Prognostic marker CD27 and its micro-environmental in multiple myeloma.

BACKGROUND: The Cluster of Differentiation 27 (CD27) is aberrantly expressed in multiple myeloma (MM) -derived. This expression facilitates the interaction between tumor and immune cells within TME via the CD27-CD70 pathway, resulting in immune evasion and subsequent tumor progression. The objective of this study is to investigate the correlation between CD27 expression and the prognosis of MM, and to elucidate its potential relationship with the immune microenvironment. METHODS: In this research, CD27 expression in T cells within the 82 newly diagnosed MM microenvironment was assessed via flow cytometry. We then examined the association between CD27 expression levels and patient survival. Subsequent a series of bioinformatics and in vitro experiments were conducted to reveal the role of CD27 in MM. RESULTS: Clinical evidence suggests that elevated CD27 expression in T cells within the bone marrow serves as a negative prognostic marker for MM survival. Data analysis from the GEO database has demonstrated a strong association between MM-derived CD27 and the immune response, as well as the hematopoietic system. Importantly, patients with elevated levels of CD27 expression were also found to have an increased presence of MDSCs and macrophages in the bone marrow microenvironment. Furthermore, the PERK-ATF4 signaling pathway has been implicated in mediating the effects of CD27 in MM. CONCLUSIONS: We revealed that CD27 expression levels serve as an indicative marker for the prognosis of MM patients. The CD27- PERK-ATF4 is a promising target for the treatment of MM.

Universal Hydrogen-Treated TiO2 Nanorod Array/Ti2COX MXene PEC Aptamer Sensor Modulated by the Transport Characteristic of Photogenerated Holes.

A semiconductor photoelectrochemical (PEC) aptamer sensor has been widely researched in recent years because of its broad application prospects. However, a universal PEC sensor has not been achieved, and its sensing mechanism based on a photogenerated carrier transfer process has yet to be elucidated. Herein, a novel hydrogen-treated TiO2 nanorod array one-dimensional (1D)/Ti2COX MXene two-dimensional (2D) (H-TiO2/Ti2COX) PEC aptamer sensor is presented, which achieved a record detection range of 10-9-103 µg/L and a limit of detection (LOD) of 1 fg/L for microcystic toxins-LR detection. Besides, the PEC sensor can also test serotonin (5-HT), aflatoxin-B1, and prostate-specific antigen (PSA) with high performance by changing the aptamers, exhibiting favorable application universality. Furthermore, a new phenomenon of a switchable enhanced/suppressed photocurrent detection signal was discovered from H-TiO2/Ti2COX PEC aptamer sensors through the variation of the length of the TiO2 nanorod. Meanwhile, it reveals that the steric hindrance effect determines the photogenerated hole transfer and depolarization processes, which is proposed for the first time as the predominant mechanism of the switchable enhanced/suppressed photocurrent signal for PEC sensors, giving possibilities to develop PEC sensors with higher efficiency.

Incorporation of trans-rectal color doppler flow imaging and risk-stratification nomogram reduce unnecessary prostate biopsies in suspected prostate cancer patients: a bi-centered retrospective validation study.

BACKGROUND: To explore the role of Trans-rectal Color Doppler Flow Imaging (TR-CDFI) and risk-stratification nomogram in a MRI-directed biopsy pathway and examine its clinical performance, via comparisons between existing four biopsy pathways. METHODS: A Bi-centered retrospective cohort study on biopsy-naïve male population who received ultrasound-guided prostate biopsy from Jan. 2015 to Feb. 2022 was proposed. All enrolled patients should have undergone serum-PSA test, TR-CDFI and multiparametric MRI before biopsy, and subsequently opted for surgical intervention, enabling more accurate pathological grading. We then utilized univariate and multivariate logistic regression analysis to construct a predictive nomogram for risk-stratification. Outcome measurements were overall prostate cancer (PCA) detection rate, clinically significant PCA (csPCA) detection rate, clinically insignificant PCA (cisPCA) detection rate, biopsy avoidance rate and missed csPCA detection rate. Decision curve analysis was used to compare the performances between diagnostic pathways. RESULTS: Under the criteria mentioned above, 752 patients from two centers were included. Reference pathway (biopsy for all) showed that overall PCA detection rate was 46.1%, csPCA and cisPCA detection rates were 32.3% and 13.8% respectively. Risk-based MRI-directed TR-CDFI pathway, which incorporated both TR-CDFI and risk stratification nomogram, exhibited PCA detection rate of 38.7%, csPCA detection rate of 28.7%, cisPCA detection rate of 7.0%, Biopsy avoidance rate of 42.4%, and missed csPCA detection rate of 3.6%. Decision curve analysis revealed that the risk-based pathway held the most net benefit, under the threshold probability level between 0.1 and 0.5. CONCLUSIONS: The risk-based MRI-directed TR-CDFI pathway out-performed other strategies, balancing csPCA detection and biopsy avoidance. This suggested that incorporation of TR-CDFI and risk-stratification nomogram in the early PCA diagnostic procedures could reduce unnecessary biopsies.

