Disfunction of dorsal raphe nucleus-hippocampus serotonergic-HTR3 transmission results in anxiety phenotype of Neuroplastin 65-deficient mice.

Anxiety disorders are the most common psychiatric condition, but the etiology of anxiety disorders remains largely unclear. Our previous studies have shown that neuroplastin 65 deficiency (NP65-/-) mice exhibit abnormal social and mental behaviors and decreased expression of tryptophan hydroxylase 2 (TPH2) protein. However, whether a causal relationship between TPH2 reduction and anxiety disorders exists needs to be determined. In present study, we found that replenishment of TPH2 in dorsal raphe nucleus (DRN) enhanced 5-HT level in the hippocampus and alleviated anxiety-like behaviors. In addition, injection of AAV-NP65 in DRN significantly increased TPH2 expression in DRN and hippocampus, and reduced anxiety-like behaviors. Acute administration of exogenous 5-HT or HTR3 agonist SR57227A in hippocampus mitigated anxiety-like behaviors in NP65-/- mice. Moreover, replenishment of TPH2 in DRN partly repaired the impairment of long-term potentiation (LTP) maintenance in hippocampus of NP65-/- mice. Finally, we found that loss of NP65 lowered transcription factors Lmx1b expression in postnatal stage and replenishment of NP65 in DRN reversed the decrease in Lmx1b expression of NP65-/- mice. Together, our findings reveal that NP65 deficiency induces anxiety phenotype by downregulating DRN-hippocampus serotonergic-HTR3 transmission. These studies provide a novel and insightful view about NP65 function, suggesting an attractive potential target for treatment of anxiety disorders.

Neuroplastin 65 deficiency reduces amyloid plaque formation and cognitive deficits in an Alzheimer's disease mouse model.

Introduction: Alzheimer's disease (AD) is characterized by increasing cognitive dysfunction, progressive cerebral amyloid beta (Aß) deposition, and neurofibrillary tangle aggregation. However, the molecular mechanisms of AD pathologies have not been completely understood. As synaptic glycoprotein neuroplastin 65 (NP65) is related with synaptic plasticity and complex molecular events underlying learning and memory, we hypothesized that NP65 would be involved in cognitive dysfunction and Aß plaque formation of AD. For this purpose, we examined the role of NP65 in the transgenic amyloid precursor protein (APP)/presenilin 1 (PS1) mouse model of AD. Methods: Neuroplastin 65-knockout (NP65-/-) mice crossed with APP/PS1 mice to get the NP65-deficient APP/PS1 mice. In the present study, a separate cohort of NP65-deficient APP/PS1 mice were used. First, the cognitive behaviors of NP65-deficient APP/PS1 mice were assessed. Then, Aß plaque burden and Aß levels in NP65-deficient APP/PS1 mice were measured by immunostaining and western blot as well as ELISA. Thirdly, immunostaining and western blot were used to evaluate the glial response and neuroinflammation. Finally, protein levels of 5-hydroxytryptamin (serotonin) receptor 3A and synaptic proteins and neurons were measured. Results: We found that loss of NP65 alleviated the cognitive deficits of APP/PS1 mice. In addition, Aß plaque burden and Aß levels were significantly reduced in NP65-deficient APP/PS1 mice compared with control animals. NP65-loss in APP/PS1 mice resulted in a decrease in glial activation and the levels of pro- and anti-inflammatory cytokines (IL-1ß, TNF-α, and IL-4) as well as protective matrix YM-1 and Arg-1, but had no effect on microglial phenotype. Moreover, NP65 deficiency significantly reversed the increase in 5-hydroxytryptamine (serotonin) receptor 3A (Htr3A) expression levels in the hippocampus of APP/PS1 mice. Discussion: These findings identify a previously unrecognized role of NP65 in cognitive deficits and Aß formation of APP/PS1 mice, and suggest that NP65 may serve as a potential therapeutic target for AD.

Inhibiting 5-hydroxytryptamine receptor 3 alleviates pathological changes of a mouse model of Alzheimer's disease.

