Interleukin 37 (IL-37) is an important regulator of the anti-inflammatory T-cell response. In this study, we investigated its expression and function in peripheral blood mononuclear cells (PBMCs) of patients with HLA-B27 associated acute anterior uveitis (AAU) and idiopathic AAU.15 patients with HLA-B27-associated AAU, 10 patients with idiopathic AAU and 22 controls were recruited to this study from August 2013 to December 2016. Complete ophthalmological examinations were performed and clinical features were clearly documented. Blood samples were collected and peripheral blood mononuclear cells were extracted. IL-37 messenger RNA (mRNA) and protein expression in peripheral blood mononuclear cells (PBMCs) were examined by performing RT-PCRs and western blot, respectively. Cytokines in the supernatants of stimulated dendritic cells (DCs) with IL-37 were assayed by multiplex immunoassay.An increased level of IL-37 mRNA and protein expression by PBMCs was found in the patient group with clinically active AAU compared to controls. There was no significant difference in IL-37 mRNA and protein expression levels between HLA-B27 associated AAU and idiopathic AAU. IL-37 significantly inhibited the production of IL-1β, IL-6, IL-10, IL-21, IL-23, TNF-α and IFN-γ. IL-37 levels of mRNA and protein expression showed a significant positive correlation with disease activity.Elevated IL-37 expression is associated with disease activity in HLA-B27 associated AAU and idiopathic AAU. IL-37 can inhibit proinflammatory cytokine productions in AAU. Manipulation of IL-37 may offer a new therapeutic target for these entities.
Whether exercise-induced venous-to-systemic shunt (EIS) during cardiopulmonary exercise testing (CPET) has different manifestations or characteristics in idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients remains unknown. We explored the differences in hemodynamics, echocardiography, and prognosis between IPAH and CTEPH patients with and without EIS.We conducted a retrospective cross-sectional cohort study and included 161 PH patients at Shanghai Pulmonary Hospital. Demographic, echocardiography, pulmonary hemodynamic, and CPET variables were compared between patients with and without EIS stratified by IPAH and CTEPH. EIS was determined by CPET. Binary logistic regression analyses were performed to explore independent influencing factors of EIS. Cox survival analysis was used to quantify the impact of EIS on the prognosis of patients.Exercise-induced venous-to-systemic shunt was found in approximately 17.4% of 86 IPAH patients and 20% of 75 CTEPH patients. All-cause mortality occurred in 43 (26.7%) patients during a median follow-up of 6.5 years. Compared with those without EIS, patients with EIS had higher peak end-tidal O2 and lower VO2/VE and tricuspid annular plane systolic excursion (TAPSE). Among the IPAH patients, EIS was associated with lower cardiac output, cardiac index, mixed venous oxygen saturation, VO2/VE, and TAPSE and higher VE/VCO2 and right ventricular end-diastolic transverse diameter. Logistic regression analysis indicated that VO2/VE was an independent factor influencing whether IPAH patients developed EIS during CPET. Cox logistic regression indicated that female IPAH patients or IPAH patients with higher VO2/VE and EIS had a better prognosis. Female IPAH patients had better 10-year survival. In IPAH patients without EIS, patients with higher VO2/VE had better 10-year survival. However, compared with CTEPH patients without EIS, those with EIS had similar echocardiographic, hemodynamic, CPET parameter results and 10-year survival.Exercise-induced venous-to-systemic shunt exhibits different profiles among IPAH and CTEPH patients. Among IPAH patients, those with EIS had worse peak end-tidal O2, VO2/VE, and TAPSE than those without EIS. VO2/VE was an independent factor of EIS among IPAH patients. IPAH patients with EIS, female sex or higher VO2/VE had better survival. However, the association between EIS and PAH severity or prognosis in CTEPH patients needs to be further explored.
Purpose. To describe the clinical manifestations and treatment outcomes of syphilitic uveitis in a Chinese population. Methods. This is a retrospective case series of 15 consecutive patients with syphilitic uveitis treated at a uveitis referral center between 2012 and 2015. Results. Fifteen patients were diagnosed with syphilitic uveitis based on positive serological tests. Nine patients were male. Coinfection with human immunodeficiency virus was detected in two patients. Twenty eyes presented with panuveitis and all patients had posterior involvement. The most frequent manifestations were retinal vasculitis and papillitis, while syphilitic posterior placoid chorioretinitis was only found in three eyes. All patients received systemic penicillin therapy according to CDC guidelines. Nine patients were misdiagnosed before presenting to our center and the delay in treatment with penicillin was associated with poor final visual outcomes (P < 0.05). Conclusions. In our series, both male and female were almost equally affected and coinfection of syphilis with human immunodeficiency virus was uncommon. All patients in this study had posterior involvement and the most common manifestations were retinal vasculitis and papillitis. Syphilis should be considered as an important differential diagnosis especially for posterior uveitis and panuveitis. Early diagnosis and appropriate treatment are important for visual prognosis.
