Hepatitis B virus directly promotes collagen I expression of LX-2 cells without infection in vitro

Aim: To investigate direct effects of hepatitis B virus (HBV) on collagen type I in vitro. Methods: Collagen type I were measured after LX‐2 cell cultured with purified or serum HBV for 12, 24 and 48 h. Furthermore, evidence of HBV infection to LX‐2 were detected, and different inhibitors were used to identify pathways regulating collagen I expression. Results: The 3 × 10⁵ IU/mL purified/serum HBV increased collagen type I mRNA expression by 2.2‐/3.2‐ and 1.3‐/1.5‐fold at 24 and 48 h, respectively. Collagen type I protein in the supernatant of purified/serum HBV group also increased compared to the control group (408.0 ± 8.0/384.4 ± 6.8 vs 262.7 ± 15.7 ng/mL, P < 0.05). However, the 3 × 10⁷ IU/mL purified/serum HBV increased collagen type I expression similar to that of 3 × 10⁵ IU/mL, while 3 × 10³ IU/mL group showed no effect. Human HBV immunoglobulin alleviated HBV‐induced collagen I expression, but no evidence of HBV infection was found. Neutralization of transforming growth factor beta, tumor necrosis factor alpha, platelet‐derived growth factor, extracellular signal‐regulated kinase and TGF‐β receptor had no obvious inhibitory effects; only inhibition of p38 mitogen‐activated protein kinase decreased collagen type I mRNA expression by 0.5‐/0.4‐ and 0.4‐/0.3‐fold at 24 and 48 h, respectively. It reduced collagen type I protein in the purified/serum HBV group for 48 h (252.1 ± 14.1/251.7 ± 18.8 vs 403.9 ± 4.9/385.0 ± 4.2 ng/mL, P < 0.05). Conclusion: HBV directly promotes collagen type I expression of LX‐2 cells without infection in vitro.     

Clinical significance of interventional therapeutic bronchoscopy combined with bronchial arterial embolization in the treatment of hypervascular primary airway tumors in children

Importance:Pediatric hypervascular primary airway tumors are progressive,fatal lesions with a low incidence,and the disease is often more serious than that in a...     

Negative correlations of psychological distress with quality of life and immunotherapy efficacy in patients with advanced NSCLC

To evaluate the relationships between psychological distress and immunotherapy efficacy, adverse reactions and quality of life scores in patients with advanced non-small cell lung cancer (NSCLC). A total of 104 NSCLC patients who received 4-6 cycles of standard immunotherapy were enrolled and evaluated with the Distress Thermometer (DT) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The aim was to analyze the correlation between psychological distress and quality of life and to analyze whether psychological distress affects the efficacy of and adverse reactions to immunotherapy. The objective response rate (ORR) and disease control rate (DCR) of the psychological distress group were 6% and 50%, respectively, and those of the no psychological distress group were 18.5% and 83.3%, respectively. The differences were statistically significant (χ²=14.131, P<0.05). The progression-free survival (PFS) of advanced NSCLC patients who received comprehensive immunotherapy and had no psychological distress was significantly better than that of the psychological distress group (HR, 0.338; 95% CI, 0.192-0.592; P<0.05). The PFS of advanced NSCLC patients who received immunotherapy combined with chemotherapy in the no psychological distress group was significantly better than that in the psychological distress group (HR, 0.458; 95% CI, 0.296-0.709; P<0.05). Psychological distress in advanced NSCLC patients affects the efficacy of immunotherapy, and psychological distress is negatively correlated with quality of life during immunotherapy.     

国谈抗肿瘤药配备机构的空间可达性评价研究——以武汉市为例

目的：本研究旨在评估武汉市中心城区国谈抗肿瘤药配备机构的空间可达性水平,为优化药物供应与配置提供经验证据。方法：以武汉市为例,采用基于高斯衰减函数的两步移动搜索法(2-Step Floating Catchment Area, 2SFCA)评估研究区域内各个需求单元在不同交通出行方式下的国谈抗肿瘤药配备机构的可达性,同时运用空间自相关分析和K-means聚类分析识别需求单元可达性的分布态势和分类模式。结果：在驾车或公交出行的情况下,武汉市中心城区各需求单元的配药定点机构的可达性呈现出明显的空间分异特征。江汉区、汉阳区等可达性水平较高且均衡,而青山区和洪山区可达性水平较低且内部存在明显分层。此外,各需求单元呈现显著正相关空间分布,区域内高值集聚与分区内部分化现象并存。结论：武汉市中心城区配药机构可达性整体较高,但存在从核心城区向边缘城区递减的趋势;多数辖区的可达性良好且较为均衡,但少数辖区的可达性较差且存在明显的内部等级分层。     