Extracellular amyloid beta (Aß) plaques are main pathological feature of Alzheimer's disease. However, the specific type of neurons that produce Aß peptides in the initial stage of Alzheimer's disease are unknown. In this study, we found that 5-hydroxytryptamin receptor 3A subunit (HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice (an Alzheimer's disease model) and patients with Alzheimer's disease. To investigate whether HTR3A-positive interneurons are associated with the production of Aß plaques, we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aß plaques in the mouse model. Some amyloid precursor protein-positive or ß-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aß plaques were co-localized with HTR3A interneurons. These results suggest that HTR3A -positive interneurons may partially contribute to the generation of Aß peptides. We treated 5.0-5.5-month-old model mice with tropisetron, a HTR3 antagonist, for 8 consecutive weeks. We found that the cognitive deficit of mice was partially reversed, Aß plaques and neuroinflammation were remarkably reduced, the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice. These findings suggest that HTR3A interneurons partly contribute to generation of Aß peptide at the initial stage of Alzheimer's disease and inhibiting HTR3 partly reverses the pathological changes of Alzheimer's disease.

CO2 and Formate Pathway of Methanol Electrooxidation at Rhodium Electrodes in Alkaline Media: An In Situ Electrochemical Attenuated Total Refection Surface-Enhanced Infrared Absorption Spectroscopy and Infrared Reflection Absorption Spectroscopy Investigation.

Rh catalysts exhibit unexpected high activity for the methanol oxidation reaction (MOR) in alkaline conditions, making them potential anodic catalysts for direct methanol fuel cells (DMFCs). Nevertheless, the MOR mechanism on Rh electrodes has not been clarified thus far, which impedes the development of high-efficiency Rh-based MOR catalysts. To investigate it, a combination of in situ electrochemical techniques called attenuated total refection surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS) and infrared reflection absorption spectroscopy (IRAS) is used. Cyclic voltammograms of MOR at Rh electrodes show considerable activity in alkaline media rather than acidic media, although the real-time ATR-SEIRA spectral results demonstrate that methanol can rarely self-decompose on Rh at open-circuit conditions. Meanwhile, in combination of ATR-SEIRAS and IRAS results, CO2 and formate are thought to be MOR products, suggesting a dual-pathway mechanism ("CO2 pathway" and "formate pathway"). Specifically, COad species, which are the major intermediates in the CO2 pathway, can produce at lower potentials and be oxidized into CO2 at a potential of 0.5-0.75 V. Concurrently, the formate can be produced from 0.5 V and diffuse into the bulk electrolyte to become one of the MOR products, while the further electrochemical conversion of formate to CO2 is essentially negligible. More directly, the apparent selectivity (r) of the CO2 pathway is estimated to reach ca. 0.63 at 0.9 V, confirming the potential-dependent selectivity of MOR at Rh surfaces. This study might provide fresh insights into the design and fabrication of effective Rh-based catalysts for MOR.

Detection of hepatocellular carcinoma in a population at risk: iodine-enhanced multidetector CT and/or gadoxetic acid-enhanced 3.0 T MRI.

OBJECTIVE: To evaluate the diagnostic performance of iodine-enhanced multidetector CT and gadoxetic acid-enhanced 3.0 Tesla (T) MRI for detection of hepatocellular carcinoma of patients. DESIGN: Retrospective, multicentre cohort study. SETTING: The Gong'an County People's Hospital, Gong'an County, China and the First People's Hospital of Jingzhou City, China. PARTICIPANTS: Reports of CT, MRI and liver biopsies/histopathology data of a total of 815 patients who at risk were reviewed. PRIMARY AND SECONDARY OUTCOME MEASURES: The lesions that possessed detection in the plain scan phase, enhanced arterial phase and/or enhanced portal phase of CT images and the lesions that possessed enhancements in the plain scan phase, enhanced arterial phase, enhanced portal phase and/or hepatobiliary phases of MRI were considered hepatocellular carcinoma. The decision of hepatocellular carcinoma was made based on the current Liver Imaging and Data Reporting System for diagnosing hepatocellular carcinoma. RESULTS: True positive hepatocellular carcinoma (563 vs 521, p=0.0314), true negative hepatocellular carcinoma (122 vs 91, p=0.0275), false positive hepatocellular carcinoma (88 vs 123, p=0.0121), false negative hepatocellular carcinoma (42 vs 80, p=0.0005), specificity (58.10 vs 42.52, p=0.0478) and negative clinical utility (0.1 vs 0.073, p=0.0386) were superior for gadoxetic acid-enhanced 3.0 T MRI than those of iodine-enhanced multidetector CT. Sensitivity and accuracy for gadoxetic acid-enhanced 3.0 T MRI were 93.06% and 77.40 %, respectively, and those for iodine-enhanced multidetector CT were 86.69% and 75.09 %, respectively. Likelihood to detect hepatocellular carcinoma for gadoxetic acid-enhanced 3.0 T MRI was 0-0.894 diagnostic confidence/lesion, and that for iodine-enhanced multidetector CT was 0-0.887 diagnostic confidence/lesion. CONCLUSION: Gadoxetic acid-enhanced 3.0 T MRI facilitates the confidence of initiation of treatment of hepatocellular carcinoma. LEVEL OF EVIDENCE: III. TECHNICAL EFFICACY STAGE: 4.