Objective To analyze the change of tear film after phacoemulsification in patient with renal transplantation and discuss the problem of dry eye.Methods A non-randomized cases-controlled study was designed.26 cataract patients with renal transplantation (the experimental group) (34 eyes) and matched 33 patients (40 eyes) with age-related cataract(control group) were included in this study.Before and after different time phacoemulsification and IOL implantation respectively was performed on the all patients,dry eye-related symptom was surveyed and scored by questionnaire,and tear film break-up time (BUT),Schirmer I test (SIt) and corneal fluorescein (FL) were examined.Results The experimental group is significantly heavier than control group obviously postoperatively in patients with dry eye symptom score,FL,BUT,the overall differences were statistically significant(P ＜ 0.05),but after 3 months FL preoperatively with no significant difference (P ＞ 0.05).Conclusion Tear film function of renal transplantation patients is poor after cataract phacoemulsification.And are susceptible population for dry eye.Dry eye appears more early and severer in renal transplantation patients after phacoemulsification combined with IOL implantation.
Key words:
Renal transplantation; Cataract ; Phacoemulsification; Dry eye
The survival of patients with pulmonary arterial hypertension is closely related with right ventricular function. During the progression of right ventricular remodeling, energetic metabolism shifts from oxidative mitochondrial metabolism to glycolysis. In normal physiological conditions, cardiomyocytes use major sources of glucose and fatty acids to sustain a continuous systolic workload and energy supply. This allows the heart to choose the most efficient substrate to response to environmental stimuli. Therefore, ATP production of glucose is the preferred energy source than fatty acids in right ventricular remodeling. However, the metabolic fate of glucose altered because mitochondrial metabolism is actively suppressed. Metabolic shift towards aerobic glycolysis and down-regulation of mitochondrial oxidation, is called the Warburg effect. Studies on animal models and human RVF suggest that there is reduced glucose oxidation and increased glycolysis in both adaptive and maladaptive right ventricular failure. Accordingly, a gate-keeping enzyme, pyruvate dehydrogenase kinase (PDK) is activated and inhibited pyruvate into the mitochondria with increased lactate dehydrogenase. Therefore, augmentation of glucose oxidation is beneficial in right ventricular remodeling and can be achieved by inhibition of PDK and fatty acid oxidation. As a PDK inhibitor, Dicholoracetate (DCA) can reduce pyruvate dehydrogenase phosphorylation and partially restore RV structure and function by promoting glucose and mitochondrial oxidation. Moreover, the partial inhibitors of fatty acid oxidation would be offered the utilization to improve right ventricular function. Although metabolic targeting drugs can be beneficial to right ventricular remodeling, the advantage of modulating metabolic shift into an enhanced clinical performance still remains to be determined. Keywords: Pulmonary arterial hypertension, right ventricular remodeling, mitochondrial metabolism, metabolic shift, glycolysis.
Abstract BACKGROUND: Platelet distribution width (PDW) has been recognized as risk predictors of idiopathic pulmonary arterial hypertension. This study aims to investigate whether in-hospital PDW would be useful to predict all-cause death in patients with severe pulmonary hypertension due to chronic lung diseases (CLD-PH). METHODS: Early in-hospital PDW was measured in 67 severe CLD-PH patients who were confirmed by right heart catheterization and followed up. Event-free survival was estimated using the Kaplan–Meier method and analyzed with the log-rank test. Cox proportional hazards models were performed to determine the association between the PDW level and all-cause death. RESULTS: Pulmonary function test and echocardiography parameters were different among patients divided by 17% (the upper reference range of the PDW). There were no significant differences in both clinical variables and RHC parameters among patients with PDW ≥ or < 17%. During median of 2.4 (2.5, 3.7) years of follow-up, 44 patients died. A significant association was noted between in-hospital PDW level and the adjusted risk of all-cause mortality (hazard ratio [HR], 1.245; 95% confidence interval [CI], 1.099-1.409). Compared with those with PDW < 17%, the HR for all-cause death increased to 5.067 (95% CI: 2.420-10.609, P < 0.001) among patients with PDW ≥ 17 %. Higher levels of PDW were also associated with increased risk of all-cause death. CONCLUSIONS: In-hospital PDW was independently associated with all-cause death in patients with severe CLD-PH. This potentially could be used to estimate the severity of severe CLD-PH.