HNRNPA2B1-mediated m6A modification of TLR4 mRNA promotes progression of multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is a malignancy of plasma cells that remains incurable. Toll-like receptor 4 (TLR4) acts as a stress-responsive signal, protecting mitochondria during proteasome inhibitor (PI) exposure, maintaining mitochondrial metabolism and increasing drug resistance in MM. However, the mechanism of TLR4 regulation remains elusive. AIMS: The purpose of this study was to investigate the methylation pattern of multiple myeloma and its effect on the expression of HNRNPA2B1 and downstream targets. METHODS: The methylation level in MM and normal bone marrow specimens was detected using a colorimetric assay. HNRNPA2B1 gene knockdown was achieved in RPMI 8226 MM cells via adenovirus transfection. CCK8 and flow cytometric assays were used to detect proliferation and apoptosis, respectively. Transcriptome sequencing and m6A methylation MeRIP sequencing were applied, and differentially expressed genes (DEGs) were detected. Three independent NCBI GEO datasets were applied to examine the effects of HNRNPA2B1 and TLR4 expression on MM patient survival. RESULTS: HNRNPA2B1 promoted MM progression. Clinical data from database revealed that HNRNPA2B1 was adverse prognostic factor for survival among MM patients. Furthermore, transcriptome sequencing and methylation sequencing showed that HNRNPA2B1 recognized and was enriched at the m6A sites of TLR4 and TLR4 was down-regulated of both the m6A level and transcription level in HNRNPA2B1-knockdown MM cells. Moreover, TLR4 was an adverse survival prognostic factor based on database analysis. CONCLUSION: Overall, our study implies that the RNA-binding protein HNRNPA2B1 increases cell proliferation and deregulates cell apoptosis in MM through TLR4 signaling. Our study suggests HNRNPA2B1 as a potential therapeutic target for MM.

Spatio-Temporal Dynamics of Entropy in EEGS during Music Stimulation of Alzheimer's Disease Patients with Different Degrees of Dementia.

Music has become a common adjunctive treatment for Alzheimer's disease (AD) in recent years. Because Alzheimer's disease can be classified into different degrees of dementia according to its severity (mild, moderate, severe), this study is to investigate whether there are differences in brain response to music stimulation in AD patients with different degrees of dementia. Seventeen patients with mild-to-moderate dementia, sixteen patients with severe dementia, and sixteen healthy elderly participants were selected as experimental subjects. The nonlinear characteristics of electroencephalogram (EEG) signals were extracted from 64-channel EEG signals acquired before, during, and after music stimulation. The results showed the following. (1) At the temporal level, both at the whole brain area and sub-brain area levels, the EEG responses of the mild-to-moderate patients showed statistical differences from those of the severe patients (p < 0.05). The nonlinear characteristics during music stimulus, including permutation entropy (PmEn), sample entropy (SampEn), and Lempel−Ziv complexity (LZC), were significantly higher in both mild-to-moderate patients and healthy controls compared to pre-stimulation, while it was significantly lower in severe patients. (2) At the spatial level, the EEG responses of the mild-to-moderate patients and the severe patients showed statistical differences (p < 0.05), showing that as the degree of dementia progressed, fewer pairs of EEG characteristic showed significant differences among brain regions under music stimulation. In this paper, we found that AD patients with different degrees of dementia had different EEG responses to music stimulation. Our study provides a possible explanation for this discrepancy in terms of the pathological progression of AD and music cognitive hierarchy theory. Our study has adjunctive implications for clinical music therapy in AD., potentially allowing for more targeted treatment. Meanwhile, the variations in the brains of Alzheimer's patients in response to music stimulation might be a model for investigating the neural mechanism of music perception.

