Immune checkpoint inhibitors (ICIs) have been approved for the treatment of urothelial carcinoma(UC). However, the use of antibiotics, proton pump inhibitors, corticosteroids, beta-blockers, metformin, and statin concomitant medications in some patients due to complications during the treatment process may affect the clinical efficacy of ICIs through different pathway, making it difficult for patients to derive clinical benefit or making it more likely to develop drug resistance. In this paper, we present a review of the effects of the above concomitant drugs on ICIs in the treatment of patients with advanced UC, with a view to provide reference for the application of individualized treatment strategies of ICIs in patients with advanced UC.

Objective:To understand the prevalence and epidemiological characteristics of glaucoma among people over 40 years old in rural areas of Chongqing.Methods:From August to October 2018, a stratified cluster random sampling method was used to investigate the cases of glaucoma among people over 40 years old in a rural population of the Rongchang and Qijiang Districts in Chongqing.The subjects had been living in the local area for over ten years.Basic information for each patient, including gender and age was documented, and their visual acuity and intraocular pressure were routinely measured.The Van Herick method was used to evaluate the depth of the central and peripheral anterior chamber, a preset lens was used to examine the fundus, and the cup to disc ratio(C/D) of the optic disc was emphasized.All suspected glaucoma patients underwent further standard glaucoma examinations.This study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Army Medical University.Results:A total of 4 680 people were identified, and 4 073 respondents participated in the survey, and the response rate was 87%.The prevalence of glaucoma was 1.72% (70/4 073). There were no significant differences in the prevalence of primary angle-closure glaucoma (PACG) and primary open angle glaucoma (POAG) between different genders ( χ2=0.042, P=0.837; χ2=2.838, P=0.092). The prevalence of glaucoma in people over 70 years old was 2.5%, significantly higher than that in other age groups.In patients with glaucoma, the rate of visual impairment was 68.57%(48/70), and the rate of blindness was 47.14%(33/70). There was no significant difference in the incidence of low vision between different types of glaucoma ( χ2=2.785, P=0.248), but there was a significant difference in the rate of blindness ( χ2=10.668, P=0.005). The highest rate of blindness was found in secondary glaucoma.The detection rate of intraocular pressure, anterior chamber depth and C/D was statistically significant ( χ2=43.325, P<0.001), and the positive rate of C/D was the highest.When the factors of intraocular pressure, and C/D were considered jointly, the detection rate of glaucoma could be increased to 55.88%. Conclusions:The prevalence of glaucoma is 1.72% among people over 40 years old in rural areas of Chongqing, the prevalence of PACG is lower than previously recorded, but the proportion of glaucoma-induced visual impairment is higher.In field screening, the morphological examination of the fundus optic nerve is very important for the diagnosis of glaucoma.

Objective To investigate the safety of autologous bone marrow mesenchymal stem cells (ABMSCs) transplantation into the subretinal space for the treatment of proliferative diabetic retinopathy (PDR). Methods The clinical data of four PDR patients ( four eyes ) who received ABMSCs transplantation into the subretinal space were collected in Army Medical University,Southwest Eye Hospital from March 2014 to December 2015,including 3 males and 1 female;the average age was 55 years old;the average course of diabetes was 10 years, and the blood glucoses were all well controlled before treatment. All the patients underwent conventional ophthalmologic examination,and visual acuity,slit lamp microscope,color fundus photography,fluorescein angiography (FFA) and optical coherence tomography ( OCT) examination were performed at 1 week,1 month,3 months,6 months,9 months and 12 months after surgery. This study protocol was approved by Ethic Committee of Army Medical University,Southwest Eye Hospital (No. 2013-34). Results Four patients diagnosed as PDR were enrolled in this study. All patients were performed ABMSC transplantation,and no one felt discomfort after treatment. FFA and OCT showed that the transplanted cells were present in the subretinal space until 1 month after transplantation. The macular edema of one patient diagnosed as macular edema preoperatively was relived gradually after transplantation,and the effects lasted 3 months after transplantation. The preoperative best corrected visual acuity (BCVA) of the two patients were improved from hand movement and finger counting to 20/20 ( 84 ETDRS) and 20/200 ( 38 ETDRS) after transplantation,respectively,and the visual acuities of the other two eyes were both stable. All patients underwent panretinal photocoagulatio 3 months after transplantation, and the follow-up treatment complied with the routine of post-vitrectomy for DR, no complications occurred during the follow-up period. Conclusions Subretinal transplantation of ABMSCs for PDR is safe. The transplanted cells show local anti-inflammatory effect,and no effect on cell proliferation or circulatory improvement are observed.

