Synthesis and Application of Specific N2H4 Fluorescent Probes with AIE Effect Based on Pyrazole Structure.

Two fluorescent probes, Y1-2 were synthesized from 2-acetonaphthone, 4-acetylbiphenyl, and phenyl hydrazine by Vilsmeier-Haack reaction and Knoevenagel condensation. Their recognition efficacies for N2H4 were tested by UV-visible absorption spectroscopy and fluorescence emission spectroscopy. The recognition mechanism were studies by density-functional theory calculations, and the effect of pH on N2H4 recognition was also studied. The results showed that the probe Y1-2 has high selectivity and a low detection limit for N2H4, and the recognition of N2H4 can be accomplished at physiological pH. The probes have had obvious aggregation-induced luminescence effect, large Stokes shift, high sensitivity, and can be successfully applied to live cell imaging.

Enhancing Multi-species Liver Microsomal Stability Prediction through Artificial Intelligence.

Liver microsomal stability, a crucial aspect of metabolic stability, significantly impacts practical drug discovery. However, current models for predicting liver microsomal stability are based on limited molecular information from a single species. To address this limitation, we constructed the largest public database of compounds from three common species: human, rat, and mouse. Subsequently, we developed a series of classification models using both traditional descriptor-based and classic graph-based machine learning (ML) algorithms. Remarkably, the best-performing models for the three species achieved Matthews correlation coefficients (MCCs) of 0.616, 0.603, and 0.574, respectively, on the test set. Furthermore, through the construction of consensus models based on these individual models, we have demonstrated their superior predictive performance in comparison with the existing models of the same type. To explore the similarities and differences in the properties of liver microsomal stability among multispecies molecules, we conducted preliminary interpretative explorations using the Shapley additive explanations (SHAP) and atom heatmap approaches for the models and misclassified molecules. Additionally, we further investigated representative structural modifications and substructures that decrease the liver microsomal stability in different species using the matched molecule pair analysis (MMPA) method and substructure extraction techniques. The established prediction models, along with insightful interpretation information regarding liver microsomal stability, will significantly contribute to enhancing the efficiency of exploring practical drugs for development.

[Retracted] Tanshinone IIA enhances the inhibitory effect of imatinib on proliferation and motility of acute leukemia cell line TIB­152 in vivo and in vitro by inhibiting the PI3K/AKT/mTOR signaling pathway.

Following the publication of the above article, a concerned reader drew to the Editor's attention that the Transwell cell invasion assay data featured in Figs. 2D and 4E, certain of the tumor images in Fig. 5A and the TUNEL assay data in Fig. 5C were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Oncology Reports, or which under consideration for publication at around the same time (some papers of which have been retracted). In view of the fact that certain of these data had already apparently been published prior to the submission of this article for publication, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 43: 503­515, 2020; DOI: 10.3892/or.2019.7453].

Nasal microbes in allergic rhinitis children with or without sublingual immunotherapy.

The mechanism of allergic rhinitis (AR) remains unclear. Most researchers believe that AR is the result of a combination of environmental and genetic factors. Sublingual immunotherapy (SLIT) is a treatment that can change the natural course of AR through immunomodulatory mechanism and maintain efficacy after the treatment. Nasal cavity is the main site where AR patients contact with external allergens, produce inflammatory reactions and nasal symptoms. Therefore, in this study, we investigate the nasal microbiome in AR patients, and the changes after SLIT. In this cross-sectional study, nasal swabs for microbiome analysis were collected from 3 groups: SLIT-naïve AR patients (AR group), AR patients undergoing SLIT treatment over 2 years (SLIT group) and a control group (CG). The characteristics of nasal microbiome of each groups were produced by 16s-rDNA sequencing technology. The Simpson index of AR group was significantly higher than that of CG and SLIT groups, but not different between SLIT group and CG group. The abundance of Bacteroidete and Firmicutes remarkably increased in the AR group, but Bacteroidete reduced to CG level after SLIT. AR patients have different nasal microbiome composition, but we do not know how it happened and whether the AR condition affected nasal microbiome composition or nasal microbiome affected AR.