Genetic diversity analysis of forty-three insertion/deletion loci for forensic individual identification in Han Chinese from Beijing based on a novel panel / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Due to the virtues of no stutter peaks, low rates of mutation, and short amplicon sizes, insertion/deletion (InDel) polymorphism is an indispensable tool for analyzing degraded DNA samples from crime scenes for human identifications (Wang et al., 2021). Herein, a self-developed panel of 43 InDel loci constructed previously by our group was utilized to evaluate the genetic diversities and explore the genetic background of the Han Chinese from Beijing (HCB) including 301 random healthy individuals. The lengths of amplicons at 43 InDel loci in this panel ranged from 87 to 199 bp, which indicated that the panel could be used as an effective tool to utilize highly degraded DNA samples for human identity testing. The loci in this panel were validated and performed well for forensic degraded DNA samples (Jin et al., 2021). The combined discrimination power (PD) and combined probability of exclusion (PE) values in this panel indicated that the 43 InDel loci could be used as the candidate markers in personal identification and parentage testing of HCB. In addition, population genetic relationships between the HCB and 26 reference populations from five continents based on 19 overlapped InDel loci were displayed by constructing a phylogenetic tree, principal component analysis (PCA), and population genetic structure analysis. The results illustrated that the HCB had closer genetic relationships with the Han populations from Chinese different regions.

Artemisinin protects DPSC from hypoxia and TNF-α mediated osteogenesis impairments through CA9 and Wnt signaling pathway.

Dental pulp stem cells (DPSCs) possess the ability of multi-lineage differentiation, and are excellent sources of tissue engineering and regenerative medicine. Oxygen concentration and inflammation are two critical environmental factors that affect the osteogenic differentiation of DPSCs. We aimed to study the role of the antimalarial drug artemisinin on the osteogenic differentiation of human DPSCs under the hypoxia and inflammation conditions. We demonstrated that hypoxia (5% O2) and inflammation (20 ng/mL TNF-α), alone or in combination, significantly diminished in vitro cell survival and increased apoptotic rates. Notably, hypoxia and TNF-α exerted accumulative effect in suppressing the osteogenic differentiation of DPSCs, as evidenced by reduced expression levels of osteogenesis-associated genes including ALP, RUNX2 and OCN in osteogenic condition, as well as reduced mineral nodules formation as indicated by alizarin red staining. Artemisinin at the dose of 40 µM markedly reversed the suppression in cell survival caused by hypoxia or inflammation, and reduced apoptotic rates and the expressions of pro-apoptotic proteins. Additionally, artemisinin restored osteogenic differentiation of DPSCs under the hypoxia or/and inflammation conditions. Moreover, the beneficial effect of artemisinin was dependent on upregulated expression of CA9 and CA9-mediated antioxidant responses, as CA9 knockdown abolished the protective role of artemisinin on DPSC osteogenesis. Furthermore, while hypoxia or/and inflammation significantly inactivated the Wnt/ß-catenin signaling in DPSCs, additional exposure to artemisinin re-activated this pathway to promote osteogenic differentiation of DPSCs. Our results provide novel insight on the link between artemisinin and DPSC osteogenesis, and suggest promising artemisinin-based strategies for better dentin/pulp tissue engineering.

Effects of primary microglia and astrocytes on neural stem cells in in vitro and in vivo models of ischemic stroke.

