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There has been ample research showing that insomnia is a potential trigger of depression as well as a symptom of depression. These two factors contribute to behavioural problems and are closely related to the plasticity of hippocampal synapses. Although depression and insomnia impair hippocampal synaptic plasticity, the mechanism by which this happens remains a mystery. This study aimed to investigate the pathogenesis of insomnia comorbidity in depression and the regulatory effect of venlafaxine combined with melatonin on hippocampal synaptic plasticity in chronic unpredictable mild stress (CUMS) with sleep deprivation (SD) rats. Thus, rats were subjected to 14 days of chronic mild unpredictable stress, gradually acclimated to sleep deprivation on days 12-14. Followed by 21 consecutive days of sleep deprivation, 18 h per day, with daily gavage of venlafaxine (13.5 mg/kg) + melatonin (72 mg/kg) on days 15-36. Venlafaxine + melatonin treatment improves depression-like behaviour, pentobarbital sodium experimental sleep latency, and sleep duration in CUMS +SD rats. In addition to improving depressive-like behaviors, sleep deprivation also upregulates the expression of caspase-specific cysteine protein 3 (Caspase 3) in the pineal glial cells of chronic mild rats, as well as in hippocampal microglia. Expression of ionic calcium-binding adaptor 1 (iba-1), downregulates the secretion of several synaptic plasticity-related proteins, notably cAMP response element binding protein (CREB), glial cell line-derived neurotrophic factor (GDNF), and the synaptic scaffolding protein Spinophiline (Spinophiline). Hematoxylin-eosin staining showed that the structure of the pineal gland and hippocampus was damaged, and Golgi staining showed that the dendrites and spines in the DG area of the hippocampus were destroyed, vaguely aggregated or even disappeared, and the connection network could not be established. Western blot analysis further revealed a positive correlation between low melatonin levels and reduced Spinophiline protein. Interestingly, venlafaxine + melatonin reversed these events by promoting hippocampal synaptic plasticity by regulating melatonin secretion from the pineal gland. Therefore, it exerted an antidepressant effect in sleep deprivation combined with CUMS model rats. Overall, the results of this study suggest that the pathophysiology of depressive insomnia comorbidity is mediated by impaired pineal melatonin secretion and impaired hippocampal synaptic plasticity. In addition, these responses are associated with melatonin secretion from the pineal gland.

There are microfractures and fractures in the carbonate formation of M oilfield, which are easy to cause collapse and borehole instability. On the basis of the liquefiable cleanflo drilling fluid system for open hole completion of horizontal wells designed in the early stage, this paper has carried out the research work of matching acidizing completion fluid system. In this paper, the influence factors, cleaning ability, compatibility, acidizing situation and protection effect of acidizing completion fluid system are evaluated in laboratory. The way of density adjustment and specific dosage of NaCl and hcoona were established to inhibit the formation of salt crystallization. HTA solid acid and JCI are used to counteract each other to reduce the corrosion of casing steel. The core displacement results show that the permeability recovery value of carbonate core after completion fluid treatment can reach 97.54%, and that of sandstone core after treatment can reach 114.7%. Moreover, the completion fluid system also has a certain acidizing effect, which can not only clean and remove the plugging, but also serve as the early induction of acidizing and stimulation.

