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Acute traumatic event exposure is a direct cause of post-traumatic stress disorder (PTSD). Amygdala is suggested to be associated with the development of PTSD. In our previous findings, different activation patterns of GABAergic neurons and glutamatergic neurons in early or late stages after stress were found. However, the neural plastic mechanism underlying the role of basolateral amygdala (BLA) in post-traumatic stress disorder remains unclear. Therefore, this study mainly aimed at investigating time-dependent morphologic and electrophysiological changes in BLA during the development of PTSD. We used single prolonged stress (SPS) procedure to establish PTSD model of rats. The rats showed no alterations in anxiety behavior as well as in dendritic spine density or synaptic transmission in BLA 1 day after SPS. However, 10 days after SPS, rats showed enhancement of anxiety behavior, and spine density and frequency of miniature excitatory and inhibitory postsynaptic currents in BLA. Our results suggested that after traumatic stress, BLA displayed delayed increase in both spinogenesis and synaptic transmission, which seemed to facilitate the development of PTSD., (Copyright © 2019 Zhang, Meng, Guo, Zhang, Zhang, Chen, Lu, Yang and Xue.)

Chordoma is a slow-growing, locally invasive, lowgrade malignant tumor with a prevalence of one in 100 000, accounting for 1%-4% of all malignant bone tumors. At present, it is considered that chordoma originates from ectopic embryonic chordal tissue and can occur in any part of the spine from the skull base to the sacrum. About 50% of chordoma occurs in the sacrococcygeal region, about 30% in the skull base, and the rest occurs in the active spinal region. Cervical chordoma is rare, but it may be accompanied by difficult airways. The tumors compress the pharynx and throat forward, which can cause upper airway obstruction. If the anesthesia is not properly handled, the patient may die of asphyxia. The core issues of airway management during the perioperative period of cervical chordoma surgery involve three main parts: preoperative airway evaluation, airway management and extubation management. Difficult airway assessment often relies on physical examination indicators, such as inter-incisor gap, thyromental distance, neck circumference, Mallampati test, etc. But the accuracy is insufficient. The application of imaging examination in the observation of different tissues can make up for the inaccurate evaluation of the internal structure of the airway. Because chordoma destroys cervical vertebral body and accessories, cervical stability is impaired. Excessive cervical vertebral extention should be avoided during tracheal intubation to prevent severe compression of the spinal cord. It is better to fix the head by an assistant and perform neutral tracheal intubation. Considering that the patient with a difficult airway that could be predicted before operation, the strategy of tracheal intubation under conscious sedation with topical anesthesia was selected. After sedation and topical anesthesia, the patient was successfully intubated with optical stylet. After operation, the patient returned to ICU with tracheal catheter. On the 4th day after operation, the tracheal tube was pulled out. On the 5th day after operation, the patient was transferred to the orthopaedic ward and discharged on the 7th day after operation. It is of great significance to establish specific strategies for such operations to reduce related complications, speed up post-operative rehabilitation and save medical resources. We reported the anesthetic management of cervical chordoma cured in Peking University Third Hospital.

We report results on the searches of weakly interacting massive particles (WIMPs) with sub-GeV masses (m_{χ}) via WIMP-nucleus spin-independent scattering with Migdal effect incorporated. Analysis on time-integrated (TI) and annual modulation (AM) effects on CDEX-1B data are performed, with 737.1 kg day exposure and 160 eVee threshold for TI analysis, and 1107.5 kg day exposure and 250 eVee threshold for AM analysis. The sensitive windows in m_{χ} are expanded by an order of magnitude to lower DM masses with Migdal effect incorporated. New limits on σ_{χN}^{SI} at 90% confidence level are derived as 2×10^{-32}∼7×10^{-35}  cm^{2} for TI analysis at m_{χ}∼50-180  MeV/c^{2}, and 3×10^{-32}∼9×10^{-38}  cm^{2} for AM analysis at m_{χ}∼75  MeV/c^{2}-3.0  GeV/c^{2}.

To clarify the spatial distribution and pollution status of nutrients in the surface sediments from a macrophyte-dominated zone in Lake Taihu, total nitrogen (TN), total phosphorus (TP), alkali nitrogen (AN), available phosphorus (AP), and organic matter (OM) were measured at 60 sampling sites in Xukou Bay. A pollution evaluation and source apportionment analysis of these nutrients was also carried out. The average contents of TN, TP, AN, AP, and OM in the surface sediments of Xukou Bay were 1027.5, 423.2, 46.4, 15.3, and 17096.6 mg·kg -1 , respectively, with the OM content being significantly higher in the northeast zone than in other areas of the bay. The average value of S TN and S TP was 1.75 and 0.91, respectively, indicating that TN and TP represent moderate and mild levels of pollution, respectively. The average comprehensive pollution index (FF) was 1.57, indicated that the surface sediment was moderately polluted. The observed organic pollution index indicated that the surface sediments in Xukou Bay were generally clean. Based on C/N values, organic matter in the surface sediments is derived from the bio-deposition of non-fibrous plants and phytoplankton. Based on correlation analysis, OM and TN in the surface sediments of Xukou Bay are derived from the same source, while TP is derived from an alternative source.

Aim: The present study aimed to investigate and identify the association between the intake of allium vegetables and colorectal cancer (CRC) in population., Methods: A hospital-based matched case-control study was conducted between June 2009 and November 2011 in three hospitals. Eight hundred thirty three consecutively recruited cases of CRC were frequency matched to 833 controls by age (within 2.5 years of difference), sex, and residence area (rural/urban). Demographic and dietary information were collected via face-to-face interviews using a validated food frequency questionnaire. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated by using unconditional logistic regression., Results: A decreased CRC risk was observed for the consumption of total (aORs of high total allium intake compared with low total allium intake = 0.21, 95% CI = 0.14-0.30, P trend <0.001) and several individual allium vegetables including garlic, garlic stalks, leek, onion, and spring onion (P trend <0.05). By further sex-stratified analysis, allium vegetable intake was demonstrated to be inversely associated with the risk of CRC in both men and women. However, the association of garlic intake with cancer risk was not significant among those with distal colon cancer (aOR = 0.53, 95% CI = 0.27-1.05, P trend = 0.248)., Conclusion: In this analysis in a Northeast Chinese population, both men and women that the consumption of allium vegetables is associated with a reduced risk of CRC, regardless of colonic tumor subsite, with the exception of garlic intake in distal colon cancer., (© 2019 John Wiley & Sons Australia, Ltd.)

