Effect of DPP-4i inhibitors on renal function in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

AIMS: About 20-40% patients with type 2 diabetes mellitus (T2DM) had an increased risk of developing diabetic nephropathy (DN). Dipeptidyl peptidase-4 inhibitors (DPP-4i) were recommended for treatment of T2DM, while the impact of DPP-4i on renal function remained unclear. This study aimed to explore the effect of DPP-4i on renal parameter of estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) in T2DM. METHODS: A systematic search was performed across PubMed, Embase and Cochrane Library. A fixed or random-effects model was used for quantitative synthesis according to the heterogeneity, which was assessed with I2 index. Sensitivity analysis and publication bias were performed with standard methods, respectively. RESULTS: A total of 17 randomized controlled trials were identified. Administration of DPP-4i produced no significant effect on eGFR (WMD, -0.92 mL/min/1.73m2, 95% CI, -2.04 to 0.19) in diabetic condition. DPP-4i produced a favorable effect on attenuating ACR (WMD, -2.76 mg/g, 95% CI, -5.23 to -0.29) in patients with T2DM. The pooled estimate was stable based on the sensitivity test. No publication bias was observed according to Begg's and Egger's tests. CONCLUSIONS: Treatment with DPP-4i preserved the renal parameter of eGFR in diabetic condition. Available evidences suggested that administration of DPP-4i produced a favorable effect on attenuating ACR in patients with T2DM. INTERNATIONAL PROSPECTIVE REGISTER FOR SYSTEMATIC REVIEW (PROSPERO) NUMBER: CRD.42020144642.

Dipeptidyl peptidase-4 inhibitors alleviate cognitive dysfunction in type 2 diabetes mellitus.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are commonly at high risk for developing cognitive dysfunction. Antidiabetic agents might be repurposed for targeting cognitive dysfunction in addition to modulation on glucose homeostasis. This study aimed to evaluate the impact of dipeptidyl peptidase-4 inhibitors (DPP-4i) on cognitive function in T2DM. METHODS: PubMed, Embase, Cochrane Library and Web of Science were systematically searched from inception to September 30, 2023. Weighted mean differences were calculated using the Mantel-Haenszel (M-H) fixed or random effects model based on the degree of heterogeneity among studies. Heterogeneity was evaluated using a Chi-squared test and quantified with Higgins I2. Sensitivity analysis was performed with the leave-one-out method, and publication bias was evaluated according to Begg's and Egger's tests. RESULTS: Six clinical trials involving 5,178 participants were included in the pooled analysis. Administration of DPP-4i generally correlated with an increase of Mini-Mental State Examination (MMSE) scores (1.09, 95% CI: 0.22 to 1.96). DPP-4i alleviated cognitive impairment in the copying skill subdomain of MMSE (0.26, 95% CI: 0.12 to 0.40). Treatment with DPP-4i also resulted in an increase of Instrumental Activities of Daily Living (IADL) scores (0.82, 95% CI: 0.30 to 1.34). However, DPP-4i produced no significant effects on Barthel Activities of Daily Living (BADL) scores (0.37, 95% CI: -1.26 to 1.99) or other test scores. CONCLUSIONS: DPP-4i treatment favourably improved cognitive function in patients with T2DM. Further trials with larger samples should be performed to confirm these estimates and investigate the association of different DPP-4i with cognitive function among diabetic patients. TRIAL REGISTRATION IN PROSPERO: CRD42023430873.

Rescue of obesity-induced infertility in female mice by silencing AgRP neurons.

