Endophthalmitis in silicone oil-filled eye: A case report.

BACKGROUND: Endophthalmitis occurring in silicone oil-filled eyes is a very rare occurrence, with reported incidence rates ranging between 0.07% and 0.039%. Traditional methods of management of infectious endophthalmitis include the removal of silicone oil, washout of the vitreous cavity, administration of intravitreal antibiotics, and re-injection of silicone oil. CASE SUMMARY: Herein, we report the case of a 39-year-old man with unilateral endophthalmitis after pars plana vitrectomy and silicone oil tamponade. Intravitreal injections of full-dose antibiotics and anterior chamber washout were used to treat the patient. No signs of retinal toxicity were observed during the follow-up period. CONCLUSION: Intravitreal full-dose antibiotic injections and anterior chamber washout are promising alternatives to traditional therapies for endophthalmitis in silicone oil-filled eyes.

Acute Macular Neuroretinopathy after SARS-CoV-2 Infection: An Analysis of Clinical and Multimodal Imaging Characteristics.

BACKGROUND: This study aimed to analyze clinical and multimodal imaging characteristics of acute macular neuroretinopathy (AMN) post-recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Retrospective observational study. Medical records and multimodal imaging of 12 AMN eyes of eight patients (six female and two male) with recent SARS-CoV-2 infection were retrospectively analyzed. RESULTS: Four patients (50%) presented with bilateral AMN. Fundus ophthalmoscopy revealed a reddish-brown lesion around the macula, and two eyes had cotton-wool spots at the posterior pole. Three eyes showed mild hypo-autofluorescence. All FFA images (7 eyes) showed no abnormal signs. On OCT scans, all eyes showed outer nuclear layer (ONL) thinning, 8 eyes (66.7%) showed ONL hyperreflectivity, 5 eyes (41.7%) showed outer plexiform layer (OPL) hyperreflectivity, 8 eyes (66.7%) showed interdigitation zone (IZ) disruption, 11 eyes (91.6%) showed ellipsoid zone (EZ) disruption, 2 eyes (16.7%) showed cotton-wool spots and inner plexiform layer (IPL) hyperreflectivity, 1 eye (8.3%) had intraretinal cyst and 1 eye (8.3%) had inner nuclear layer (INL) thinning. Persistent scotoma, ONL hyperreflectivity and IZ/EZ disruption as well as recovery of OPL hyperreflectivity were reported after follow-up in three cases. CONCLUSIONS: AMN post-SARS-CoV-2 mostly affected young females and could present unilaterally or bilaterally. Dark lesions on IR reflectance and outer retinal hyperreflectivity on OCT are useful in diagnosing AMN. OPL/ONL hyperreflectivity on OCT could disappear after follow-up, but ONL thinning and IZ/EZ could persist.

[Preparation of Iron-improved Blue Algae Biochar and Its Co-adsorption Mechanism for Phosphorus in Surface Water].

To alleviate the problems of eutrophication and blue algae accumulation in water, biochar was prepared from blue algae dehydrated using polymerized ferrous sulfate(PFS) to absorb phosphate in water, and the biochar was activated using steam to adjust the pore structure. The preparation conditions of blue algae biochar were optimized using the response surface method. The optimal results were as follows:the dosage of PFS was 458 mg·L-1, the carbonization temperature was 433℃, and the mass ratio of biochar precursor to steam was 1:11. Biochar without PFS(F0H11-433) and biochar with PFS(F458H11-433) were characterized using X-ray diffraction(XRD), Fourier-transform infrared spectroscopy(FTIR), zeta potential, and Raman spectra(Raman) were used to study whether blue algae biochar and PFS had a synergic effect on phosphate removal. The results showed that:compared with F0H11-433, iron oxide appeared on the surface, the zero point of charge(pHpzc) increased from 4.41 to 6.19, and the disorder and defect degree of biochar was increased in F458H11-433. The pseudo-second-order model and Langmuir model were suitable for describing the adsorption process of F458H11-433, and the saturated adsorption capacity was 31.97 mg·g-1. F458H11-433 had excellent phosphorus removal efficiency in actual lake water, and the residual phosphate content of effluent was less than 0.025 mg·L-1. In the presence of several common anions, it still showed excellent selective adsorption. After five cycles, the phosphate removal of F458H11-433 still reached 75.78%, indicating that F458H11-433 had the characteristic of being renewable. Combined with the material characterization results before and after adsorption, the phosphorus removal mechanism of F458H11-433 mainly involved electrostatic attraction and ligand exchange.