Bimetal-S-O composites have been rarely researched in electrochemical reduction of CO 2 . Now, an amorphous Ag-Bi-S-O decorated Bi 0 catalyst derived from Ag 0.95 BiS 0.75 O 3.1 nanorods by electrochemical pre-treatment was used for catalyzing eCO 2 RR, which exhibited a formate FE of 94.3 % with a formate partial current density of 12.52 mA cm -2 at an overpotential of only 450 mV. This superior performance was attributed to the attached amorphous Ag-Bi-S-O substance. S could be retained in the amorphous region after electrochemical pre-treatment only in samples derived from metal-S-O composites, and it would greatly enhance the formate selectivity by accelerating the dissociation of H 2 O. The existence of Ag would increase the current density, resulting in a higher local pH, which made the role of S in activating H 2 O more significantly and suppressed H 2 evolution more effectively, thus endowing the catalyst with a higher formate FE at low overpotentials., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Since the use of protein therapeutics is effective for treating intractable human diseases, the production of biologic therapeutic agents has dramatically increased over the past three decades. The Chinese hamster ovary (CHO) cell lines are the most commonly used host cell expression system for recombinant protein production. High productive and stable clonal cell lines for recombinant protein production have been established from the DHFR-deficient CHO cell using the dihydrofolate reductase/methotrexate (DHFR/MTX) selection methods. Human embryonic kidney 293 (HEK293) cells are alternative host cells widely used for protein production. In most case, however, the cells are used for the transient expression, and there is no gene amplification system in HEK293 cells. In this study, we established a DHFR-deficient HEK293 cell line for the high yield of recombinant proteins. We doubly knocked out DHFR and DHFR2 in the MAN1A1/A2/B1/C1-quadruple knockout HEK293 (QD-KO) cells, using the CRISPR/Cas9 system. The DHFR-deficient QD-KO cells were used to overexpress two proteins, lysosomal acid lipase and the constant fragment of human immunoglobulin G 1 by the DHFR/MTX gene-amplification method. This method resulted in a dramatic increase in the two protein expressions in the DHFR-deficient QD-KO cells by increasing MTX concentration. Our system could be adopted in the production of several recombinant proteins including therapeutic proteins., (Copyright © 2019 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Objectives: This study explored the relationship between weight control and atrial fibrillation (AF) recurrence after catheter ablation in overweight and obese patients. Methods: We prospectively enrolled consecutive 333 overweight and obese patients aged 28 to 87 years old, who underwent catheter ablation for AF in Beijing Anzhen Hospital between October 2015 and February 2016. Data of patients' characteristics, laboratory examination and treatment were collected at baseline. Each patient was followed up at 3, 6 and 12 months after ablation to collect information on weight, AF recurrence, stroke, major bleeding, hospitalization for cardiovascular reasons and death, etc. Patients were divided into weight controlled group (ΔBMI<-1 kg/m(2)) and weight uncontrolled group (ΔBMI≥-1 kg/m(2)), according to the changes in the most recent exposure BMI before AF recurrence in patients with recurrence or the BMI at 12 months' follow-up in patients without recurrence and the BMI at baseline. Multivariate logistic regression was performed to adjust other known risk factors of AF recurrence and to explore the association between weight control and AF recurrence after catheter ablation. Results: There were 54 patients in weight controlled group and 279 patients in weight uncontrolled group. There were no significant differences in age, gender, education level, left atrial size and history of hypertension between the two groups (all P> 0.05). The proportion of patients using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was higher in the weight controlled group (50.0%(27/54) vs. 34.8%(97/279), P= 0.034). However, there was no significant difference in the proportion of patients with obesity (33.3% (18/54) vs. 29.7% (83/279)), paroxysmal AF (59.3% (32/54) vs. 56.6% (158/279)) and AF duration less than 5 years (76.9% (40/52) vs. 65.4% (178/272)) between the weight controlled group and the uncontrolled group. During 1-year follow-up after ablation, the recurrence rate of AF was significantly lower in the weight controlled group than that in the weight uncontrolled group (14.8% (8/54) vs. 32.6%(91/279), P= 0.009). Multivariable logistic regression analysis shows that weight control is independently associated with a lower postoperative AF recurrence rate ( OR= 0.40, 95 %CI 0.18-0.90, P= 0.026). Conclusion: Weight control is strongly associated with a lower AF recurrence rate after catheter ablation in overweight and obese patients.

Background: Novel therapeutic strategies are urgently needed for patients with a delayed diagnosis of pancreatic ductal adenocarcinoma (PDAC) in order to improve their chances of survival. Recent studies have shown potent anti-neoplastic effects of curcumin and its analogues. In addition, the role of histone methyltransferases on cancer therapeutics has also been elucidated. However, the relationship between these two factors in the treatment of pancreatic cancer remains unknown. Our working hypothesis was that L48H37, a novel curcumin analog, has better efficacy in pancreatic cancer cell growth inhibition in the absence of histone-lysine N-methyltransferase 2D (KMT2D)., Aim: To determine the anti-cancer effects of L48H37 in PDAC, and the role of KMT2D on its therapeutic efficacy., Methods: The viability and proliferation of primary (PANC-1 and MIA PaCa-2) and metastatic (SW1990 and ASPC-1) PDAC cell lines treated with L48H37 was determined by CCK8 and colony formation assay. Apoptosis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) levels, and cell cycle profile were determined by staining the cells with Annexin-V/7-AAD, JC-1, DCFH-DA, and PI respectively, as well as flow cytometric acquisition. In vitro migration was assessed by the wound healing assay. The protein and mRNA levels of relevant factors were analyzed using Western blotting, immunofluorescence and real time-quantitative PCR. The in situ expression of KMT2D in both human PDAC and paired adjacent normal tissues was determined by immunohistochemistry. In vivo tumor xenografts were established by injecting nude mice with PDAC cells. Bioinformatics analyses were also conducted using gene expression databases and TCGA., Results: L48H37 inhibited the proliferation and induced apoptosis in SW1990 and ASPC-1 cells in a dose- and time-dependent manner, while also reducing MMP, increasing ROS levels, arresting cell cycle at the G2/M stages and activating the endoplasmic reticulum (ER) stress-associated protein kinase RNA-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/activating transcription factor 4 (ATF4)/CHOP signaling pathway. Knocking down ATF4 significantly upregulated KMT2D in PDAC cells, and also decreased L48H37-induced apoptosis. Furthermore, silencing KMT2D in L48H37-treated cells significantly augmented apoptosis and the ER stress pathway, indicating that KMT2D depletion is essential for the anti-neoplastic effects of L48H37. Administering L48H37 to mice bearing tumors derived from control or KMT2D-knockdown PDAC cells significantly decreased the tumor burden. We also identified several differentially expressed genes in PDAC cell lines expressing very low levels of KMT2D that were functionally categorized into the extrinsic apoptotic signaling pathway. The KMT2D high- and low-expressing PDAC patients from the TCGA database showed similar survival rates,but higher KMT2D expression was associated with poor tumor grade in clinical and pathological analyses., Conclusion: L48H37 exerts a potent anti-cancer effect in PDAC, which is augmented by KMT2D deficiency., Competing Interests: Conflict-of-interest statement: There is no conflict of interest.

Currently, preliminary results have confirmed the existence of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL)-dependent necroptosis of pancreatic acinar cells during early acute pancreatitis (AP), which might be a potential target for the effective regulation of necroinflammatory injury. However, the exact effect of receptor-interacting protein kinase 1 (RIPK1)-dependent regulated acinar cell necrosis on AP is still uncertain. In our study, we first explored the changes in the degree of local and systemic inflammation in AP rats when the activation of acinar cell RIPK1 was inhibited. The RIPK1 inhibitor Nec-1 was used to treat rats, and the levels of related inflammatory markers, necrosis indicators and apoptotic indicators were measured. Changes in pancreatic nuclear factor κB (NF-κB) and aquaporin 8 (AQP8) expression were noted. Next, the expression of AQP8 in AR42J cells was inhibited, and the degree of cell necrosis and inflammatory damage was found to be significantly reduced. Most importantly, we demonstrated that the RIPK1/NF-ĸB/AQP8 axis might be a potential regulatory pathway mediating RIPK1-dependent regulated acinar cell necrosis in early AP. Finally, we used the NF-κB inhibitor PDTC and Nec-1 to treat rats in different groups and measured the degree of pathological pancreatic injury, the activation of RIPK1, and the expression of NF-κB and AQP8. In summary, we hypothesized that there might be a RIPK1/NF-ĸB/AQP8 pathway controlling RIPK1-dependent regulated necrosis of acinar cells in AP, which might be a promising therapeutic target against AP-related injury.

The present study was designed to examine the therapeutic effects of Botulinum neurotoxin A (BoNT/A) on depression-like behaviors in mice and to explore the potential mechanisms. These results revealed that a single facial injection of BoNT/A induced a rapid and prolonged improvement of depression-like behaviors in naïve and space-restriction-stressed (SRS) mice, reflected by a decreased duration of immobility in behavioral despair tests. BoNT/A significantly increased the 5-hydroxytryptamine (5-HT) levels in several brain regions, including the hippocampus and hypothalamus, in SRS mice. BoNT/A increased the expression of the N-methyl-D-aspartate receptor subunits NR1 and NR2B in the hippocampus, which were significantly decreased in SRS mice. Furthermore, BoNT/A significantly increased the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus, hypothalamus, prefrontal cortex, and amygdala, which were decreased in SRS mice. Finally, BoNT/A transiently increased the levels of phosphorylated extracellular signal-regulated kinase (p-ERK) and cAMP-response element binding protein (p-CREB), which were suppressed in the hippocampus of SRS mice. Collectively, these results demonstrated that BoNT/A treatment has anti-depressant-like activity in mice, and this is associated with increased 5-HT levels and the activation of BDNF/ERK/CREB pathways in the hippocampus, supporting further investigation of BoNT/A therapy in depression.