Peritoneal fibrosis (PF) is a disease caused by prolonged exposure of the peritoneum to high levels of dialysis fluid. Astragalus total saponins (ATS) is a phytochemical naturally occurring in Radix Astragali that has anti-inflammatory and anti-oxidant properties. In this study, we constructed an in vivo model of PF using 4.25% glucose-containing administered intraperitoneally to rats and incubated peritoneal mesothelial cells (PMCs) with 4.25% glucose-containing peritoneal dialysis fluid to construct an in vitro model of PF. Furthermore, siRNA of PGC-1[Formula: see text] was used to inhibit the expression of PGC-1[Formula: see text] to further investigate the mechanism of the protective effect of ATS on PF. In both in vivo and in vitro models, ATS treatment showed a protective effect against PF, with ATS reducing the thickness of peritoneal tissues in PF rats, increasing the viability of PMCs, increasing the mitochondrial membrane potential and reducing apoptosis ratio. ATS treatment also reduced the expressions of peritoneal fibrosis markers (Smad2, p-Smad2 and [Formula: see text]-SMA) and apoptosis markers (Caspase3, cleaved-Caspase3 and Bax) and restored the expressions of mitochondrial synthesis proteins (PGC-1[Formula: see text], NRF1 and TFAM) in ATS-treated peritoneal tissues or PMCs. Furthermore, in the presence of PGC-1[Formula: see text] inhibition, the protective effect of ATS on PF was blocked. In conclusion, ATS treatment may be an effective therapeutic agent to inhibit high glucose-induced in peritoneal fibrosis through PGC-1[Formula: see text]-mediated apoptosis.

Currently, the most commonly applied method for the determination of breast cancer subtypes is to test estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 by immunohistochemistry (IHC). However, the IHC method has substantial intraobserver and interobserver variability. ESR1, PGR, ERBB2, and MKi67 mRNA tests by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay may improve the diagnostic objectivity and efficiency. Here, we compared the concordance between RT-qPCR and IHC for assessment of the same biomarkers and evaluated the subtypes.A total of 265 eligible cases were divided into a training cohort and a validation cohort, and the expressions of ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 were tested by IHC and RT-qPCR. Then, the appropriate cutoff of RT-qPCR was calculated in the training cohort. The concordance between RT-qPCR and IHC was calculated for individual marker. In addition, we investigated the subtypes based on the RT-qPCR results.The Spearman correlation coefficients between ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 by IHC and RT-qPCR were 0.768, 0.699, 0.762, and 0.387, respectively. The cutoff values for the RT-qPCR assay of ESR1 (1%), PGR (1%), ERBB2, and MKi67 (14%) were 35.539, 32.139, 36.398, and 29.176, respectively. The overall percent agreement (OPA) between ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 by IHC and RT-qPCR was 92.48%, 73.68%, 92.80%, and 74.44%, respectively. A total of 224 (84.53%) specimens were concordant for the breast cancer subtypes (IHC-based type) by RT-qPCR.Evaluation of breast cancer biomarker status by RT-qPCR was highly concordant with IHC. RT-qPCR can be used as a supplementary method to detect molecular markers of breast cancer.

BackgroundMucinous appendiceal adenocarcinoma (MAA) is a rare, heterogeneous disease. Patients with unrespectable mucinous appendiceal adenocarcinoma presenting with peritoneal spread are treated by intraperitoneal chemotherapy, hyperthermic intraperitoneal chemotherapy, systemic chemotherapy, or targeted therapy. However, there are no guidelines for efficacious drugs against mucinous appendiceal adenocarcinoma. Therefore, relevant high-fidelity models should be investigated to identify effective drugs for individual therapy.MethodsSurgical tumor specimens were obtained from a mucinous appendiceal adenocarcinoma patient. The tissue was digested and organoid culture was established. H&E and immunohistochemistry staining as well as DNA sequencing was performed on tissue and organoid. The pathological characteristics and gene mutations of the organoid were compared to those of the original tumor. Drug sensitivity tests were performed on organoid and the patient clinical responds to chemotherapy and targeted therapy was compared.ResultsOrganoids were successfully established and stably passaged. Pathological characteristics of organoids including H&E staining and expression of protein markers (CK20, CDX-2, STAB2, CD7, PAX8) were consistent to those of the original tumor. Moreover, the organoids carried the same gene mutations as the primary tumor. Sensitivity of the organoids to chemotherapeutic drugs and tyrosine kinase inhibitors included: 5-FU (IC50 43.95 μM), Oxaliplatin (IC50 23.49 μM), SN38 (IC50 1.02 μM), Apatinib (IC50 0.10 μM), Dasatinib (IC50 2.27 μM), Docetaxel (IC50 5.26 μM), Regorafenib (IC50 18.90 μM), and Everolimus (IC50 9.20 μM). The sensitivities of organoid to these drugs were comparable to those of the patient's clinical responses.ConclusionThe mucinous appendiceal adenocarcinoma organoid model which retained the characteristics of the primary tumor was successfully established. Combined organoid-based drug screening and high throughput sequencing provided a promising way for mucinous appendiceal adenocarcinoma treatment.