Systemic combined with intravitreal methotrexate for relentless placoid chorioretinitis: A case report.

BACKGROUND: We describe a case of relentless placoid chorioretinitis (RPC) that progressed despite administration of peribulbar and systemic corticosteroids, and was resolved by systemic combined with intravitreal methotrexate. CASE SUMMARY: A 16-year-old male reported painless blurred vision and a temporal scotoma in his right eye for one week. Due to widespread distribution and continuous enlargement, multimodal imaging of the lesions led to the diagnosis of RPC. Lesions in the right eye extended despite peribulbar injection of triamcinolone acetonide, but the progression was immediately terminated by a single dose of intravitreal methotrexate. A new fresh lesion occurred in the contralateral eye despite systemic prednisolone but was resolved by oral methotrexate. CONCLUSION: Systemic immunosuppressants should be given upon RPC diagnosis. Intravitreal methotrexate immediately halted progression and may be considered for sight-threatening cases as part of the initial therapy.

Real-world outcomes of anti-vascular endothelial growth factor therapy for retinal vascular vein occlusion in Tibet, China.

AIM: To evaluate the outcomes of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents for patients with retinal vein occlusion (RVO) related-macular edema (ME) in Tibetan. METHODS: A retrospective, observational, single-center study. The demographic and clinical data of 90 RVO Tibetan patients (93 eyes) treated with either ranibizumab or conbercept in Tibet Autonomous Region People's Hospital from Jan 2018 to December 2019 were collected. RESULTS: The mean patient age was 56.8±10.6y, 45 (50%) of them were female. The mean living altitude was 3867.8±567.9 m. At the last visit, the best-corrected visual acuity (BCVA) significantly increased (52.2±21.8 letters) in comparison with the baseline (38.2±24.1 letters, P<0.001); while the central retinal thickness (CRT) significantly reduced (245.5±147.6 µm) in comparison with the baseline (504.1±165.2 µm, P<0.001). The 43.0% of the eyes gained ≥15 letters, 60.2% of the eyes gained ≥10 letters, and 78.5% of the eyes gained ≥5 letters. No vision loss was noted in 92.5% of the eyes, 4 eyes lost more than 10 letters during follow-up period. The mean number of injections was 2.4±1.8. No severe ocular or systemic adverse events related to either the drug or injection were noted. CONCLUSION: Anti-VEGF therapy is effective and safe in Tibetan patients for the treatment of RVO related ME.

Bioconversion of cyanobacteria by black soldier fly larvae (Hermetia illucens L.): Enhancement by antioxidants.

Cyanobacterial blooms have been a global environmental problem for decades. Bioconversion by black soldier fly larvae (BSFL) has been widely reported to be a clean and efficient method to remove organic pollutants. In this study, BSFL bioconversion was used to treat cyanobacterial blooms. Antioxidants (a mixture of l-ascorbic acid [180 mg/kg fresh feed] and α-tocopherol [360 mg/kg fresh feed]) were added to compare bioconversion performance against a non-supplemented group. With increasing proportions of cyanobacteria (0%-25% dry mass), the bioconversion efficiency of the antioxidant group improved significantly compared to the control group, and the survival rate of larvae rose from 96.50-45.50% to 98.00-55.83% with antioxidant addition. The toxic effects of exogenous anti-nutrients could be reduced by the antioxidants through inactivation of trypsin inhibitor and enhancement of the microcystin-LR degradation rate. Overall, the BSFL bioremediation capacity was improved with addition of exogenous antioxidants, verifying both the effects and mechanism of antioxidant addition in promoting the bioconversion of cyanobacteria by BSFL and providing a basis for future application and study.

