Overexpression of CENPU promotes cancer growth and metastasis and is associated with poor survival in patients with nasopharyngeal carcinoma.

Background: Centromere protein U (CENPU) is key for mitosis in the carcinogenesis of cancers. However, the roles of CENPU have not been inspected in nasopharyngeal carcinoma (NPC). Thus, we aimed to explore the functions and mechanisms of CENPU in NPC. Methods: Expression of CENPU was evaluated by real-time quantitative polymerase chain reaction, western blotting and immunohistochemistry. The biological functions of CENPU were evaluated in vitro and in vivo. Gene chip analysis, ingenuity pathway analysis, and coimmunoprecipitation experiments were used to explore the mechanisms of CENPU. Results: CENPU was highly expressed in NPC. High expression of CENPU was associated with advanced tumor, node and metastasis (TNM) stage and poor overall survival. Cox regression analysis demonstrated that CENPU expression was an independent prognostic factor in NPC. Knockdown of CENPU inhibited proliferation and migration in vitro and in vivo. Knockdown of CENPU upregulated dual specificity phosphatase 6 (DUSP6) expression. The expression of CNEPU was inversely correlated with the expression of DUSP6 in NPC tissues. Mechanistic studies confirmed that CENPU increased the activation of the ERK1/2 and p38 signaling pathways by suppressing the expression of DUSP6. Conclusions: CENPU acts as an oncogene in NPC by interacting with DUSP6, and may represent a promising prognostic biomarker for patients with NPC.

Risk-adapted locoregional radiotherapy strategies based on a prognostic nomogram for de novo metastatic nasopharyngeal carcinoma patients treated with chemoimmunotherapy.

To develop a prognostic nomogram for individualized strategies on locoregional radiation therapy (LRRT) in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC) treated with chemoimmunotherapy. Ninety patients with dmNPC treated with chemoimmunotherapy and diagnosed between 2019 and 2022 were included in our study. Cox regression analysis was performed to identify independent prognostic factors for overall survival (OS) and progression-free survival (PFS) to establish a nomogram. With a median follow-up of 17.5 months, the median PFS and OS were 24.9 months and 29.4 months, respectively. Sixty-nine patients and twenty-one patients were included in the LRRT group and without LRRT group, respectively. Multivariate analysis revealed that younger age, lower EBV DNA copy number before treatment, a single metastatic site, more cycles of chemotherapy and immunotherapy were significantly associated with better OS. A prognostic nomogram was constructed incorporating the above 5 independent factors, with a C-index of 0.894. Patients were divided into low- and high-risk cohorts based on nomogram scores. A significant improvement in OS was revealed in the LRRT group compared with the without-LRRT group for patients in the high-risk cohort (HR = 2.46, 95% CI 1.01-6.00, P = 0.049), while the OS was comparable between the two groups in the low-risk cohort. Our study indicates that LRRT may be associated with better prognosis in high-risk patients with dmNPC in the era of immunotherapy.

Production of Tone 2 in disyllabic words in Mandarin Chinese speaking children aged 3-5 with a cochlear implant and a contralateral hearing aid.

To investigate Mandarin Tone 2 production of disyllabic words of prelingually deafened children with a cochlear implant (CI) and a contralateral hearing aid (HA) and to evaluate the relationship between their demographic variables and tone-production ability. Thirty prelingually Mandarin-speaking preschoolers with CI+HA and 30 age-matched normal-hearing (NH) children participated in the study. Fourteen disyllabic words were recorded from each child. A total of 840 tokens (14 × 60) were then used in tone-perception tests in which four speech therapists participated. The production of T2-related disyllabic words of the bimodal group was significantly worse than that of the NH group, as reflected in the overall accuracy (88.57% ± 16.31% vs 99.29% ± 21.79%, p < 0.05), the accuracy of T1+T2 (93.33% vs 100%), the accuracy of T2+T1 (66.67 ± 37.91% vs 98.33 ± 9.13%), and the accuracy of T2+T4 (78.33 ± 33.95% vs 100%). In addition, the bimodal group showed significantly inferior production accuracy of T2+T1 than T2+T2 and T3+T2, p < 0.05. Both bimodal age and implantation age were significantly negatively correlated with the overall production accuracy, p < 0.05. For the error patterns, bimodal participants experienced more errors when T2 was in the first position of the tone combination, and T2 was most likely to be mispronounced as T1 and T3. Bimodal patients aged 3-5 have T2-related disyllabic lexical tone production defects, and their performances are related to tone combination, implantation age, and bimodal age.

Efficacy and safety of DBPR108 (prusogliptin) as an add-on to metformin therapy in patients with type 2 diabetes: A 24-week, multi-centre, randomized, double-blind, placebo-controlled, superiority, phase III clinical trial.