This paper describes a video coding technology proposal submitted by MediaTek in April 2018 in response to a joint call for proposals (CfP) issued by ITU-T VCEG and ISO/IEC MPEG. The proposal uses the conventional block-based hybrid coding approach with a breakthrough design of block structure, substantial improvements of coding tools, and new inventions of loop filtering techniques. First, the block structure is designed using a highly flexible partitioning scheme, where each coding tree unit in a picture is split into multiple coding units (CUs) by a recursive quaternary tree followed by a recursive binary-ternary tree. The prediction unit (PU) and transform unit (TU) concepts are unified with the CU concept, i.e., PU and TU are basically the same as CU. Moreover, inter prediction, intra prediction, transform, quantization, in-loop filtering, and entropy coding are all improved. Finally, new loop filtering techniques are invented, where the proposed convolutional neural network loop filtering is of particular interest. The proposed video codec achieves 43.81% average bit rate savings based on objective measures compared to the High Efficiency Video Coding (HEVC) anchors and is among the best-performing CfP responses both objectively and subjectively. It has been partially adopted into the working draft of the Versatile Video Coding (VVC) standard.

Depression has become one of the most commonly prevalent neuropsychiatric disorders, and the main characteristics of depression are sleep disorders and melatonin secretion disorders caused by circadian rhythm disorders. Abnormal endogenous melatonin alterations can contribute to the occurrence and development of depression. However, molecular mechanisms underlying this abnormality remain ambiguous. The present review summarizes the mechanisms underlying the antidepressant effects of melatonin, which is related to its functions in the regulation of the hypothalamic-pituitary-adrenal axis, inhibition of neuroinflammation, inhibition of oxidative stress, alleviation of autophagy, and upregulation of neurotrophic, promotion of neuroplasticity and upregulation of the levels of neurotransmitters, etc. Also, melatonin receptor agonists, such as agomelatine, ramelteon, piromelatine, tasimelteon, and GW117, have received considerable critical attention and are highly implicated in treating depression and comorbid disorders. This review focuses on melatonin and various melatonin receptor agonists in the pathophysiology and treatment of depression, aiming to provide further insight into the pathogenesis of depression and explore potential targets for novel agent development.

To observe the analgesic effect of auricular point sticking therapy during the perioperative stage in the patients with partial lung resection.A total of 92 patients with partial lung resection were randomized into an auricular point group (31 cases, 1 case dropped off), the sham-auricular point group (30 cases) and a medication group (31 cases, 1 case dropped off). The routine medication for analgesia was provided in all of the three groups. In the auricular point group, 1 day before operation, the auricular point sticking therapy was applied at shenmen (TFIn 8, 16, 24, 48 h and 72 h after operation, VAS scores in the auricular point group were lower than those in the sham-auricular point group and the medication group separately (Auricular point sticking therapy relieves perioperative pain, shortens analgesic time, releases anxious and depressive emotions and reduces postoperative adverse reaction in the patients with partial lung resection. The analgesic mechanism is probably related to the increase of plasma concentration of β-endorphin.

This article identifies and analyzes the priority ways of naming the trade organizations of Chelyabinsk and Heihe cities in the zone of cross-border economic cooperation between China and Russia. The typology of the names of shops and other enterprises providing goods and services shows ethnic and cultural features that manifest themselves in the modern language space of the two countries. A large variety of organization names was found in Chelyabinsk city: single words (including complex ones) both Russian and foreign, word groups consisting of Russian and foreign words, abbreviations as well as words with non-traditional spelling and unclear meaning. Six types of naming were found in Heihe city: words with positive connotations, words pointing to the major function of an organization, names containing a company’s location, words including the owner’s name, unsuitable names and samples of erroneous translation. The first 4 can be considered strategic ways of naming as far as they help promote companies that they name on the market of goods and services and play a considerable role in forming potential customers loyalty.