Obesity impacts multiple sites of the hypothalamus-pituitary gland-ovary axis (HPO axis) and has become a leading cause of female infertility. However, the critical hypothalamic neurons that participate in the development of obesity-induced infertility have not been well defined yet. Previous studies suggested that metabolic-sensing agouti-related peptide-expressing (AgRP) neurons in the arcuate nucleus (ARC) are hyperactive in diet-induced obesity (DIO) mice. We hypothesize that these neurons may convey metabolic dysfunction onto the HPO axis and contribute to obesity-induced infertility's pathophysiological process. To determine if AgRP neurons in obesity play a necessary role in the development of reproductive impairment in obesity, we used the chemogenetic method to normalize the neuronal activity of AgRP neurons in DIO female mice and test if their fertility can be restored. Our results indicated that chemogenetic inhibition of AgRP neurons could fully rescue the reproductive performance of DIO female mice, as manifested by recovered sex hormonal levels, ovulation, and fecundity. Moreover, we assayed serum AgRP levels in normal-weight and obese women and found elevated AgRP levels in obese subjects, suggesting the correlation between obesity and AgRP neuronal hyperactivity. Our results indicated that AgRP neurons constitute a central node connecting metabolism and reproduction, and dysfunctions of these neurons play a crucial role in reproductive impairment induced by metabolic abnormalities.

The PI3K/AKT/mTOR signaling pathway is aberrantly activated in primary central nervous system lymphoma and correlated with a poor prognosis.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a specific subtype of non-Hodgkin lymphoma that is highly invasive and confined to the central nervous system (CNS). The vast majority of PCNSLs are diffuse large B-cell lymphomas (DLBCLs). PCNSL is a highly heterogeneous disease, and its pathogenesis has not yet been fully elucidated. Further studies are needed to guide individualized therapy and improve the prognosis. METHODS: In this study, we detected 1) the expression of p-AKT, p-mTOR, p-S6 and p-4E-BP1 by immunohistochemistry (IHC) and Western blotting, 2) the mRNA expression by real-time qPCR and 3) the deletion of PTEN gene by immunofluorescence in situ hybridization (FISH) in order to investigate the activation status of the PI3K/AKT/mTOR signaling pathway in PCNSL. Samples of reactive hyperplasia lymphnods were used as the control group. The correlations between the clinical characteristics and prognosis of PCNSL patients and the expression of p-AKT, p-mTOR, p-S6 and p-4E-BP1 and the deletion of PTEN were assessed. RESULTS: The IHC results showed that the positive expression rates of p-AKT, p-mTOR, p-S6 and p-4E-BP1 in PCNSL were significantly higher in the PCNSL group than in the control group (P < 0.05). The relative mRNA expression level of MTOR in PCNSL samples was significantly increased (P = 0.013). Correlation analysis revealed that the expression of p-mTOR was correlated with that of p-AKT, p-S6, p-4E-BP1. PTEN deletion was found in 18.9% of PCNSL samples and was correlated with the expression of p-AKT (P = 0.031). Correlation analysis revealed that the PCNSL relapse rate in the p-mTOR-positive group was 64.5%, significantly higher than that in the negative group (P = 0.001). Kaplan-Meier survival analysis showed inferior progression-free survival (PFS) in the p-mTOR- and p-S6-positive groups (P = 0.002 and 0.009, respectively), and PTEN deletion tended to be related to shorter overall survival (OS) (P = 0.072). Cox regression analysis revealed p-mTOR expression as an independent prognostic factor for a shorter PFS (hazard ratio (HR) =7.849, P = 0.046). CONCLUSIONS: Our results suggest that the PI3K/AKT/mTOR signaling pathway is aberrantly activated in PCNSL and associated with a poor prognosis, which might indicate new therapeutic targets and prognostic factors.

Relationship between sperm NAD + concentration and reproductive aging in normozoospermia men:A Cohort study.