Objective To improve the quality standard ofKangjing pills.Methods The qualities of Angelica sinensis, Taxillus sutchuenensis, Radix paeoniae Alba, Eucommia ulmoides and Ligusticum chuanxiong Hort in the pills were identified by microscopic examination; the natures of Radix rehmanniae Praeparata, Radix paeoniae Rubra, Radix paeoniae Alba,Angelica sinensis and Ligusticum chuanxiong Hort were detected by thin layer chromatography (TLC); the content of Paeoniflorin were measured by high performance liquid chromatography (HPLC). The operating conditions by HPLC were InertSustain C18 (4.6 mm×250 mm, 5μm ), the mixture of acetonitrile-0.2% Phosphoric acid water (15:85) as mobile phase, 1.0 ml/min as flow speed and wavelength 316 nm.Results The results observed by microscopy were obvious; The results showed that the TLC spots of Radix rehmanniae Praeparata, Radix paeoniae Rubra, Radix paeoniae Alba, Angelica sinensis and Ligusticum chuanxiong Hort were fairly clear, and the according blank test showed no interference. Ferulic Acid showed a good linear relationship within the range of 0.067-0.168μg (r=0.9997) with an average recovery of 99.84% (RSD=1.22%). Conclusions Microscopy, TLC and HPLC are handy, safe and accurate forKangjing pills to determine the quality.

Objective To observe safety of intravitreal injection of mouse nerve growth factor and its distribution in retina in rabbits .Methods The behavioral observation ,slit lamp examination ,fundus examination ,eye B ultrasonic and histopathological ex‐amination were carried out on 1 ,7 and 30 d after intravitreal injection 30 μg/100 μL mNGF to determine the safety in eye .The dis‐tribution and peak time in retina were investigated at 15 ,30 min ,1 ,3 ,6 ,8 ,12 ,24 ,48 h after intravitreal injection 125 I‐NGF 30 μg/100 μL .Results No abnormal changes were found in their cornea ,lens ,vitreous body and retina after mNGF intravitreal injection . And the each layer of retinal cells layout were regular according to the result of morphological observation on 30 days after treat‐ment .The peak concentration of mNGF in retina and the highest in whole eye was (118 .32 ± 18 .74)% ID/g and the peak time was at 3 hour after injection .Conclusion It is safe for intravitreal injection of mNGF and mNGF could gather in retina quickly after in‐travitreal injection .

Objective To observe the clinical efficacy of bevacizumab intravitreal injection combined with laser photocoagulation for di-abetic retinopathy macular edema(DME). Methods 25 DME patients (15 patients, 24 eyes in control group and 10 patients,13 eyes in treatment group) were selected from January 2013 to November 2014 in our hospital. The control group received single Krypton laser (510 nm red and 483 nm yellow) grid photocoagulation or big“C” photocoagulation, while the treatment group received bevacizumab intrav-itreal injection after Krypton laser photocoagulation. The visual acuity were checked, and the macular retinal thickness was detected by opti-cal coherence tomography ( OCT) . Results The difference in preoperative visual acuity between the two groups was not statistically signifi-cant (P>0. 05). All visual acuity improved significantly (P<0. 05) after treatment and the treatment group got a better result compared to the control group(P <0. 05). The preoperative macular retinal thickness in treatment and control groups were respectively (510. 75 ± 61. 06)μm and(487. 47 ± 43. 41)μm, and the difference between them was not statistically significant (P>0. 05). And the macular retinal thickness were respectively ( 253. 41 ± 39. 12 )μm and ( 358. 81 ± 43. 24 )μm after treatment, which were all decreased than before (P<0. 05). The macular retinal thickness of the treatment group was better than that of the treatment group after treatment (P<0. 05). Conclusion Single Krypton laser photocoagulation and bevacizumab intravitreal injection combined with Krypton laser photocoagulation are all effective for DME. But treatment combined with Krypton laser photocoagulation could get significantly better postoperative visual acuity re-covery and significantly faster absorption of macular edema.