Deleted in liver cancer 2 (DLC2) is a tumor suppressor, associated with various types of cancer. The aim of the present study was to analyze the expression of DLC2 in breast cancer, its clinical significance and its effect on breast cancer cell behavior. The expression of DLC2 was evaluated by immunohistochemistry in 131 cases of breast cancer. Associations among DLC2 expression and clinicopathological features were analyzed, and its effects on proliferation, motility, migration and invasion in DLC2-knockdown breast cancer cell lines were observed. The results indicated that DLC2 was expressed in 42.75% of breast cancer cases (56/131) and in 79.39% of adjacent normal tissues (104/131). Lower expression of DLC2 in breast cancer was associated with tumor differentiation (P

To explore the application of early airway management in accelerated rehabilitation of patients undergoing cervical spine surgery. A total of 76 anterior cervical spine surgery patients admitted to our hospital from May 2018 to June 2019 were selected and the patients were divided into a routine group and an intervention group with 38 cases each according to the random number table method. The conventional group received traditional nursing intervention during the perioperative period and the intervention group received early aerosolization based on traditional nursing during the perioperative period to strengthen airway management. The airway resistance and peak airway pressure of the two groups after intervention were compared and analyzed, work of breathing and other respiratory mechanics indicators, interleukin-8, C-reactive protein, procalcitonin levels and other respiratory tract infection related indicators, treatment satisfaction, complicates the situation and its infection rate and recovery progress. Before treatment, there was no significant difference between the two groups of airway resistance, peak airway pressure, work of breathing and serum interleukin-8, C-reactive protein, procalcitonin indicators; after treatment, the two groups of airway resistance, peak airway pressure, work of breathing indicators and serum interleukin-8, C-reactive protein, procalcitonin indicators were significantly lower than before treatment and the observation group was lower than the control group, the difference was statistically significant (p

The COVID-19 pandemic has dramatically changed the general population&rsquo, s life worldwide. People may spend more time on social media because of policies like &ldquo, work at home&rdquo, Using a cross-sectional dataset collected through an online survey in February 2020, in China, we examined (1) the relationships between social media activities and people&rsquo, s mental health status and (2) the moderation effect of emotional-regulation strategies. The sample included people aged &ge, 18 years from 32 provinces and regions in China (N = 3159). The inferential analyses included a set of multiple linear regressions with interactions. Our results showed that sharing timely, accurate, and positive COVID-19 information, reducing excessive discussions on COVID-19, and promoting caring online interactions rather than being judgmental, might positively associate with the general public&rsquo, s psychological well-being. Additionally, the relationships between social media activities and psychological well-being varied at different emotion-regulation strategy levels. Adopting the cognitive reappraisal strategy might allay the adverse relationships between certain social media activities and mental health indicators. Our findings expanded the theory of how social media activities can be associated with a human being&rsquo, s mental health and how it can interact with emotion-regulation strategies during the COVID-19 pandemic.

The extraction, purification, structure and hepatoprotective activity of a homogenous polysaccharide (SPS60) from Sabia parviflora were investigated. SPS60 was screened after purification with Sephadex G-100 and showed the excellent hepatoprotective activity. Its structural characteristics were investigated by Time of flight mass spectrometry (TOF-MS), PMP Pre-column derivatization-HPLC (PMP-HPLC), nuclear magnetic resonance (NMR) spectroscopy and Atomic Force Microscopy (AFM). The results showed that SPS60 possessed the molecular weight of 16900 Da and the monosaccharide component was glucose, as well as a 1 → 6 glycosidic bond. The results of atomic force microscopy (AFM) show that SPS60 is a blocky sphere in solution. Furthermore, the SPS60 could significantly improve the survival rate of LO2 hepatocytes which were damaged by CCl4. Therefore, SPS60 may be an active substance of S. parviflora as a local functional tea.