Torus Tubarius Hypertrophy After Adenoidectomy.

Backgrounds: Adenoidectomy is widely used to cure sleep-disordered breathing symptoms in children, torus tubarius hypertrophy (TTH) after adenoidectomy causing recurred snoring, sleep apnea, nasal obstruction, or mouth breathing was rarely reported, and the causes of TTH are still unclear. Objectives: To report a rare complication TTH after adenoidectomy, and the features of TTH. Material and Methods: A total of 36 pediatric patients with TTH diagnosed by our hospital from January 2017 to 2023 were included in this study. All children were treated conservatively for a month at first, and 13 patients underwent partial resection of TTH. The influencing factors (sex, age, allergic rhinitis [AR], and first operation way) were analyzed. Results: There were 36 patients with TTH: 27 boys and 9 girls. The age of the first operation ranged from 20 to 63 months, and the interval time of TTH after operation ranged from 3 to 55 months. Thirteen patients underwent partial resection of TTH. Thirteen children had definite symptoms and signs of AR. Conclusions and Significance: TTH is a rare complication after adenoidectomy, which is common in male children (75.0%) and in patients who took adenoidectomy before the age of 5 years (94.4%). TTH can occur as early as 3 months after adenoidectomy. AR and the operation way might have relationships with TTH.

Behavior analysis and formative assessments in online oral medicine education during the COVID-19 pandemic.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, traditional teaching methods were disrupted and online teaching became a new topic in education reform and informatization. In this context, it is important to investigate the necessity and effectiveness of online teaching methods for medical students. This study explored stomatology education in China to evaluate the development and challenges facing the field using massive open online courses (MOOCs) for oral medicine education during the pandemic. AIM: To investigate the current situation and challenges facing stomatology education in China, and to assess the necessity and effectiveness of online teaching methods among medical students. METHODS: Online courses were developed and offered on personal computers and mobile terminals. Behavioral analysis and formative assessments were conducted to evaluate the learning status of students. RESULTS: The results showed that most learners had already completed MOOCs and achieved better results. Course behavior analysis and student surveys indicated that students enjoyed the learning experience. However, the development of oral MOOCs during the COVID-19 pandemic faced significant challenges. CONCLUSION: This study provides insights into the potential of using MOOCs to support online professional learning and future teaching innovation, but emphasizes the need for careful design and positive feedback to ensure their success.

Oropharyngeal microbiome in children with adenotonsillar hypertrophy and after adenotonsillectomy.

BACKGROUND: The microbiome of tonsils and adenoid in adenotonsillar hypertrophy (ATH) has been profiled. Adenotonsillectomy (AT) is widely used for ATH in children. The variation of the oropharyngeal microecology in children with ATH or after AT have never been studied. OBJECTIVES: Here we aimed to evaluate the change in oropharyngeal microbiome in ATH Children after AT. MATERIALS AND METHODS: In this cross-sectional study, throat swabs for microbiome analysis were collected from ATH, AT and control groups. Using 16s rDNA sequencing, this study investigated the characteristics of oropharyngeal microbiome. RESULTS: The α-diversity showed a statistical difference in richness and the ß-diversity was significantly different among the three groups. The relative abundance of Haemophilus (member of Proteobacteria) increased but that of Actinomyces (member of Actinobacteriota) decreased in the ATH group compared to those in the AT and control groups, but their abundances showed no statistical difference between the AT and control groups. CONCLUSIONS: The oropharyngeal microbial diversity and composition are disrupted in children with ATH and can be restored after AT. This microbiome analysis provides a new understanding about the pathogenesis of ATH in children.SummaryIn this study, we aimed to evaluate the change in oropharyngeal microbiome in ATH Children after AT. The oropharyngeal microbial diversity and composition are disrupted in children with ATH and can be restored after AT.