Improvement of crop drought resistance and water-use efficiency (WUE) has been a major endeavor in agriculture. Arabidopsis ENHANCED DROUGHT TOLERANCE1/HOMEODOMAIN GLABROUS11 (AtEDT1/HDG11), a homeodomain-START transcription factor we previously identified from the enhanced drought tolerance1 mutant (edt1), has been demonstrated to improve drought tolerance and WUE significantly in multiple plant species when constitutively overexpressed. Here, we report the genetic evidence suggesting a genetic pathway, which consists of EDT1/HDG11, ERECTA, and E2Fa loci, and regulates WUE by modulating stomatal density. AtEDT1/HDG11 transcriptionally activates ERECTA by binding to homeodomain-binding (HD) cis-elements in the ERECTA promoter. ERECTA, in turn, depends on E2Fa to modulate the expression of cell cycle-related genes. This modulation affects the transition from mitosis to endocycle, leading to increased ploidy levels in leaf cells, and therefore increased cell size and decreased stomatal density. Our results suggest a possible EDT1/HDG11-ERECTA-E2Fa genetic pathway that reduces stomatal density by increasing cell size and provide a new avenue to improve WUE of crops., (No claim to US Government works New Phytologist 2019 New Phytologist Trust.)

Successful prevention and treatment of hypertension depend on the appropriate combination of antihypertensive drug therapy and nondrug lifestyle modification. While most hypertension guidelines recommend moderate- to high-intensity exercise, we decided to explore a mild yet effective type of exercise to add to hypertension management, especially in populations with complications or frailty. After comparing the short-term cardiovascular effects of low-speed walking versus high-speed walking for 3 kilometers (km) (3 km/h versus 6 km/h) in young, healthy volunteers, we delivered low-speed walking (low-intensity walking, 2.5 metabolic equivalents of task, METs) as exercise therapy in 42 prehypertensive and 43 hypertensive subjects. We found that one session of 3 km low-intensity walking exerted a transient pressure-lowering effect as well as a mild negative chronotropic effect on heart rate in both the prehypertensive and hypertensive subjects; these short-term benefits on blood pressure and heart rate were accompanied by a brief increase in urine β-endorphin output. Then we prescribed regular low-intensity walking with a target exercise dose (exercise volume) of 500-1000 METs·min/week (50-60 min/day and 5-7 times/week) in hypertensive subjects in addition to their daily activities. Regular low-intensity walking also showed mild but significant blood pressure-lowering and heart rate-reducing effects in 7 hypertensive subjects within two months. It is hypothesized that regular low-intensity exercise of the necessary dose could be taken as a pragmatic and supplementary medication for hypertension management.

Pancreatic disease, including pathologies such as acute pancreatitis (AP), chronic pancreatitis (CP), and pancreatic cancer (PC), is a complicated and dangerous clinical condition involving the disruption of exocrine or endocrine function. PC has one of the highest mortality rates among cancers due to insufficient diagnosis in early stages. Furthermore, efficient treatment options for the disease etiologies of AP and CP are lacking. Thus, the identification of new therapeutic targets and reliable biomarkers is required. As essential couriers in intercellular communication, exosomes have recently been confirmed to play an important role in pancreatic disease, but the specific underlying mechanisms are unknown. Herein, we summarize the current knowledge of exosomes in pancreatic disease with respect to diagnosis, molecular mechanisms, and treatment, proposing new ideas for the study of pancreatic disease., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Objective: To investigate residual hearing of children severe and profound sensorineural deafness in whom wave V was not found in auditory brainstem response(ABR) testing, and to emphasize the importance of objective audiological tests. Methods: Two hundred and fifty-two children who were admitted to the Second Affiliated Hospital of Zhengzhou University between January 2015 and April 2018, with an average age of 20 months from 72 days to 4 years, received a full battery of objective audiological tests consisting of distortion product otoacoustic emission(DPOAEs), tympanometry, auditory brainstem responses(ABRs), 40 Hz auditory event related potential(40 HzAERP) and auditory steady-state response(ASSRs).There were 159 males(318 ears) and 93 females(186 ears). Residual hearing obtained by 40 HzAERP、ASSR of 252 children with sensorineural deafness was studied in relation to the absence of wave V in click ABR. SPSS 16.0 software was used to analyze the data. Results: Four hundred and forty-four ears of 504 ears have residual hearing of different degrees at different frequencies(88.1%),60 ears (11.9%) were found in whom responses was not found in 40 HzAERP、ASSR testing; Seventy-two ears(14.3%) in 38 patients were tested cochlear microphonic potentials (CMs). Conclusion: In children hearing evaluations,a full battery of objective audiological tests could better investigate residual hearing; The CMs were tested could provide the Audiotery Neuropathy diagnosis in infants with OAEs and ABR absent.

The underlying mechanisms of macrophage polarization have been detected by genome-wide transcriptome analysis in a variety of mammals. However, the transcriptome profile of rat genes in bone marrow-derived macrophages (BMM) at different activation statuses has not been reported. Therefore, we performed RNA-Sequencing to identify gene expression signatures of rat BMM polarized in vitro with different stimuli. The differentially expressed genes (DEGs) among unactivated (M0), classically activated pro-inflammatory (M1), and alternatively activated anti-inflammatory macrophages (M2) were analyzed by using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. In this study, not only we have identified the changes of global gene expression in rat M0, M1 and M2, but we have also made clear systematically the key genes and signaling pathways in the differentiation process of M0 to M1 and M2. These will provide a foundation for future researches of macrophage polarization., (Copyright © 2018. Published by Elsevier Inc.)

Programmed death receptor 1 (PD-1) and its ligand PD-L1 have been shown to play an important role in evading the immune system. In recent years, PD-1/PD-L1 blockade has shown significant clinical effects in many malignancies, including malignant melanoma, renal cell carcinoma, classic Hodgkin lymphoma, non-small cell lung cancer and so on. PD-1/PD-L1 signaling pathway has become a new target of immunotherapy in patients with malignant tumors. However, there are few researches on immunotherapy in malignant bone tumors, and the progress of clinical research on PD-1/PD-L1 remains to be elucidated. This review started from the mechanism of PD-1/PD-L1 signaling in tumor immunity, and analyzed the application prospect of PD-1/PD-L1 antibodies in malignant bone tumors. We hope to provide a theoretical basis for the treatment of malignant bone tumors based on PD-1/PD-L1 signaling pathway in China.

Objective: To explore the association between dust exposure and the incidence of hypertension in male coal miners. Methods: Using the method of retrospective cohort study,a hypertension cohort of colliery in Henan Province was established in January 2006. From 2006 to 2017,all the male coal miners in a colliery who were exposed to dust were selected into the exposure group including tunneling, mining,auxiliary and combining workers, and workers from administrative logistics departments who were not exposed to dust were selected into the control group. The eligible participants should satisfy following conditions: working more than one year, with clear and complete record of occupation change, and with complete archives and reliable diagnosis of occupational health surveillance. The exclusion criteria of participants were with hypertension at the baseline of study or with heart,liver,kidney diseases and malignant tumors. A total of 12 647 participants were enrolled in this study (11 663 in the exposure group and 984 in the control group). The follow-up period was from January 2006 to December 2017,with a total follow-up of 89 259.75 person-years. Questionnaires and physical measurements were used to collect general demographic characteristics, occupational exposure history and occupational health surveillance data of all participants. The Cox proportional hazards regression model was used to estimate the association between the dust exposure and the incidence of hypertension. Results: During the follow-up period, 2 549 new-onset hypertension patients were identified with an incidence density of hypertension about 2 855.71 per 100 000 person-years. The incidence density of hypertension was 2 967.58 per 100 000 person-years in the exposure group, and 1 643.85 per 100 000 person-years in the control group. The results of multivariate Cox proportional hazards regression model showed that after the adjustment of marriage, age, smoking, alcohol drinking and body mass index,the risk of hypertension was higher in the exposure group compared with the control group ( HR =1.692, 95 %CI : 1.410-2.032). Further analysis showed that compared with workers from administrative logistics departments,the risk of hypertension in tunneling,mining and auxiliary working was 1.629(1.345-1.973),1.677(1.374-2.046) and 1.782(1.475-2.151),respectively. Conclusion: Dust exposure may increase the risk of hypertension in male coal miners.