Efficacy and Safety of Aqueous Interleukin-8-Guided Treatment in Cytomegalovirus Retinitis after Bone Marrow Hematopoietic Stem Cell Transplantation.

PURPOSE: To explore the optimal treatment for cytomegalovirus retinitis (CMVR) in patients status-post Allogeneic bone marrow hematopoietic stem cell transplantation (Allo-HSCT), based on aqueous humor indicators. METHODS: A randomized controlled study with 35 eyes. Eyes were randomized with a 1:1 ratio to standard treatment group (Group 1, with treatment endpoint as aqueous CMV-DNA load＜103 copy/ml), and interleukin (IL)-8 group (Group 2, with treatment endpoint as aqueous IL-8 level ＜30 pg/ml or CMV-DNA load＜103 copy/ml) to receive antiviral intravitreal injections. Number of injections, CMVR recurrence rate, complication rate, and vision changes were analyzed and compared. RESULTS: The mean number of injections in group 2 was less than in group 1 (6 vs 8 respectively, p<0.05). There were no significant differences in CMVR recurrence, complication and vision recovery rate. CONCLUSION: Incorporating aqueous humor IL-8 level into the criteria of CMVR treatment decision can safely and effectively reduce the number of intravitreal injections needed and can be used as important indicators to assess treatment endpoint.

Vitrectomy With Silicone Oil Tamponade and Without Internal Limiting Membrane Peeling for the Treatment of Myopic Foveoschisis With High Risk of Macular Hole Development.

Purpose: To explore the efficiency and safety of the surgical procedure of pars plana vitrectomy (PPV) with silicone oil (SO) tamponade and without internal limiting membrane (ILM) peeling for myopic foveoschisis (MF) eyes with high risk of macular hole formation. Methods: Three eyes (three patients) with MF and foveal detachment were enrolled into the study. Comprehensive preoperative ophthalmological assessments, including best corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT) were performed on the eyes. Central foveal thickness (CFT) and thickness of continuous neurosensory retina at foveola were measured. All patients underwent PPV followed by SO tamponade and without ILM peeling. SO was removed when MF and retinal detachment were resolved. Patients were followed up postoperative at month 1, 3, 6, and 12. Results: All the three eyes achieved complete resolution of MF and foveal reattachment with an average SO tamponade period of 11.67 ± 0.58 months. The average CFT at 6 months was 91 ± 27.5 µm, hence reduced significantly from baseline at 365.3 ± 137.85 µm (P = 0.037). There was no postoperative macular hole formation despite the average preoperative sensory retina thickness of 58 ± 20.07 µm. Mean BCVA was improved from logMAR 1.43 ± 0.75 to logMAR 0.8 ± 0.75 on the last follow-up. Manageable SO-related complications were reported, including SO emulsification, ocular hypertension, and cataract. Conclusion: Vitrectomy with SO tamponade and without ILM peeling as an optional surgical protocol to treat MF is effective and safe, especially for MF eyes vulnerable to macular hole formation.