Proteomics-Based Approach Reveals the Involvement of SERPINB9 in Recurrent and Relapsed Multiple Myeloma.

Multiple myeloma (MM) is a common hematological malignancy with poorly understood recurrence and relapse mechanisms. Notably, bortezomib resistance leading to relapse makes MM treatment significantly challenging. To clarify the drug resistance mechanism, we employed a quantitative proteomics approach to identify differentially expressed protein candidates implicated in bortezomib-resistant recurrent and relapsed MM (RRMM). Bone marrow aspirates from five patients newly diagnosed with MM (NDMM) were compared with those from five patients diagnosed with bortezomib-resistant RRMM using tandem mass tag-mass spectrometry (TMT-MS). Subcellular localization and functional classification of the differentially expressed proteins were determined by gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and hierarchical clustering analyses. The top candidates identified were validated with parallel reaction monitoring (PRM) analysis using tissue samples from 11 NDMM and 8 RRMM patients, followed by comparison with the NCBI Gene Expression Omnibus (GEO) dataset of 10 MM patients and 10 healthy controls (accession no.: GSE80608). Thirty-four differentially expressed proteins in RRMM, including proteinase inhibitor 9 (SERPINB9), were identified by TMT-MS. Subsequent functional enrichment analyses of the identified protein candidates indicated their involvement in regulating cellular metabolism, apoptosis, programmed cell death, lymphocyte-mediated immunity, and defense response pathways in RRMM. The top protein candidate SERPINB9 was confirmed by PRM analysis and western blotting as well as by comparison with an NCBI GEO dataset. We elucidated the proteome landscape of bortezomib-resistant RRMM and identified SERPINB9 as a promising novel therapeutic target. Our results provide a resource for future studies on the mechanism of RRMM.

Patients' Preferences for Artificial Intelligence Applications Versus Clinicians in Disease Diagnosis During the SARS-CoV-2 Pandemic in China: Discrete Choice Experiment.

BACKGROUND: Misdiagnosis, arbitrary charges, annoying queues, and clinic waiting times among others are long-standing phenomena in the medical industry across the world. These factors can contribute to patient anxiety about misdiagnosis by clinicians. However, with the increasing growth in use of big data in biomedical and health care communities, the performance of artificial intelligence (Al) techniques of diagnosis is improving and can help avoid medical practice errors, including under the current circumstance of COVID-19. OBJECTIVE: This study aims to visualize and measure patients' heterogeneous preferences from various angles of AI diagnosis versus clinicians in the context of the COVID-19 epidemic in China. We also aim to illustrate the different decision-making factors of the latent class of a discrete choice experiment (DCE) and prospects for the application of AI techniques in judgment and management during the pandemic of SARS-CoV-2 and in the future. METHODS: A DCE approach was the main analysis method applied in this paper. Attributes from different dimensions were hypothesized: diagnostic method, outpatient waiting time, diagnosis time, accuracy, follow-up after diagnosis, and diagnostic expense. After that, a questionnaire is formed. With collected data from the DCE questionnaire, we apply Sawtooth software to construct a generalized multinomial logit (GMNL) model, mixed logit model, and latent class model with the data sets. Moreover, we calculate the variables' coefficients, standard error, P value, and odds ratio (OR) and form a utility report to present the importance and weighted percentage of attributes. RESULTS: A total of 55.8% of the respondents (428 out of 767) opted for AI diagnosis regardless of the description of the clinicians. In the GMNL model, we found that people prefer the 100% accuracy level the most (OR 4.548, 95% CI 4.048-5.110, P<.001). For the latent class model, the most acceptable model consists of 3 latent classes of respondents. The attributes with the most substantial effects and highest percentage weights are the accuracy (39.29% in general) and expense of diagnosis (21.69% in general), especially the preferences for the diagnosis "accuracy" attribute, which is constant across classes. For class 1 and class 3, people prefer the AI + clinicians method (class 1: OR 1.247, 95% CI 1.036-1.463, P<.001; class 3: OR 1.958, 95% CI 1.769-2.167, P<.001). For class 2, people prefer the AI method (OR 1.546, 95% CI 0.883-2.707, P=.37). The OR of levels of attributes increases with the increase of accuracy across all classes. CONCLUSIONS: Latent class analysis was prominent and useful in quantifying preferences for attributes of diagnosis choice. People's preferences for the "accuracy" and "diagnostic expenses" attributes are palpable. AI will have a potential market. However, accuracy and diagnosis expenses need to be taken into consideration.