There is little evidence of the effectiveness of switching from the endothelin receptor antagonists (ERAs) bosentan and ambrisentan to a novel ERA, macitentan, in patients with pulmonary arterial hypertension (PAH). Therefore, a systematic review and meta-analysis was performed to evaluate the efficacy and safety of patients with PAH switching from other ERAs to macitentan.We retrieved the relevant literature published before January 2022 for the meta-analysis from the PubMed, EMBASE, and Cochrane Library databases. Efficacy included changes in the 6-min walk distance (6MWD), World Health Organization functional class (WHO-FC), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, hemodynamics, echocardiography and survival.Nine studies, consisting of 408 PAH patients, that met the inclusion criteria were included. The switch from bosentan or ambrisentan to macitentan effectively increased the 6MWD by 20.71 m (95% CI: 10.35-31.07, P < 0.00001, I2 = 0%). Six months after conversion, the tricuspid annular plane systolic excursion was found to improve from 19.0 ± 4.0 to 21.0 ± 5.0 mm in adults and from 16.00 ± 5.0 to 18.25 ± 4.8 mm in children. Ordinal logistic regression showed that the WHO-FC significantly improved by 0.412 (95% CI: 0.187-0.908, P = 0.028). The switch did not show significant improvement in NT-proBNP levels. In addition, the switch was well tolerated.The switch from bosentan or ambrisentan to macitentan significantly increased the 6MWD in PAH patients, improved the WHO-FC, and exerted safety benefits. The effects of the switch on NT-proBNP levels, hemodynamics, and echocardiography still need to be further confirmed.[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021292554].
To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10- and 15-μg bimatoprost implant in subjects with open-angle glaucoma (OAG) and ocular hypertension (OHT) after initial and repeated administrations.Randomized, 20-month, multicenter, subject- and efficacy evaluator-masked, parallel-group, phase 3 clinical study.Adults with OAG or OHT in each eye, open iridocorneal angle inferiorly in the study eye, and study eye baseline IOP (hour 0; 8 am) of 22-32 mmHg after washout.Study eyes received bimatoprost implant 10 μg (n = 198) or 15 μg (n = 198) on day 1 with readministration at weeks 16 and 32, or twice-daily topical timolol maleate 0.5% (n = 198). Intraocular pressure was measured at hours 0 and 2 at each visit.Primary end points were IOP and change from baseline IOP through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD).Both dose strengths of bimatoprost implant were noninferior to timolol in IOP lowering after each administration. Mean diurnal IOP was 24.0, 24.2, and 23.9 mmHg at baseline and from 16.5-17.2, 16.5-17.0, and 17.1-17.5 mmHg through week 12 in the 10-μg implant, 15-μg implant, and timolol groups, respectively. The incidence of corneal and inflammatory TEAEs of interest (e.g., corneal endothelial cell loss, iritis) was higher with bimatoprost implant than timolol and highest with the 15-μg dose strength. Incidence of corneal TEAEs increased after repeated treatment; with 3 administrations at fixed 16-week intervals, incidence of ≥20% CECD loss was 10.2% (10-μg implant) and 21.8% (15-μg implant). Mean best-corrected visual acuity (BCVA) was stable; 3 implant-treated subjects with corneal TEAEs had >2-line BCVA loss at their last visit.Both dose strengths of bimatoprost implant met the primary end point of noninferiority to timolol through week 12. One year after 3 administrations, IOP was controlled in most subjects without additional treatment. The risk-benefit assessment favored the 10-μg implant over the 15-μg implant. Ongoing studies are evaluating other administration regimens to reduce the potential for CECD loss. The bimatoprost implant has potential to improve adherence and reduce treatment burden in glaucoma.
To establish an easy and repeatable method for determination of pulmonary vascular resistance in normal and pulmonary arterial hypertension (PAH) rats.Forty-five Sprague-Dawley rats were randomly assigned into three groups: control group, low dose monocrotaline (MCT) group (50 mg/kg) and high dose MCT group (60 mg/kg). Rats in PAH groups received single subcutaneous injection of MCT. We measured pulmonary artery pressure by right heart catheterization using an improved hand-made PE-50 catheter. Cardiac output was calculated through thermodilution method. Pulmonary vascular resistance equals the mean pulmonary artery pressure divided by cardiac output.The total percentages of success to detect pulmonary artery pressure, cardiac output and pulmonary vascular resistance were 98%, 100% and 96% respectively in 3 groups. Twenty-one days after MCT injection, mean pulmonary artery pressure significantly increased in MCT group compared to control group [(43.1 ± 0.8), (54.8 ± 2.2) vs. (17.4 ± 1.0) mm Hg (1 mm Hg = 0.133 kPa), P < 0.001], and the mPAP was also significantly higher in high dose MCT group than in low dose MCT group (P < 0.001). Cardiac output was significantly lower in PAH rats than in control rats [(77.5 ± 6.9), (71.0 ± 6.7) vs. (126.8 ± 3.9) ml/min, P < 0.001]. Pulmonary vascular resistance was significantly increased in PAH rats compared with control rats [(0.56 ± 0.06), (0.76 ± 0.08) vs. (0.13 ± 0.01) mm Hg×min(-1)×ml(-1), P < 0.001]. There were significant differences in both MCT-treated groups (P = 0.01).Pulmonary vascular resistance in rats could be reliably detected using the improved hand-made PE-50 right heart catheter.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)