Efficacy and Safety of Mulberry Twig Alkaloids Tablet for the Treatment of Type 2 Diabetes: A Multicenter, Randomized, Double-Blind, Double-Dummy, and Parallel Controlled Clinical Trial.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids [SZ-A]) in the treatment of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: This was a multicenter, randomized, double-blind, double-dummy, and parallel controlled noninferiority clinical trial that was conducted for 24 weeks. A total of 600 patients were randomly allocated to the SZ-A group (n = 360) or acarbose group (n = 240). The primary efficacy end point was the change of glycosylated hemoglobin (HbA1c) compared with baseline. In addition, adverse events (AEs), severe AEs (SAEs), treatment-related AEs (TAEs), and gastrointestinal disorders (GDs) were monitored. RESULTS: After treatment for 24 weeks, the change in HbA1c was -0.93% (95% CI -1.03 to -0.83) (-10.2 mmol/mol [-11.3 to -9.1]) and -0.87% (-0.99 to -0.76) (-9.5 mmol/mol [-10.8 to -8.3]) in the SZ-A and acarbose groups, respectively, and the least squares mean difference was -0.05% (95% CI -0.18 to 0.07) (-0.5 mmol/mol [-2.0 to 0.8]) between the two groups, with no significant difference on the basis of covariance analysis (P > 0.05). The incidence of TAEs and GDs was significantly lower in the SZ-A group than the acarbose group (P < 0.01), but no differences for AEs or SAEs between the two groups were observed (P > 0.05). CONCLUSIONS: SZ-A exhibited equivalent hypoglycemic effects to acarbose in patients with T2D. Nevertheless, the incidence of TAEs and GDs was lower following SZ-A treatment than acarbose treatment, suggesting good safety.

Degradation of diclofenac sodium using Fenton-like technology based on nano-calcium peroxide.

A nano-calcium peroxide (nCaO2) powder with a purity of 89.1% was prepared using an improved traditional method. Then, the as-prepared nCaO2 was used as the source of hydrogen peroxide (H2O2) for the Fenton-like degradation of diclofenac sodium (DCF). The results showed that nCaO2 performed better for DCF removal when compared to nCaO2 prepared by a conventional method and commercial calcium peroxide (CaO2). Further experimental results indicated that 97.5% of DCF could be removed in 180 min at a nCaO2/Fe2+-EDTA/DCF molar ratio of 16/8-8/1, which was more efficient than in the H2O2/EDTA-Fe2+/DCF and nCaO2/Fe2+/DCF systems. The best removal rate of DCF was at pH 6.0, unlike previous claims that stated that the lower the pH in the buffer system, the better the degradation of DCF. In addition, the influence of water quality parameters, such as Cl-, NO3-, SO42-, HCO3-, and humic acid (HA), on DCF removal were evaluated. A free radical masking experiment revealed the existence of hydroxyl radical (OH), superoxide radical (O2-) and singlet oxygen (1O2), and indicated that the degradation of DCF was mainly due to oxidation caused by OH. Electron paramagnetic resonance (EPR) studies for different systems and different active oxygen species were carried out, and it was further confirmed that OH radicals have high intensity in the Fenton-like system based on nCaO2. EPR results also showed that the addition of EDTA can promote the production of OH. According to the identification of the dominant reactive species and GC-MS, the possible theoretical DCF degradation pathways were proposed.

Characterization of algal organic matter as precursors for carbonaceous and nitrogenous disinfection byproducts formation: Comparison with natural organic matter.

Algal organic matter (AOM) and natural organic matter (NOM) from a typical eutrophic lake were comprehensively investigated in terms of their physico-chemical property, components and disinfection byproduct formation potentials (DBPFPs). The relationships between specific chemical properties of AOM and NOM with their corresponding DBPFPs were further evaluated during chlorination. Results indicated that AOM had lower specific UV absorbance (SUVA) but richer organic nitrogen contents than NOM. Fluorescence excitation emission matrix spectroscopy further demonstrated that AOM were chiefly composed of aromatic protein-like and soluble microbial byproduct-like matters, while NOM were mainly contributed from humic acid-like and soluble microbial byproduct-like substances. Although the molecular weight (MW) distribution of AOM and NOM showed no significant difference, size-exclusion chromatography with organic carbon as well as organic nitrogen detection (LC-OCD-OND) revealed that AOM were concentrated with the fraction of building blocks and NOM had higher concentrations of biopolymers and humics (HS). Moreover, AOM displayed higher DBPFPs than NOM, especially for nitrogenous DBPFP (N-DBPFP). MW < 1 kDa fractions both in AOM and NOM contributed the largest proportion to the formation of carbonaceous disinfection byproducts (C-DBPs). In addition, Pearson correlation analysis showed that bulk parameter SUVA was significantly relevant to the formation potentials of trihalomethane both in AOM and NOM, but was ineffective for carbonaceous DBPFP (C-DBPFP) prediction. Dissolved organic nitrogen contents in biopolymer and HS characterized by LC-OCD-OND had strong correlations with N-DBPFPs from AOM and NOM, indicating that LC-OCD-OND quantitative analysis could improve the prediction accuracy of the DBP formation than bulk parameters during NOM and AOM chlorination.