High copper levels in follicular fluid affect follicle development in polycystic ovary syndrome patients: Population-based and in vitro studies.

Although the adverse effects of copper overexposure on the liver, kidney, spleen and intestinal organs are well known, information about the impact of copper toxicity on human reproduction is limited. A total of 348 infertile patients were enrolled in our present study, including 89 with polycystic ovary syndrome (PCOS), 145 with fallopian tube obstruction and 114 controls. The follicular fluid concentrations of 22 trace elements were measured by inductively coupled plasma mass spectrometry (ICP-MS). Principal component analysis was used to identify trace element profile alterations in different groups. The mRNA levels of steroidogenesis-related genes were measured by real-time PCR. Our results showed that the trace element profile in follicular fluid was obviously altered in PCOS patients. Copper concentrations were significantly (p < .05) higher in the PCOS group than in the other two groups. Increased copper levels in follicular fluid were associated with a higher number of retrievable oocytes in the PCOS group (B = 1.785, p = .001) but a lower rate of high-quality embryos (B = -6.360, p = .050). Moreover, follicular fluid copper levels were positively correlated with follicular fluid progesterone levels (r = 0.275, p = .010) and testosterone levels (r = 0.250, p = .022). Cultured human granulosa cells overexposed to copper showed significantly (p < .05) increased estradiol secretion and decreased testosterone levels. Real-time quantitative PCR revealed a significant (p < .05) increase in CYP19A1 and HSD3b mRNA expression. Our results indicate that increased copper levels in follicular fluid could affect follicle development in PCOS patients, and the mechanism may be related to copper-induced abnormalities in steroidogenesis.

Enhanced antitumor effect of combination of annexin A1 knockdown and bortezomib treatment in multiple myeloma in vitro and in vivo.

Bortezomib (BTZ) is one of the most frequently used drugs in treatment of multiple myeloma (MM), but drug-resistance often occurs and limits its clinical efficacy. Annexin A1 (ANXA1) is upregulated in MM, and its knockdown enhances chemosensitivity in MM. However, whether ANXA1 inhibition can increase antitumor activity of BTZ in MM cells remains unknown. In the present study, Cell Counting Kit-8 (CCK-8) and colony formation assays showed that ANXA1 silencing combined with BTZ treatment led to a more significant inhibition of MM cell proliferation than each treatment alone. Cell apoptosis was dramatically promoted in MM cells following silencing of ANXA1 and BTZ administration versus that in ANXA1-silenced alone or BTZ-treated alone cells, as evidenced by decreased expression of phosphorylated signal transducers and activators of transcription 3 and BCL2, and increased expression of BAX. Moreover, we demonstrated that the levels of IL-6 and IL-23 were markedly downregulated in ANXA1-silenced and BTZ-treated MM cells. Furthermore, the combination of ANXA1 knockdown and BTZ treatment distinctly suppressed tumor growth in vivo compared with BTZ treatment alone. Taken together, our results show that downregulation of ANXA1 enhances antitumor activity of BTZ in MM in vitro and in vivo, indicating that ANXA1 may be a promising target for enhancing the chemosensitivity of MM to BTZ.

[Effect of basic fibroblast growth factor on endogenous neural stem cell in rat cerebral cortex with global cerebral ischemia-reperfusion].

