Search

Background This work aimed to report a small family of Primary Failure of Eruption(PFE) with a novel PTH1R variant. One of the patients has a rare clinical phenotype of the anterior tooth involved only.Case presentation The proband was a 13-year-old young man with an incomplete eruption of the right upper anterior tooth(11,12,13), resulting in a significant open-bite. His left first molar 26 partially erupted. Family history revealed that the proband's 12-year-old brother and father also had teeth eruption disorders. Genetic testing found a novel PTH1R variant (c.1325-1336del), which has never been reported before. The diagnosis of PFE was based on clinical and radiographic characteristics and the result of genetic testing. Bioinformatic analysis predicted this variant would result in the truncation of the G protein-coupled receptor encoded by the PTH1R, affecting its structure and function.Conclusion A novel PTH1R variant identified through whole-exome sequencing further expands the mutation spectrum of PFE. Patients in this family have different phenotypes, which reflects the characteristics of variable phenotypic expression of PFE.

It is well established that glutamate plays an important role in drug-induced and cue-induced reinstatement of drug seeking. However, the role of glutamate in drug reward is unclear. In this study, we systemically evaluated the effects of multiple glutamate transporter (GLT) inhibitors on extracellular glutamate and dopamine (DA) in the nucleus accumbens (NAc), intravenous cocaine self-administration, intracranial brain-stimulation reward (BSR), and reinstatement of cocaine seeking in male and female rats. Among the five GLT inhibitors we tested, TFB-TBOA was the most potent. Microinjections of TFB-TBOA into the NAc, but not the ventral tegmental area (VTA), or dorsal striatum (DS), dose-dependently inhibited cocaine self-administration under fixed-ratio and progressive-ratio (PR) reinforcement schedules, shifted the cocaine dose–response curve downward, and inhibited intracranial BSR. Selective downregulation of astrocytic GLT-1 expression in the NAc by GLT-1 antisense oligonucleotides also inhibited cocaine self-administration. The reduction in cocaine self-administration following TFB-TBOA administration was NMDA GluN2B receptor dependent, and rats self-administering cocaine showed upregulation of GluN2B expression in NAc DA- and cAMP-regulated phosphoprotein 32 (DARPP-32)-positive medium-spiny neurons (MSNs). In contrast, TFB-TBOA, when locally administered into the NAc, VTA, or ventral pallidum (VP), dose-dependently reinstated cocaine-seeking behavior. Intra-NAc TFB-TBOA-evoked drug-seeking was long-lasting and NMDA/AMPA receptor dependent. These findings, for the first time, indicate that glutamate in the NAc negatively regulates cocaine's rewarding effects, while an excess of glutamate in multiple brain regions can trigger reinstatement of drug-seeking behavior.SIGNIFICANCE STATEMENTIt is well known that glutamate plays an important role in relapse to drug seeking. However, the role of glutamate in drug reward is less clear. Here, we report that TFB-TBOA, a highly potent glutamate transporter (GLT) inhibitor, dose-dependently elevates extracellular glutamate and inhibits cocaine self-administration and brain-stimulation reward (BSR), when administered locally into the nucleus accumbens (NAc), but not other brain regions. Mechanistic assays indicate that cocaine self-administration upregulates NMDA-GluN2B receptor subtype expression in striatal dopaminoceptive neurons and activation of GluN2B by TFB-TBOA-enhanced glutamate inhibits cocaine self-administration. TFB-TBOA also reinstates cocaine-seeking behavior when administered into the NAc, ventral tegmental area (VTA), and ventral pallidum (VP). These findings demonstrate that glutamate differentially regulates cocaine reward versus relapse, reducing cocaine reward, while potentiating relapse to cocaine seeking.

Background As hospitals are under increasing pressure to improve quality and safety, safety culture has become a focal issue for high-risk organizations, including hospitals. Prior research has explored some of the factors that influence patient safety culture (PSC). However, there are relatively few related studies. In this study, we explored the relationship between silence behaviour, psychological empowerment, and PSC to find factors that affect the PSC in the hospital. Our study can serve as reference for hospital managers and for improving hospital service quality and patient safety. Methods The data for this study were from a multi-centre cross-sectional survey among hospital staff from six provinces/municipalities in China (N = 1034). Using correlation analysis and regression analysis to explore the impact of silence behaviour and psychological empowerment on PSC, we used a mediation model to explore the mediation effect among these three factors. Results Hospital staff PSC was correlated with silence behaviour and psychological empowerment. Furthermore, the effect of silence behaviour on PSC was mediated entirely through psychological empowerment. We found statistically significant differences in the perception of safety culture among respondents with different residential regions, sexes, education levels, and positions (P

Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, its diagnosis and prognosis evaluation mainly depends on tissue biopsy and imaging examination. As a part of liquid biopsy, circulating tumor DNA (ctDNA) is a novel noninvasive and real-time tumor-specific biomarker, which can reliably reflect the comprehensive tumor genetic profiles, and it plays an important role in assisting early diagnosis, monitoring the curative effect, prognosis evaluation and prediction of recurrence of DLBCL. This review summarized recent research progress of ctDNA in DLBCL.循环肿瘤DNA在弥漫大B细胞淋巴瘤中的临床应用及研究进展.弥漫性大B细胞淋巴瘤（DLBCL）是最常见的非霍奇金淋巴瘤，其诊断和预后评估主要依赖于组织病理活检和影像学检查。作为液体活检的一部分，循环肿瘤DNA是一种新型无创的、实时的肿瘤特异性生物标志物，能够可靠地反映出全面的肿瘤遗传特征，在协助DLBCL早期诊断、疗效监测、预后评估及预测复发等方面均能发挥重要作用。本文对循环肿瘤DNA在DLBCL中的最新研究进展作一综述。.