Transplantation of neural stem cells (NSCs) can protect neurons in animal stroke models; however, their low rates of survival and neuronal differentiation limit their clinical application. Glial niches, an important location of neural stem cells, regulate survival, proliferation and differentiation of neural stem cells. However, the effects of activated glial cells on neural stem cells remain unclear. In the present study, we explored the effects of activated astrocytes and microglia on neural stem cells in vitro stroke models. We also investigated the effects of combined transplantation of neural stem cells and glial cells after stroke in rats. In a Transwell co-culture system, primary cultured astrocytes, microglia or mixed glial cells were exposed to glutamate or H2O2 and then seeded in the upper inserts, while primary neural stem cells were seeded in the lower uncoated wells and cultured for 7 days. Our results showed that microglia were conducive to neurosphere formation and had no effects on apoptosis within neurospheres, while astrocytes and mixed glial cells were conducive to neurosphere differentiation and reduced apoptosis within neurospheres, regardless of their pretreatment. In contrast, microglia and astrocytes induced neuronal differentiation of neural stem cells in differentiation medium, regardless of their pretreatment, with an exception of astrocytes pretreated with H2O2. Rat models of ischemic stroke were established by occlusion of the middle cerebral artery. Three days later, 5 × 105 neural stem cells with microglia or astrocytes were injected into the right lateral ventricle. Neural stem cell/astrocyte-treated rats displayed better improvement of neurological deficits than neural stem cell only-treated rats at 4 days after cell transplantation. Moreover, neural stem cell/microglia-, and neural stem cell/astrocyte-treated rats showed a significant decrease in ischemic volume compared with neural stem cell-treated rats. These findings indicate that microglia and astrocytes exert different effects on neural stem cells, and that co-transplantation of neural stem cells and astrocytes is more conducive to the recovery of neurological impairment in rats with ischemic stroke. The study was approved by the Animal Ethics Committee of Tongji University School of Medicine, China (approval No. 2010-TJAA08220401) in 2010.

Bilateral, buccinator myomucosal advancement flaps to reconstruct central upper labial myomucosal defects after ablation of early-stage cancer in minor salivary glands.

BACKGROUND: Reconstruction of upper labial myomucosal defects is surgically challenging. AIMS: We evaluated whether central defects could be repaired using bilateral, buccinator myomucosal advancement flaps (b-BMAFs). METHODS: We evaluated five patients with early-stage, minor salivary gland mucoepidermoid carcinomas (low-grade [n = 2], intermediate-grade [n = 2], and high-grade [n = 1]) who underwent central, upper labial myomucosal reconstruction using b-BMAFs after cancer ablation. We treated two men and three women aged 25-59 years. Tumors ranged in size from 1.8 × 1.8 to 2.5 × 2.2 cm. Clinical stages were I and II in two and three patients, respectively. Defect dimensions ranged from 2.8 × 2.8 to 3.5 × 3.2 cm. RESULTS: All patients underwent successful reconstruction of central, upper labial myomucosal defects using b-BMAFs and were satisfied with the esthetic results. Adequate orbicularis oris and speech function were maintained. No reduction in mouth opening was observed. Patients were followed up for 24-36 months; one pulmonary metastasis was observed at 36 months postoperatively. CONCLUSION: Placement of b-BMAFs is safe and feasible when reconstructing central, upper labial myomucosal defects after ablation of early-stage, minor salivary gland cancer.

Ethanol Electrooxidation on Rhodium-Lead Catalysts in Alkaline Media: High Mass Activity, Long-Term Durability, and Considerable CO2 Selectivity.

Rhodium (Rh)-based catalysts may solve the long-standing inefficient oxidation of ethanol for direct ethanol fuel cells (DEFCs); however, the performance of ethanol oxidation reaction (EOR) on existing Rh-based catalysts are far limited. Herein, the Rh-Pb catalysts are synthesized by building Pb and Pb oxide around Rh nanodomain, which shows highly efficient splitting CC bond and facile further oxidation of as-generated C1 intermediates (COad and CHx fragments). It exhibits an ever-highest EOR peak mass activity of ≈2636 mA mg-1 Rh among Rh-based catalysts in alkaline media. Meanwhile, its anodic current remains ≈50% even after a 4 h durability test at 0.53 V versus RHE. As for the C1-pathway selectivity, in situ infrared adsorption spectral (IRAS) results demonstrate that it could significantly improve the production of CO2 . More directly, the apparent faraday efficiency of EOR C1 pathway is estimated to be as high as 20% (at 0.53 V versus RHE). This Rh-Pb catalyst could hold great promise for developing the commercial DEFCs.