Continuous High-Dose (6 mg) vs. Low-Dose (3 mg) Intravitreal Ganciclovir for Cytomegalovirus Retinitis After Haploidentical Hematopoietic Stem Cell Transplantation: A Randomized Controlled Study.

Purpose: To evaluate the safety and efficacy of continuous high-dose (6 mg) intravitreal ganciclovir injections (IVG) for cytomegalovirus (CMV) retinitis (CMVR) after haploidentical hematopoietic stem cell transplantation (Haplo-HSCT), and to explore factors that may influence the treatment procedure. Design: Prospective, randomized, single-blinded, positive-controlled, interventional, comparative study. Methods: A total of 22 patients with CMVR (32 eyes) were randomized to either high-dose group (IVG 6 mg weekly) or low-dose group (IVG 3 mg given twice weekly for 2 weeks as induction phase and weekly thereafter as maintenance phase). Patients who were recorded any positive CMV DNAemia or other active CMV diseases and needed systemic anti-CMV treatment during the study period were excluded. The vision outcome, variables of the treatment procedure, and incidence of complication and CMVR recurrence were analyzed and compared. Logistic regression was applied to determine the factors that may have an impact on the treatment process at baseline. Results: Compared to the low-dose group, the high-dose group resulted in a median of two less intravitreal injections (4 vs. 6 times, respectively, P = 0.016), while the rate of vision stability or improvement (81.2 vs. 87.5%), the incidence of complication (6.2 vs. 18.8%), and CMVR recurrence (12.5% vs. 6.2%) were similar (all P > 0.05). No drug-related toxicity was observed. Initial aqueous CMV-DNA load (OR: 6.872, 95% CI: 1.335-35.377, P = 0.021) and extension of lesion (OR: 0.942, 95% CI: 0.897 to .991, P = 0.020), but not dosing regimen (P = 0.162), were predictors of the treatment duration. Conclusions: Continuous high-dose regimen was well tolerated and resulted in less intravitreal injections, with similar vision outcomes and safety profiles. The clinical course of CMVR after Haplo-HSCT was determined by its own nature at baseline and could not be modified by treatment protocols under consistent immune background.

Chiglitazar monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomized, double-blind, phase 3 trial (CMAS).

Chiglitazar (Carfloglitazar) is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes. In this randomized phase 3 trial, we compared the efficacy and safety of chiglitazar with sitagliptin in patients with type 2 diabetes who had insufficient glycemic control despite a strict diet and exercise regimen. Eligible patients were randomized (1:1:1) to receive chiglitazar 32 mg (n = 245), chiglitazar 48 mg (n = 246), or sitagliptin 100 mg (n = 248) once daily for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin A1C (HbA1c) from baseline at week 24 with the non-inferiority of chiglitazar over sitagliptin. Both chiglitazar and sitagliptin significantly reduced HbA1c at week 24 with values of -1.40%, -1.47%, and -1.39% for chiglitazar 32 mg, chiglitazar 48 mg, and sitagliptin 100 mg, respectively. Chiglitazar 32 and 48 mg were both non-inferior to sitagliptin 100 mg, with mean differences of -0.04% (95% confidential interval (CI) -0.22 to 0.15) and -0.08% (95% CI -0.27 to 0.10), respectively. Compared with sitagliptin, greater reduction in fasting and 2-h postprandial plasma glucose and fasting insulin was observed with chiglitazar. Overall adverse event rates were similar between the groups. A small increase in mild edema in the chiglitazar 48 mg group and slight weight gain in both chiglitazar groups were reported. The overall results demonstrated that chiglitazar possesses good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions, thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.

