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•A strategy for recovering partial nitritation in a mainstream PN/A system is proposed.•Selectively reviving AOB after thoroughly inhibiting AOB and NOB by FNA is applied.•NOB reduced ...largely whereas AOB declined merely after 1.35 mg/L FNA treatment.•Ca. Kuenenia and Ca. Brocadia formed important links with other N cycle processes.
Starting up or recovering partial nitritation is a major challenge for achieving or maintaining stable partial nitritation/anammox (PN/A) during mainstream wastewater treatment. This study presents a novel strategy for recovering the nitrite pathway by selectively reviving ammonium oxidizing bacteria (AOB) after thoroughly inhibiting AOB and nitrite oxidizing bacteria (NOB) using free nitrous acid (FNA). A sequencing batch reactor was operated for PN/A to treat real domestic wastewater for 423 days, during which twice FNA treatment was temporarily implemented. Results showed that with a single 0.45 mg/L FNA treatment on flocculent sludge, the NO3−-N concentration during the aerobic period showed an uptrend again and the partial nitritation performance was deteriorated. In contrast, 1.35 mg/L FNA treatment induced the inhibition of both AOB and NOB leading to regressive ammonium oxidation, but a subsequently higher DO (1.5 mg/L) and longer aeration duration recovered partial nitritation. For the relative abundances of the acquired biomass related to nitrogen conversion, Nitrosomonas, Nitrospira and Nitrolancea increased to 9.65%, 10.27% and 4.35%, respectively, at the beginning of the 1.35 mg/L FNA treatment, and Nitrospira and Nitrolancea decreased to 2.80% and 0.03% whereas Nitrosomonas declined to 8.71% after 76 days. Ca. Brocadia showed less resilience after the 1.35 mg/L FNA treatment, with the relative abundance decreasing from 13.38% to 0.62% due to insufficient nitrite. Molecular ecological network analysis indicates that among anammox taxa, Ca. Kuenenia and Ca. Brocadia formed important links with other N cycle processes. Moreover, the proposed strategy shows operational flexibility because it can be easily used to control NOB in mainstream PN/A applications offered by flocculent sludge systems.
The aim of the present study was to investigate the factors influencing the short-term response to the initial radioiodine therapy (RT) course in patients with intermediate- and high-risk papillary ...thyroid carcinoma (PTC). A total of 182 patients with intermediate- and high-risk PTC who underwent RT in our hospital from March 2018 to October 2020 were retrospectively enrolled. The patients were divided into incomplete response (IR) and nonincomplete response (Non-IR) groups according to the response observed in clinical follow-up within 6–12 months after RT. Univariate and multivariate logistic regression analyses were used to investigate the effects of 15 observed factors on the response to RT. Receiver operating characteristic (ROC) curve analysis was used to determine the value of factors found to be significant in multivariate analyses for predicting an IR. A total of 182 patients with intermediate- and high-risk PTC were analyzed; the percentage of patients with a Non-IR was 61.54% (112/182), and the percentage of patients with an IR was 38.46% (70/182). The CD4
+
T-cell percentage (
t
= 4.757,
P
= 0.000), CD4/CD8 (
z
= − 2.632,
P
= 0.008), stimulated thyroglobulin (sTg) level (
z
= − 8.273,
P
= 0.000) and M stage (
χ
2
= 17.823,
P
= 0.000) of the two groups were significantly different. Multivariate analysis showed that only the sTg level (OR: 1.116, 95% CI 1.068–1.165,
P
< 0.001) and CD4
+
T-cell percentage (OR: 0.909, 95% CI 0.854–0.968,
P
= 0.003) were independent factors associated with the therapeutic response to RT. The cutoff sTg level and CD4
+
T-cell percentage for predicting an IR were 7.62 μg/L and 40.95%, respectively. The sTg level and CD4
+
T-cell percentage were verified to be independent predictive factors of RT response. Higher sTg levels and lower CD4
+
T-cell percentages were related to an IR in patients with intermediate- and high-risk PTC.