The present paper is aimedto investigate the effect of basic fibroblast growth factor (bFGF) on proliferation, migration and differentiation of endogenous neural stem cell in rat cerebral cortex with global brain ischemia-reperfusion. A global brain ischemia-reperfusion model was established. Immunohistochemistry was used to observe the pathological changes and the expression of BrdU and Nestin in cerebral cortex. RT-PCR was used to measure the NSE mRNA in brain tissue. The results of measurements indicated that in sham operation group, there was no positive cell in cerebral cortex, and the content of NSE mRNA did not change. In the operation group, the expression of BrdU and Nestin increased significantly at the end of the 3rd day, and peaked on the 7th day. NSE mRNA expression did not significantly increase. In bFGF group, compared with sham operation group and model group, the number of BrdU-positive and Nestin-positive cells increased significantly at each time point (P<0. 05), and peaked at the end of the 11th day, and the content of NSE mRNA increased significantly (P<0. 05). This research demonstrated that the proliferation of endogenous neural stem cells in situ could be induced by global cerebral ischemia and reperfu- sion, and could be promoted and extended by bFGF. In additiion, bFGF might promote endogenous neural stem cells differentiated into neurons.

A systematic review and meta-analysis of balance training in patients with chronic ankle instability.

BACKGROUND: Chronic ankle instability (CAI) is a common yet serious problem for elder patients. This meta-analysis aimed to evaluate the effects of balance training for CAI, to provide evidence for the clinical treatment, and care of CAI patients. METHODS: Two investigators searched PubMed, EMBASE, Science Direct, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and Weipu Databases up to May 20, 2023, for randomized controlled trials (RCTs) on the effects of balance training for CAI. The mean difference (MD) with 95% confidence intervals (95%CIs) was calculated for each outcome with a fixed or random effect model. Review Manager 5.3 software was used for meta-analysis. RESULTS: Nine RCTs involving 341 patients were included. Meta-analysis results showed that compared with blank controls, balanced training treatment of CAI could significantly improve the score of CAI [MD = 3.95, 95% CI (3.26, 4.64), P < 0.00001], SEBT-PM [MD = 4.94, 95% CI (1.88, 8.00), P = 0.002], SEBT-PL [MD = 5.19, 95% CI (1.57, 8.81), P = 0.005], and FAAM Sports [MD = 17.74, 95% CI (14.36, 21.11), P < 0.00001]. Compared with strength training, balance training treatment of CAI improved the score of CAIT [MD = 2.36, 95% CI (0.29, 4.44), P = 0.03], FAAM-ADL [MD = 4.06, 95% CI (1.30, 6.83), P = 0.004]. CONCLUSION: The analysis outcomes indicate that balance training enhances daily activity capability, motor function, and dynamic balance to different extents. Additionally, when comparing the results of balance training and strength training, no significant difference was observed between the two methods in improving the dynamic stability of CAI patients. However, it is noteworthy that balance training exhibits a more pronounced impact on enhancing functional scale scores.

Effects of chitosan on body weight gain, growth hormone and intestinal morphology in weaned pigs.

The study was conducted to determine the effects of chitosan on the concentrations of GH and IGF-I in serum and small intestinal morphological structure of piglets, in order to evaluate the regulating action of chitosan on weaned pig growth through endocrine and intestinal morphological approaches. A total of 180 weaned pigs (35 d of age; 11.56±1.61 kg of body weight) were selected and assigned randomly to 5 dietary treatments, including 1 basal diet (control) and 4 diets with chitosan supplementation (100, 500, 1,000 and 2,000 mg/kg, respectively). Each treatment contained six replicate pens with six pigs per pen. The experiment lasted for 28 d. The results showed that the average body weight gain (BWG) of pigs was improved quadratically by dietary chitosan during the former 14 d and the later 14 d after weaned (p<0.05). Furthermore, dietary supplementation of chitosan tended to quadratically increase the concentration of serum GH on d 14 (p = 0.082) and 28 (p = 0.087). Diets supplemented with increasing levels of chitosan increased quadratically the villus height of jejunum and ileum on d 14 (p = 0.089, p<0.01) and 28 (p = 0.074, p<0.01), meanwhile, chitosan increased quadratically the ratio of villus height to crypt depth in duodenum, jejunum and ileum on d 14 (p<0.05, p = 0.055, p<0.01) and 28 (p<0.01, p<0.01, p<0.01), however, it decreased quadratically crypt depth in ileum on d 14 (p<0.05) and that in duodenum, jejunum and ileum on d 28 (p<0.01, p<0.05, p<0.05). In conclusion, these results indicated that chitosan could quadratically improve growth in weaned pigs, and the underlying mechanism may due to the increase of the serum GH concentration and improvement of the small intestines morphological structure.