NEOVASCULAR COMPLICATIONS FROM CYTOMEGALOVIRUS NECROTIZING RETINOPATHY IN PATIENTS AFTER HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION.

PURPOSE: To report the incidence and clinical features of neovascular complications from cytomegalovirus (CMV) necrotizing retinopathy in patients after haploidentical hematopoietic stem cell transplantation. METHODS: Thirty-nine patients (58 eyes) of CMV necrotizing retinopathy after haploidentical hematopoietic stem cell transplantation in our institute between January 2018 and June 2020 were retrospectively reviewed, and cases that developed neovascular complications during follow-up were identified and described. RESULTS: Two (2 eyes) cases that developed neovascular glaucoma from CMV necrotizing retinopathy were identified. Both of them manifested as granular peripheral retinitis, panretinal occlusive vasculitis, and some degree of intraocular inflammation, which were consistent with chronic retinal necrosis. Insidious progression of isolated immune-mediated occlusive vasculitis that could only be observed on fundus fluorescein angiography without active retinitis or intraocular inflammation was recognized to be the cause in one of two cases. CONCLUSION: Neovascular glaucoma developed in 5.1%/cases and 3.4%/eyes complicated by CMV chronic retinal necrosis and vasculitis in patients after haploidentical hematopoietic stem cell transplantation, which warrants the needs for long-term follow-up. Immune-mediated CMV vasculitis could be an isolated manifestation in patients with a minimal immune deviation and may only be found on fundus fluorescein angiography, which emphasizes the importance of fundus fluorescein angiography on a regular basis during follow-up.

[Restoration of River Sediment by Calcium Peroxide(CaO2) Combined with Biochar].

The internal source pollution of sediment is the main factor leading to the repetition of black-odorous river channels. In order to prevent this situation, a river channel in the Binhu District of Wuxi City was used as an experimental site. In-situ CaO2 combined with a biochar covering technology was used to repair the black odorous river sediment in this channel. The effects of this technology on the quality of mud water, sedimentary volatile sulfide (AVS) and phosphorus forms, microorganisms, and restoration of black odorous sediment were investigated. The results showed that CaO2 combined with biochar coverage could significantly increase the dissolved oxygen (DO) concentration and redox potential (ORP) of the muddy water system. The DO concentration and ORP in the overlying water were maintained above 2 mg·L-1 and 50 mV, respectively. The removal rates of interstitial water ammonia-nitrogen (NH4+-N), chemical oxygen demand (COD), and total phosphorus (TP) reached 43.40%, 41.18%, and 50.97%, respectively. The removal rate of AVS in the sediment reached 37.03%. The high-throughput sequencing showed that the relative abundance of anaerobic microorganisms in the sediment was significantly reduced, and that nitrogen and sulfur removal microorganisms appeared (e.g., Thermomonas, Dechloromonas, Proteus hauser, Desulfomicrobium, and Thiobacillus). Phosphorus in the sediment was converted into Fe/Al-P and Ca-P. Therefore, in-situ CaO2 combined with biochar coverage had a good repairing effect on black odorous sediment.

Resveratrol Modulates the Gut Microbiota and Inflammation to Protect Against Diabetic Nephropathy in Mice.