Improved GNNs for Log D7.4 Prediction by Transferring Knowledge from Low-Fidelity Data.

The n-octanol/buffer solution distribution coefficient at pH = 7.4 (log D7.4) is an indicator of lipophilicity, and it influences a wide variety of absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties and druggability of compounds. In log D7.4 prediction, graph neural networks (GNNs) can uncover subtle structure-property relationships (SPRs) by automatically extracting features from molecular graphs that facilitate the learning of SPRs, but their performances are often limited by the small size of available datasets. Herein, we present a transfer learning strategy called pretraining on computational data and then fine-tuning on experimental data (PCFE) to fully exploit the predictive potential of GNNs. PCFE works by pretraining a GNN model on 1.71 million computational log D data (low-fidelity data) and then fine-tuning it on 19,155 experimental log D7.4 data (high-fidelity data). The experiments for three GNN architectures (graph convolutional network (GCN), graph attention network (GAT), and Attentive FP) demonstrated the effectiveness of PCFE in improving GNNs for log D7.4 predictions. Moreover, the optimal PCFE-trained GNN model (cx-Attentive FP, Rtest2 = 0.909) outperformed four excellent descriptor-based models (random forest (RF), gradient boosting (GB), support vector machine (SVM), and extreme gradient boosting (XGBoost)). The robustness of the cx-Attentive FP model was also confirmed by evaluating the models with different training data sizes and dataset splitting strategies. Therefore, we developed a webserver and defined the applicability domain for this model. The webserver (http://tools.scbdd.com/chemlogd/) provides free log D7.4 prediction services. In addition, the important descriptors for log D7.4 were detected by the Shapley additive explanations (SHAP) method, and the most relevant substructures of log D7.4 were identified by the attention mechanism. Finally, the matched molecular pair analysis (MMPA) was performed to summarize the contributions of common chemical substituents to log D7.4, including a variety of hydrocarbon groups, halogen groups, heteroatoms, and polar groups. In conclusion, we believe that the cx-Attentive FP model can serve as a reliable tool to predict log D7.4 and hope that pretraining on low-fidelity data can help GNNs make accurate predictions of other endpoints in drug discovery.

Structural Analysis and Prediction of Hematotoxicity Using Deep Learning Approaches.

Hematotoxicity has been becoming a serious but overlooked toxicity in drug discovery. However, only a few in silico models have been reported for the prediction of hematotoxicity. In this study, we constructed a high-quality dataset comprising 759 hematotoxic compounds and 1623 nonhematotoxic compounds and then established a series of classification models based on a combination of seven machine learning (ML) algorithms and nine molecular representations. The results based on two data partitioning strategies and applicability domain (AD) analysis illustrate that the best prediction model based on Attentive FP yielded a balanced accuracy (BA) of 72.6%, an area under the receiver operating characteristic curve (AUC) value of 76.8% for the validation set, and a BA of 69.2%, an AUC of 75.9% for the test set. In addition, compared with existing filtering rules and models, our model achieved the highest BA value of 67.5% for the external validation set. Additionally, the shapley additive explanation (SHAP) and atom heatmap approaches were utilized to discover the important features and structural fragments related to hematotoxicity, which could offer helpful tips to detect undesired positive substances. Furthermore, matched molecular pair analysis (MMPA) and representative substructure derivation technique were employed to further characterize and investigate the transformation principles and distinctive structural features of hematotoxic chemicals. We believe that the novel graph-based deep learning algorithms and insightful interpretation presented in this study can be used as a trustworthy and effective tool to assess hematotoxicity in the development of new drugs.

Neutrophil extracellular traps-associated modification patterns depict the tumor microenvironment, precision immunotherapy, and prognosis of clear cell renal cell carcinoma.