Objective: To investigate the relationship between the magnesium intake and patterns of diary and the risk of type 2 diabetes in Harbin residents. Methods: On April 2010, 24 communities in 7 districts of Harbin were selected as research sites using multi-stage stratified random cluster sampling method. A total of 9 734 residents aged 20-74 years was investigated using general questionnaire survey, dietary survey and biochemical indicators test. A total of 9 376 subjects were included in the study. Factor analysis was used to analyze dietary patterns. According to the quartile of dietary magnesium intake, the subjects were divided into four groups, from Q (1) to Q (4) group. The multivariate logistic regression model was used to analyze the relationship between dietary magnesium intake and the risk of type 2 diabetes within different dietary patterns. Results: A total of 998 subjects with type 2 diabetes were screened. The median age of the diabetic group and the non-diabetic group were 54.8 and 50.8, respectively, and the males accounted for 43.4% (2 896 cases) and 34.6% (433 cases), respectively. The magnesium intake median ( P (25), P (75)) of two groups was 336.36 (257.31, 440.65) and 339.50 (264.51, 443.78) mg/d. Four dietary patterns were identified as western dietary mode, savvy dietary mode, traditional dietary mode, and staple food mode. In the western dietary model, the Q (4) group had a higher risk of type 2 diabetes than Q (1) group, with an OR (95 %CI ) value of 1.56 (1.06 to 2.32). However, in the savvy diet mode, compared with the Q (1) group, the risk of diabetes in the Q (4) group was lower, and the OR (95% CI ) value was 0.61 (0.37 to 0.96). There was no statistically significant association between dietary magnesium intake and the risk of type 2 diabetes without considering dietary patterns ( P> 0.05). Conclusion: Dietary magnesium intake has a different relationship with the risk of type 2 diabetes within different dietary patterns.

Objective: The study was conducted to evaluate the effects of night light regimen on growth performance, antioxidant status and health of Lingnan Yellow broiler chickens from 1 to 21 days of age., Methods: A completely randomized factorial design involved 2 photoperiods (constant lighting [CL], 24 L:0 D and intermittent lighting [INL], 17 L:3 D:1 L:3 D)×2 light intensities (10 lx and 30 lx). A total of one thousand six hundred and eighty 1-d-old Lingnan Yellow broiler chicks were randomly divided into 4 treatments with 6 replicates (70 birds per replicate). The experiment lasted for 21 d., Results: Photoperiods and light intensities had no effect on average daily gain, feed conversion ratio, and mortality of the broiler chickens (p>0.05). The INL had a significant effect on average daily feed intake (p<0.05) of broiler chickens compared with CL. Photoperiod and light intensity had an interactive effect on melatonin (MT) concentration (p<0.05). At CL, reducing light intensity increased MT concentration; INL birds had higher MT but MT concentration was not affected by light intensity. There was an interactive effect on glutathione peroxidase (GPx) and catalase (CAT) in serum and total antioxidant capability (T-AOC) in liver between photoperiod and light intensity. With the decrease of light intensity, the activities of GPx and CAT in serum and T-AOC in liver increased in CL group (p<0.05). Broiler chickens reared under INL had better antioxidant status and 10 lx treatments had higher activities of CAT in serum than 30 lx (p<0.05). Different photoperiods and light intensities had no effect on malondialdehyde. There was an interaction between photoperiod and light intensity on serum creatine kinase (CK) concentration (p<0.05). At CL, the elevated light intensity resulted in an increase in CK content; INL birds had lower CK concentration especially in low light intensity group. Besides, INL and low light intensity significantly reduced the concentration of serum corticosterone and heat shock protein 70 (p<0.05). Serum immunoglobulin M contents were increased in broiler chickens reared under the INL compared with CL group (p<0.05)., Conclusion: Results above suggest that the night light regimen of INL and 10 lx could be beneficial to the broiler chickens from 1 to 21 days of age due to the better health status and electricity savings.

Canine parvovirus (CPV) causes acute gastroenteritis in domestic dogs, cats, and several wild carnivore species. In this study, the full-length VP2 gene of 36 CPV isolates from dogs and cats infected between 2016 and 2017 in Beijing was sequenced and analyzed. The results showed that, in dogs, the new CPV-2a strain was the predominant variant (n = 18; 50%), followed by the new CPV-2b (n = 6; 16.7%) and CPV-2c (n = 3; 8.3%) strains, whereas, among cats, the predominant strain was still CPV-2 (n = 9; 25%). One new CPV-2a strain, 20170320-BJ-11, and two CPV-2c strains, 20160810-BJ-81 and 20170322-BJ-26, were isolated and used to perform experimental infections. Multiple organs of beagles that died tested PCR positive for CPV, and characteristic histopathological lesions were observed in organs, including the liver, spleen, lungs, kidneys, small intestines, and lymph nodes. Experimental infections showed that the isolates from the epidemic caused high morbidity in beagles, indicating their virulence in animals and suggesting the need to further monitor evolution of CPV in China., (Copyright© by the Polish Academy of Sciences.)

Phosphorothioate CpG oligodeoxynucleotides (ODN) are reported to be recognized by the membrane-bound TLR9 and trigger the MyD88-dependent up-regulation of Type I interferons and pro-inflammatory cytokines. Whether plasmids containing multiple CpG motifs stimulate the same signaling pathway is yet to be determined. The present results show that the CpG motifs enrich plasmid pUC18-CpG stimulates RAW 264.7 in vitro, mainly through the TBK1-mediated signaling pathway, causing the up-regulation of IFN-β, and pro-inflammatory cytokines TNF-α and IL-6. When pUC18-CpG is co-administered with the recombinant Echinococcus granulosus antigen, the antigen-specific antibody titers are markedly increased compared to the Quil-A adju- vanted group. Antigen specific cytokine quantification shows that cytokine profiles from the pUC18-CpG adjuvanted-group are switched to a Th1-biased immune response., (Copyright© by the Polish Academy of Sciences.)

Three new prenylated stilbenes, named as cajanusins A-C (1-3), and one new natural product cajanusin D (4), along with six known derivatives (5-10) were isolated from the leaves of Cajanus cajan. Their structures were fully elucidated by means of extensive spectroscopic methods and comparison with data in the reported literatures. The new compounds of 1 and 2 were evaluated for in vitro cytotoxic activities against a panel of human cancer cell lines., (Copyright © 2019 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Anthracnose is a major leaf disease in tea plant induced by Colletotrichum , which has led to substantial losses in yield and quality of tea. The molecular mechanism with regards to responses or resistance to anthracnose in tea remains unclear. A de novo transcriptome assembly dataset was generated from healthy and anthracnose-infected leaves on tea cultivars "Longjing-43" (LJ43) and "Zhenong-139" (ZN139), with 381.52 million pair-end reads, encompassing 47.78 billion bases. The unigenes were annotated versus Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), National Center for Biotechnology Information (NCBI) non-redundant protein sequences (Nr), evolutionary genealogy of genes: Non-supervised Orthologous Groups (eggNOG) and Swiss-prot. The number of differential expression genes (DEGs) detected between healthy and infected leaves was 1621 in LJ43 and 3089 in ZN139. The GO and KEGG enrichment analysis revealed that the DEGs were highly enriched in catalytic activity, oxidation-reduction, cell-wall reinforcement, plant hormone signal transduction and plant-pathogen interaction. Further studies by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and high-performance liquid chromatography (HPLC) showed that expression of genes involved in endogenous salicylic acid biosynthesis and also accumulation of foliar salicylic acid are involved in the response of tea plant to anthracnose infection. This study firstly provided novel insight in salicylic acid acting as a key compound in the responses of tea plant to anthracnose disease. The transcriptome dataset in this study will facilitate to profile gene expression and metabolic networks associated with tea plant immunity against anthracnose.