BACKGROUND: The mechanisms of age-dependent reproductive decline in men are largely overlooked. An age-dependent reduction in nicotinamide adenine dinucleotide (NAD+) levels has been reported in multiple somatic and female reproductive tissues, including oocytes and ovarian tissue. However, the relationship between NAD + levels and male reproduction has not yet been studied. In the current study, the association between sperm NAD + level and paternal age was investigated. In addition, we also investigated whether sperm NAD + levels were related to semen quality. METHODS: In this pilot observational cohort study, semen samples from 51 male subjects who visited a university-affiliated reproductive medical center for preconception consultation (< 30 years: n = 13, 30-40 years: n = 19, > 40 years: n = 19) were recruited. Their anthropometric characteristics were recorded, and semen analysis was performed. Their sperm NAD + levels were evaluated spectrophotometrically. RESULTS: There were significant differences among the three age groups in the major parameters of semen quality. The sperm NAD + level was, however, similar among the three groups (< 30 years: 91.61 ± 15.59 nmol/106 sperm, 30-40 years: 125.60 ± 16.28 nmol/106 sperm, > 40 years: 115.59 ± 16.55 nmol/106 sperm). Additionally, linear regression also revealed no correlation between sperm NAD + concentration and the age of the participants (r2 = 0.018, p = 0.35). Noticeably, a negative correlation was found between the sperm NAD + concentrations and the sperm quality parameters, including sperm concentration (r2 = 0.78, p < 0.0001), sperm count (r2 = 0.47, p < 0.0001), mobile sperm number (r2 = 33, p < 0.0001), and DFI (r2 = 0.35, p < 0.0001). The semen volume and mobility rate were not related to the sperm NAD + concentration. CONCLUSION: Unlike the age-related decrease of NAD + levels in oocytes and ovarian tissue, the sperm NAD + concentration is not age dependent. Sperm NAD + levels are negatively correlated with sperm quality, suggesting a unique role of NAD + in spermatogenesis, which warrants further study and opens opportunities for pharmaceutical interventions for oligozoospermia.

Transcriptome sequencing of endometrium revealed alterations in mRNAs and lncRNAs after ovarian stimulation.

RESEARCH QUESTION: Using RNA-sequencing analysis, we investigated the relationship between ovarian stimulation and endometrial transcriptome profiles during the window of implantation (WOI) to identify candidate predictive factors for the WOI and to optimize timing for embryo transfer. METHODS: Twelve women with normal basal hormone levels and regular ovulation were randomly assigned into three groups based on sampling time: late-proliferate phase (P group), and receptive phase in natural cycles (LH+7, N group) and stimulated cycles (hCG+7, S group). Transcriptome profiles of mRNAs and long non-coding RNAs (lncRNAs) were then compared among the three groups. Validation was performed using real-time qPCR. RESULTS: Comparison of transcriptome profiles between the natural and stimulated endometrium revealed 173 differentially expressed genes (DEGs), with a > 2-fold change (FC) and p < 0.05, under the influence of supraphysiological estradiol (E2) induced by ovarian stimulation. By clustering and KEGG pathway analysis, molecules and pathways associated with endometrial receptivity were identified. Of the 39 DEGs common to the three groups, eight genes were validated using real-time PCR. ESR1, MMP10, and HPSE were previously reported to be associated with endometrial receptivity. In addition, three novel genes (IL13RA2, ZCCHC12, SRARP) and two lncRNAs (LINC01060, LINC01104) were new potential endometrial receptivity-related markers. CONCLUSION: Using mRNA and lncRNA sequencing, we found that supraphysiological E2 levels from ovarian stimulation had a marked impact upon endometrial transcriptome profiles and may result in a shift of the WOI. The precise mechanisms underlying the supraphysiological hormone-induced shift of the WOI require further research. REGISTRATION NUMBER: ChiCTR180001453.

Parenchymal central nervous system involvement in aggressive B-cell lymphoma: retrospective analysis of clinical and MRI features in a Chinese population.

BACKGROUND: Secondary central nervous system lymphoma (SCNSL) is defined as secondary central nervous system (CNS) involvement in patients with systemic lymphoma. It is considered a profoundly adverse complication with inferior clinical outcome. Parenchymal involvement in the CNS in aggressive B-cell lymphoma is not frequently seen and remains a diagnostic dilemma. METHODS: In our study, we retrospectively analyzed the clinical and magnetic resonance imaging (MRI) features of 26 parenchymal SCNSL patients. In addition, we compared MRI features of SCNSL and primary CNS lymphoma (PCNSL) patients after 1:1 propensity score matching. Also we presented two SCNSL cases with atypical MRI appearance. RESULTS: Among SCNSL patients, the median CNS relapse time was 3 months, and multiple lesions were found in 76.9% of the cases. In PCNSL, this percentage was 42.3% (p = 0.011). None of the SCNSL patients and 23.1% of the PCNSL patients had solitary infratentorial lesions (p = 0.003). CONCLUSIONS: The majority of parenchymal involvement occurred within the first year of systemic lymphoma, in which mostly cases presenting with multiple and supratentorial locations, unlike what was found in PCNSL.

