be preferred for the first treatment. The choice of repeat treatment should be considered from the final retinal structure and functional prognosis. Laser therapy is advisable for the abnormal vascular regression slower and abnormalities in the posterior pole. It can reduce the number of reexaminations and prolong the interval between re-examinations. However, the premature use of laser has an inevitable effect on peripheral vision field. Excluding the above problems, supplemental therapy can still choose anti-VEGF therapy again. Most of the children with twice anti-VEGF therapy are sufficient to control the disease. Anti-VEGF therapy should be terminated when there are signs such as plus regression, threshold or pre-threshold lesions controlled without recurrence, peripheral vascularization, etc.
Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis, typically as chronic anterior uveitis with insidious onset. Delayed and inadequate treatment may result in loss of patients' vision and even blindness. For refractory or severe uveitis related to juvenile idiopathic arthritis, systemic immunosuppressive agents should be used as early as possible. With the advantage of controlling ocular inflammation, avoiding ocular complications and reducing the use of traditional immunosuppressant drugs and glucocorticoid, tumor necrosis factor-α inhibitors have been new therapeutic options for uveitis associated with juvenile idiopathic arthritis, although methotrexate is known as the first-line approach. However, there are no internationally unified guidelines for clinical issues regarding the timing of application, reduction and withdrawal of tumor necrosis factor-α inhibitors, and no agreement on the application of tumor necrosis factor-α inhibitors in the management of ocular complications either. An in-depth understanding of the application status and progress of tumor necrosis factor alpha inhibitors in the treatment of juvenile idiopathic arthritis-associated uveitis has important clinical significance.
Objective To observe the effect of celecoxib on the expression vascular endothelial growth factors (VEGF) in diabetic rats. Methods Thirty-six wistar rats were used to establish the diabetic models by intraperitoneal injection with streptozotocin. The diabetic rats were divided into 2 groups: diabetic group (n=18) and celecoxib group (n=18). Celecoxib (50 mg/kg) was administered orally to the rats in celecoxib group and the physiological saline with the same volume was given orally to the rats in diabetic group. Eighteen else rats were in normal control group. All of the rats were executed 3 months later. The expression of VEGF protein was detected by immunohistochemistry method. Reverse transcription-polymerase chain reaction（RT-PCR） analysis was used to examine the expression of retinal VEGF mRNA and cyclooxygenase-2 mRNA. Results Lower positive expression of VEGF mRNA and cyclooxygenase-2 mRNA, weakly positive action of immunohistochemistry of VEGF, and lower expression of VEGF protein were detected in normal control group; in the diabetic group, the expression of VEGF mRNA and cyclooxygenase-2 mRNA increased obviously comparing with which in the control group (Plt;0.05), and the bly positive action of immunohistochemistry of VEGF and increased expression of VEGF protein were detected (Plt;0.01); in celecoxib group, the expression of VEGF mRNA was lower than that in the diabetic group (Plt;0.05), the expression of cyclooxygenase-2 mRNA didnprime;t decrease much (Pgt;0.05), the positive action of immunohistochemistry of VEGF decreased, and the expression of VEGF protein decreased (Plt;0.01). Conclusion By inhibiting the activation of cyclooxygenase-2, celecoxib can inhibit the expression of retinal VEGF mRNA and protein in diabetic rats induced by streptozotocin. (Chin J Ocul Fundus Dis,2007,23:265-268)
Objective To observe the inhibitory effect of kallikrein-binding protein (KBP) on choroidal neovascularization. Methods Forty Brown Norway rats were randomly divided into the KBP groups and the control group, 20 rats in each group, the right eye as the experimental eye. The rats were photocoagulated by 532 nm laser to induce CNV model. One week after laser photocoagulation, the rats were received FFA examination. At the second day after FFA examination, the rats of KBP group were received an intravitreal injection of KBP 5 mu;l (4 mg/ml KBP). The same volume of deionized water was injected into the rats in the control group. The rats of two groups received FFA examination at one, two and three weeks after injection. The expressions of vascular endothelial growth factor and pigment epithelium derived factor were observed using hematoxylin and eosin stain and immunohistochemistry stain. CNV leakage area and the cumulative absorbance of laser spot area were analyzed by Image-Pro plus 6.0 software. Results FFA examination showed that there were CNV and fluorescence leakage at one week after laser photocoagulation; one, two and three weeks after injection, the leakage decreased gradually in KBP group, but increased with time in control group. Compared with control group, the spot area and CNV in KBP group reduced gradually, but CNV was always there in control group. The differences of VEGF (F=1.29) and PEDF (F=6.29) expressions at one week after laser photocoagulation were not statistically significant (P＞0.05). The differences of VEGF and PEDF expressions at one, two and three weeks after injection were statistically significant（VEGF:F=14.16,66.89,24.34; PEDF：F=4.22,62.04,233.05;P＜0.001）.Conclusion Intravitreal injection with KBP can inhibit CNV.
Interleukin-18 is an inactive precursor which lacks a signal peptide, it has a role in regulating retinal pathological angiogenesis. It also inhibits experimental choroidal neovascularization (CNV) via interferon-γand thrombospondin-1. Currently little is known about its mechanisms of inhibition for CNV, may be speculated to be due to effects of anti-angiogenesis, down-regulates vascular permeability and lower vascular endothelial growth factor (VEGF) levels via directly acting on the vascular endothelial cell and epithelial cells. Exogenous administration of mature recombinant interleukin-18 has no adverse effect on retinal pigment epithelial cell viability. In addition, the anti-VEGF role of interleukin-18 is tested to be safe and effective for humans. Interleukin-18 alone or in combination with anti-VEGF shows to be a good prospect for improving the prognosis of experimental CNV. However, more large clinical studies are required to confirm the exact efficacy of interleukin-18 for CNV.
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.