Oncolytic virus oHSV2 combined with PD-1/PD-L1 inhibitors exert antitumor activity by mediating CD4 + T and CD8 + T cell infiltration in the lymphoma tumor microenvironment.

A novel therapeutic regimen showed that the oncolytic type II herpes simplex virus (oHSV2) was able to prevent colorectal cancer growth, recurrence, and metastasis. However, no study has yet explored whether oHSV2 has an impact on the development of diffuse large B-cell lymphoma (DLBCL). We chose the clinical chemotherapeutic drug doxorubicin (DOX) as a positive control to evaluate the effect of oHSV2 infection on the apoptotic, invasive, and proliferative capacity of DLBCL cells. We next further explored the therapeutic efficacy of oncolytic virus oHSV2 or DOX in DLBCL tumor bearing BALB/c mice, and evaluated the infiltration of CD8 + T cells and CD4 + T cells in tumor tissues. A pathological approach was used to explore the effects of oHSV2 on various organs of tumor bearing mice, including the heart, liver, and kidney. Next, SU-DHL-4 cells were co-cultured with cytotoxic T lymphocytes (CTLs) to mimic the tumor immune microenvironment (TME), to explore the impact of oHSV2 on the immune environment at the cellular level, and then analyzed the relationship between oHSV2 and the PD-1/PD-L1 immune-checkpoint. Subsequently, we further validated the efficacy of combined oHSV2 and PD-L1 treatment on transplanted tumor growth in mice at the in vivo level. DLBCL cells were sensitive to the action of the oncolytic virus oHSV2, and the decline in their proliferative activity showed a time-and dose-dependent manner. oHSV2 and DOX intervention preeminently increased the cell apoptosis, restrained cell proliferation and invasion, with the greatest changes occurring in response to oHSV2 infection. oHSV2 application effectively improved the immune status of the tumor microenvironment, favoring the invasion of CD8 + T and CD4 + T cells, thereby enhancing their antitumor effects. Besides, oHSV2 treatment has a safety profile in the organs of tumor bearing mice and indeed inhibits the PD-1/PD-L1 immune checkpoint in DLBCL. Interestingly, the combination of oHSV2 and PD-L1 antibodies results in more profound killing of DLBCL cells than oHSV2 infection alone, with a significant increase in the proportion of CD4 + T cells and CD8 + T cells. The antitumor effect was the best after combining oHSV2 and PD-L1 antibodies, suggesting that the combination therapy of oHSV2 and PD-L1 would have a better prospect for clinical application.

MiR-525-5p inhibits diffuse large B cell lymphoma progression via the Myd88/NF-κB signaling pathway.

Diffuse large B-cell lymphoma (DLBCL) is a B-cell lymphoma with a high degree of aggressiveness. Recently, evidence has shown that miR-525-5p is decreased in DLBCL, suggesting its possible involvement in tumor progression. In this study, miR-525-5p suppressed proliferation, invasion and clonogenicity, and increased apoptosis of U2932 cells, whereas miR-525-5p silencing enhanced tumor cell growth. Next, miR-525-5p targets the 3'-UTR of Myd88, and Myd88 protein was increased in lymphoma tissues. Similar to the miR-525-5p mimic, Myd88 siRNA suppressed proliferation, invasion, and clonogenicity, and enhanced apoptosis of U2932 cells. We observed that Myd88 reversed the inhibitory effect of miR-525-5p on tumor cell growth by transfecting cells with miR-525-5p mimics alone or together with Myd88 overexpression vector. In addition, in vivo studies have shown that compared to the control group, U2932 cells with upregulated miR-525-5p expression have a reduced ability to induce tumor formation. In conclusion, our results demonstrate that miR-525-5p inhibits the progression of DLBCL through the Myd88/NF-κB pathway, which largely fills the gap of previous studies, and our results may provide a new reference for the targeted treatment of DLBCL.