Oral administration of resveratrol is able to ameliorate the progression of diabetic nephropathy (DN); however, its mechanisms of action remain unclear. Recent evidence suggested that the gut microbiota is involved in the metabolism therapeutics. In the current study, we sought to determine whether the anti-DN effects of resveratrol are mediated through modulation of the gut microbiota using the genetic db/db mouse model of DN. We demonstrate that resveratrol treatment of db/db mice relieves a series of clinical indicators of DN. We then show that resveratrol improves intestinal barrier function and ameliorates intestinal permeability and inflammation. The composition of the gut microbiome was significantly altered in db/db mice compared to control db/m mice. Dysbiosis in db/db mice characterized by low abundance levels of Bacteroides, Alistipes, Rikenella, Odoribacter, Parabacteroides, and Alloprevotella genera were reversed by resveratrol treatment, suggesting a potential role for the microbiome in DN progression. Furthermore, fecal microbiota transplantation, derived from healthy resveratrol-treated db/m mice, was sufficient to antagonize the renal dysfunction, rebalance the gut microbiome and improve intestinal permeability and inflammation in recipient db/db mice. These results indicate that resveratrol-mediated changes in the gut microbiome may play an important role in the mechanism of action of resveratrol, which provides supporting evidence for the gut-kidney axis in DN.

[Effect of Ozonation on Microorganism in the Biological Activated Carbon and Disinfection By-Products in the Effluent].

This study was carried out in the ozone (O3) and biological activated carbon (BAC) section of a drinking water plant to investigate the effects of O3 on microbial and effluent disinfection by-products (DBPs) in BAC during drinking water treatment. The water quality, dissolved organic matter (DOM) characteristics, microbial activity, and DBPs formation at different O3 concentrations were analyzed. Results showed that the effect of O3 on microorganisms is mainly that it increased the utilization efficiency of DOM. However, excessive O3 increased the amount of organic matter such as protein and microbial metabolites (SMPs) in the effluent. When the O3 concentration increased from 0 mg·L-1 to 2.0 mg·L-1, the survival rate of microorganisms in the BAC decreased from 95.10% to 62.60%. However, since O3 transforms organic matter into a biodegradable substance, we found that microbial activity increased by 62.52% and that the biofiltration of the BAC was enhanced. When the O3 concentration was further increased to 4.0 mg·L-1, the microbial survival rate decreased to 49.9% and the protein and SMPs produced by the microorganisms increased. This resulted in an increased formation of carbon-containing DBPs (C-DBPs) and nitrogen-containing DBPs (N-DBPs) by 41.93% and 7.18%, respectively. In summary, an appropriate dosage of O3 was beneficial for removing DOM by O3-BAC, but we found that an excessive O3 concentration caused the formation of new DBPs precursors.

Efficacy and safety of insulin degludec/insulin aspart versus biphasic insulin aspart 30 in Chinese adults with type 2 diabetes: A phase III, open-label, 2:1 randomized, treat-to-target trial.

AIMS: To assess the efficacy and safety of twice-daily insulin degludec/insulin aspart (IDegAsp) versus biphasic insulin aspart 30 (BIAsp 30) twice daily, both ± metformin, in Chinese adults (N = 543) with type 2 diabetes (T2D) inadequately controlled on premixed/self-mixed or basal insulin ± metformin. MATERIALS AND METHODS: We conducted a 26-week, phase III, open-label, treat-to-target, 2:1 randomized trial. Hierarchical testing was used with non-inferiority of glycated haemoglobin (HbA1c) change from baseline to week 26 as the primary endpoint and superiority for the confirmatory secondary endpoints which were as follows: change from baseline in fasting plasma glucose (FPG); nocturnal confirmed hypoglycaemic episodes (12:01-5:59 am, inclusive); total confirmed hypoglycaemic episodes (severe or plasma glucose <3.1 mmol/L with/without symptoms); body weight; and percentage of responders (HbA1c <53 mmol/mol [<7.0%]) without confirmed hypoglycaemic episodes. RESULTS: Non-inferiority for change from baseline to week 26 in HbA1c and superiority of IDegAsp twice daily versus BIAsp 30 twice daily for change in FPG, nocturnal confirmed and total confirmed hypoglycaemic episodes, was demonstrated. Estimated rates of nocturnal confirmed and total confirmed hypoglycaemic episodes were 47% and 43% lower, respectively, with IDegAsp twice daily versus BIAsp 30 twice daily. Superiority for change in body weight was not confirmed. Participants were more likely to reach the HbA1c goal of <53 mmol/mol (<7.0%) without confirmed hypoglycaemia with IDegAsp twice daily versus BIAsp 30 twice daily by trial end. No new safety signals were identified. CONCLUSIONS: The efficacy and safety of IDegAsp in Chinese patients with T2D was demonstrated, confirming results from international trials.