The decline in serum estradiol on the second day after oocyte retrieval affects the outcome of IVF/ICSI-ET treatment in high ovarian responders.

OBJECTIVE: To investigate the predictive value of the decline in serum estradiol on the second day after oocyte retrieval on the outcomes of in vitro fertilization (IVF) or intra-cytoplasmic sperm injection and embryo transfer (ICSI-ET) among high ovarian responders. DESIGN: Retrospective single-center cohort study. SETTING: Tertiary-care, university-affiliated teaching hospital. Patients Women aged 20-45 years undergoing assisted reproduction treatment from June 2014 to December 2015. INTERVENTIONS: A total of 980 cycles were included; 395 high responders (Group 1) and 256 normal responders (Group 3) underwent embryo transfer (ET) in fresh ET cycles. A total of 329 high ovarian responders who underwent cryopreservation of all embryos (Group 2) were recruited as controls. The cases were divided into the following five subgroups according to the rate of serum estradiol decline on the second day after oocyte retrieval: 50.00-59.99% (Subgroup A), 60.00-69.99% (Subgroup B), 70.00-79.99% (Subgroup C), 80.00-89.99% (Subgroup D) and ≥ 90.00% (Subgroup E). The clinical outcomes were analyzed. MAIN OUTCOME MEASURES: Clinical pregnancy rate, implantation rate. RESULTS: In Group 1, the pregnancy rate decreased from 51.33 to 36.72% and the implantation rate decreased from 30.93 to 21.70% when the level of serum estradiol on the second day after oocyte retrieval decreased by more than 80%, which was a statistically significant decline (p < 0.05). The peak estradiol (E2) value and implantation rate were also significantly different (p < 0.05). In Group 2, the decline of serum E2 on the second day after oocyte retrieval had no significant effect on the clinical pregnancy rate or the implantation rate. The trend was similar in Group 3. CONCLUSIONS: A decline in the E2 level of > 80% after oocyte retrieval may play an important role in unsatisfactory IVF/ICSI-ET outcomes among high ovarian responders.

Report: Discussion on the development of nano Ag/TiO2 coating bracket and its antibacterial property and biocompatibility in orthodontic treatment.

This paper aims to explore the antibacterial property of nano Ag/TiO2 coating bracket for the common bacteria in oral cavity, and discuss its biocompatibility. Micro morphology in the surface of nano Ag/TiO2 coating bracket was detected by scanning electron microscope (SEM), and surface roughness of ordinary mental bracket, nano TiO2 coating bracket and nano Ag/TiO2 coating bracket were measured. First, antibacterial property of nano Ag/TiO2 coating bracket on the common bacteria in oral cavity was studied by sticking membrane method. Secondly, bonding strength of nano TiO2 coating and nano Ag/TiO2 coating bracket in groups were detected by scratching test. The result showed that, the synthetic nano Ag/TiO2 coating was nanogranular films with rigorous organizational structure, presenting as smooth and clean surface, and antibacterial rate of nano Ag/TiO2 coating for the common bacteria in oral cavity for 20 min was more than 79% in the dark. All the findings suggested that, nano Ag/TiO2 coating bracket not only has antibacterial effect but also has good biocompatibility, therefore, it can satisfy the clinical request of orthodontic treatment.

Effect of dipeptidyl peptidase-4 inhibitors on tumor necrosis factor alpha levels in patients with type 2 diabetes mellitus.