To clarify the pollution characteristics of heavy metals in the surface sediments of rivers in economically developed areas, analysis of the contents of eight heavy metals, assessment of ecological risks, and identification of the source of heavy metals in surface sediments from typical rivers of Lake Taihu Basin were carried out in this study. The results showed that the average contents of Zn, Cr, Ni, Cu, Pb, As, Cd, and Hg in the surface sediments of Lake Taihu Basin were 163.62, 102.46, 45.50, 44.71, 37.00, 13.34, 0.479, and 0.109 mg·kg -1 , respectively. Except for Hg, the average contents of other 7 heavy metals were higher than their background values. The geo-accumulation index indicated that Pb, Ni, Zn, Cu, and Cd amount to a low pollution state. According to the pollution load index, Pb, Ni, Zn, and Cu represent a moderately polluted state, while Cd, Cr, and As a low degree pollution state. Based on the potential ecological risk index, Cd and Hg represent moderate potential ecological risk, and the others low potential ecological risk. Source identification of heavy metals by multivariate statistical analysis showed that Pb was largely from non-point pollutions; Cr, Ni, and Zn stemmed from electroplating, alloy manufacturing industries, and nature; Cu and As were mainly from pesticides and discharge of industrial wastewater; Cd was dominantly from smelting industry; and Hg was mainly derived from fossil fuel combustion and petroleum products.

BACKGROUND Oral anticoagulants (OACs) such as warfarin and non-VKA oral anticoagulants (NOACs) have been recommended for patients with atrial fibrillation (AF) who are at risk for stroke. Whether NOACs have a higher persistence than warfarin is still unclear. This is especially true in China. MATERIAL AND METHODS Data from a large hospital-based cohort in China (China-AF Registry) from 2011 to 2017 were used for this study. Non-valvular AF patients with newly initiated OACs were included. A time-to-event approach was used to analyze patient persistence. The survival distributions of persistence were compared using the log-rank test. A multivariable Cox regression model was used to explore predictors of warfarin and NOACs non-persistence. RESULTS Patients with newly initiated warfarin (n=4845) or NOACs (n=854) were included in this study. Persistence rates at 1, 2, and 3 years were 93.2%, 89.4%, and 87.2% in the warfarin group and 88.8%, 84.3%, and 81.3% in the NOAC group respectively. Non-persistence was significantly higher with NOACs than with warfarin. On multivariate analysis, age <75 years old, outpatient clinic visits, asymptomatic AF, paroxysmal AF, duration of AF <3 years, history of peptic ulcer, and no previous TIA, stroke or thromboembolism were strong predictors of warfarin non-persistence, while in the NOACs group, age <75 years old, outpatient clinic visits, lower education status and no history of congestive heart failure were predictors. CONCLUSIONS Treatment persistence of NOACs was lower than that of warfarin among Chinese patients with AF. Patients with characteristics of non-persistence predictors need special attention to maintain their therapy.

Rice blast caused by Magnaporthe oryzae ( M. oryzae ) is a major threat to global rice production. In recent years, small interference RNAs (siRNAs) and host-induced gene silencing (HIGS) has been shown to be new strategies for the development of transgenic plants to control fungal diseases and proved a useful tool to study gene function in pathogens. We here tested whether in vitro feeding artificial siRNAs (asiRNAs) could compromise M. oryza e virulence and in vivo HIGS technique could improve rice blast resistance. Our data revealed that silencing of M. oryzae MoAP1 by feeding asiRNAs targeting MoAP1 (i.e., asiR1245, asiR1362, and asiR1115) resulted in inhibited fungal growth, abnormal spores, and decreased pathogenicity. Among the asiRNAs, asiR1115 was the most inhibitory toward the rice blast fungus. Conversely, the asiRNAs targeting three other genes (i.e., MoSSADH , MoACT , and MoSOM1 ) had no effect on fungal growth. Transgenic rice plants expressing RNA hairpins targeting MoAP1 exhibited improved resistance to 11 tested M. oryzae strains. Confocal microscopy also revealed profoundly restricted appressoria and mycelia in rice blast-infected transgenic rice plants. Our results demonstrate that in vitro asiRNA and in vivo HIGS were useful protection approaches that may be valuable to enhance rice blast resistance.

The aim of this study was to investigate the time-dependent effects of acupuncture on the excitability and long-term potentiation- (LTP-) like plasticity induced by paired-associative stimulation (PAS) over the primary motor cortex (M1). The present examination is the first to report the influence of acupuncture on the motor-evoked potential (MEP) throughout the treatment process, including baseline (before acupuncture), the needle in situ, and the needle removal. Subsequently, the LTP-like plasticity induced by paired-associative stimulation (PAS) was explored, which consisted of 200 pairs of electrical stimulation of the ulnar nerve at the first dorsal interosseous (FDI), followed by transcranial magnetic stimulation (TMS) over the bilateral M1. TMS-MEP amplitudes over the bilateral M1 in resting conditions were measured throughout the whole treatment process. Finally, we confirmed the behavioral measurements. Significant changes were found in both the contralateral and ipsilateral acupuncture sizes as compared to the baseline values. Our results indicated that acupuncture modulated the excitability of M1, and the synaptic plasticity was time-dependent. We concluded that acupuncture should be combined with rehabilitation techniques to improve the motor function in stroke patients. Therefore, we put forward the combined application of the acupuncture timing and rehabilitation for higher therapeutic effectiveness. This trial was registered in the Chinese Clinical Trial Registry (registration no. ChiCTR-IPR-1900020515).

Background: Baoyuan decoction (BYD), a well-known traditional Chinese medicine (TCM) formula, is clinically used for the treatment of aplastic anemia, chronic renal failure, coronary heart disease, etc. PURPOSE: The purpose of this study was to develop a large-volume direct injection liquid chromatography-mass spectrometry (LC-MS) method for simultaneous determination of 16 representative flavonoids and saponins in rat plasma after oral administration of BYD., Methods: The rat plasma sample was injected directly into a pre-column, which was eluted firstly by 0.05% formic acid in water. Then, the accumulated components were eluted from the pre-column and transferred into a Waters BEH C18 column with acetonitrile and water system (contain 0.05% formic acid) as the mobile phase at a rate of 0.3 ml/min. The detection was accomplished in a negative mode using the schedule multiple-reaction monitoring (sMRM)., Results: The correlation coefficients for calibration curves were all higher than 0.9920 for formononetin, ononin, calycosin, liquiritigenin, isoliquiritigenin, glycyrrhizic acid, glycyrrhetinic acid, liquiritin, isoliquiritin, liquiritin apioside, isoliquiritin apioside, ginsenoside Rb1, ginsenoside Re, ginsenoside Rd, ginsenoside Rg1 and astragaloside. The intra- and inter-day precisions (RSD) and accuracy (RE) for the investigated components were in the range of -10.9 to 13.7%. The average recoveries were in the range of 75.7-108.6%. This method was successfully applied to investigate the pharmacokinetics of 16 compounds of BYD in rats. The absorption and elimination rates of the representative saponins were significantly slower than most of the targeted-flavonoids after oral administration of BYD in rats., Conclusion: The results demonstrated that the large-volume direct injection LC-MS method provided a rapid and efficient approach for multi-components pharmacokinetics of TCM., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Background: Gastric cancer is the second most common cause of cancer-related mortality; thus, the mechanisms underlying tumor metastasis and growth in gastric cancer need to be extensively explored., Methods: Differentially expressed genes were examined in gastric cancer samples with lymph node metastasis (LNM) and without LNM using mRNA microarray and RT-qPCR. The effects of G antigen 7B (GAGE7B) on the metastasis, growth, and angiogenesis of gastric cancer were investigated in vitro and in vivo. GAGE7B protein expression was detected by immunohistochemical (IHC) analysis. Microarray, RT-qPCR, and western blot assays were performed to detect downstream target genes of GAGE7B. Dual-luciferase reporter and western blot assays were used to identify miRNAs that could negatively regulate GAGE7B., Results: GAGE7B was significantly overexpressed in samples with LNM. High expression levels of GAGE7B were associated with advanced clinical stage and poor patient survival. GAGE7B dramatically enhanced the metastasis, growth, and angiogenesis ability of gastric cancer. GAGE7B was further demonstrated to promote the progression of gastric cancer by activating the p38δ/pMAPKAPK2/pHSP27 pathway. However, the GAGE7B-induced p38δ/pMAPKAPK2/pHSP27 pathway was inactivated by miR-30c, as the expression levels of both GAGE7B and p38δ were found to be directly suppressed by miR-30c. Intriguingly, GAGE7B was found to be a ceRNA for p38δ, as it activated the p38δ/pMAPKAPK2/pHSP27 pathway by competitively binding miR-30c., Conclusions: GAGE7B may serve as a prognostic indicator in gastric cancer. GAGE7B significantly promotes gastric cancer progression by upregulating the p38δ/pMAPKAPK2/pHSP27 pathway, but it is negatively regulated by miR-30c. GAGE7B and miR-30c may be potential therapeutic targets in gastric cancer.