Background: Neutrophil extracellular traps (NETs) are web-like structures formed by neutrophils, and their main function is antimicrobial defense. Moreover, NETs have numerous roles in the pathogenesis and progression of cancers. However, the potential roles of NET-related genes in renal cell carcinoma remain unclear. In this study, we comprehensively investigated the NETs patterns and their relationships with tumor environment (TME), clinicopathological features, prognosis, and prediction of therapeutic benefits in the clear cell renal cell carcinoma (ccRCC) cohort. Methods: We obtained the gene expression profiles, clinical characteristics, and somatic mutations of patients with ccRCC from The Cancer Genome Atlas database (TCGA), Gene Expression Omnibus (GEO), and ArrayExpress datasets, respectively. ConsensusCluster was performed to identify the NET clusters. The tumor environment scores were evaluated by the "ESTIMATE," "CIBERSORT," and ssGSEA methods. The differential analysis was performed by the "limma" R package. The NET-scores were constructed based on the differentially expressed genes (DEGs) among the three cluster patterns using the ssGSEA method. The roles of NET scores in the prediction of immunotherapy were investigated by Immunophenoscores (TCIA database) and validated in two independent cohorts (GSE135222 and IMvigor210). The prediction of targeted drug benefits was implemented using the "pRRophetic" and Gene Set Cancer Analysis (GSCA) datasets. Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to identify the reliability of the core genes' expression in kidney cancer cells. Results: Three NET-related clusters were identified in the ccRCC cohort. The patients in Cluster A had more metabolism-associated pathways and better overall survival outcomes, whereas the patients in Cluster C had more immune-related pathways, a higher immune score, and a poorer prognosis than those in Cluster B. Based on the DEGs among different subtypes, patients with ccRCC were divided into two gene clusters. These gene clusters demonstrated significantly different immune statuses and clinical features. The NET scores were calculated based on the ten core genes by the Gene Set Variation Analysis (GSVA) package and then divided ccRCC patients into two risk groups. We observed that high NET scores were associated with favorable survival outcomes, which were validated in the E-MTAB-1980 dataset. Moreover, the NET scores were significantly associated with immune cell infiltration, targeted drug response, and immunotherapy benefits. Subsequently, we explored the expression profiles, methylation, mutation, and survival prediction of the 10 core genes in TCGA-KIRC. Though all of them were associated with survival information, only four out of the 10 core genes were differentially expressed genes in tumor samples compared to normal tissues. Finally, RT-PCR showed that MAP7, SLC16A12, and SLC27A2 decreased, while SLC3A1 increased, in cancer cells. Conclusion: NETs play significant roles in the tumor immune microenvironment of ccRCC. Identifying NET clusters and scores could enhance our understanding of the heterogeneity of ccRCC, thus providing novel insights for precise individual treatment.

Transcriptome profiling reveals the developmental regulation of NaCl-treated Forcipomyia taiwana eggs.

BACKGROUND: The biting midge, Forcipomyia taiwana, is one of the most annoying blood-sucking pests in Taiwan. Current chemical control methods only target the adult, not the immature stages (egg to pupa), of F. taiwana. Discovering new or alternative tactics to enhance or replace existing methods are urgently needed to improve the effectiveness of F. taiwana control. The egg is the least understood life stage in this pest species but may offer a novel point of control as addition of NaCl to the egg environment inhibits development. Thus, the objective of this study was to use RNA profiling to better understand the developmental differences between wild-type melanized (black) and NaCl-induced un-melanized (pink), infertile F. taiwana eggs. RESULTS: After de novo assembly with Trinity, 87,415 non-redundant transcripts (Ft-nr) with an N50 of 1099 were obtained. Of these, 26,247 (30%) transcripts were predicted to have long open reading frames (ORFs, defined here as ≥300 nt) and 15,270 (17.5%) transcripts have at least one predicted functional domain. A comparison between two biological replicates each of black and pink egg samples, although limited in sample size, revealed 5898 differentially expressed genes (DEGs; 40.9% of the transcripts with long ORFs) with ≥2-fold difference. Of these, 2030 were annotated to a Gene Ontology biological process and along with gene expression patterns can be separated into 5 clusters. KEGG pathway analysis revealed that 1589 transcripts could be assigned to 18 significantly enriched pathways in 2 main categories (metabolism and environmental information processing). As expected, most (88.32%) of these DEGs were down-regulated in the pink eggs. Surprisingly, the majority of genes associated with the pigmentation GO term were up-regulated in the pink egg samples. However, the two key terminal genes of the melanin synthesis pathway, laccase2 and DCE/yellow, were significantly down-regulated, and further verified by qRT-PCR. CONCLUSION: We have assembled and annotated the first egg transcriptome for F. taiwana, a biting midge. Our results suggest that down-regulation of the laccase2 and DCE/yellow genes might be the mechanism responsible for the NaCl-induced inhibition of melanization of F. taiwana eggs.