Purpose This two-center study aimed to explore the main prognostic factors affecting the final disease status in children and adolescents with differentiated thyroid cancer (caDTC) following total ...thyroidectomy and radioiodine therapy (RAIT). Materials and methods All caDTC patients from two centers in the period from 2004-2022 were retrospectively included. At the last follow-up, the patients’ disease status was assessed and classified as an incomplete response (IR) or as an excellent or indeterminate response (EIDR). Then, the difference in preablation stimulated thyroglobulin (ps-Tg) levels between the two groups was compared, and the threshold for predicting IR was determined using receiver operating characteristic (ROC) analysis. Moreover, univariate and multivariate analyses were conducted to identify the factors influencing the patients’ ultimate disease outcomes. Results A total of 143 patients (98 females, 45 males; median age 16 years) were recruited. After a median follow-up of 42.9 months, 80 patients (55.9%) exhibited an EIDR, whereas 63 patients (44.1%) exhibited an IR. Patients with an IR had significantly greater ps-Tg levels than did those with an EIDR (median ps-Tg 79.2 ng/mL vs. 9.3 ng/mL, p<0.001). The ROC curve showed that ps-Tg ≥20 ng/mL was the most accurate for predicting IR at the last follow-up. According to multivariate analysis, only ps-Tg, T stage and the therapeutic response to initial RAIT were significantly associated with IR. Conclusion In caDTC patients, the ps-Tg level, T stage, and response to initial RAIT are critical final outcome indicators.
Objective
We aimed to explore the predictive value of stimulated thyroglobulin (sTg) and pre-ablation antithyroglobulin (pa-TgAb) products for the effect of radioiodine therapy (RAIT) on ...TgAb-positive differentiated thyroid cancer (DTC) patients.
Methods
In this study, we enrolled 265 patients with TgAb-positive DTC who underwent RAIT after total thyroidectomy (TT). Based on the last follow-up result, the patients were divided into two groups: the excellent response (ER) group and the non-excellent response (NER) group. We analyzed the factors related to the effect of RAIT.
Results
The ER group consisted of 197 patients. The NER group consisted of 68 patients. For the univariate analysis, we found that the maximal tumor diameter, whether with extrathyroidal extension (ETE), bilateral or unilateral primary lesion, multifocality, preoperative TgAb (preop-TgAb), pa-TgAb, sTg × pa-TgAb, initial RAIT dose, N stage, and surgical extent (modified radical neck dissection or not), showed significant differences between the ER group and NER group (all
p
-values <0.05). The receiver operating characteristic (ROC) curves showed that the cutoff value was 724.25 IU/ml, 424.00 IU/ml, and 59.73 for preop-TgAb, pa-TgAb, and sTg × pa-TgAb, respectively. The multivariate logistic regression analysis results indicated that pa-TgAb, sTg × pa-TgAb, initial RAIT dose, and N stage were independent risk factors for NER (all
p
-values <0.05). For the Kaplan–Meier analysis of disease-free survival (DFS), the median DFS of the patients with sTg × pa-TgAb < 59.73 and initial RAIT dose ≤ 100 mCi was significantly longer than that of the patients with sTg × pa-TgAb ≥ 59.73 (50.27 months vs. 48.59 months,
p
= 0.041) and initial RAIT dose >100 mCi (50.50 months vs. 38.00 months,
p
= 0.030).
Conclusion
We found the sTg and pa-TgAb conducts is a good predictor of the efficacy of RAIT in TgAb-positive DTC patients. It can play a very positive and important role in optimizing treatment, improving prognosis, and reducing the burden of patients.
Introduction
This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD).
...Methods
This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50 years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73–34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2 mg (0.05 ml) in the study eye every 4 weeks for the first 3 months, followed by 2 mg every 8 weeks until week 48, stratified by baseline BCVA ≥ or < 45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was ± 5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated.
Results
A total of 366 patients were enrolled (QL1207 group,
n
= 185; aflibercept group,
n
= 181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changes was − 1.1 letters (95% confidence interval − 3.0 to 0.7;
P
= 0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% 132/185 vs. aflibercept: 71.8% 130/181) and serious TEAE (QL1207: 14.1% 26 vs. aflibercept: 12.7% 23) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups.
Conclusions
QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice.
Trial Registration
ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019).
With the size of SiC boule increasing, the problem of crystal creaking becomes more and more serious. In this work, residual stress in SiC boule is calculated by conducting stress simulation based on ...COMSOL and STR-VR software. A direct diagram comparing on crystal stress distribution is given. Besides, we provide relevant indications for the complete realization of large size SiC bulk with low stress for growing mainstream 6-inch SiC bulk with competitive thickness (40–50 mm) and low residual stress. And a 6-inch stress-free SiC bulk with improved quality was successfully fabricated based on our theoretical investigations.