Autophagy has been shown to play an important role in Parkinson's disease. We hypothesized that skin-derived precursor cells exhibit neuroprotective effects in Parkinson's disease through affecting autophagy. In this study, 6-hydroxydopamine-damaged SH-SY5Y cells were pretreated with a culture medium containing skin-derived precursors differentiated into Schwann cells (SKP-SCs). The results showed that the SKP-SC culture medium remarkably enhanced the activity of SH-SY5Y cells damaged by 6-hydroxydopamine, reduced excessive autophagy, increased tyrosine hydroxylase expression, reduced α-synuclein expression, reduced the autophagosome number, and activated the PI3K/AKT/mTOR pathway. Autophagy activator rapamycin inhibited the effects of SKP-SCs, and autophagy inhibitor 3-methyladenine had the opposite effect. These findings confirm that SKP-SCs modulate the PI3K/AKT/mTOR pathway to inhibit autophagy, thereby exhibiting a neuroprotective effect in a cellular model of Parkinson's disease. This study was approved by the Animal Ethics Committee of Laboratory Animal Center of Nantong University (approval No. S20181009-205) on October 9, 2018.

Objective: To explore the antiarrhythmic effect and mechanism of dexmedetomidine, a myocardial α2 receptor agonist in vitro. Methods: Fifty Wistar rats were randomly divided into five groups (n = 10): sham operation group (Ctl), arrhythmia model group (Model), arrhythmia + dexmedetomidine group (Dex), arrhythmia + yohimbine + dexmedetomidine group (Yoh + Dex), arrhythmia + yohimbine group (Yoh). The Ctl group just thread left anterior descending coronary artery without ligation. Model group recorded 10 minutes of normal ECG, ligated the left anterior descending coronary artery, and continued to record the ECG for 2 hours. Dex group, Yoh + Dex group and Yoh group were ligated left anterior descending coronary artery after administration. Use BL-420E system to record ECG; Curtis and Walker arrhythmia scores were used to analyze the severity of arrhythmia; perform survival analysis according to the life span of each group of rats; after 21 days of modeling, measure the area of myocardial infarction by TTC staining. The pH value of extracellular fluid was decreased to simulate myocardial ischemia. Patch clamp technique was used to detect the action potential duration of myocardial cells. Results: Compared with the Ctl group, the arrhythmia score and myocardial infarction area in the Model group was increased (P < 0.05), the mortality and myocardial infarction area were alsosignificantly reduced (P < 0.05). Compared with Model group and Yoh group, the arrhythmia score of Dex group was significantly lower (P < 0.001), the mortality and myocardial infarction area were significantly lower (P < 0.05); Dexmedetomidine shortened QTc interval (P < 0.01), APD50 and APD90 (P < 0.05). The α2 receptor blocker Yohimbine inhibited the effect of dexmedetomidine. Conclusion: Dexmedetomidine affects the action potential repolarization process by stimulating myocardial α2 receptors, and prevents ischemia-induced ventricular arrhythmia.

Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system. The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release of growth factors that nourish host cells. In this study, we first established a cellular model of Parkinson's disease using 6-hydroxydopamine. When SH-SY5Y cells were pretreated with conditioned medium from skin-derived precursor Schwann cells, their activity was greatly increased. The addition of insulin-like growth factor-2 neutralizing antibody markedly attenuated the neuroprotective effects of skin-derived precursor Schwann cells. We also found that insulin-like growth factor-2 levels in the peripheral blood were greatly increased in patients with Parkinson's disease and in a mouse model of Parkinson's disease. Next, we pretreated cell models of Parkinson's disease with insulin-like growth factor-2 and administered insulin-like growth factor-2 intranasally to a mouse model of Parkinson's disease induced by 6-hydroxydopamine and found that the level of tyrosine hydroxylase, a marker of dopamine neurons, was markedly restored, α-synuclein aggregation decreased, and insulin-like growth factor-2 receptor down-regulation was alleviated. Finally, in vitro experiments showed that insulin-like growth factor-2 activated the phosphatidylinositol 3 kinase (PI3K)/AKT pathway. These findings suggest that the neuroprotective effects of skin-derived precursor Schwann cells on the central nervous system were achieved through insulin-like growth factor-2, and that insulin-like growth factor-2 may play a neuroprotective role through the insulin-like growth factor-2 receptor/PI3K/AKT pathway. Therefore, insulin-like growth factor-2 may be an useful target for Parkinson's disease treatment.