In traumatic brain injury, absent in melanoma 2 (AIM2) has been demonstrated to be involved in pyroptotic neuronal cell death. Although the pathophysiological mechanism of spinal cord injury is similar to that of brain injury, the expression and cellular localization of AIM2 after spinal cord injury is still not very clear. In the present study, we used a rat model of T9 spinal cord contusive injury, produced using the weight drop method. The rats were randomly divided into 1-hour, 6-hour, 1-day, 3-day and 6-day (post-injury time points) groups. Sham-operated rats only received laminectomy at T9 without contusive injury. Western blot assay revealed that the expression levels of AIM2 were not significantly different among the 1-hour, 6-hour and 1-day groups. The expression levels of AIM2 were markedly higher in the 1-hour, 6-hour and 1-day groups compared with the sham, 3-day and 7-day groups. Double immunofluorescence staining demonstrated that AIM2 was expressed by NeuN + (neurons), GFAP + (astrocytes), CNPase + (oligodendrocytes) and CD11b + (microglia) cells in the sham-operated spinal cord. In rats with spinal cord injury, AIM2 was also found in CD45 + (leukocytes) and CD68 + (activated microglia/macrophages) cells in the spinal cord at all time points. These findings indicate that AIM2 is mainly expressed in neurons, astrocytes, microglia and oligodendrocytes in the normal spinal cord, and that after spinal cord injury, its expression increases because of the infiltration of leukocytes and the activation of astrocytes and microglia/macrophages., Competing Interests: None

Objective: To further recognize the clinical characteristics of non-syndromic enlarged vestibular aqueduct through the retrospective analysis of cases, with the purpose of providing references for clinical diagnosis and treatment. Method: Collect 54 cases of non-syndromic enlarged vestibular aqueduct, and analyze their clinical characteristics after history taking, physical examination, audiometry and imaging examination. Measure the biggest width of midpoint between internal and external of vestibular aqueduct on temporal bone thin-section CT, and analyze the relationship between the pipe width and sides of ear, types of hearing loss and degree of hearing loss through t test. Result: All 54 patients with non-syndromic enlarged vestibular aqueduct had bilateral ear involvement. There were 42 cases with prelingual deafness, 12 cases with postlingual deafness, and there were 38 ears with severe deafness, 70 ears with profound deafness. Ninety-six ears of hearing loss showed sensorineural deafness, and 12 ears manifested mixed deafness. The biggest width of midpoint between internal and external of vestibular aqueduct spread over 1.60-3.90 mm, and the average was 2.60 mm. There were no significant differences in data between left and right sides, degree of hearing loss and type of hearing loss. Conclusion: Non-syndromic enlarged vestibular aqueduct mainly manifests serious sensorineural deafness, and the diagnosis depends on imaging examination. There is no difference in the degree of expanding between left and right ear, and the extent of enlargement is not related to the type and the severity of hearing loss., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: Diet and exercise during pregnancy have been used to prevent gestational diabetes mellitus (GDM) with some success., Objective: To examine the effectiveness of lifestyle intervention on GDM prevention and to identify key effectiveness moderators to improve the prevention strategy., Search Strategy: Pubmed, Scopus, Cochrane, and cross-references were searched., Selection Criteria: Randomised controlled trials (RCTs) evaluating lifestyle interventions during pregnancy for GDM prevention., Data Collection and Analysis: Two independent reviewers extracted data. A random-effects model was used to analyse the relative risk (RR) and 95% confidence interval (95% CI). Meta-regressions and subgroup analyses were used to investigate important moderators of effectiveness., Main Results: Forty-seven RCTs involving 15 745 participants showed that diet and exercise during pregnancy were preventive of GDM (RR 0.77, 95% CI 0.69-0.87). Four key aspects were identified to improve the preventive effect: targeting the high-risk population; an early initiation of the intervention; the correct intensity and frequency of exercise; and gestational weight gain management. Although 24 RCTs targeted women who were overweight or obese, body mass index (BMI) failed to predict the effectiveness of an intervention. Instead, interventions are most effective in high-incidence populations rather than simply in women who are overweight or obese. Furthermore, exercise of moderate intensity for 50-60 minutes twice a week could lead to an approximately 24% reduction in GDM., Conclusion: The best strategy to prevent GDM is to target the high-risk population predicted by risk evaluation models and to control the gestational weight gain of women through intensified diet and exercise modifications early in their pregnancy., Tweetable Abstract: Four key effectiveness moderators of lifestyle interventions for GDM prevention., (© 2018 Royal College of Obstetricians and Gynaecologists.)

Previous studies by our group have demonstrated that the transplantation of exogenous platelet-derived growth factor (PDGF)-AA-overexpressing oligodendrocyte progenitor cells (OPCs) promotes tissue repair and recovery of neurological function in a rat model of spinal cord injury (SCI). However, it remains unclear whether treatment with PDGF-AA also affects endogenous oligodendrocytes (OLs) or even neurons, thus promoting further functional recovery after SCI. In the present study, we evaluated the therapeutic potential of PDGF-AA treatment by direct subcutaneous injection of PDGF-AA immediately after SCI. We demonstrated that PDGF-AA injection resulted in increased tissue sparing, myelination and functional recovery in rats following SCI. Further experimentation confirmed that PDGF-AA increased the survival of endogenous OPCs and OLs, and promoted the proliferation of OPCs and their differentiation into OLs. Moreover, PDGF-AA also protected motor neurons from death in the injured spinal cord. These results indicated that PDGF-AA administration may be an effective treatment for SCI.

With the prestressed carbon fiber reinforced polymer (CFRP) strengthening technique widely used in reinforced concrete (RC) structures, it is more and more important to study the fatigue performance of RC structures. Since the fracture of a tensile steel bar at the main cracked section is the leading reason for the failure of RC beams reinforced by prestressed CFRP, a fatigue life prediction model of RC beams reinforced by prestressed CFRP was developed based on an accumulative damage model. Moreover, gradual degradation of the performance of the concrete was considered in the fatigue life prediction model. An experimental study was also conducted to research the fatigue behavior of RC beams reinforced by prestressed or non-prestressed carbon fiber laminate (CFL). During the tests, fatigue crack patterns were captured using a digital image correlation (DIC) technique, and the fatigue lives of a total of 30 beams were recorded. The results showed that the predicted main crack propagation curves and the fatigue lives were close to the experimental data. This study also exhibited that the prestressed CFRP could reduce the stress of main steel bars in RC beams and effectively improve the fatigue performance of the RC beams.