BACKGROUNDLowering intraocular pressure (IOP) is currently the only therapeutic approach in primary open-angle glaucoma. and the fixed-combination medications are needed to achieve sufficiently low target IOP. A multicenter prospective study in the Chinese population was needed to confirm the safety and efficacy of Bimatoprost/Timolol Fixed Combination Eye Drop in China. In this study, we evaluated the safety and efficacy of Bimatoprost/Timolol Fixed Combination with concurrent administration of its components in Chinese patients with open-angle glaucoma or ocular hypertension.

METHODSIn this multicenter, randomized, double-masked, parallel controlled study, patients with open-angle glaucoma or ocular hypertension who were insufficiently responsive to monotherapy with either topical β-blockers or prostaglandin analogues were randomized to one of two active treatment groups in a 1:1 ratio at 11 Chinese ophthalmic departments. Bimatoprost/timolol fixed combination treatment was a fixed combination of 0.03% bimatoprost and 0.5% timolol (followed by vehicle for masking) once daily at 19:00 P.M. and concurrent treatment was 0.03% bimatoprost followed by 0.5% timolol once daily at 19:00 P.M. The primary efficacy variable was change from baseline in mean diurnal intraocular pressure (IOP) at week 4 visit in the intent-to-treat (ITT) population. Primary analysis evaluated the non-inferiority of bimatoprost/ timolol fixed combination to concurrent with respect to the primary variable using a confidence interval (CI) approach. Bimatoprost/timolol fixed combination was to be considered non-inferior to concurrent if the upper limit of the 95% CI for the between-treatment (bimatoprost/timolol fixed combination minus concurrent) difference was ≤ 1.5 mmHg. Adverse events were collected and slit-lamp examinations were performed to assess safety. Between-group comparisons of the incidence of adverse events were performed using the Pearson chi-square test or Fisher's exact test.

RESULTSOf the enrolled 235 patients, 121 patients were randomized to receive bimatoprost/timolol fixed combination and, 114 patients were randomized to receive concurrent treatment. At baseline the mean value of mean diurnal IOP was (25.20 ± 3.06) mmHg in the bimatoprost/timolol fixed combination group and (24.87 ± 3.88) mmHg in the concurrent group. The difference between the treatment groups was not statistically significant. The mean change from baseline in mean diurnal IOP (± standard deviation) in the bimatoprost/timolol fixed combination group was (-9.38 ± 4.66) mmHg and it was (-8.93 ± 4.25) mmHg in the concurrent group (P < 0.01). The difference between the two treatment groups (bimatoprost/timolol fixed combination minus concurrent) in the change from baseline of mean diurnal IOP was -0.556 mmHg (95% CI: -1.68, 0.57, P = 0.330). The upper limit of the 95% CI was less than 1.5 mmHg, the predefined margin of non-inferiority. Adverse events occurred in 26.4% (32/121) of the bimatoprost/timolol fixed combination patients and 30.7% (35/114) of the concurrent patients. The most frequent adverse event was conjunctival hyperemia, which was reported as treatment related in 16.5% (20/121) in the bimatoprost/timolol fixed combination group and 18.4% (21/114) in the concurrent group (P > 0.05).

CONCLUSIONSBimatoprost/Timolol Fixed Combination administered in Chinese patients with open-angle glaucoma or ocular hypertension was not inferior to concurrent dosing with the individual components. Safety profiles were similar between the treatment groups.