Physical exercise is rewarding and protective against drug abuse and addiction. However, the neural mechanisms underlying these actions remain unclear. Here, we report that long-term wheel-running produced a more robust increase in c-fos expression in the red nucleus (RN) than in other brain regions. Anatomic and functional assays demonstrated that most RN magnocellular portion (RNm) neurons are glutamatergic. Wheel-running activates a subset of RNm glutamate neurons that project to ventral tegmental area (VTA) dopamine neurons. Optogenetic stimulation of this pathway was rewarding, as assessed by intracranial self-stimulation and conditioned place preference, whereas optical inhibition blocked wheel-running behavior. Running wheel access decreased cocaine self-administration and cocaine seeking during extinction. Last, optogenetic stimulation of the RNm-to-VTA glutamate pathway inhibited responding to cocaine. Together, these findings indicate that physical exercise activates a specific RNm-to-VTA glutamatergic pathway, producing exercise reward and reducing cocaine intake.

Cannabinoid CB(2) receptors (CB(2)R) are importantly involved in drug reward and addiction. However, the cellular mechanisms underlying CB(2)R action remain unclear. We have previously reported that cocaine self-administration upregulates CB(2)R expression in midbrain dopamine (DA) neurons. In the present study, we investigated whether cocaine or heroin also alters CB(2)R expression in striatal medium-spiny neurons that express dopamine D(1) or D(2) receptors (D(1)-MSNs, D(2)-MSNs) and microglia. Due to the concern of CB(2)R antibody specificity, we developed three mouse CB(2)-specific probes to detect CB(2)R mRNA using quantitative RT-PCR and RNAscope in situ hybridization (ISH) assays. We found that a single injection of cocaine failed to alter, while repeated cocaine injections or self-administration dose-dependently upregulated CB(2)R gene expression in both brain (cortex and striatum) and periphery (spleen). In contrast, repeated administration of heroin produced a dose-dependent reduction in striatal CB(2) mRNA expression. RNAscope ISH assays detected CB(2)R mRNA in striatal D(1)- and D(2)-MSNs, not in microglia. We then used transgenic CX3CR1(eGFP/+) microglia reporter mice and D(1)- or D(2)-Cre-RiboTag mice to purify striatal microglia or ribosome-associated mRNAs from CX3CR1(eGFP/+), D(1)-MSNs, or D(2)-MSNs, respectively. We found that CB(2)R upregulation occurred mainly in D(1)-MSNs, not in D(2)-MSNs or microglia, in the nucleus accumbens rather than the dorsal striatum. These findings indicate that repeated cocaine exposure may upregulate CB(2)R expression in both brain and spleen, with regional and cell type-specific profiles. In the striatum, CB(2)R upregulation occurs mainly in D(1)-MSNs in the nucleus accumbens. Given the important role of D(1)-MSNs in brain reward function, the present findings provide new insight into mechanisms by which brain CB(2)Rs modulate cocaine action.

Objective To evaluate the clinical effect of ultrasound guided foam sclerotherapy (UGFS) combined with high ligation of great saphenous vein (GSV) in treatment of severe varicose veins of lower extremity (grade C4-C6). Methods A total of 354 patients with primary GSV dysfunction (CEAP classification C4-C6) were recruited to the 928 Hospital of the PLA Joint Logistic Support Force from January 2015 to January 2019, and randomly treated with UGFS (164 cases), or surgical treatment (190 cases). Patients in UGFS group received UGFS with high ligation of GSV, and in surgical treatment group received high ligation and stripping of GSV or TIPP. Follow-up was conducted at 1, 6 and 12 months after treatment. By exclusion of non-compliance and loss of follow-up patients (76 cases), 278 cases were finally included, including 130 patients of UGFS group and 148 patients from control group. Operative time, reflux recurrence rate, surgical-related adverse events, hemodynamic parameters, treatment costs, and quality of life were compared between the two groups. Results No significant difference existed between UGFS group and control group 12 months after treatment on the cumulative recurrence rate (13.8% vs. 13.5%, P>0.05), and the incidence of mild complications (27.7% vs. 21.6%, P>0.05) and severe complications (3.1% vs. 2.7%, P>0.05). Compared with those before treatment, venous filling index, venous clinical severity score (VCSS) and Aberdeen varicose vein questionnaire (AVVQ) scores were significantly improved after treatment in both groups (P0.05). Conclusion UGFS combined with GSV high ligation for the treatment of severe varicose veins in the lower extremity has a definite clinical curative effect, short operation time and recovery time, obvious improvement of hemodynamic parameters, and low treatment cost, so is worthy of clinical popularization and application. DOI: 10.11855/j.issn.0577-7402.2020.12.13

Alzheimer's disease(AD) has an unknown pathogenesis, which is one of the key factors leading to the death of the elderly.Recent studies have shown that glial cells, including microgli、 astrocytes、oligo-dendrocytes and oligodendrocyte progenitor cells (NG2 glial cells), are closely related to the pathogenesis of AD.It is believed that activated microglial cells are very easy to induce neuritis and then lead to neurodegeneration.In this paper, the characteristics of the above four glial cells, their functions and their correlation with AD were reviewed, in order to provide a reference for the further study of the pathogenesis of AD.