•Comsol and STR-VR simulations were conducted to verify the influence of parasitic polytypes, temperature gradient and thermal expansion coefficient differences on SiC stress.•The mechanism of SiC boule residual stress was revealed.•A direct diagram comparing on crystal stress distribution is given.•Relevant indications for the complete realization of large size SiC bulk with low stress was provided.
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•Sludge concentration affected FNA pretreatment performance.•Flocs sizes declined and more EPS was released to resist FNA inactivation.•FNA/MLVSS was used to characterize FNA ...intensity relative to sludge concentration.•FNA/MLVSS is more valuable than solely FNA as a criterion for inhibiting NOB.•FNA/MLVSS increment favors the achievement of nitritation in a range of 0.16–0.30.
This study investigated the effect of sludge concentration (expressed by mixed liquor volatile suspended solids, MLVSS) on free nitrous acid (FNA) pretreatment strategy to achieve nitritation. Results showed when FNA was 0.308 mgHNO2-N/L, nitrite oxidizing bacteria (NOB) activity increased by 70.2% as MLVSS increased from 8.4 to 16.8 g/L. Nitrite accumulation ceased as MLVSS increased to 12.6 g/L, indicating that FNA inhibition of NOB gradually weakened with increasing MLVSS. When FNA was higher than 0.770 mgHNO2-N/L, NOB activity was completely inhibited and the effect of MLVSS on FNA inhibition was negligible, with nitrite accumulation potential (NAP) varying from 88.1% to 90.0%. Mechanism investigation demonstrated flocs sizes distinctly declined, with more extracellular polymeric substances (EPS) released to resist FNA inactivation. Linear fitting showed NAP increased with FNA/MLVSS increment. Therefore, MLVSS affected FNA pretreatment performance, with FNA/MLVSS proposed as a more valuable criterion in FNA pretreatment strategy development, than the solely FNA.
•PD-1+ B cells were significantly upregulated in differentiated thyroid tumors.•Long-term stimulation upregulated PD-1/PD-L1 in B cells.•PD-1+ B cells suppressed the proliferation and viability of ...CD4+ and CD8+ T cells.•PD-1+ B cells inhibited autologous T cell expansion via PD-L1-dependent pathway.•Surgery and radioiodine therapy reduced the frequency of PD-1+ B cells.
B cell-mediated regulatory function is instrumental to the maintenance of tolerance, but may also contribute to immune dysfunction during infectious diseases and malignancies. In this study, we investigated a subset of B cells characterized by PD-1 expression. Data showed that these PD-1+ B cells were rare in peripheral blood, but were significantly upregulated in differentiated thyroid tumors. The PD-1+ B cells also expressed significantly higher level of PD-L1. Continuous, but not short-term, anti-Ig/CD40 L stimulation could upregulate the expression of PD-1 and PD-L1 in B cells. In in vitro experiments, PD-1+ B cells significantly suppressed the proliferation of CD4+ and CD8+ T cells and reduced their viability upon CD3/CD28 stimulation, thus suggesting that these PD-1+ B cells presented regulatory functions. However, unlike other IL-10-secreting Breg cell subsets, the PD-1+ B cells did not express high level of IL-10. Instead, it seemed that PD-L1 was instrumental to the suppressive effects mediated by PD-1+ B cells, since the blockade of PD-L1 significantly increased the proliferation and viability of T cells in the coculture. Interestingly, compared to untreated patients with differentiated thyroid tumor, the thyroidectomy and 131I-treated patients presented significantly lower frequencies of PD-1+ B cells. Together, our investigation demonstrated that the PD-1+ B cells possessed regulatory capacity toward T cell responses, and although rare in peripheral blood, they were significantly enriched in thyroid tumors.
In the last five years, China has seen the technological development of intelligent mining and the application of the longwall automation technology developed by the Longwall Automation Steering ...Committee. This paper summarizes this great achievement, which occurred during the 12th Five-Year Plan （2011-2015）, and which included the development of a set of intelligent equipment for hydraulic-powered supports, information transfers, dynamic decision-making, performance coordination, and the achievement of a high level of reliability despite difficult conditions. Within China, the intelligent system of a set of hydraulic-powered supports was completed, with our own intellectual property rights. An intelligent mining model was developed that permitted unmanned operation and single-person inspection on the work face. With these technologies, the number of miners on the work face can now be significantly reduced. Miners are only required to monitor mining machines on the roadway or at the surface control center, since intelligent mining can be applied to extract middle-thick or thick coal seams. As a result, miners＇ safety has been improved. Finally, this Darter discusses theprospects and challenges of intelligent mining over the next ten years.
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