Establishment and evaluation of a nomogram for predicting the survival outcomes of patients with diffuse large B-cell lymphoma based on International Prognostic Index scores and clinical indicators.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma, treatment outcomes of patients vary greatly. The current International Prognostic Index (IPI) is not enough to distinguish patients with poor prognosis, and genetic testing is very expensive, so a inexpensive risk prediction tool should be developed for clinicians to quickly identify the poor prognosis of DLBCL patients. Methods: DLBCL patients (n=420; 18-80 years old) who received a combination of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) with or without rituximab (R-CHOP) at our hospital between 2008 and 2017 were included in the study. Potential predictors of survival were determined by univariate and multivariate Cox regression analyses, and significant variables were used to construct predictive nomograms. The new prediction models were assessed using concordance indexes (C-indexes), calibration curves, and their clinical utility was assessed by decision curve analyses (DCAs). Results: The 5-year overall survival (OS) rate was 70.62% and the 5-year progression-free survival (PFS) rate was 59.02%. The multivariate Cox analysis indicated that IPI, Ki-67, the lymphocyte/monocyte ratio, and first-line treatment with rituximab were significantly associated with survival. The C-index results indicated that a predictive model that included these variables had better discriminability for OS (0.73 vs. 0.67) and PFS (0.68 vs. 0.63) than the IPI-based model. The calibration plots showed good agreement with observations and nomogram predictions. The DCAs demonstrated the clinical value of the nomograms. Conclusions: Our study identified prognostic factors in patients who were newly diagnosed with DLBCL to construct an individualized risk prediction model, combined IPI with common clinical indicators. Our model might be a valuable tool that could be used to predict the prognosis of DLBCL patients who receive standard first-line treatment regimens. It enables clinicians to quickly identify some patients with possible poor prognosis and choose more active treatment for patients, such as chimeric antigen receptor T-cell (CART) Immunotherapy and other new drugs therapy, so as to prolong the PFS and OS of patients.

Effects of exposure to the explosive and environmental pollutant 2,4,6-trinitrotoluene on ovarian follicle development in rats.

Although 2,4,6-trinitrotoluene (TNT) is a dangerous carcinogen in environmental pollution, information on the reproductive effects of TNT explosive contamination is limited. To explore the possible ovarian effects, TNT explosive-exposed rat models were established, and Wistar female rats were exposed to low and high TNT (40 g and 80 g, air and internal) explosives. After a month of exposure, the estrous cycle, ovarian histopathology, and follicle counting were conducted. Serum hormones follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), progesterone, testosterone, and estradiol were detected, and the mRNA and protein expression of steroidogenic enzymes were measured. The results showed that the diestrus phase duration was significantly (P < 0.05) increased in the high TNT-exposed groups. In addition, the proportions of preantral follicles were significantly (P < 0.05) decreased in the high TNT-exposed groups, as well as the proportions of atretic follicles. The serum estradiol levels were significantly (P < 0.05) increased, and the follicle-stimulating hormone and luteinizing hormone levels were significantly (P < 0.05) decreased in the high TNT-exposed groups. The mRNA levels of steroidogenic acute regulatory protein (Star), cytochrome P450 cholesterol side chain cleavage (Cyp11a1, Cyp17a1 and Cyp19a1), hydroxysteroid dehydrogenase 3b (Hsd3b) and steroidogenic factor-1 (SF-1) were significantly (P < 0.05) increased in the TNT-exposed groups. The protein levels of Star, Cyp11a1 and Hsd3b were increased (P < 0.05) in the TNT-exposed groups. These results indicate that the exposure of rats to TNT explosive can subsequently affect ovarian follicle development, suggesting that the mechanism may involve disrupting steroidogenesis.

[Investigation of the Performance of Organic Contaminant Degradation by Fe2+/PDS Under Environmentally Relevant pH Conditions].