AIMS: Dipeptidyl peptidase-4 inhibitors (DPP-4i) served as oral antidiabetic agents for treatment of type 2 diabetes mellitus (T2DM). Although an action on glucose homeostasis was identified, no well-rounded illustration had been established on the changes of tumor necrosis factor alpha (TNF-alpha) levels during DPP-4i treatment. This study aimed to explore the anti-inflammatory effect of DPP-4i on TNF-alpha in patients with T2DM. METHODS: PubMed, Embase and Cochrane Library were systematically searched from inception to May 31, 2024. Randomized controlled trials exploring the impact of DPP-4i on TNF-alpha levels were identified. Risk of bias was assessed according to the Cochrane criteria. A fixed or random-effects model was selected to pool estimate on whether the heterogeneity was present. Subgroup analysis were performed to explore the potential factors that influenced heterogeneity. Related meta-analysis was conducted with the software of Revman 5.3 and STATA 12.0. RESULTS: Eleven trials involving 884 participants with T2DM were included. Pooled estimates suggested that DPP-4i did not significantly modulate TNF-alpha levels (WMD, - 0.70, 95% CI - 1.94 to 0.53, P = 0.26) in T2DM. DPP-4i produced a significant effect on TNF-alpha (WMD, - 4.50 pg/mL, 95% CI - 4.68 to - 4.32, P < 0.00001) when compared to placebo, and a comparable effect was demonstrated on TNF-alpha (WMD, 0.10 pg/mL, 95% CI - 0.11 to 0.30, P = 0.35) in comparison with active agents. Estimate was stable according to the sensitivity test. Subgroup analysis revealed that heterogeneity might not correlate with baseline glycated hemoglobin (HbA1c), age or treatment duration. CONCLUSIONS: A significant effect of DPP-4i on TNF-alpha levels was present in T2DM when compared to placebo. Administration of DPP-4i produced no significant effect on TNF-alpha in comparison with active comparators. Further studies with large samples should be performed to illustrate the impact of DPP-4i on TNF-alpha levels in T2DM. Trial registration International Prospective Register for Systematic Review (PROSPERO) number: CRD42020185479.

Soil organic carbon fractions and their stability under different land uses in wind erosion area of Northeast China.

Exploring the physical fractions of organic carbon and influencing mechanisms in grassland, forest, and farmland soils in wind erosion area can provide scientific basis for carbon sequestration, land utilization, wind prevention measure making, and fertility restoration of sloping farmland in the region. We examined the differentiation of aggregate organic carbon and density fractionation organic carbon in 0-15 cm soil layer across grassland, forest, and sloping farmland with 350 m long and 5° slope gradient in the wind erosion area of Meilisi District, Qiqihar, Heilongjiang, as well as the sloping farmland in the downhill section, middle section, and uphill section with every 100 m apart from the bottom to the top. The results showed that soil aggregates >2 mm were all destroyed across grassland, forest, and farmland soils, while the percentage of aggregates <0.053 mm was significantly higher than that of other sizes. The percentage of various soil aggregates, organic carbon content from density fractionations, and the proportion of organic carbon in the heavy fraction aggregates in farmland were significantly lower than that in grassland and forest soils. Soil aggregates in the uphill section of farmland were completely destroyed, and organic carbon content in various size aggregates and density fractionations gradually decreased with increasing slope. The proportion of organic carbon in the heavy fraction aggregates decreased, but that in light fraction aggregates increased gradually. Soil organic carbon and available potassium were key factors affecting aggregate stability, aggregate organic carbon content, and organic carbon content in density fractionations, while the loss of organic carbon in aggregate led to a decrease in aggregate stability. In summary, compared with grassland and forest soils, the stability of soil aggregates, the aggregate organic carbon content, the organic carbon content in density fractionations, and the proportion of organic carbon in heavy fraction aggregates in farmland all decreased in the wind erosion area of Northeast China. With the increases of slope, the aggregate organic carbon content, the organic carbon content in density fractionations, and the proportion of organic carbon in the heavy fraction aggregates in sloping farmland all decreased. Planting trees, conserving and expanding grassland area, and increasing the application of organic materials in sloping farmland in wind erosion area are effective approaches to stabilize and increase carbon storage, improve soil structure, and enhance soil quality.