Global stability for a class of HIV virus-to-cell dynamical model with Beddington-DeAngelis functional response and distributed time delay.

A HIV virus-to-cell dynamical model with distributed delay and Beddington-DeAngelis functional response is proposed in this paper. Using the characteristic equations and analytical means, the principle reproduction number R0 on the local stability of infection-free and chronic-infection equilibria is established. Furthermore, by constructing suitable Lyapunov functionals and using LaSalle invariance principle, we show that if R0 ≤ 1 the infection-free equilibrium is globally asymptotically stable, while if R0 > 1 the chronic-infection equilibrium is globally asymptotically stable. Numerical simulations are presented to illustrate the theoretical results. Comparing the effects between discrete and distributed delays on the stability of HIV virus-to-cell dynamical models, we can see that they could be same and different even opposite.

Tanshinone IIA enhances the inhibitory effect of imatinib on proliferation and motility of acute leukemia cell line TIB­152 in vivo and in vitro by inhibiting the PI3K/AKT/mTOR signaling pathway.

Acute lymphoblastic leukemia (ALL) is a malignant hematological disease. Tanshinone IIA (Tan IIA) has antitumor activity in vitro and in vivo. The aim of the present study was to investigate the effects of Tan IIA in combination with imatinib (IM) on the proliferation, apoptosis, migration and invasion of acute T lymphocytic leukemia TIB­152 cells in vivo and in vitro, and analyze the potential underlying mechanism. Tan IIA and IM, alone and in combination, significantly inhibited proliferation, migration and invasion of TIB­152 cells, and promoted apoptosis; the effect of co­treatment with Tan IIA plus IM was enhanced. IGF­1 promoted the proliferation, migration and invasion of TIB­152 cells and inhibited apoptosis, while Tan IIA treatment significantly reversed these effects. In vivo experiments demonstrated that treatment with Tan IIA and IM, alone or in combination, significantly inhibited tumor growth in TIB­152 xenograft mice; the growth inhibition of Tan IIA plus IM was the strongest observed. Western blot analysis revealed that the combination of Tan IIA and IM resulted in significantly lower levels of p­PI3K, p­AKT and p­mTOR in cells and tissues compared with the IM and Tan alone treatment groups. In addition, the combination of Tan IIA and IM significantly decreased the levels of Ki67, cleaved caspase­3, VEGF and MMP­9 in cells and tissues, and the level of caspase­3 was significantly increased. Taken together, the results revealed that Tan IIA enhanced the inhibitory effect of imatinib on TIB­152 cell proliferation, migration and invasion, and induced apoptosis, which may be associated with inhibition of the PI3K/AKT/mTOR signaling pathway.

Down-regulated RBM5 inhibits bladder cancer cell apoptosis by initiating an miR-432-5p/ß-catenin feedback loop.