A CpG Methylation Classifier to Predict Relapse in Adults with T-Cell Lymphoblastic Lymphoma.

PURPOSE: Adults with T-cell lymphoblastic lymphoma (T-LBL) generally benefit from treatment with acute lymphoblastic leukemia (ALL)-like regimens, but approximately 40% will relapse after such treatment. We evaluated the value of CpG methylation in predicting relapse for adults with T-LBL treated with ALL-like regimens. EXPERIMENTAL DESIGN: A total of 549 adults with T-LBL from 27 medical centers were included in the analysis. Using the Illumina Methylation 850K Beadchip, 44 relapse-related CpGs were identified from 49 T-LBL samples by two algorithms: least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE). We built a four-CpG classifier using LASSO Cox regression based on association between the methylation level of CpGs and relapse-free survival in the training cohort (n = 160). The four-CpG classifier was validated in the internal testing cohort (n = 68) and independent validation cohort (n = 321). RESULTS: The four-CpG-based classifier discriminated patients with T-LBL at high risk of relapse in the training cohort from those at low risk (P < 0.001). This classifier also showed good predictive value in the internal testing cohort (P < 0.001) and the independent validation cohort (P < 0.001). A nomogram incorporating five independent prognostic factors including the CpG-based classifier, lactate dehydrogenase levels, Eastern Cooperative Oncology Group performance status, central nervous system involvement, and NOTCH1/FBXW7 status showed a significantly higher predictive accuracy than each single variable. Stratification into different subgroups by the nomogram helped identify the subset of patients who most benefited from more intensive chemotherapy and/or sequential hematopoietic stem cell transplantation. CONCLUSIONS: Our four-CpG-based classifier could predict disease relapse in patients with T-LBL, and could be used to guide treatment decision.

A gene-expression-based signature predicts survival in adults with T-cell lymphoblastic lymphoma: a multicenter study.

We aimed to establish a discriminative gene-expression-based classifier to predict survival outcomes of T-cell lymphoblastic lymphoma (T-LBL) patients. After exploring global gene-expression profiles of progressive (n = 22) vs. progression-free (n = 28) T-LBL patients, 43 differentially expressed mRNAs were identified. Then an eleven-gene-based classifier was established using LASSO Cox regression based on NanoString quantification. In the training cohort (n = 169), high-risk patients stratified using the classifier had significantly lower progression-free survival (PFS: hazards ratio 4.123, 95% CI 2.565-6.628; p < 0.001), disease-free survival (DFS: HR 3.148, 95% CI 1.857-5.339; p < 0.001), and overall survival (OS: HR 3.790, 95% CI 2.237-6.423; p < 0.001) compared with low-risk patients. The prognostic accuracy of the classifier was validated in the internal testing (n = 84) and independent validation cohorts (n = 360). A prognostic nomogram consisting of five independent variables including the classifier, lactate dehydrogenase levels, ECOG-PS, central nervous system involvement, and NOTCH1/FBXW7 status showed significantly greater prognostic accuracy than each single variable alone. The addition of a five-miRNA-based signature further enhanced the accuracy of this nomogram. Furthermore, patients with a nomogram score ≥154.2 significantly benefited from the BFM protocol. In conclusion, our nomogram comprising the 11-gene-based classifier may make contributions to individual prognosis prediction and treatment decision-making.

Study on safe storage moisture content of Rhei Radix et Rhizoma using moisture absorbing math model / 中草药