Erratum: LncRNA-MALAT1, as a biomarker of neonatal BPD, exacerbates the pathogenesis of BPD by targeting miR-206.

[This corrects the article on p. 462 in vol. 13, PMID: 33594304.].

Effects of application of phosphate and phosphate-solubilizing bacteria on bacterial diversity and phosphorus fractions in a Phaeozems.

The aim of this study is to improve the utilization of phosphorus (P) in soil, and to study the effects of phosphate-solubilizing bacteria (PSB) on P fractions and bacterial communities. In this experiment, we reduced the amount of P fertilizer by 30 % and 40 % respectively to studied the effects of combined application of bacterial fertilizers on soil microbial community and phosphate transformation process under different fertilization rates. The results showed that the application of PSB affected the transformation process of different P fractions. PSB had the most significant impact on organic phosphorus (p < 0.05). Correlation analysis showed that the abundance of bacteria was significantly correlated to the P fractions, indicating that the application of PSB had affected the bacterial community structure. In addition, Structural Equation Model (SEM) analysis showed that there was a causal relationship between the various visual variables. SEM confirmed the response relationship between bacterial communities and P components. Based on these results, we concluded that the application of PSB increased the sensitivity of P components, especially Olsen-P and MBP, to soil microorganisms. The application of PSB is an effective method to improve P utilization.

Grafting (S)-2-Phenylpropionic Acid on Coordinatively Unsaturated Metal Centers of MIL-101(Al) Metal-Organic Frameworks for Improved Enantioseparation.

Chiral metal-organic frameworks (cMOFs) are emerging chiral stationary phases for enantioseparation owing to their porosity and designability. However, a great number of cMOF materials show poor separation performance for chiral drugs in high-performance liquid chromatography (HPLC). The possible reasons might be the irregular shapes of MOFs and the low grafting degree of chiral ligands. Herein, MIL-101-Ppa@SiO2 was synthesized by a simple coordination post-synthetic modification method using (S)-(+)-2-Phenylpropionic acid and applied as the chiral stationary phase to separate chiral compounds by HPLC. NH2-MIL-101-Ppa@SiO2 prepared via covalent post-synthetic modification was used for comparison. The results showed that the chiral ligand density of MIL-101-Ppa@SiO2 was higher than that of NH2-MIL-101-Ppa@SiO2, and the MIL-101-Ppa@SiO2 column exhibited better chiral separation performance and structural stability. The binding affinities between MIL-101-Ppa@SiO2 and chiral compounds were simulated to prove the mechanism of the molecular interactions during HPLC. These results revealed that cMOFs prepared by coordination post-synthetic modification could increase the grafting degree and enhance the separation performance. This method can provide ideas for the synthesis of cMOFs.

Non-Myeloablative Chemotherapy as Consolidation Strategy After High-Dose Methotrexate-Based Chemoimmunotherapy in Patients With Primary CNS Lymphoma: A Retrospective Single Center Study in China.

Primary central nervous system lymphoma (PCNSL) remains a disease with poor outcome and high recurrence rate. We retrospectively analyzed the clinical data of 243 immunocompetent patients with PCNSL in Beijing Tiantan Hospital. The median age of PCNSL patients was 57 years (range 10-95 years). For induction therapy, 94.7% of patients received high-dose methotrexate (HD-MTX) containing regimens, and 59.3% received rituximab, which increased over time. The overall response rate was 72.8%, with 58.8% achieving complete response. With a median follow-up of 27.0 months (95% confidence interval 23.6-30.4), the median progression-free survival (PFS) time was 14.0 months (95% CI 9.45-18.55), and the 2-year PFS rate was 33.2%. The median overall survival (OS) was not reached (NR), with an estimated overall survival rate at 4 years of 61.6%. Among 95 patients who completed sequential consolidation chemotherapy with either pemetrexed or etoposide plus cytarabine, the median PFS was 28 months (95% CI 17.11-38.89), and the estimated overall survival at 4 years was 78.7%. In conclusion, HD-MTX based induction chemotherapy with non-myeloablative sequential consolidation chemotherapy is an alternative feasible treatment option.