AIM: To evaluate the efficacy and safety of DBPR108 (prusogliptin), a novel dipeptidyl peptidase-4 (DPP-4) inhibitor, as an add-on therapy in patients with type 2 diabetes (T2D) that is inadequately controlled with metformin. MATERIALS AND METHODS: In this 24-week, multi-centre, randomized, double-blind, placebo-controlled, superiority, phase III study, adult T2D patients with HbA1c levels ranging from 7.0% to 9.5% on stable metformin were enrolled and randomized (2:1) into the DBPR108 + metformin and placebo + metformin groups. The primary endpoint was the change from baseline in HbA1c at week 24 of DBPR108 versus placebo as an add-on therapy to metformin. RESULTS: At week 24, the least-square mean (standard error) change from baseline in HbA1c was significantly greater in the DBPR108 group (-0.70% [0.09%]) than in the placebo group (-0.07% [0.11%]) (P < .001), with a treatment difference of -0.63% (95% confidence interval: -0.87%, -0.39%) on the full analysis set. A higher proportion of patients achieved an HbA1c of 6.5% or less (19.7% vs. 8.5%) and an HbA1c of 7.0% or less (50.0% vs. 21.1%) at week 24 in the DBPR108 + metformin group. Furthermore, add-on DBPR108 produced greater reductions from baseline in fasting plasma glucose and 2-hour postprandial plasma glucose without causing weight gain. The overall frequency of adverse events was similar between the two groups. CONCLUSIONS: DBPR108 as add-on therapy to metformin offered a significant improvement in glycaemic control, was superior to metformin monotherapy (placebo) and was safe and well-tolerated in patients with T2D that is inadequately controlled with metformin.

[Long-term Storage and Rapid Activity Recovery of ANAMMOX Granular Sludge].

At 4℃ and with no substrate, the activity recovery of ANAMMOX granular sludge was examined after 230 days of storage, and the effect of adding two organic carbon sources (glucose and sodium propionate) on the recovery was explored. After 230 days of long-term storage, the activity of ANAMMOX bacteria was 0.013 g·(g·d)-1, which was just 6.02% of the baseline, and the average particle size was 135.05 µm, which was 38.23% lower. The sludge disintegration, black in color. In the activity recovery stage, the R2 and R3 reactors added glucose and sodium propionate as organic carbon sources. The recovery results showed that after 15 days of recovery, the PN content of the R1, R2, and R3 reactors reached 126.30, 188.86, and 168.82 mg·g-1, respectively, and the activity of the ANAMMOX bacteria was improved, reaching 0.145, 0.185, and 0.126 g·(g·d)-1, respectively. The R2 reactor with glucose as the organic carbon source had the highest ANAMMOX bacteria activity, which recovered 85.65% before preservation, and the total nitrogen removal rate reached 81.61%. On the 20th day, the particle sizes of the ANAMMOX granular sludge in the R1, R2, and R3 reactors were 289.81, 359.66, and 314.37 µm, respectively, indicating that the long-term preservation of ANAMMOX granular sludge is not an insurmountable problem. Furthermore, adding glucose during the recovery phase can not only effectively increase the EPS content and promote particle growth and adhesion, but also enrich the reaction pathways of ANAMMOX, enhancing recovery rates.

Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese.

Blood lipids are important risk factors for coronary artery disease (CAD). Here we perform an exome-wide association study by genotyping 12,685 Chinese, using a custom Illumina HumanExome BeadChip, to identify additional loci influencing lipid levels. Single-variant association analysis on 65,671 single nucleotide polymorphisms reveals 19 loci associated with lipids at exome-wide significance (P<2.69 × 10(-7)), including three Asian-specific coding variants in known genes (CETP p.Asp459Gly, PCSK9 p.Arg93Cys and LDLR p.Arg257Trp). Furthermore, missense variants at two novel loci-PNPLA3 p.Ile148Met and PKD1L3 p.Thr429Ser-also influence levels of triglycerides and low-density lipoprotein cholesterol, respectively. Another novel gene, TEAD2, is found to be associated with high-density lipoprotein cholesterol through gene-based association analysis. Most of these newly identified coding variants show suggestive association (P<0.05) with CAD. These findings demonstrate that exome-wide genotyping on samples of non-European ancestry can identify additional population-specific possible causal variants, shedding light on novel lipid biology and CAD.

[The protective effects of ischemic preconditioning on the kidney injury following with ischemia/reperfusion of limbs and the possible mechanisms].

AIM: To explore the protective effects of ischemic preconditioning on the kidney injury following with ischemia/reperfusion (I/R) of limbs. METHODS: The models of I/R injury of limbs were constructed in rabbits. The blood from right external jugular vein, renal artery and renal vein represent the peripheral blood, into and out-flowing kidney blood (IKB, OKB) respectively. Superoxide dismutase (SOD), malondialdehyde (MDA), blood uria nitrogen (BUN) in peripheral blood and SOD, MDA, nitric oxide (NO) in IKB and OKB were measured, as well as SOD, MDA, induced nitric oxide synthase (iNOS) in kidney were detected in different groups. The effects of ischemic preconditioning (IPC) on the kidney injury were observed. RESULTS: Compared with control group, the activity of SOD in peripheral blood, IKB, OKB and kidney decreased, and the content of MDA increased after 4 h ischemia followed by 4 h reperfusion. The content of BUN in peripheral blood, NO in IKB, OKB and iNOS in kidney increased remarkably as well. SOD increased and MDA, NO, BUN, iNOS decreased significantly by ischemic preconditioning (IPC) before ischemia/reperfusion. The correlation analysis indicated that MDA was negatively correlated with SOD and positively correlated with NO, BUN. CONCLUSION: Oxygen free radicals metabolic confusion of kidney occurred in the course of I/R of limbs, IPC could strengthen the resistance of peroxidation in kidney and had protective effects on the kidney injury following with ischemia/reperfusion (I/ R) of limbs