RNA-binding motif protein 5 (RBM5) acts as a tumor suppressor in various human cancers and presents with several important characteristics, such as the potentiation of apoptosis, inhibition of the cell cycle, and alternative splicing of Fas and caspase-2 precursor mRNA. However, its role in bladder urothelial carcinoma (BUC) remains unknown. In this study, we found that RBM5 expression was significantly down-regulated in BUC tissues when compared with the adjacent nontumor tissues. The down-regulation of RBM5 activates ß-catenin, which binds to the T-cell factor/lymphocyte enhancer factor element of the miR-432-5p promoter and elevates the expression of miR-432-5p in bladder cancer cells. The up-regulated miR-432-5p directly targets 3'-UTR and depresses RBM5 expression. Thus, RBM5-miR-432-5p-ß-catenin forms a feedback loop in regulating bladder cancer cell apoptosis. Our findings provide evidence that the regulatory feedback loop among RBM5, miR-432-5p, and Wnt-ß-catenin is responsible for the progress of bladder cancer cells.-Zhang, Y.-P., Liu, K.-L., Wang, Y.-X., Yang, Z., Han, Z.-W., Lu, B.-S., Qi, J.-C., Yin, Y.-W., Teng, Z.-H., Chang, X.-L., Li, J.-D., Xin, H., Li, W. Down-regulated RBM5 inhibits bladder cancer cell apoptosis by initiating an miR-432-5p/ß-catenin feedback loop.

[Research progress on the effects of atmospheric nitrogen dioxide on plant growth and metabo-lism]. / 大气NO2å½±å“æ¤ç‰©ç”Ÿé•¿ä¸Žä»£è°¢çš„ç ”ç©¶è¿›å±•.

Nitrogen dioxide (NO2) is one type of the atmospheric nitrogen oxides, which is the main component of atmospheric aerosol particles. Reducing the concentration of atmospheric NO2 can decrease the haze in the air. Atmospheric NO2 deposits on plant leaves by both dry and wet deposition. After leaf absorption, atmospheric NO2 was reduced by two metabolism ways: one was the nitrogen metabolism by reductase mainly in cytoplasm and chloroplast, and the other was the pathway of NO2 decomposition reaction in the apoplast and cytoplasm. Plant absorption of NO2 disturbs plant normal growth and physiological metabolism, including vegetative growth and reproductive growth, nitrate reductase (NaR) activity, nitrite reductase (NiR) activity, nitrogen uptake, photosynthetic and other physiological metabolic processes. Here, we reviewed the research progress on the effects of atmospheric NO2 on plant growth and metabolism, and proposed the future research direction of physiological and molecular mechanism of atmospheric NO2 absorption by plants.

TALENs-mediated homozygous CCR5Δ32 mutations endow CD4+ U87 cells with resistance against HIV­1 infection.

Since evidence suggests that transplantation of bone marrow stem cells with the C­C chemokine receptor type 5 (CCR5)Δ32/Δ32 genotype may cure patients infected with human immunodeficiency virus (HIV)­1, the present study aimed to reproduce the CCR5Δ32 mutation in cluster of differentiation (CD)4+ U87 cells using genome engineering methods. A modified transcription activator­like effector nucleases (TALENs) technique, combined with homologous recombination for site­specific, size­controlled and homozygous DNA deletions, was used to reproduce the homozygous CCR5Δ32 mutation in CD4+ U87 cells. The results indicated that the frequency of the TALENs­targeted mutation reached 50.4% without any selection, whereas homologous recombination from CCR5 to CCR5Δ32 occurred in 8.8% of targeted cells. Notably, a HIV­1 challenge test demonstrated that CCR5Δ32/Δ32 CD4+ U87 cells were resistant to HIV infection. In conclusion, engineered CCR5Δ32/Δ32 mutations endowed CD4+ U87 cells with resistance against HIV­1 infection; this site­specific, size­controlled and homozygous DNA deletion technique was able to induce precise genomic editing, i.e., the deletion or insertion of a predetermined length of DNA sequence at a specific locus throughout the genome.

