An α-hemoglobin-derived peptide (m)VD-hemopressin (α) promotes NREM sleep via the CB1 cannabinoid receptor.

Hemopressin and related peptides have shown to function as the endogenous ligands or the regulator of cannabinoid receptors. The previous studies demonstrated that the endocannabinoid system played important roles in modulating several physiological functions such as sleep, olfaction, emotion, learning and memory, and reward behaviors. Mouse VD-hemopressin (α) [(m)VD-HPα], an 11-residue peptide derived from the α1 chain of hemoglobin, was recently presumed as a selective agonist of the CB1 receptor. The present study was undertaken to investigate the effects of (m)VD-HPα on the sleep-wake cycle and power spectrum of cortical EEG in freely moving rats and the potential neurons in the brain activated by (m)VD-HPα. The results showed that 20.1 nmol of (m)VD-HPα i.c.v. administration increased non-rapid eye movement (NREM) sleep in the first 2 h section accompanied by an increase in EEG delta (0.5-4 Hz) activity. The (m)VD-HPα-induced NREM sleep enhancement was due to extended episode duration instead of the episode number. In addition, the effect of (m)VD-HPα (20.1 nmol) on sleep-wake states was significantly attenuated by an antagonist of the CB1 receptor, AM251 (20 nmol, i.c.v.) but not by the CB2 receptor antagonist, AM630 (20 nmol, i.c.v.). In comparison with vehicle, (m)VD-HPα increased Fos-immunoreactive (-ir) neurons in the ventrolateral preoptic nucleus (VLPO), but reduced Fos-ir neurons in the lateral hypothalamus (LH), tuberomammillary nucleus (TMN), and locus coeruleus (LC). These findings suggest that (m)VD-HPα promotes NREM sleep via the CB1 cannabinoid receptor to probably activate VLPO GABAergic neurons, but inactivates the LH orexinergic, LC noradrenergic, and TMN histaminergic neurons.

[Diagnosis and Treatment Outcomes and Influencing Factors of Multidrug-Resistant Tuberculosis Based on Patient Pathway].

Multidrug-resistant tuberculosis (MDR-TB) has become one of the major challenges in the global tuberculosis (TB) control.Despite years of efforts on MDR-TB control,the treatment success rates in China have increased slowly,which indicates possible deficiencies in the management of prevention and control work.Therefore,it is necessary to analyze the current status of MDR-TB prevention and treatment based on the patient pathway.This review summarizes the current drop-out situation of MDR-TB patients in the diagnosis and treatment pathway and the factors affecting patients' outcomes in the whole pathway,so as to provide a scientific reference for the prevention and control of MDR-TB.

Anesthesia management for cesarean section in a pregnant woman with odontogenic infection: A case report.

BACKGROUND: In recent years, people have paid more attention to oral health with the development of stomatology. Due to the various physiological changes during pregnancy, such as changing hormone levels and immune functions, oral diseases have a high incidence during pregnancy, and the prevention and treatment of oral diseases have also received the attention of both dentists and obstetricians. However, the anesthetic management of pregnant patients with oral disease, especially severe maxillofacial infections, and patients who need surgical treatment or have obstetric emergencies and need to terminate their pregnancy is not clear. CASE SUMMARY: This article describes a parturient patient with a severe masseteric space infection who had an emergency cesarean section. CONCLUSION: This case report aims to discuss the important anesthetic considerations for these patients.

Neuropeptide S Attenuates the Alarm Pheromone-Evoked Defensive and Risk Assessment Behaviors Through Activation of Cognate Receptor-Expressing Neurons in the Posterior Medial Amygdala.

Neuropeptide S (NPS) acts by activating its cognate receptor (NPSR). High level expression of NPSR in the posterior medial amygdala suggests that NPS-NPSR system should be involved in regulation of social behaviors induced by social pheromones. The present study was undertaken to investigate the effects of central administration of NPS or with NPSR antagonist on the alarm pheromone (AP)-evoked defensive and risk assessment behaviors in mice. Furthermore, H129-H8, a novel high-brightness anterograde multiple trans-synaptic virus, c-Fos and NPSR immunostaining were employed to reveal the involved neurocircuits and targets of NPS action. The mice exposed to AP displayed an enhancement in defensive and risk assessment behaviors. NPS (0.1-1 nmol) intracerebroventricular (i.c.v.) injection significantly attenuated the AP-evoked defensive and risk assessment behaviors. NPSR antagonist [D-Val5]NPS at the dose of 40 nmol completely blocked the effect of 0.5 nmol of NPS which showed the best effective among dose range. The H129-H8-labeled neurons were observed in the bilateral posterodorsal medial amygdala (MePD) and posteroventral medial amygdala (MePV) 72 h after the virus injection into the unilateral olfactory bulb (OB), suggesting that the MePD and MePV receive olfactory information inputs from the OB. The percentage of H129-H8-labeled neurons that also express NPSR were 90.27 ± 3.56% and 91.67 ± 2.46% in the MePD and MePV, respectively. NPS (0.5 nmol, i.c.v.) remarkably increased the number of Fos immunoreactive (-ir) neurons in the MePD and MePV, and the majority of NPS-induced Fos-ir neurons also expressed NPSR. The behavior characteristic of NPS or with [D-Val5]NPS can be better replicated in MePD/MePV local injection within lower dose. The present findings demonstrated that NPS, via selective activation of the neurons bearing NPSR in the posterior medial amygdala, attenuates the AP-evoked defensive and risk assessment behaviors in mice.

Early use of dexamethasone increases Nr4a1 in Kupffer cells ameliorating acute liver failure in mice in a glucocorticoid receptor-dependent manner.