Objective: The moisture absorption of Rhei Radix et Rhizoma (RRR) with different initial moisture content was studied under the conditions of relative humidity of 20%-85% and temperature of 5, 15, 25 and 35 ℃, respectively, so as to provide reference for the control of safe storage moisture and reasonable storage of RRR. Methods: RRR was stored at temperature of 5, 15, 25 and 35 ℃ and humidity of 45%, 60% and 75%, respectively. The samples were taken at different time points to determine its safe water activity with powder color and mildew as indicators. The isotherm adsorption data of RRR at 5, 15, 25 and 35 ℃ and water activity of 0.2-0.8 were obtained by static weighing method and six isotherm adsorption models, GAB, Oswin, Smith, Halsey, Henderso and Peleg, were used for fitting and evaluation. Results: The absolute safe water activity and relative safe water activity of RRR were 0.5 and 0.6, respectively. The adsorption isotherms of RRR at 5, 15, 25 and 35 ℃ were "S" type, which belonged to type II isotherm. Oswin model was the best fitting model and the model expression was: Meq=A[Aw/(1-Aw)B. According to the model, the absolute safe water content of RRR with different initial moisture content at 5 ℃ was 9.00%, 9.59%, 8.00%, 6.71% and relative safe water content was 10.17%, 10.89%, 9.20% and 8.07%, respectively; The absolute safe water content of RRR with different initial moisture content at 15 ℃ was 8.24%, 8.83%, 7.24%, 5.86% and relative safe water content was 9.57%, 10.17%, 8.59% and 7.20%, respectively; The absolute safe water content of that at 25 ℃ was 7.17%, 7.75%, 5.73%, 4.70% and the relative safe water content was 8.72%, 9.26%, 7.26% and 6.25%, respectively; The absolute safe water content of that at 35 ℃ was 8.00%, 8.45%, 6.53%, 5.21% and the relative safe water content was 9.74%, 9.85%, 8.40%, 7.27%, respectively. Conclusion: Oswin model can be used to predict the equilibrium moisture content of RRR in storage, which can provide reference for the control of safe moisture and scientific maintenance of RRR.

New Opportunities and Challenges for Forensic Medicine in the Era of Artificial Intelligence Technology / 法医学杂志

Traditional forensic identification relies on forensic experts to manually extract information and provide identification opinions based on medicine, biology and other fields of knowledge combined with personal work experience, which is not only time-consuming and require great effort, but also affected by subjective factors that are difficult to overcome. In the era of big data, the booming development of artificial intelligence brings new ideas to forensic medicine. In recent years, forensic researchers at home and abroad have conducted many studies based on artificial intelligence technology, such as face recognition, age and gender identification, DNA analysis, postmortem interval estimation, injury and cause of death identification, showing the feasibility and advantages of using artificial intelligence technology to solve forensic identification problems. As a new means of technology that has adapted to the development of the times, artificial intelligence has brought new vitality to forensic medicine, but at the same time also some new challenges. How to deal with these challenges scientifically and form a new mode of 'artificial intelligence plus forensic medicine' with artificial intelligence and forensic medicine developing collaboratively is a new direction for the development of forensic medicine in the era of big data.

Effect of dapagliflozin on obstructive sleep apnea in patients with type 2 diabetes: a preliminary study.

OBJECTIVE: The aim of this case-control study was to assess the efficacy of dapagliflozin combined with metformin for type-2 diabetes mellitus (T2DM) with obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: A total of 36 patients with newly-diagnosed T2DM and OSAHS were randomized divided into two groups. Eighteen OSAHS patients with T2DM, who were treated with dapagliflozin and metformin, were assigned as the dapagliflozin group. These patients were given dapagliflozin and metformin for 24 weeks between February 2017 and February 2018. Another 18 OSAHS patients with T2DM, who were treated with glimepiride and metformin for 24 weeks, were assigned as the control group. Fasting plasma glucose (FPG) level, postprandial blood glucose (PPG), hemoglobin A1C (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), blood lipids, body mass index (BMI), blood pressure, apnea-hypopnea index (AHI), minimum oxygen saturation (LSpO2), and Epworth Somnolence Scale (ESS) score were measured before and at 24 weeks after the initiation of treatment. RESULTS: In the dapagliflozin group, triglyceride (TG), systolic pressure (SBP) and diastolic pressure (DBP) significantly decreased following treatment, while high-density lipoprotein cholesterol (HDL-C) significantly increased (P < 0.05). Furthermore, a reduction in AHI, an increase in LSpO2 and a decrease in ESS score were observed in the dapagliflozin group (P < 0.05), but not in the control group. Moreover, blood glucose, HbA1c, HOMA-IR, and BMI significantly decreased in these two groups, and the decrease was more significant in the dapagliflozin group. CONCLUSION: These present results indicate that dapagliflozin can significantly reduce glucose, BMI, blood pressure and AHI, and improve hypoxemia during sleep and excessive daytime sleepiness, which thereby has potential as an effective treatment approach for OSAHS.

Analysis of the circular RNA transcriptome in the grade 3 endometrial cancer.