Chief Executive Officer Proactive Personality and Acquisitions: A Fuzzy Set Qualitative Comparative Analysis of China's Listed Firms.

The role of the CEO in an enterprise's management decisions renders their individual characteristics influential in decisions about mergers and acquisitions (M&As). Personal characteristics are based on many aspects, therefore, we provide a multi-angle insight into the personal characteristics of managers. Drawing on the upper echelons theory, we examine whether CEOs' proactive personality affects merger and acquisition decisions. The fuzzy-set qualitative comparative analysis (fsQCA) is performed using a sample of 64 listed firms in China for the period 2010-2019. There are three solutions for cross-industry mergers, and five for intra-industry mergers. The results suggest that: (a) proactive and overconfident CEOs are inclined toward cross-industry mergers; (b) non-proactive and low-educated CEOs are inclined toward intra-industry mergers; (c) emerging industry enterprises tend to choose intra-industry mergers; (d) overconfident CEOs are more likely to undertake cross-industry mergers in traditional industries.

LncRNA-MALAT1, as a biomarker of neonatal BPD, exacerbates the pathogenesis of BPD by targeting miR-206.

Neonatal bronchopulmonary dysplasia (BPD) is one of the common causes of premature birth complications, which is caused by lung dysplasia. Long non-coding RNA (LncRNA) has been proved to be related to BPD and other disease processes, but the molecular mechanism of metastasis-related lung adenocarcinoma transcript 1 (MALAT1) in BPD has not been fully understood. This study focused on exploring the clinical and molecular mechanism of MALAT1 in neonatal BPD, aiming to provide new insights for the management of neonatal BPD. In our study, we first found that serum MALAT1 was up-regulated in neonatal BPD and severe BPD. Further, through receiver operating characteristic curve (ROC) analysis, it was found that the area under the curve of MALAT1 for differentiating neonatal BPD from severe BPD was 0.943 and 0.866, respectively. Then, we established BPD models in vivo and in vitro with C57BL/6J mice and BEAS-2B cells, and found that MALAT1 was also highly expressed in them and increased with the induction time of the models. Pathological evaluation confirmed that down-regulating MALAT1 or up-regulating miR-206 might improve the pathological condition of BPD. Obvious inflammatory response, oxidative stress and up-regulated apoptosis were observed in BPD models in vivo and in vitro. However, after MALAT1 knockdown treatment, the above abnormal phenomena were alleviated to varying degrees. Furthermore, we also found that MALAT1 has a targeted relationship with miR-206, and miR-206 is down-regulated in BPD in vivo and in vitro. Down-regulating miR-206 could also eliminate the anti-BPD effect after knocking down MALAT1. The above results indicated that MALAT1 has the potential as a blood biomarker of neonatal BPD, and MALAT1-miR-206 axis mediates BPD process, which may be a new target for neonatal BPD treatment.

Treatment of secondary central nervous system involvement in systemic aggressive B cell lymphoma using R-MIADD chemotherapy: a single-center study.

BACKGROUND: Secondary central nervous system lymphoma (SCNSL) is defined as lymphoma involvement within the central nervous system (CNS) that originated elsewhere, or a CNS relapse of systemic lymphoma. Prognosis of SCNSL is poor and the most appropriate treatment is still undetermined. METHODS: We conducted a retrospective study to assess the feasibility of an R-MIADD (rituximab, high-dose methotrexate, ifosfamide, cytarabine, liposomal formulation of doxorubicin, and dexamethasone) regimen for SCNSL patients. RESULTS: Nineteen patients with newly diagnosed CNS lesions were selected, with a median age of 58 (range 20 to 72) years. Out of 19 patients, 11 (57.9%) achieved complete remission (CR) and 2 (10.5%) achieved partial remission (PR); the overall response rate was 68.4%. The median progression-free survival after CNS involvement was 28.0 months (95% confidence interval 11.0-44.9), and the median overall survival after CNS involvement was 34.5 months. Treatment-related death occurred in one patient (5.3%). CONCLUSIONS: These single-centered data underscore the feasibility of an R-MIADD regimen as the induction therapy of SCNSL, further investigation is warranted.