A novel combined chemo/photodynamic therapy has been developed to use pH/ROS/MMP-2 triple-responsive drug nanocarriers for treating solid tumor with an extraordinarily high efficiency. The designed poly(ethylene glycol)-peptide-poly(ω-pentadecalactone-co-N-methyldiethyleneamine-co-3,3'-thiodipropionate) (PEG-M-PPMT) nanoparticles (NPs) encapsulating anticancer drug sorafenib (SRF) and photosensitizer chlorin e6 (Ce6) are stable in serum-containing aqueous media and can effectively accumulate in tumor as a result of the EPR effect after intravenous administration in vivo. In the presence of MMP-2 overexpressed in extracellular tumor matrix, the PEG-M-PPMT NPs can partially shed PEG corona to form smaller particles and penetrate deep into tumor tissue. After uptake by tumor cells, the acidic endosomal pH and high intracellular ROS level would trigger substantial swelling of the NPs to accelerate the drug release for rapid killing of the cancer cells. In the current combined chemo/photodynamic therapy, the intracellular ROS generation in tumor is amplified by photosensitizer Ce6 activated with external laser irradiation. As the result, the highly elevated intracellular ROS concentration can both directly induce apoptosis of ROS-stressed tumor cells and magnify acceleration of the drug release from the ROS-responsive PEG-M-PPMT NPs to gain extraordinary therapeutic efficacy. In particular, after the chemo-photodynamic therapeutic treatment with SRF/Ce6-loaded PEG-M-PPMT nanoparticles, all human lung tumors (A549) xenografted in nude mice shrank substantially with approximately 29% of the tumors being completely eradicated. Additionally, SRF/Ce6-loaded PEG-M-PPMT NPs show negligible in vivo toxicity toward major organs such as heart, liver, spleen, lung and kidney. These results demonstrate great potential of the combined chemo/photodynamic therapy based on the stimuli-responsive PEG-M-PPMT nanoparticles for efficient tumor treatment.

Novel multifunctional drug nanocarriers have been successfully fabricated from a new type of enzymatically synthesized, biodegradable block copolymer, PEG–poly(ω-pentadecalactone-co-N-methyldiethyleneamine-co-3,3′-thiodipropionate) (PEG–PPMT), which was responsive to tumor-relevant acidic pH (5.0–6.5) and intracellular reactive oxygen species (ROS) of tumor cells. The PEG–PPMT copolymers could self-assemble to form nano-scaled particles in aqueous solutions, which are stable in physiological solutions, but swell substantially upon reducing the pH from 7.4 to 5.0 and/or in the presence of ROS on account of the protonation of the tertiary amino groups and oxidation of the thioether groups, causing a hydrophobic to hydrophilic transition in the nanoparticle cores. Consistently, docetaxel (DTX) encapsulated in PEG–PPMT nanoparticles can be triggered in a synergistic manner by acidic pH and a high-ROS environment in tumor cells to release the hydrophobic drug at accelerated rates for efficient tumor growth inhibition. In particular, DTX encapsulated in PEG–PPMT–11% PDL and PEG–PPMT–28% PDL nanoparticles exhibit extraordinarily enhanced potency (95% and 93% tumor-inhibiting efficiency, respectively) in inhibiting the growth of ROS-rich CT-26 tumors xenografted in mice. Importantly, biosafety analyses show minimal toxicity of DTX-loaded PEG–PPMT nanoparticles toward normal organs including liver and kidneys during the in vivo antitumor treatments. These results demonstrate that the PEG–PPMT nanoparticles are promising pH and ROS dual-responsive multifunctional nanocarriers for tumor site specific, controlled release of anticancer drugs to treat ROS-rich tumors.