HIV-1 p55-gag protein induces senescence of human bone marrow mesenchymal stem cells and reduces their capacity to support expansion of hematopoietic stem cells in vitro.

Patients with human immunodeficiency virus-1 (HIV-1) infection often present with hematopoietic failure. As the important hematopoietic support cells in the bone marrow (BM), the BM mesenchymal stem cells (BMSCs) can be impacted by HIV proteins that are released by infected cells within BM. In this study, we tested whether HIV protein p55-gag could induce senescence of BMSCs and reduce their capacity to support expansion of hematopoietic stem cells in vitro. BMSCs were chronically treated with p55-gag (BMSCgag ) for up to 20 days, and their proliferative activity and senescence makers were compared to nontreated cells (BMSCcon ). Then, we analyzed the hematopoietic support function of BMSCcon and BMSCgag by determining cellular proliferation, colony-forming ability, and primitive hematopoietic populations of hematopoietic progenitors grown on the BMSCs. In addition, we compared the gene expression patterns for supporting hematopoiesis of BMSCcon and BMSCgag. The results show that when compared to BMSCcon , BMSCgag reduced their proliferative activity and underwent senescence. The ability of BMSCgag to support the expansion of committed hematopoietic progenitors from umbilical cord blood-derived CD34+ cells may be impaired, while the expression of genes associated with maintaining and enhancing hematopoiesis appeared to be decreased in treated BMSCs compared to control BMSCs. In conclusion, senescence induced by p55-gag resulted in decreased hematopoietic support function of BMSCs through reducing a series of hematopoietic cytokine expression.

[Efficacy of alpha-lipoic acid combined with tamoxifen citrate in the treatment of oligoasthenospermia].

OBJECTIVE: To investigate the effect of alpha-lipoic acid (α-LA) combined with tamoxifen citrate (TC) in the treatment of oligoasthenospermia. METHODS: From June to November 2016, we treated 60 patients with oligoasthenospermia in our Department of Andrology, 30 (the trial group) with oral α-LA (0.6 g, qd) + TC (20 mg, qd) and the other 30 (the control group) with oral L-carnitine (1g, bid) + TC (20 mg, qd). Before and after 3 months of medication, we examined the semen parameters of the patients and the levels of their seminal oxidative stress biomarkers, including methylenedioxyamphetamine (MDA) and total antioxidant capacity (TAC) in the seminal plasma. We also compared the pregnancy rate and adverse reactions between the two groups. RESULTS: Totally, 57 of the patients completed the treatment, 28 in the trial group and 29 in the control. Compared with the baseline, the patients of the trial group showed significant improvement after 3 months of medication in the semen volume (ï¼»2.50 ± 0.71ï¼½ vs ï¼»3.37 ± 0.70ï¼½ ml, P <0.05), sperm concentration (ï¼»12.00 ± 1.65ï¼½ vs ï¼»19.34 ± 2.04ï¼½ ×106/ml, P <0.05), percentage of progressively motile sperm (PMS) (ï¼»18.01 ± 3.01ï¼½% vs ï¼»35.41 ± 6.49ï¼½%, P<0.05), MDA level (ï¼»14.96 ± 2.76ï¼½ vs ï¼»10.04 ± 1.04ï¼½ nmol/ml, P <0.05), and TAC in the seminal plasma (ï¼»9.83 ± 1.02ï¼½ vs ï¼»12.25 ± 1.11ï¼½ U/ml, P <0.05), and so did the controls in the semen volume (ï¼»2.76 ± 0.67ï¼½ vs ï¼»3.36 ± 0.93ï¼½ ml, P <0.05), sperm concentration (ï¼»11.47 ± 1.10ï¼½ vs ï¼»17.77 ± 3.56ï¼½ ×106/ml, P <0.05), percentage of PMS (ï¼»19.22 ± 1.41ï¼½ vs ï¼»36.01 ± 5.22ï¼½ %, P <0.05), MDA level (ï¼»14.66 ± 2.75ï¼½ vs ï¼»10.14 ± 1.01ï¼½ nmol/ml, P <0.05), and TAC in the seminal plasma (ï¼»9.84 ± 0.90ï¼½ vs ï¼»11.14 ± 0.84ï¼½ U/ml, P <0.05). There were no statistically significant differences in the above post-medication parameters between the trial and control groups (P >0.05) except in TAC, which was markedly more improved in the former than in the latter (P <0.05), nor in the percentage of morphologically normal sperm before and after treatment in either of the two groups (P >0.05). After 3 months of treatment, 3 pregnancies were achieved in the trial group and 1 in the control (10.7% vs 3.45%, P >0.05). No obvious adverse events occurred during the treatment. CONCLUSIONS: Alpha-lipoic acid combined with tamoxifen citrate can evidently improve semen parameters in oligoasthenospermia patients by relieving oxidative stress injury.