Efficacy and safety of three-times-daily versus twice-daily biphasic insulin aspart 30 in patients with type 2 diabetes mellitus inadequately controlled with basal insulin combined with oral antidiabetic drugs.

AIMS: To compare the efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) administered three times daily (TID) vs. twice daily (BID), plus metformin, in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on basal insulin ± 1 oral antidiabetic drug (OAD). METHODS: Randomised, multinational, open-label, treat-to-target trial. Subjects inadequately controlled (HbA1c 7.5-10.0%) on basal insulin and metformin ±â€¯1 OAD were randomised to BIAsp30 TID (n = 220) or BIAsp30 BID (n = 217). Primary endpoint was change from baseline in HbA1c after 24 weeks of treatment. RESULTS: Most (400/437, 91.5%) subjects completed the trial. The majority (276/400 [69.0%]) were from the China region. After 24 weeks, HbA1c decreased comparably in both BIAsp 30 groups (-1.7% vs. -1.6% [-19 vs. -18 mmol/mol], for TID and BID dosing, respectively; estimated treatment difference: -0.09% [-0.23; 0.06]95% CI, -1 mmol/mol [-3; 1], p = 0.26). Safety profiles, including number of subjects experiencing hypoglycaemia, were similar. CONCLUSIONS: BIAsp 30 administered either TID or BID with metformin was a safe and effective option when intensifying treatment after failure of basal insulin and OADs in patients with T2DM. Adding a third injection at lunchtime may be preferable if HbA1c remains above target, if the lunchtime meal is the largest meal of the day, or if persistent postprandial hyperglycaemia after lunch is observed. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT02582242.

Safety and efficacy of ertugliflozin in Asian patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy: VERTIS Asia.

AIM: Phase III, randomized, double-blind study evaluating the efficacy and safety of ertugliflozin in Asian patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin, including evaluation in the China subpopulation. MATERIALS AND METHODS: A 26-week, double-blind study of 506 Asian patients (80.2% from mainland China), randomized 1:1:1 to placebo, ertugliflozin 5- or 15 mg, was performed. Primary endpoint was change from baseline in HbA1c at week 26. Secondary endpoints were change from baseline at week 26 in fasting plasma glucose (FPG), body weight (BW), systolic/diastolic blood pressure (SBP/DBP), and proportion of patients with HbA1c <7.0%. Hypotheses for the primary endpoint and FPG and BW secondary endpoints were tested in the China subpopulation. RESULTS: At week 26, least squares mean (95% CI) change from baseline HbA1c was significantly greater with ertugliflozin 5- and 15 mg versus placebo: -1.0% (-1.1, -0.9), -0.9% (-1.0, -0.8), -0.2% (-0.3, -0.1), respectively. Ertugliflozin significantly reduced FPG, BW and SBP. Reductions in DBP with ertugliflozin were not significant. At week 26, 16.2%, 38.2% and 40.8% of patients had HbA1c <7.0% with placebo, ertugliflozin 5- and 15 mg, respectively. 59.3%, 56.5% and 53.3% of patients experienced adverse events with placebo, ertugliflozin 5- and 15 mg, respectively. Incidence of symptomatic hypoglycaemia was higher for ertugliflozin 15 mg vs placebo. Results in the China subpopulation were consistent. CONCLUSIONS: Ertugliflozin significantly improved glycaemic control and reduced BW and SBP in Asian patients with T2DM. Ertugliflozin was generally well-tolerated. Results in the China subpopulation were consistent with the overall population. ClinicalTrials.gov: NCT02630706.