The phospholipase C (PLC) is a family of kinases that hydrolyze phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] to generate two second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), which stimulate distinct downstream signaling. Recently, it has been reported that PLC signaling is activated by multiple viruses for efficient replication and the virus-induced inflammatory response. In this study, we demonstrated that PLC-specific inhibitor U73122 strongly suppressed porcine reproductive and respiratory syndrome virus (PRRSV) productive infection in cell cultures. The inhibitor affected both viral post-binding cell entry and post-entry processes. The virus infection led to an early transient activation of PLCγ-1 at 0.5 h post-infection (hpi), and sustained event at a stage from 4 to 16 hpi in MARC-145 cells. In addition, U73122 inhibited the activation of p38 MAPK signaling stimulated by PRRSV infection, suggesting that PLC signaling may be associated with the virus infection-induced inflammatory response. Taken together, these studies suggested that PLC signaling played an important role in PRRSV infection or pathogenesis. Keywords: PRRSV; U73122; phospholipase C; PLCγ-1.

Ganoderma lucidum is a famous medicinal mushroom that is rich in antioxidants. The content of antioxidant components of grains can be effectively improved by G. lucidum as the fermenting strain. Optimization of the solid-state fermentation medium and optimization of the fermentation conditions were studied. The optimal fermentation substrate combination of G. lucidum TS (GL-TS) was 46.79% buckwheat, 53.21% rice; the optimal fermentation substrate combination of G. lucidum Am (GL-Am) was 4.17% soybean, 95.83% rice. The optimal fermentation conditions of GL-TS and GL-Am were as follows: inoculum amounts of 4.5% and 7.5%, temperatures of 30°C and 32°C, medium moisture content of 70% for both media, material granularities of 0.212-0.355 mm and 0.500-0.710 mm, and optimal fermentation time of 12.0 d and 10.5 d, respectively. Results of the analysis of antioxidant components in the fermentation substrates indicated that the antioxidant components were rich in antioxidant varieties and high in content. The contents of the antioxidant components (triterpenoids, total polyphenols, reducing sugars, anthocyanins, superoxide dismutase, glutathione, vitamin C, and vitamin E) in the full-fermentation substrates were greater than those in the nonfennentation substrates (except for flavonoids in the full-fermentation substrates, which were less than in the nonfennentation substrates). Glutathione was the major antioxidant component in the fermentation substrates, and the glutathione content was the highest. Therefore, the fermentation substrates of G. lucidum can be used to make antioxidant foods. This research contributes to the foundation for developing antioxidant foods based on G. lucidum.

Background: Previous studies suggest that dexmedetomidine has a protective effect against local anaesthetic-induced nerve injury in regional nerve blocks. Whether this potentially protective effect exists in the context of diabetes mellitus is unknown., Methods: A diabetic state was established in adult male Sprague-Dawley rats with intraperitoneal injection of streptozotocin. Injections of ropivacaine 0.5%, dexmedetomidine 20 μg kg -1 (alone and in combination), or normal saline (all in 0.2 ml) were made around the sciatic nerve in control and diabetic rats (n=8 per group). The duration of sensory and motor nerve block and the motor nerve conduction velocity (MNCV) were determined. Sciatic nerves were harvested at post-injection day 7 and assessed with light and electron microscopy or used for pro-inflammatory cytokine measurements., Results: Ropivacaine and dexmedetomidine alone or in combination did not produce nerve fibre damage in control non-diabetic rats. In diabetic rats, ropivacaine induced significant nerve fibre damage, which was enhanced by dexmedetomidine. This manifested with slowed MNCV, decreased axon density, and decreased ratio of inner to outer diameter of the myelin sheath (G ratio). Demyelination, axon disappearance, and empty vacuoles were also found using electron microscopy. An associated increase in nerve interleukin-1β and tumour necrosis factor-α was also seen., Conclusions: Ropivacaine 0.5% causes significant sciatic nerve injury in diabetic rats that is greatly potentiated by high-dose dexmedetomidine. Although the dose of dexmedetomidine used in this study is considerably higher than that used in clinical practice, our data suggest that further studies to assess ropivacaine (alone and in combination with dexmedetomidine) use for peripheral nerve blockade in diabetic patients are warranted., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Isorhamnetin, a flavonoid ingredient derived from Vernonia anthelmintica (L.) Willd., has shown a spectrum of antitumor activity. However, the chemopreventive potential of isorhamnetin on advanced pancreatic cancer and the underlying molecular mechanism remain unknown. In the current study, treatment of the advanced pancreatic adenocarcinoma cell line PANC-1 with isorhamnetin resulted in robust cell growth arrest. PI-annexin V double staining and Hoechst 33258 staining revealed that isorhamnetin moderately induced early apoptosis without morphological alterations of nuclei. Instead, isorhamnetin caused cell cycle S-phase arrest through downregulation of cyclin A. In addition, isorhamnetin decreased the phosphorylation levels of MEK and ERK in the Ras/MAPK pathway, which is involved in regulating cell proliferation, differentiation and apoptosis. Wound-healing experiments demonstrated isorhamnetin significantly reduced the migratory behavior of PANC-1 cells. Altogether, the present study suggests that isorhamnetin may be a potential agent for prevention of pancreatic carcinoma., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: To investigate whether PET/CT-guided bone marrow biopsy adds complementary information for evaluation of bone marrow involvement (BMI) in newly diagnosed lymphomas., Methods: Patients with newly diagnosed lymphomas that received both 18 F-FDG PET/CT and bone marrow biopsy (BMB) were included in this retrospective study. PET/CT classification of bone lesions was classified as isolated, multifocal (2 lesions or more), diffuse (homogeneous uptake of the entire axial skeleton), or negative. BMBs included PET/CT-guided targeted BMB and/or the routine unilateral iliac crest biopsy. Of 34 patients with focal lesions on PET/CT scan, 30 received both PET/CT-guided targeted BMB and iliac crest biopsy, and 4 patients received targeted biopsy without iliac crest biopsy. The final diagnosis of BMI depends on BMB results., Results: A total of 299 patients with lymphomas were included. PET/CT classification of bone lesions was isolated (16/5.4%), multifocal (67/22.4%), diffuse (52/17.4%), and negative (164/54.8%). If only positive iliac crest biopsy was considered as the reference standard, the sensitivity of 18 F-FDG PET/CT for identifying focal and diffuse BMI was 48 and 56%, respectively, and the respective specificities were 70 and 83%. Three of 30 patients (10.0%) with focal lesions on PET/CT were confirmed to be false-positive by targeted BMB, and 25 of 30 patients (83.3%) with focal lesions on PET/CT were confirmed as false-negative by iliac crest biopsy., Conclusion: It is insufficient to evaluate BMI in newly diagnosed lymphomas using both 18 F-FDG PET/CT and routine iliac crest biopsy. 18 F-FDG PET/CT imaging should be performed before BMB. In focal bone lesions, PET/CT-guided targeted BMB may complement the results of possible false-positive PET/CT and false-negative iliac crest biopsy findings. However, in diffuse and negative lesions, iliac crest biopsy cannot be safely omitted.

Fifteen new structurally unique monoterpenoid carbazole alkaloids, including two pairs of epimers (1/2 and 3/4), three pairs of enantiomers (6a/6b, 7a/7b, and 8a/8b), and five optically pure analogues (5, 9-12), were obtained from a 95% aqueous EtOH extract of Murraya microphylla by a combination of bioassay- and LC-MS-guided fractionation procedures. Their structures were established based on NMR and HRESIMS data interpretation. The absolute configuration of compound 1 was determined via X-ray crystallographic data analysis and for all compounds by comparison of experimental and calculated ECD data. Compounds 1-5 were assigned as five new thujane-carbazole alkaloids, and compounds 6-12 as 10 new menthene-carbazole alkaloids linked through an ether or carbon-carbon bond. Compounds 1-12 promoted insulin secretion in the HIT-T15 cell line, 1.9-3.1-fold higher than the gliclazide control at 100 μM.