Peroxydisulfate (PDS) activation by Fe2+ has proven to be a promising method to abate emerging organic contaminants by generating reactive oxidation species. Nevertheless, this process may only achieve good decontamination performance under acidic conditions, which has markedly limited its application in real practice. To address this issue, we comprehensively investigated the performance of the Fe2+/PDS process toward some probe contaminants at different pH levels and explored the potential change in reactive oxidative species and the influence of oxygen. Both SO4-· and Fe(Ⅳ) were identified to be involved in the Fe2+/PDS process, and the types of these oxidative species did not change with varying pH values. Although dissolved oxygen could compete with PDS for Fe2+, especially at high pH values, this competition process was not the major reason for the declined performance of the Fe2+/PDS process, since 37.6%-100% of PDS could also be activated with the presence of oxygen. Instead, the overdosing of Fe2+could greatly inhibit carbamazepine removal, indicating that the nonproductive consumption of reactive oxidants by Fe2+should account for the declined performance of Fe2+/PDS under environmentally relevant pH conditions. Accordingly, the feasibility of applying zero-valent iron and sulfidated zero-valent iron was further evaluated, and the formation of corrosion products was characterized using X-ray absorption fine structure spectroscopy. All these findings will improve our understanding about the Fe2+/PDS process and thus facilitate its application.

Proteome and transcriptome analysis revealed florfenicol via affected drug metabolism and lipid metabolism induce liver injury of broilers.

In order to explore the mechanism of liver injury induced by florfenicol (FFC) in broilers. Sixty broilers were randomly divided into 2 groups: control group: normal drinking water and feed were given every d; FFC group: tap water containing FFC (0.15g/L) was given every d and feed was taken freely; each group was given 5 dd of continuous medication and feed was taken freely. The results showed that compared with the control group, FFC could significantly inhibit the weight gain of broilers (P < 0.05), and significantly inhibit the expression of CYP1A1 and CYP2H1 in liver tissue (P < 0.05). It was found that the expression of genes related to the effect of cytochrome P450 on the metabolism of exogenous substances, the peroxisome proliferators-activated receptors signal pathway, peroxisome pathway and glutathione metabolic pathway in the liver of broilers. The results of qPCR of UDP glucuronosyltransferase family 2A1 (UGT2A1), glutathione S-transferase-like 2 (GSTAL2), hematopoietic prostaglandin D synthase (HPGDS), glutathione S-transferase theta 1(GSTT1), isocitrate dehydrogenase (NADP(+)) 1 (IDH1), acyl-CoA oxidase 2 (ACOX2), fatty acid binding protein 1 (FABP1), adenylosuccinate lyase (ADSL), and phosphoribosyl aminoim idazolesuccino carboxamide synthase (PAICS) genes which were randomly selected from the most significant genes were consistent with those of RNA-seq. The results showed that FFC can affect the drug metabolism and lipid synthesis in the liver of broiler, thus impairing the normal function of liver and the growth and development of broiler.

Cost-utility analysis of newborn hepatitis B immunization in Beijing.

OBJECTIVES: To evaluate cost-utility of universal Hepatitis B vaccination program in the Beijing city (Beijing). METHODS: A decision-Markov model was constructed to determine the cost-utility of the universal immunization program for infants (universal vaccination program) by comparing with a hypothetic nonvaccination strategy in Beijing. Parameters in models were extracted from Beijing Center for Disease Control and Prevention (CDC) annual work report, Beijing health statistical yearbook, National Health Survey report, Beijing 1% population sample survey report, Beijing Health and Medical Price Monitoring Data Platform, and public literatures. The incremental cost­utility ratio (ICUR) was used to compare alternative scenarios. One-way sensitivity analysis and probabilistic sensitivity analysis were used to assess parameter uncertainties. RESULTS: The universal vaccination program had increased the utility and reduced cost among infants born in 2016 in Beijing. The ICUR was CNY -24,576.61 (US$ -3779.16) per QALY for universal vaccination program comparing with non-vaccination scenario from healthcare perspective. It was estimated that the universal vaccination would save direct medical treatment cost of CNY 2,262,869,173.50 (US$ 347,962,414.43) and prevent loss of 18322.25 QALYs within lifetime of target cohort. Discount rate accounted for the most remarkable influence on ICUR in one-way sensitivity analysis. The result of probabilistic sensitivity analysis illustrated that all of the ICURs were located in the fourth quadrant of the cost-utility incremental plot undergone 5000 times of Monte Carlo simulation. CONCLUSIONS: Current universal hepatitis B vaccination program in Beijing was highly cost utility. The investment was reasonable for current universal vaccination program in Beijing.