STAT3 Activation Is Associated with Interleukin-10 Expression and Survival in Primary Central Nervous System Lymphoma.

BACKGROUND: The findings from several studies have confirmed that signal transducer and activator of transcription 3 (STAT3) is constitutively phosphorylated in primary central nervous system lymphoma (PCNSL). However, the underlying mechanism and prognostic significance of STAT3 activation have not yet been clarified. METHODS: The expression of STAT3, phosphorylated STAT3 (p-STAT3), and interleukin (IL)-10 was examined in 32 PCNSL samples using immunohistochemistry. The relationship between IL-10 expression and STAT3 phosphorylation was determined. In addition, the associations of the expression of these proteins with the clinical factors and survival were analyzed. RESULTS: Expression of STAT3, p-STAT3, and IL-10 was detected in 28 (87.5%), 17 (53.1%), and 25 (78.1%) samples, respectively. IL-10 expression was significantly associated with STAT3 phosphorylation in PCNSL (P = 0.033). STAT3 phosphorylation and IL-10 expression were associated with the presence of multiple brain lesions (P = 0.004 and P = 0.027, respectively), suggesting that STAT3 activation might enhance the intracranial spread of tumors in PCNSL. The 2-year overall survival and progression-free survival (PFS) rates were 67.8% and 35.5%, respectively. Kaplan-Meier survival analysis demonstrated that STAT3 phosphorylation, IL-10 expression, and multiple brain lesions were significantly associated with PFS in those with PCNSL (P = 0.009, P = 0.030, and P = 0.040, respectively). However, Cox regression analysis indicated that only STAT3 phosphorylation was significantly associated with shorter PFS (hazard ratio, 3.22; 95% confidence interval, 1.24-8.37; P = 0.016). CONCLUSION: Our results have indicated that STAT3 activation is closely related to IL-10 expression and that p-STAT3 might be a novel biomarker predictive of poor survival in those with PCNSL.

Expression of hypoxia-inducible factor 1α, glucose transporter 1, and hexokinase 2 in primary central nervous system lymphoma and the correlation with the biological behaviors.

BACKGROUND: It has been indicated that abnormal glucose metabolism mediated by hypoxia-inducible factor 1α (HIF-1α) played an essential role in the development of solid tumor. However, there were rare studies about the role of them in primary central nervous system lymphoma (PCNSL). OBJECTIVE: To investigate the protein levels of HIF-1α, glucose transporter 1 (GLUT1), and hexokinase 2 (HK2) in PCNSL and whether their levels are associated with prognostic factors. METHODS: Expression of HIF-1α, GLUT1, and HK2 in 39 tumor tissues was evaluated by immunohistochemical stainning. The correlation of the expression of HIF-1α with the protein level of GLUT1 and HK2 was investigated. In addition, the association between these protein expression levels and clinical parameters and prognosis was analyzed. RESULTS: In the tumor specimens of PCNSL, positive stainings of HIF-1α, GLUT1, and HK2 were in 23 patients (58.97%), 25 patients (64.1%), and 26 patients (66.67%), respectively, which were associated with the expression level of lactic dehydrogenase (LDH), but not with age, gender, number of lesion, ECOG score, or deep structure. The expression of HIF-1α was positively correlated with the expression of GLUT1 (p < .01, r = .749) and HK2 (p < .01, r = .787). Univariate analysis showed that upregulated GLUT1 was unfavorable predictors of progression-free survival (PFS) in PCNSL. The results of Cox proportional hazards model showed GLUT1 was significantly associated with shorter PFS (hazard ration: 5.65; 95% confidence interval: 1.23-25.84; p = .026). CONCLUSIONS: This study indicated that there was a hypoxic microenvironment and HIF-1α was involved in the regulation of glycolysis pathway in PCNSL. GLUT1 might be a potential marker for shorter PFS in PCNSL.