Our general purpose was to provide a theoretical and practical foundation for the use of exosomes (EXOs) that have high levels of CD47 as stable and efficient drug carriers. Thus, we prepared EXOs from adipose tissue-derived mesenchymal stromal cells (ADMSCs) that had high levels of CD47 (EXOsCD47) and control EXOs (without CD47), and then compared their immune escapein vivoand their resistance to phagocytosisin vitro. Nanoflow cytometry was used to determine the CD47 level in these EXOs, and the amount of EXOsCD47that remained in rat plasma at 3 h after intraperitoneal injection. Phagocytosis of the EXOs was also determined usingin vitrorat macrophage bone marrow (RMA-BM) experiments. Ourin vitroresults showed that macrophages ingested significantly more control EXOs than EXOsCD47(p< 0.01), with confirmation by ultra-high-definition laser confocal microscopy. Consistently, ourin vivoresults showed that rats had 1.377-fold better retention of EXOsCD47than control EXOs (p< 0.01). These results confirmed that these engineered EXOsCD47had improved immune escape. Our results therefore verified that EXOsCD47had increased immune evasion relative to control EXOs, and have potential for use as drug carriers.

The complete mitochondrial genome of Brachionus rubens was sequenced using primers design, clone culture, DNA extraction, LONG-PCR amplification, purification and clone sequencing. We found that it is composed of two circular chromosomes, designated mtDNA I (11,398 bp) and mtDNA II (12,820 bp). The gene content of the B. rubens mitochondrial genome was similar to that of the previously reported mitochondrial genome of B. plicatilis. It contained 22 tRNA genes, 2 rRNA genes and 12 protein-coding genes (PCGs). Four of the 12 PCGs had an incomplete stop codons, TA（cob, atp6, nd3）or T(cox3). The A + T content of B. rubens mitochondrial genome was apparently higher (mtDNA-I 70.2% and mtDNA II 70.4%) than that of the mitochondrial genome of B. plicatilis (mtDNA-I 63.9% and mtDNA-II 62.9%).

Thyrotropin-releasing hormone (TRH) plays an important role in the regulation of energy balance. While the regulation of TRH in the paraventricular nucleus (PVN) in response to changes of energy balance has been well studied, how TRH is regulated in the dorsomedial hypothalamus (DMH) in maintaining energy homeostasis remains unclear. Here, we assessed the effects of food restriction and exercise on hypothalamic Trh expression using Otsuka Long-Evens Tokushima Fatty (OLETF) rats. Sedentary ad lib fed OLETF rats (OLETF-SED) became hyperphagic and obese. These alterations were prevented in OLETF rats with running wheel access (OLETF-RW) or food restriction in which their food was pair-fed (OLETF-PF) to the intake of lean control rats (LETO-SED). Evaluation of hypothalamic gene expression revealed that Trh mRNA expression was increased in the PVN of OLETF-SED rats and normalized in OLETF-RW and OLETF-PF rats compared to LETO-SED rats. In contrast, the expression of Trh in the DMH was decreased in OLETF-SED rats relative to LETO-SED rats. This alteration was reversed in OLETF-RW rats as seen in LETO-SED rats, but food restriction resulted in a significant increase in DMH Trh expression in OLETF-PF rats compared to LETO-SED rats. Strikingly, while Trh mRNA expression was decreased in the PVN of intact rats in response to acute food deprivation, food deprivation resulted in increased expression of Trh in the DMH. Together, these results demonstrate the differential regulation of Trh expression in the PVN and DMH in OLETF rats and suggest that DMH TRH also contributes to hypothalamic regulation of energy balance.

East Asian countries, such as China, Japan and South Korea, are major importers in the international oil market. Therefore, oil import security is critical to sustainable economic development in these countries. This paper uses a modified two-stage DEA-like model to investigate the impact of the Organization of Petroleum Exporting Countries (OPEC) on oil import security in the East Asian region over time. Specifically, three dimensional variables were introduced to the model: the OPEC internal dimension, the OPEC and Asian country interaction dimension, and the international external dimension. The empirical results show a substantial difference between China and the other two countries in terms of these dimensions. Although the impact of OPEC on China's oil security has increased over time, its impact on Japan has declined. Political uncertainty in OPEC countries and oil price volatility are the major issues for China, whereas cost is the key area of concern for Japan. South Korea's concerns are less clear. The results of this study lay an important foundation for discussing policy issues involved in regional cooperation, integration and sustainable growth in the East Asian region.

Mannosylxylarinolide (1), a new 3,4-seco-ergostane-type steroidal saponin featuring a β-d-mannose moiety, was isolated from the culture of the endophytic fungus Xylaria sp. that had been isolated from an ornamental plant of Hoya sp. The gross structure was determined by spectroscopic data, and the absolute configuration of the new 3,4-seco-ergostane-type steroidal saponin (1) was determined by X-ray diffraction analysis.