An association of type 1 diabetes mellitus with auditory dysfunction: A systematic review and meta-analysis.

OBJECTIVE: To establish the relationship between the presence of type 1 diabetes mellitus (DM) and auditory dysfunction in clinical settings by a systematic review and meta-analysis of currently available published data. DATA SOURCES AND REVIEW METHODS: The electronic databases PubMed, Embase, and Wanfang Data were searched for eligible relevant studies up to May 2016, and the reference lists of the retrieved articles were used for additional manual search. All the articles included in this pooled analysis were determined according to the preset inclusion and exclusion criteria. Meta-analysis of pooled data was performed using Review Manager 5.3. RESULTS: A total of 15 studies were included for further combined analysis. The results showed that patients with type 1 diabetes had a significantly higher prevalence of hearing loss than controls (odds ratio = 49.08, 95% confidence interval = 12.03-200.31, P < 0.00001); standardized mean of differences (SMD) of pure tone audiometry at 4,000 Hz between diabetes and controls was 0.87 (Z = 2.22, P = 0.03, I2 = 95%); SMD of the latency time was 0.54 (Z = 2.69, P = 0.007, I2 = 78%) for waves III and 0.61 (Z = 2.38, P = 0.02, I2 = 86%) for wave V, respectively; and SMD of the interpeak latency time was 0.41 (Z = 2.84, P = 0.005, I2 = 39%) for waves I to III and 0.61 (Z = 2.67, P = 0.008, I2 = 81%) for waves I to V, respectively, between diabetics and controls. CONCLUSION: Our study reveals that there is relationship between the presence of type 1 DM and an increased risk for developing mild and subclinical hearing impairment. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:1689-1697, 2017.

Viral Etiology Relationship between Human Papillomavirus and Human Breast Cancer and Target of Gene Therapy.

OBJECTIVE: To explore the viral etiology of human breast cancer to determine whether there are novel molecular targets for gene therapy of breast cancer and provide evidence for the research of gene therapy and vaccine development for breast cancer. METHODS: PCR was used to screen HPV16 and HPV18 oncogenes E6 and E7 in the SKBR3 cell line and in 76 paraffin embedded breast cancer tissue samples. RNA interference was used to knock down the expression of HPV18 E6 and E7 in SKBR3 cells, then the changes in the expression of cell-cycle related proteins, cell viability, colony formation, metastasis, and cell cycle progression were determined. RESULTS: HPV18 oncogenes E6 and E7 were amplified and sequenced from the SKBR3 cells. Of the patient samples, 6.58% and 23.68% were tested to be positive for HPV18 E6 and HPV18 E7. In the cell culture models, the knockdown of HPV18 E6 and E7 inhibited the proliferation, metastasis, and cell cycle progression of SKBR3 cell. The knockdown also clearly affected the expression levels of cell cycle related proteins. CONCLUSION: HPV was a contributor to virus caused human breast cancer, suggesting that the oncogenes in HPV were potential targets for gene therapy of breast cancer.