BACKGROUND/AIMS: Circular RNAs (circRNAs), a class of newly discovered endogenous noncoding RNAs, have shown large capabilities in gene regulation. Patients with the grade 3 endometrial cancer (EC) have a generally poor prognosis, and the specific role of circRNAs in the grade 3 EC remains unclear. This study aims to investigate the roles of circRNAs in the grade 3 EC. METHODS: In the current study, we screened the expression profiles of circRNAs taken from two women with the grade 3 EC and adjacent non-cancerous endometrial tissue using circRNAs sequencing. Bioinformatic analyses were applied to study these differentially expressed circRNAs. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) of six dysregulated circRNAs was performed to validate the sequencing results. Bioinformatic analyses, including the negative correlation network analyses of circRNAs-microRNAs (miRNAs)-messenger RNAs (mRNAs) and the Cytoscape, were used to delineate the interaction of circRNAs/miRNAs of the entire network. RESULTS: Data of circRNA sequencing showed a significant change in 75,928 unique circRNAs (P<0.05). The upregulated hsa_circ_0039569 and hsa_circ_0001610 and downregulated hsa_circ_0000437, hsa_circ_0001776, and hsa_circ_0009043 were validated by qRT-PCR analysis. Using bioinformatical methods, we found that hsa_circ_0039569 has the MRE of hsa-miR-542-3p and hsa-let-7c-5p. Hsa-miR-542-3p and hsa-let-7c-5p were downregulated in the grade 3 EC validated by qRT-PCR analysis. In the clinicopathological parameters, the expression level of hsa_circ_0039569 was significantly correlated with tumor differentiation (P=0.001). CONCLUSION: This is the first study demonstrated that there were a lot of differences between the tissue of the grade 3 EC and adjacent non-cancerous endometrial in circRNA expression and may offer novel molecular candidates for diagnosis and clinical treatment of the grade 3 EC.

Prognostic and predictive value of a microRNA signature in adults with T-cell lymphoblastic lymphoma.

New prognostic factors are needed to establish indications for haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) for T-cell lymphoblastic lymphoma (T-LBL) patients. We used microarray to compare T-LBL tissue samples (n = 75) and fetal thymus tissues (n = 20), and identified 35 differentially expressed miRNAs. Using 107 subjects as the training group, we developed a five-miRNA-based classifier to predict patient survival with LASSO Cox regression: lower risk was associated with better prognosis (disease-free survival (DFS): hazard ratio (HR) 4.548, 95% CI 2.433-8.499, p < 0.001; overall survival (OS): HR 5.030, 95% CI 2.407-10.513, p < 0.001). This classifier displayed good performance in the internal testing set (n = 106) and the independent external set (n = 304). High risk was associated with more favorable response to HSCT (DFS: HR 1.675, 95% CI 1.127-2.488, p = 0.011; OS: HR 1.602, 95% CI 1.055-2.433, p = 0.027). When combined with ECOG-PS and/or NOTCH1/FBXW7 status, this classifier had even better prognostic performance in patients receiving HSCT (DFS: HR 2.088, 95% CI 1.290-3.379, p = 0.003; OS: HR 1.996, 95% CI 1.203-3.311, p = 0.007). The five-miRNA classifier may be a useful prognostic biomarker for T-LBL adults, and could identify subjects who could benefit from HSCT.

Electroacupuncture promotes peripheral nerve regeneration after facial nerve crush injury and upregulates the expression of glial cell-derived neurotrophic factor.