Despite extensive research, the rewarding effects of cannabinoids are still debated. Here, we used a newly established animal procedure called optogenetic intracranial self-stimulation (ICSS) (oICSS) to re-examine the abuse potential of cannabinoids in mice. A specific adeno-associated viral vector carrying a channelrhodopsin gene was microinjected into the ventral tegmental area (VTA) to express light-sensitive channelrhodopsin in dopamine (DA) neurons of transgenic dopamine transporter (DAT)-Cre mice. Optogenetic stimulation of VTA DA neurons was highly reinforcing and produced a classical “sigmoidal”-shaped stimulation–response curve dependent upon the laser pulse frequency. Systemic administration of cocaine dose-dependently enhanced oICSS and shifted stimulation–response curves upward, in a way similar to previously observed effects of cocaine on electrical ICSS. In contrast, Δ(9)-tetrahydrocannabinol (Δ(9)-THC), but not cannabidiol, dose-dependently decreased oICSS responding and shifted oICSS curves downward. WIN55,212-2 and ACEA, two synthetic cannabinoids often used in laboratory settings, also produced dose-dependent reductions in oICSS. We then examined several new synthetic cannabinoids, which are used recreationally. XLR-11 produced a cocaine-like increase, AM-2201 produced a Δ(9)-THC-like reduction, while 5F-AMB had no effect on oICSS responding. Immunohistochemistry and RNAscope in situ hybridization assays indicated that CB(1)Rs are expressed mainly in VTA GABA and glutamate neurons, while CB(2)Rs are expressed mainly in VTA DA neurons. Together, these findings suggest that most cannabinoids are not reward enhancing, but rather reward attenuating or aversive in mice. Activation of CB(1)R and/or CB(2)R in different populations of neurons in the brain may underlie the observed actions.

Cannabinoids produce a number of central nervous system effects via the CB(2) receptor (CB(2)R), including analgesia, antianxiety, anti-reward, hypoactivity and attenuation of opioid-induced respiratory depression. However, the cellular distributions of the CB(2)Rs in the brain remain unclear. We have reported that CB(2)Rs are expressed in midbrain dopamine (DA) neurons and functionally regulate DA-mediated behavior(s). Unexpectedly, high densities of CB(2)-like signaling were also found in a neighboring motor structure – the red nucleus (RN) of the midbrain. In the present study, we systematically explored CB(2)R expression and function in the RN. Immunohistochemistry and in situ hybridization assays showed high densities of CB(2)R-immunostaining and mRNA signal in RN magnocellular glutamate neurons in wildtype and CB(1)-knockout, but not CB(2)-knockout, mice. Ex vivo electrophysiological recordings in midbrain slices demonstrated that CB(2)R activation by JWH133 dose-dependently inhibited firing rates of RN magnocellular neurons in wildtype, but not CB(2)-knockout, mice, while having no effect on RN GABA neurons in transgenic GAD67-GFP reporter mice, suggesting CB(2)-mediated effects on glutamatergic neurons. In addition, microinjection of JWH133 into the RN produced robust ipsilateral rotations in wildtype, but not CB(2)-knockout mice, which was blocked by pretreatment with either a CB(2) or DA D1 or D2 receptor antagonist, suggesting a DA-dependent effect. Finally, fluorescent tract tracing revealed glutamatergic projections from the RN to multiple brain areas including the ventral tegmental area, nucleus accumbens, thalamus, and cerebellum. These findings suggest that CB(2)Rs in RN glutamate neurons functionally modulate motor activity, and therefore, constitute a new target in cannabis-based medication development for motor disorders.

To investigate the value of fluorescence in situ hybridization (FISH) in the diagnosis and prognosis evaluation of patients with chronic lymphocytic leukemia (CLL).Ninty-three patients with newly diagnosed CLL were tested by five probes including RB1 (13q14.1), D13S25 (13q14.3), p53(17p13.1), ATM( 11q22.3) and CSP12, while conventional cytogenetics (CC) was used for karyotype analysis. Then the correlation of the molecular cytogenetic abnormalities with the clinical Binet stages, Rai stages and the other related laboratory examinations was analyzed.The detection rate of chromosome abnormality in 93 patients was 79.6%, out of which detection rate of 13q (13q- was the highest and accounted for 45.2%), followed by trisomy 12 (+12) 26.9%, p53 deletion (17p-) 19.4% and ATM deletion (11p-) 17.2%. There were 27 cases (29.0%) with 2 or more abnormalities, including 13 cases with 13q-/17q-, 5 with 13q-/11q-, and 4 with 13q-/+12. Compared with CC test results, the positive rate of FISH detection was significantly higher (χFISH can greatly increase the detection rate of molecular cytogenetic abnormalities in CLL patients, which, as a powerful supplement to the conventional cytogenetics, can be applied for the clinical staging and prognosis evaluation of CLL patients.荧光原位杂交技术检测慢性淋巴细胞白血病分子遗传学异常.探讨荧光原位杂交技术（fluorescence in situ hybridization, FISH）在慢性淋巴细胞白血病（CLL）诊断和预后评估中的价值.采用 RB1（13q14.1）、D13S25（13q14.3）、p53（17p13.1）、ATM（11q22.3）及CSP12 5组探针对93例初诊CLL患者进行检测, 同期进行常规染色体核型（conventional cytogenetics, CC）分析。分析FISH检测出的遗传学异常与患者的临床Binet分期、Rai分期及其他检测指标的相关性.93例初诊CLL患者分子遗传学异常检出率为79.6%（74/93）, 其中13q缺失（13q-）阳性率最高, 占45.2%；其次为12号染色体三体（+12）占26.9%、p53缺失（17p-）占19.4%、ATM缺失（11p-）占17.2%。同时伴有2种及2种以上染色体异常患者27例（29.0%）, 其中13q-伴17p-者8例, 13q-伴11q-者5例, 13q-伴+12者4例。CC检测结果相比较, FISH检测结果中患者的阳性率非常显著高于CC检测结果（χFISH技术能够大大地提高CLL患者分子遗传学异常的检出率, 是常规细胞遗传学有力的补充, 对CLL患者的临床分期及预后判断均有重要的应用价值.