Lactobacillus levels and prognosis of patients with acute myocardial infarction

OBJECTIVETo explore the relationship between Lactobacillus and prognosis of acute myocardial infarction (AMI) patients treated by percutaneous coronary intervention (PCI) and its correlation with clinical parameters.METHODSConsecutive patients with AMI in the coronary care unit of Tianjin Chest Hospital in China who received emergency PCI between July 2017 and December 2018 were enrolled. Subjects’ fecal 16S rDNA gene sequencing data were analyzed and subjects were categorized into low, medium and high level groups according to stool Lactobacillus measurements. The primary endpoints were major adverse cardiac events. Cox regression analysis was used to analyze the relationship between Lactobacillus and prognosis. Spearman correlation analysis and trend tests were used to assess the relationship between Lactobacillus and the clinical indicators.RESULTSThe data of 254 patients were included in the analysis. Mean age was 65.90 ± 11.56 years, and 152 patients (59.84%) were male. Follow-up time was 652 (548.25−753.00) days. Multivariate Cox regression analysis showed a significantly lower risk of major adverse cardiac events in patients with Lactobacillus > 7.1 copies/g [adjusted hazard ratio (HR) = 0.216, 95% CI: 0.094−0.493,P < 0.001] compared to patients with Lactobacillus ≤ 3.6 copies/g. Statistically significant differences were shown in ST-segment elevation myocardial infarction (STEMI) (HR = 0.217, 95% CI: 0.085−0.551, P = 0.001). Lactobacillus was a protective factor for male smokers aged over 60 years whose brain natriuretic peptide was over 1,000 pg/mL. Spearman correlation analysis showed that Lactobacillus correlated negatively with white blood cells, neutrophils, high-sensitivity C-reactive protein, TroponinT, creatine kinase, creatine kinase-MB and brain natriuretic peptide (downward trend), and correlated positively with left ventricular ejection fraction (upward trend). CONCLUSIONSThis study is the first to reveal the correlation between Lactobacillus and inflammation and myocardial damage after STEMI. STEMI patients, especially male smokers aged over 60 years with severe impairment of cardiac function, have better outcomes with high levels of Lactobacillus, suggesting new therapeutic strategies for improving the prognosis and quality of life of AMI patients.

With the aging of society and changes in life style, the incidence of acute myocardial infarction (AMI) is increasing year by year, which has become the main cause of death worldwide and poses a serious threat to human health.^[1] Recently, however, the success rate of AMI rescue has significantly improved, and the rate of death and disability has decreased. The mortality of patients receiving percutaneous coronary intervention (PCI) and optimized drug therapy remain as high as 7% to 18% within one year.^[2,3] New treatments to improve the prognosis and the quality of life of AMI patients are essential. Recently, increased attention is being given to the relationship between gut microbiota and cardiovascular diseases.^[4–6] Our previous study found that the abundance of Lactobacillaceae in the stool of acute coronary syndrome (ACS) patients was significantly decreased.^[7] Also, animal experiments have confirmed that Lactobacillus has the effects of anti-inflammation, regulating blood lipids and improving cardiac injury after myocardial infarction (MI).^[8–10] Therefore, we speculated that the level of Lactobacillus may be associated with the prognosis of patients with AMI. The purpose of this study was to quantitatively analyze the association between Lactobacillus and outcomes of AMI patients treated by emergency PCI, as well as the relationship between Lactobacillus and inflammation, myocardial injury and other biomarkers, and to evaluate the effect of Lactobacillus on long-term prognosis to provide new ideas for early and long-term clinical intervention.     

Olfactory regulation by dopamine and DRD2 receptor in the nose

Olfactory behavior is important for animal survival, and olfactory dysfunction is a common feature of several diseases. Despite the identification of neural circuits and circulating hormones in olfactory regulation, the peripheral targets for olfactory modulation remain relatively unexplored. In analyzing the single-cell RNA sequencing data from mouse and human olfactory mucosa (OM), we found that the mature olfactory sensory neurons (OSNs) express high levels of dopamine D2 receptor (Drd2) rather than other dopamine receptor subtypes. The DRD2 receptor is expressed in the cilia and somata of mature OSNs, while nasal dopamine is mainly released from the sympathetic nerve terminals, which innervate the mouse OM. Intriguingly, genetic ablation of Drd2 in mature OSNs or intranasal application with DRD2 antagonist significantly increased the OSN response to odorants and enhanced the olfactory sensitivity in mice. Mechanistic studies indicated that dopamine, acting through DRD2 receptor, could inhibit odor-induced cAMP signaling of olfactory receptors. Interestingly, the local dopamine synthesis in mouse OM is down-regulated during starvation, which leads to hunger-induced olfactory enhancement. Moreover, pharmacological inhibition of local dopamine synthesis in mouse OM is sufficient to enhance olfactory abilities. Altogether, these results reveal nasal dopamine and DRD2 receptor as the potential peripheral targets for olfactory modulation.