The herbal medicine combination of notoginseng-safflower has been commonly used clinically for the prevention and treatment of cardiovascular diseases. A reliable liquid chromatography-tandem mass spectrometry (LC⁻MS/MS) method was developed for simultaneous determination of six bioactive components (hydroxysafflor yellow A, notoginsenoide R1, ginsenoside Rb1, Re, Rd, and Rg1) in rat urine and feces after oral administration of notoginseng total saponins (NS), safflower total flavonoids (SF), and the combination of NS and SF (CNS). The chromatographic separation was achieved on a Waters HSS T3 column under gradient elution with acetonitrile and water containing formic acid as the mobile phase. The calibration curves were linear, with correlation coefficient ( r ) > 0.99 for six components. The intra- and interday precision (RSD) and accuracy (RE) of QC samples were within -14.9% and 14.9%, respectively. The method was successfully applied to study of the urinary and fecal excretion of six bioactive constituents following oral administration of NS, SF, and CNS in rats. Compared to the single herb, the cumulative excretion ratios of six constituents were decreased in the herbal combination. The study indicated that the combination of notoginseng and safflower could reduce the renal and fecal excretion of the major bioactive constituents and promote their absorption in rats.

Objective: The aim of this meta-analysis is to explore the beneficial role of granulocyte colony-stimulating factor (G-CSF) on infertile women under artificial reproduction technology treatment., Method: Medline, Embase and ISI Web of Science databases were searched to identify relevant randomized control trials. Studies before July, 2017 were included for primary screening. Meta-analysis of the total and subgroup patients was conducted, and relative risks (RRs) and their 95% confidence intervals (95% CI) were calculated by a fixed-effect model if no heterogeneity (evaluated as I 2 statistic) existed. Otherwise, a random-effects model was adopted. Subgroup analysis was performed by administrating route or clinical indication. Egger test and influence analysis were conducted to evaluate the publication bias and study power, respectively., Results: The final selection enrolled 10 RCTs, involving 1016 IVF-ET cycles (521 distributed to the G-CSF group and 495 to the control). Compared with control group, G-CSF administration could significantly improve clinical pregnancy rate (CPR, RR 1.89, 95% CI 1.53-2.33), while it had no beneficial effect on embryo implantation rate (IR, RR 1.84, 95% CI 0.84-4.03). The subgroup analysis by administration route showed that both uterine infusion and subcutaneous injection can produce a substantial increase in CPR, with the pooled RRs (95% CI) 1.46 (1.04-2.05) and 2.23 (1.68-2.95), respectively. Nevertheless, most of included RCTs dealt with the RIF subjects, and the pooled analysis of this data showed a higher PR and IR in G-CSF group as compared to that in the control, with the RRs (95% CI) 2.07 (1.64-2.61) and 1.52 (1.08-2.14), respectively. Egger regression test did not demonstrate any significance for the publication bias., Conclusion: G-CSF administration has a beneficial role on the clinical outcome after embryo transfer by both routes of local infusion and systematic administration, especially for the cases with RIF. Further RCTs are needed to investigate the role of G-CSF in thin endometrium patients.

Extra-hypothalamic growth hormone-releasing hormone (GHRH) plays an important role in reproduction. To study the treatment effect of Grin (a novel hGHRH homodimer), the infertility models of 85 male Chinese hamsters were established by intraperitoneally injecting 20 mg/kg of cyclophosphamide once in a week for 5 weeks and the treatment with Grin or human menopausal gonadotropin (hMG) as positive control was evaluated by performing a 3-week mating experiment. 2-8 mg/kg of Grin and 200 U/kg of hMG showed similar effect and different pathological characteristics. Compared to the single cyclophosphamide group (0%), the pregnancy rates (H-, M-, L- Grin 26.7, 30.8, 31.3%, and hMG 31.3%) showed significant difference, but there was no difference between the hMG and Grin groups. The single cyclophosphamide group presented loose tubules with pathologic vacuoles and significant TUNEL positive cells. Grin induced less weight of body or testis, compactly aligned tubules with little intra-lumens, whereas hMG caused more weight of body or testis, enlarging tubules with annular clearance. Grin presented a dose-dependent manner or cell differentiation-dependentincrease in testicular GHRH receptor, and did not impact the levels of blood and testicular GH, testosterone. Grin promotes fertility by proliferating and differentiating primitive cells through up-regulating testicular GHRH receptor without triggering GH secretion, which might solve the etiology of oligoasthenozoospermia., Competing Interests: CONFLICTS OF INTEREST: The authors declare no conflicts of interest.

Objective: To explore postoperative delirium (POD)risk factors for geriatric patients who suffered hip fracture under the care of orthogeriatric unit mode. Methods: Patients aged 65 years or older, who were admitted to the orthogeriatric unit in Beijing Jishuitan Hospital from April to October 2017 for hip fracture surgery, were eligible for this prospective cohort study. After univariable analysis, significant risk factors associated with POD were further evaluated with multivariable analysis, to establish independent risk factors associated with POD. Results: A total of 203 patients with an average age of 80(65-96)years were enrolled in the study. The overall incidence of POD was 9.4%(19/203)in which hyperactive and hypoactive type accounting for 84.2%(16/19)and 15.8%(3/19), respectively. Significant difference was found between POD and non-POD groups in patients' age ( P =0.003), albumin( P =0.006), TSH( P =0.018), PaCO(2) level( P =0.003), visual analogue scale (VAS )both at rest ( P =0.013)and movement( P =0.010) on post-operative day 1.The further Logistic stepwise regression analysis showed that significant differences existed between groups in age( P =0.027), albumin( P =0.003), PaCO(2)( P =0.014)and VAS at rest( P =0.002). Conclusion: The independent risk factors of POD in geriatric patients undergoing hip fracture under the orthogeriatric unit mode include patients' age, pre-operative albumin as well as PaCO(2) level and post-operative VAS at rest.

Ethnopharmacological Relevance: Baoyuan decoction (BYD), a traditional Chinese medicine (TCM) formula, is composed of four herbs and widely used with western drugs to treat coronary heart disease, aplastic anemia and chronic renal failure in clinic. However, no study of the effect of BYD on the cytochrome P450 (CYP) activities has been reported., Aim of the Study: The purpose of the present study was to evaluate the potential influences of BYD on the activities of seven CYP isozymes (CYP1A2, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4) in rats., Materials and Methods: A sensitive and selective UPLC-MS/MS method for simultaneous determination of seven probe drugs and internal standard (IS) in rat plasma was developed and validated. The influence of BYD on the activities of CYP isozymes and mRNA expression levels were carried out by comparing plasma pharmacokinetics and real-time reverse transcription-polymerase chain reaction (RT-PCR) of probe drugs between control and BYD treatment groups respectively., Results: The calibration curve were linear, with correlation coefficient (r) > 0.99 for seven probe drugs. The intra and inter-assay accuracy and precision of the method were within ± 14.9% and the recoveries ranged from 83.2% to 106.1%. Compared with control group, BYD at low (1.46 g/kg) and high (7.30 g/kg) dosages could significantly increase C max and AUC 0-t of chlorzoxazone and testosterone, while decrease AUC 0-t of phenacetin at high dosage and increase AUC 0-t of tolbu t amide and metoprolol. Additionally, BYD had increased AUC 0-t of bupropion at low dosage and decreased it at high dosage. The mRNA expression results were in accordance with those of pharmacokinetic., Conclusion: BYD exhibited inhibitory effects on CYP2C9, CYP2E1, and CYP3A4. Moreover, BYD had induction effects on CYP1A2, and CYP2D6 activities. However, no significant change in CYP2C19 activity was observed. It would be useful for the safe and effective usage of BYD in clinic., (Copyright © 2018 Elsevier B.V. All rights reserved.)