Background Enteral nutrition (EN) therapy is widely used in clinical practice to provide artificial nutrition to patients, while the incidence of adverse events are relatively highly. In the clinical setting, the occurrence of adverse events is associated with the nurse’s risk perception. Thus, using tool to evaluate nurse’s risk perception of enteral nutrition is necessary. Methods The draft questionnaire with 37-items was formed by comprehensive literature reviews and semi-structured in-depth interviews with 11 nurses. Two iterations of expert consultations were used to evaluate the content validity, and 4 items were deleted in this phrase. A 33-items questionnaire was used to survey 352 nurses from five tertiary hospitals in China from May to July 2019 with convenience sampling. Content validity, construct validity and known-groups validity were evaluated by content validity index (CVI), exploratory factor analysis, and the comparisons of the different EN risk perception levels of nurses at different working departments and different educational backgrounds, respectively. Reliability was tested by internal consistency, test-retest reliability, and split-half reliability. Results After the exploratory factor analysis, four items were excluded. Finally, the newly developed questionnaire included 29 items explaining 71.356% of the total variance. It consisted of three factors: Risks of operation (15 items); Risks of EN-related adverse events (11 items), and Risks of EN solution selection (3 items). The CVI of the questionnaire was 0.95 and the CVI of items ranged from 0.875–1.0. The results of known-groups validity showed that the nurses with different educational backgrounds had a statistically significant difference of EN risk perception (z = − 3.024, p = 0.002), whereas there was not significantly different between EN risk perception of nurses working in different departments (z = − 1.644, p = 0.100). The Cronbach’s α, test-retest reliability, and split-half reliability of the questionnaire were 0.967, 0.818, and 0.815, respectively. Conclusions The newly developed questionnaire for assessing nurse’s EN risk perception showed good reliability and validity. It can be used as a tool for nursing managers to assess Chinese nurses’ EN risk perception ability, so as to help to reduce the occurrence of adverse events during EN implementation.

Deformation map provides a comprehensive understanding on various deformation mechanisms governed at different conditions. In this work, for the first time we observed a significant mean stress effect on the deformation map of a typical metallic glass (MG), i.e., the tensile mean stress could largely promote the deformation mode transition from shear localization to homogeneous deformation while the compressive one may suppress that. The present results emphasize the important role of stress state in the high-temperature deformation of MGs, implying that the thermoplastic forming of MGs could be better controlled via adjusting the local stress state.

Hepatitis E virus (HEV) is increasingly found to cause hepatitis in allogeneic haematopoietic stem cell transplantation (HSCT) patients. However, little is known about HEV infection in patients receiving haploidentical HSCT (haplo-HSCT). Here, we retrospectively evaluate the incidence and clinical course of HEV infection in haplo-HSCT patients. From January 2014 to July 2017, 177 patients with unexplained elevated transaminases after receiving haplo-HSCT at Peking University Institute of Haematology were screened for HEV using HEV serology. HEV RNA was assessed in blood samples when HEV-IgG and/or IgM antibodies were positive. Acute HEV infection was identified in 7 patients (3·9%), 1 of whom had developed a chronic HEV infection. The median time from haplo-HSCT to HEV infection was 17·5 (range, 6-55) months. HEV infection was confirmed by the presentation of anti-HEV IgM + anti-HEV IgG (rising) (n = 5) or HEV-RNA + anti-HEV IgM + anti-HEV IgG (n = 2). None of the patients died of HEV infection directly: 2 patients with HEV infection died showing signs of ongoing hepatitis, and 5 patients cleared HEV with a median duration of HEV infection of 1·5 (range, 1·0-5·7) months. In conclusion, HEV infection is a rare but serious complication after haplo-HSCT. We recommend screening of HEV in haplo-HSCT.