Olfactory behavior is important for food seeking and animal survival. On the other hand, olfactory dysfunction is a common feature of several diseases such as psychiatric disorders, neurodegeneration, and COVID-19 (1–3). Interestingly, the olfactory ability can be regulated by feeding status and external environments (4, 5). Recent studies have made progress in identifying the neural circuits and circulating hormones in olfactory regulation (6–11). However, the peripheral targets modulating olfactory ability remain relatively unexplored (12).Dopamine (DA) is a monoamine neurotransmitter (13, 14), which plays important roles in a variety of brain functions. DA is released by dopaminergic neurons in the central nervous system. In addition, DA can be released by sympathetic nerves in the peripheral tissues including the olfactory mucosa (OM) (15–18). The sympathetic innervation of rodent OM originates predominantly from the superior cervical ganglion (SCG) (17). Tyrosine hydroxylase (TH) is the rate-limiting enzyme for DA synthesis (19). Intriguingly, the Th mRNA is locally translated in the sympathetic nerve axons, which facilitates local DA synthesis (20, 21).There are two types of DA receptors based on sequence homology and function: The excitatory D1-like receptors (DRD1 and DRD5) and inhibitory D2-like receptors (DRD2–DRD4) (22). Activation of DRD2, a Gα_i/o-coupled receptor, can reduce the intracellular levels of cyclic adenosine monophosphate (cAMP). Drd2 is associated with several neuropsychiatric diseases and is the target of some antipsychotic drugs (23–28). In the central nervous system including the olfactory bulb (OB), DA-DRD2 signaling plays important roles in regulating synaptic transmission and plasticity (29–33). However, the function and regulation of DA-DRD2 signaling in the peripheral tissues are relatively less understood.Here we show that DRD2 is expressed in the cilia and somata of mature olfactory sensory neurons (OSNs) in mice. We provide evidence that DA-DRD2 signaling has a tonic inhibition on OSN activity and olfactory function in mice. Intriguingly, hunger greatly reduces the N4-acetylcytidine (ac⁴C) modification of Th mRNA and local DA synthesis in mouse OM, which causes the olfactory enhancement during starvation. We further show that inhibition of local DA synthesis or DRD2 receptor in mouse OM recapitulates enhanced olfactory abilities during starvation. Collectively, these results reveal nasal DA and DRD2 receptor as the potential peripheral targets for olfactory regulation.     

A Frequency-Adjustable Tuning Fork Electromagnetic Energy Harvester

In this paper, a frequency-adjustable tuning fork electromagnetic energy harvester is introduced. The electromagnetic vibration energy harvester can adjust its natural frequency according to a change in the environmental excitation frequency without any change to the structure. In the frequency-adjustable range, it can make the energy harvester resonant with the environment excitation, and the output frequency stays the same. The frequency-adjustable tuning fork electromagnetic energy harvester significantly increases the range of frequencies used. The operating frequency of the centre can be easily switched from 9.2 to 20 Hz, enabling the application of multiple excitation frequencies. In addition, the output power and power density are significantly increased compared to a piezoelectric tuning fork energy harvester of the same size. The peak power is 23.59 mW at 9.2 Hz, the power increases by 14.85 mW, and the power density increases by 169.88%. The experimental results show that the electromagnetic tuning fork frequency-adjustable conversion energy harvester can make the LED lamp work.     

子痫前期和凝血功能异常

子痫前期孕妇表现为病理性高凝状态,凝血功能的监测对妊娠期高血压疾病及其并发症的预防和治疗具有一定的临床意义.随着对子痫前期凝血机制的深入研究,阿司匹林、低分子肝素等抗凝剂在改善子痫前期母胎预后方面的作用受到了更多关注.     

Membrane Loaded Copper Oleate PEGylated Liposome Combined with Disulfiram for Improving Synergistic Antitumor Effect <Emphasis Type="BoldItalic">In Vivo</Emphasis>

Purpose

This work aims to create a novel Cu²⁺ liposome with excellent loading stability and develop synergistic effect with disulfiram (DSF) for the treatment of tumor.

Methods

Copper oleate was incorporated into the liposome membrane via alcohol injection method in this work. In vitro release test was applied to evaluate the release profile of the liposomes. Pharmacokinetic studies were performed in rats and the antitumor efficacy was assessed in mice bearing hepatoma xenografts.

Results

The copper oleate liposome (Cu(OI)₂-L) was formulated and the loading efficiency were more than 85%. TEM images confirmed that the Cu(OI)₂-L had a spherical morphology with an average diameter of 100 nm. Cu(OI)₂-L displayed a biphasic release profile, with >70% retained drug over 8 h incubation in PBS at pH 7.4. Pharmacokinetic studies demonstrated that Cu(OI)₂-L had a prolonged circulation time and increased AUC when compared to the injection of copper oleate solution. The antitumor efficacy test demonstrated an enhanced tumor inhibition rate with the treatment of Cu(OI)₂-L and DSF nanoparticles, indicating an improved synergistic antitumor effect.

Conclusions

The Cu(OI)₂-L was suitable to be employed in combination with disulfiram for tumor treatment and can also open up opportunities for targeted delivery of copper.