The efficacy of electroacupuncture in the treatment of peripheral facial paralysis is known, but the specific mechanism has not been clarified. Glial cell-derived neurotrophic factor (GDNF) has been shown to protect neurons by binding to N-cadherin. Our previous results have shown that electroacupuncture could increase the expression of N-cadherin mRNA in facial neurons and promote facial nerve regeneration. In this study, the potential mechanisms by which electroacupuncture promotes nerve regeneration were elucidated through assessing the effects of electroacupuncture on GDNF and N-cadherin expression in facial motoneurons of rabbits with peripheral facial nerve crush injury. New Zealand rabbits were randomly divided into a normal group (normal control, n = 21), injury group (n = 45) and electroacupuncture group (n = 45). Model rabbits underwent facial nerve crush injury only. Rabbits in the electroacupuncture group received facial nerve injury, and then underwent electroacupuncture at Yifeng (TE17), Jiache (ST6), Sibai (ST2), Dicang (ST4), Yangbai (GB14), Quanliao (SI18), and Hegu (LI4; only acupuncture, no electrical stimulation). The results showed that in behavioral assessments, the total scores of blink reflex, vibrissae movement, and position of apex nasi, were markedly lower in the EA group than those in the injury group. Hematoxylin-eosin staining of the right buccinator muscle of each group showed that the cross-sectional area of buccinator was larger in the electroacupuncture group than in the injury group on days 1, 14 and 21 post-surgery. Toluidine blue staining of the right facial nerve tissue of each group revealed that on day 14 post-surgery, there was less axonal demyelination and fewer inflammatory cells in the electroacupuncture group compared with the injury group. Quantitative real time-polymerase chain reaction showed that compared with the injury group, N-cadherin mRNA levels on days 4, 7, 14 and 21 and GDNF mRNA levels on days 4, 7 and 14 were significantly higher in the electroacupuncture group. Western blot assay displayed that compared with the injury group, the expression of GDNF protein levels on days 7, 14 and 21 were significantly upregulated in the electroacupuncture group. The histology with hematoxylin-eosin staining and Nissl staining of brainstem tissues containing facial neurons in the middle and lower part of the pons exhibited that on day 7 post-surgery, there were significantly fewer apoptotic neurons in the electroacupuncture group than in the injury group. By day 21, there was no significantly difference in the number of neurons between the electroacupuncture and normal groups. Taken together, these results have confirmed that electroacupuncture promotes regeneration of peripheral facial nerve injury in rabbits, inhibits neuronal apoptosis, and reduces peripheral inflammatory response, resulting in the recovery of facial muscle function. This is achieved by up-regulating the expression of GDNF and N-cadherin in central facial neurons.

Genetic distribution and forensic evaluation of multiplex autosomal short tandem repeats in the Chinese Xinjiang Mongolian group / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

To further enrich the genetic data of the Chinese Xinjiang Mongolian group, the genetic distribution and forensic parameters of 19 autosomal short tandem repeats (STRs) were investigated. Altogether, 249 alleles were observed in these 19 STRs. The mean values of the polymorphism information content (PIC), match probability (MP), discrimination power (DP), and probability of exclusion (PE) for these 19 STRs were 0.7775, 0.0699, 0.9301, and 0.6085, respectively. Additionally, the cumulative DP and PE values obtained in the Mongolian group were 0.999 999 999 999 999 999 999 995 67 and 0.999 999 992 163, respectively. Furthermore, population genetic analysis of the Mongolian group and 20 published populations was conducted based on the population data of 15 overlapping STRs. Genetic distances indicated that the Mongolian group had closer genetic similarities with the Uyghur, Xibe, and other Chinese populations rather than the other continental populations. Multidimensional scaling analysis further revealed that the Mongolian group possessed similar genetic distributions as most Chinese populations. To sum it all up, these STRs could be used as an extremely efficient tool for forensic applications in the Xinjiang Mongolian group.

Simulated Accelerated Test to Study Correlation Between Color Change in Storage and Medicinal Ingredients of Rhei Radix et Rhizoma / 中国实验方剂学杂志

Objective: To study the correlation between the content changes of main medicinal ingredients and the color values of Rhei Radix et Rhizoma during storage based on the principle of chromaticity analysis,and to provide reference for studying on the mechanism of discoloration and improving the quality evaluation of Rhei Radix et Rhizoma. Method: Simulated accelerated test was adopted in this study, where Rhei Radix et Rhizoma was stored under high temperature(40±5)℃,high humidity RH(92.5±5)%and strong light(4 000±500)Lx conditions to accelerate its discoloration. For the samples taken at different time points,the color value was determined by spectrophotometer and the total contents of anthraquinone and free anthraquinones,sennoside A,B,catechin and gallic acid were determined by high performance liquid chromatography (HPLC). The correlation between the effective components and the color value of rhubarb was analyzed by SPSS software. Result: During the storage process,it was observed by the eye that the color of Rhei Radix et Rhizoma was significantly darker and darker in the simulated acceleration test. According to the analysis of the chromaticity value results,the changes of chromaticity values L*and E*ab of Rhei Radix et Rhizoma were significantly negatively correlated with free strontium content(PPa* was significantly negatively correlated with gallic acid(PPConclusion: There is a certain correlation between the change of color value and the content of six medicinal ingredients during Rhei Radix et Rhizoma storage.