Cancer has become the leading cause of mortality since 2010 in China. Despite the remarkable advances in cancer therapy, a low survival rate is still a burden to the society. The antineoplastic activity of aqueous extracts ofCordyceps kyushuensisKob (AECK) was measured in this study. Results showed that AECK can significantly inhibit the proliferation and viability of U937 and K562 when treated with different concentrations of AECK, and the IC50values of U937 and K562 were 31.23 μg/ml and 62.5 μg/ml, respectively. Hoechst 33258 staining showed that AECK could cause cell shrinkage, chromatin, condensation, and cytoplasmic blebbing, and DNA ladder experiment revealed the evident feature of DNA fragmentation which showed that AECK could induce cell apoptosis. Moreover, AECK gave rise to intrinsic apoptosis through increasing the amount of Ca2+and downregulating the expression of Bcl-2. Meanwhile, the level of Fas death receptor was elevated which indicated that AECK could lead to exogenous apoptosis in U937. The expressions of oncogene c-Myc and c-Fos were suppressed which manifested that AECK could negatively regulate the growth, proliferation, and tumorigenesis of U937 cells. This research presented the primary antitumor activity of AECK which would contribute to the widely use ofCordyceps kyushuensisKob as a functional food and medicine.

Cannabinoid CB1 receptors are highly expressed in the brain and functionally modulate presynaptic neurotransmitter release, while cannabinoid CB2 receptors (CB2Rs) were initially identified in the spleen and regarded as peripheral cannabinoid receptors. Recently, growing evidence indicates the presence of functional CB2Rs in the brain. However, this finding is disputed because of the specificity of CB2R antibody signals. We used two strains of currently available partial CB2-knockout (CB2-KO) mice as controls, four anti-rat or anti-mouse CB2R antibodies, and mRNA quantification to further address this issue. Western blot assays using the four antibodies detected a CB2R-like band at ~40 kD in both the brain and spleen. Notably, more bands were detected in the brain than in the spleen, and specific immune peptides blocked band detection. Immunohistochemical assays also detected CB2-like immunostaining in mouse midbrain dopamine neurons. CB2R deletion in CB2-KO mice may reduce or leave CB2R-like immunoreactivity unaltered depending on antibody epitope. Antibodies with epitopes at the receptor-deleted region detected a significant reduction in CB2R band density and immunostaining in N-terminal-deleted Deltagen and C-terminal-deleted Zimmer strain CB2-KO mice. Other antibodies with epitopes at the predicted receptor-undeleted regions detected similar band densities and immunostaining in wild-type and CB2-KO mice. Quantitative RT-PCR assays detected CB2 mRNA expression using probes that targeted upstream or downstream gene sequences but not the probe that targeted the gene-deleted sequence in Deltagen or Zimmer CB2-KO mice. These findings suggest that none of the tested four polyclonal antibodies are highly mouse CB2R-specific. Non-specific binding may be related to the expression of mutant or truncated CB2R-like proteins in partial CB2-KO mice and the use of anti-rat CB2 antibodies because the epitopes are different between rat and mouse CB2Rs.

Objective: To investigate the relationship between polymorphisms of rs1532624 and rs289741 loci in cholesteryl ester transfer protein (CETP) genes and atherosclerotic cerebral infarction (ACI). Methods: The CETP gene rs1532624 and rs289741 in 95 patients with ACI and 177 healthy subjects were genotyped by MassARRAY mass spectrometry. Each locus genotype and allele frequency distributions were compared. Results: The difference of allele frequency distribution between the rs1532624 (χ2=1.723, P =0.189) and rs289741 (χ2=2.466, P =0.116) were not statistically significant. The frequency distribution of rs1532624 genotype between the cerebral infarction group and healthy control group was statistically significant (χ2=7.096, P =0.029), while rs289741 genotype frequency distribution between the two groups was not statistically significant (χ=2.906, P =0.234). Conclusion: ACI have a positive correlation with rs1532624 polymorphism, and AA genotype may be susceptible factors of ACI.

Taking into account the attributes of the liquefied natural gas (LNG) trade and the space-time characteristics of trade flows, this paper identifies the multiple dimensional factors that influenced the global LNG trade between 2004 and 2015. Following an analysis of the data via the application of gravity models, the empirical results of this study indicate that these influencing factors possess both general and regional characteristics. In contrast to general trade, the LNG trade is mainly affected by the economic magnitude of the demand side. Regionally, pipeline natural gas has a significant substitute effect on the LNG trade within the global model, though not within the Asian model. Additionally, the LNG trade in Asia is more sensitive to the influence of import prices and research and development investment than in the global model. Our subsample analyses show that the results are robustness across different periods. Finally, this paper discusses pertinent policy implications for the LNG trade, especially as related to Asia.