Adolescent ; Adult ; Aged ; Amides ; administration & dosage ; adverse effects ; therapeutic use ; Bimatoprost ; Cloprostenol ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Female ; Glaucoma, Open-Angle ; drug therapy ; Humans ; Male ; Middle Aged ; Ocular Hypertension ; drug therapy ; Timolol ; administration & dosage ; adverse effects ; therapeutic use ; Young Adult

Objective To assess the clinical factors impacting on the effective time of endocrine therapy for patients with prostate cancer.Methods The chnical data of 432 patients with prostate cancer who accepted endocrine therapy were analyzed retrospectively.The endpoint of the study was failure of endocrine therapy which was defined as continuous elevation of prostate specific antigen (PSA) from nadir for 2 times and more than 0.2 μg/L.The clinical data such as age,clinical stage,lymph node metastasis,bone metastasis,Gleason score,initial PSA,and PSA nadir were collected and their rehtionship with the effective time of endocrine therapy were further assessed via COX regression model.Results Age of onset was 57-88(73.70 ± 7.28) years.Initial PSA was 10.30-588.10(27.15 ± 75.90) μ g/L.The effective time of endocrine therapy was 3-62 (27.01 ± 13.10) months.Univariate regression analysis showed that initial PSA,clinical stage,Gleason score,PSA nadir,lymph node metastasis,bone metastasis were correlated with the effective time of endocrine therapy (P ＜ 0.01).Multivariate regression analysis showed that only Gleason score was correlated with the effective time of endocrine therapy(P=0.001).Compared with patients with Gleason score equal to or less than 3+4,patients with Gleason score equal to or more than 4+3 showed 2.49 fold increased risk of therapy failure (OR =2.49,95％ CI 1.44-4.30).Conclusion Gleason score has close relationship with the effective time of endocrine therapy for patients with prostate cancer,Gleason score equal to or more than 4+3 is an indicator for poor response to endocrine therapy.

Objective To investigate the prevalence,clinical traits and correlates of apathy in patients with Parkinson' s disease ( PD ).Methods Seventy-seven cases of PD patients and 40 health controls were recuited in the present study.Apathy was assessed using Lille Apathy Rating Scale(LARS) and related factors,such as motor function,cognition,depression,age,sex,education level,disease duration,levodopa equivalent doses (LED) and use of antipsychotic drugs were also evaluated.Four kinds of scales,Unified Parkinson' s Disease Rating Scale (UPDRS),Hoehn-Yahr staging,Montreal Cognitive Assessment (MoCA),Hamilton Depression Rating Scale (HAMD) were employed to evaluate the motor function,cogniton and depression,respectively.Results The prevalence of apathy and depression in the 77 PD patients were 49.4％ ( 38/77 ) and 46.8％ (36/77),respectively.Of the 77 PD patients,11 cases had apathy without depression (14.3％ ); 9 cases had depression without apathy( 11.7％ ) and 27 cases had apathy combined with depression( 35.1％ ).Among the PD patients with apathy,the cognitive type is the most common one,accounting for 86.8％ (33/38).There were significant statistical differences in education level,UPDRS- Ⅱ/Ⅲ scores,Hoehn-Yahr staging,MoCA and HAMD scores between apathy ( n =38 ) and no-apathy(n =39) PD patients(t =2.309,-3.144,-4.000,-3.217,2.649,-3.909,all P＜0.05).According to the unifactoral Logistic regression analysis of apathy correlates,UPDRS-Ⅱ/Ⅲ scores,HoehnYahr staging and HAMD scores were the risk factors for apathy while education level and MoCA were the protective factors for apathy.In the multiple Logistic regression analysis,HAMD scores,UPDRS-Ⅱ scores and education level were included.Conclusions The prevalence of apathy in PD patients was significantly higher than healthy controls.Apathy could be present without depression in PD patients,and was associated with education level,motor dysfunction degree,cognitive impairment and depression severity.