Cannabinoid CB2 receptors (CB2Rs) are expressed in mouse brain dopamine (DA) neurons and are involved in several DA-related disorders. However, the cell type-specific mechanisms are unclear since the CB2R gene knockout mice are constitutive gene knockout. Therefore, we generated Cnr2-floxed mice that were crossed with DAT-Cre mice, in which Cre- recombinase expression is under dopamine transporter gene (DAT) promoter control to ablate Cnr2 gene in midbrain DA neurons of DAT-Cnr2 conditional knockout (cKO) mice. Using a novel sensitive RNAscope in situ hybridization, we detected CB2R mRNA expression in VTA DA neurons in wildtype and DAT-Cnr2 cKO heterozygous but not in the homozygous DAT-Cnr2 cKO mice. Here we report that the deletion of CB2Rs in dopamine neurons enhances motor activities, modulates anxiety and depression-like behaviors and reduces the rewarding properties of alcohol. Our data reveals that CB2Rs are involved in the tetrad assay induced by cannabinoids which had been associated with CB1R agonism. GWAS studies indicates that the CNR2 gene is associated with Parkinson’s disease and substance use disorders. These results suggest that CB2Rs in dopaminergic neurons may play important roles in the modulation of psychomotor behaviors, anxiety, depression, and pain sensation and in the rewarding effects of alcohol and cocaine.

We study the open question on determination of jumps for functions raised by Shi and Hu in 2009. An affirmative answer is given for the case that spline-wavelet series are used to approximate the functions.

Cannabis can be rewarding or aversive. Cannabis reward is believed to be mediated by activation of cannabinoid CB1 receptors (CB1Rs) on GABAergic neurons that disinhibit dopaminergic neurons in the ventral tegmental area (VTA). However, little is known about the mechanisms underlying cannabis aversion in rodents. In the present study, CB1Rs are found not only on VTA GABAergic neurons, but also on VTA glutamatergic neurons that express vesicular glutamate transporter 2 (VgluT2). We then used Cre-Loxp transgenic technology to selectively delete CB1Rs in VgluT2-expressing glutamatergic neurons (VgluT2-CB1−/−) and Cre-dependent viral vector to express light-sensitive channelrhodopsin-2 into VTA glutamatergic neurons. We found that photoactivation of VTA glutamatergic neurons produced robust intracranial self-stimulation (ICSS) behavior, which was dose-dependently blocked by DA receptor antagonists, but enhanced by cocaine. In contrast, Δ9-tetrahydrocannabinol (Δ9-THC), the major psychoactive component of cannabis, produced dose-dependent conditioned place aversion and a reduction in the above optical ICSS in VgluT2-cre control mice, but not in VgluT2-CB1−/− mice. These findings suggest that activation of CB1Rs in VgluT2-expressing glutamate neurons produces aversive effects that might explain why cannabinoid is not rewarding in rodents and might also account for individual differences in the hedonic effects of cannabis in humans.

The X-band coherence statistical characteristics related to the height of ambiguity, polarisation and resolution in two typical forested areas are investigated, using X-band multi-baseline polarimetric synthetic aperture radar interferometry (PolInSAR) data acquired by an automobile-based interferometric synthetic aperture radar (InSAR) system. The influences of the polarisation and resolution on coherence are carefully analysed. The results show that the volume decorrelation in forested areas is independent of the polarisation and the coherence decreases with the reduction of the resolution. In addition, an empirical coherence model in relation to the height of ambiguity, resolution, forest height and range slope is proposed, according to the coherence statistical characteristics of the experimental data. The model can be used to calculate the mean coherence of forested areas under a specific system baseline and therefore it can play an important role in X-band InSAR baseline configuration for forest mapping.

(±)Modafinil ((±)MOD) and its R-enantiomer (R-modafinil; R-MOD) have been investigated for their potential as treatments for psychostimulant addiction. We recently reported a series of (±)MOD analogs, of which JJC8-016 (N-(2-((bis(4-fluorophenyl)methyl)thio)ethyl)-3-phenylpropan-1-amine) was selected for further development. JJC8-016 and R-MOD were evaluated for binding across ~70 receptors, transporters, and enzymes. Although at a concentration of 10 μM, there were many hits for JJC8-016, binding affinities in the range of its DAT affinity were only observed at the serotonin transporter (SERT), dopamine D2-like, and sigma1 receptors. R-MOD was more selective, but had much lower affinity at the DAT (Ki=3 μM) than JJC8-016 (Ki=116 nM). In rats, systemic administration of R-MOD alone (10–30 mg/kg i.p.) dose-dependently increased locomotor activity and electrical brain-stimulation reward, whereas JJC8-016 (10–30 mg/kg i.p.) did not produce these effects. Strikingly, pretreatment with JJC8-016 dose-dependently inhibited cocaine-enhanced locomotion, cocaine self-administration, and cocaine-induced reinstatement of drug-seeking behavior, whereas R-MOD inhibited cocaine-induced reinstatement only at the high dose of 100 mg/kg. Notably, JJC8-016 alone neither altered extracellular dopamine in the nucleus accumbens nor maintained self-administration. It also failed to induce reinstatement of drug-seeking behavior. These findings suggest that JJC8-016 is a unique DAT inhibitor that has no cocaine-like abuse potential by itself. Moreover, pretreatment with JJC8-016 significantly inhibits cocaine-taking and cocaine-seeking behavior likely by interfering with cocaine binding to DAT. In addition, off-target actions may also contribute to its potential therapeutic utility in the treatment of cocaine abuse.