BACKGROUND AND OBJECTIVE: Acute liver failure (ALF) is a type of disease with high mortality and rapid progression with no specific treatment methods currently available. Glucocorticoids exert beneficial clinical effects on therapy for ALF. However, the mechanism of this effect remains unclear and when to use glucocorticoids in patients with ALF is difficult to determine. The purpose of this study was to investigate the specific immunological mechanism of dexamethasone (Dex) on treatment of ALF induced by lipopolysaccharide (LPS)/D-galactosamine (D-GaIN) in mice. METHODS: Male C57BL/6 mice were given LPS and D-GaIN by intraperitoneal injection to establish an animal model of ALF. Dex was administrated to these mice and its therapeutic effect was observed. Hematoxylin and eosin (H&E) staining was used to determine liver pathology. Multicolor flow cytometry, cytometric bead array (CBA) method, and next-generation sequencing were performed to detect changes of messenger RNA (mRNA) in immune cells, cytokines, and Kupffer cells, respectively. RESULTS: A mouse model of ALF can be constructed successfully using LPS/D-GaIN, which causes a cytokine storm in early disease progression. Innate immune cells change markedly with progression of liver failure. Earlier use of Dex, at 0 h rather than 1 h, could significantly improve the progression of ALF induced by LPS/D-GaIN in mice. Numbers of innate immune cells, especially Kupffer cells and neutrophils, increased significantly in the Dex-treated group. In vivo experiments indicated that the therapeutic effect of Dex is exerted mainly via the glucocorticoid receptor (Gr). Sequencing of Kupffer cells revealed that Dex could increase mRNA transcription level of nuclear receptor subfamily 4 group A member 1 (Nr4a1), and that this effect disappeared after Gr inhibition. CONCLUSIONS: In LPS/D-GaIN-induced ALF mice, early administration of Dex improved ALF by increasing the numbers of innate immune cells, especially Kupffer cells and neutrophils. Gr-dependent Nr4a1 upregulation in Kupffer cells may be an important ALF effect regulated by Dex in this process.

Neuropeptide S Displays as a Key Neuromodulator in Olfactory Spatial Memory.

Neuropeptide S (NPS) is an endogenous peptide recently recognized to be presented in the brainstem and believed to play an important role in maintaining memory. The deletion of NPS or NPS receptor (NPSR) in mice shows a deficit in memory formation. Our recent studies have demonstrated that central administration of NPS facilitates olfactory function and ameliorates olfactory spatial memory impairment induced by muscarinic cholinergic receptor antagonist and N-methyl-D-aspartate receptor antagonist. However, it remains to be determined if endogenous NPS is an indispensable neuromodulator in the control of the olfactory spatial memory. In this study, we examined the effects of NPSR peptidergic antagonist [D-Val5]NPS (10 and 20 nmol, intracerebroventricular) and nonpeptidergic antagonist SHA 68 (10 and 50 mg/kg, intraperitoneal) on the olfactory spatial memory using computer-assisted 4-hole-board olfactory spatial memory test in mice. Furthermore, immunofluorescence was employed to identify the distributions of c-Fos and NPSR immunoreactive (-ir) neurons in olfactory system and hippocampal formation known to closely relate to the olfactory spatial memory. [D-Val5]NPS dosing at 20 nmol and SHA 68 dosing at 50 mg/kg significantly decreased the number of visits to the 2 odorants interchanged spatially, switched odorants, in recall trial, and simultaneously reduced the percentage of Fos-ir in NPSR-ir neurons, which were densely distributed in the anterior olfactory nucleus, piriform cortex, subiculum, presubiculum, and parasubiculum. These findings suggest that endogenous NPS is a key neuromodulator in olfactory spatial memory.

Factors associated with a SARS-CoV-2 recurrence after hospital discharge among patients with COVID-19: systematic review and meta-analysis.

BACKGROUND: The proportion of recurrences after discharge among patients with coronavirus disease 2019 (COVID-19) was reported to be between 9.1% and 31.0%. Little is known about this issue, however, so we performed a meta-analysis to summarize the demographical, clinical, and laboratorial characteristics of non-recurrence and recurrence groups. METHODS: Comprehensive searches were conducted using eight electronic databases. Data regarding the demographic, clinical, and laboratorial characteristics of both recurrence and non-recurrence groups were extracted, and quantitative and qualitative analyses were conducted. RESULTS: Ten studies involving 2071 COVID-19 cases were included in this analysis. The proportion of recurrence cases involving patients with COVID-19 was 17.65% (between 12.38% and 25.16%) while older patients were more likely to experience recurrence (weighted mean difference (WMD)=1.67, range between 0.08 and 3.26). The time from discharge to recurrence was 13.38 d (between 12.08 and 14.69 d). Patients were categorized as having moderate severity (odds ratio (OR)=2.69, range between 1.30 and 5.58), while those with clinical symptoms including cough (OR=5.52, range between 3.18 and 9.60), sputum production (OR=5.10, range between 2.60 and 9.97), headache (OR=3.57, range between 1.36 and 9.35), and dizziness (OR=3.17, range between 1.12 and 8.96) were more likely to be associated with recurrence. Patients presenting with bilateral pulmonary infiltration and decreased leucocyte, platelet, and CD4+ T counts were at risk of COVID-19 recurrence (OR=1.71, range between 1.07 and 2.75; WMD=-1.06, range between -1.55 and -0.57, WMD=-40.39, range between -80.20 and -0.48, and WMD=-55.26, range between -105.92 and -4.60, respectively). CONCLUSIONS: The main factors associated with the recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after hospital discharge were older age, moderate severity, bilateral pulmonary infiltration, laboratory findings including decreased leucocytes, platelets, and CD4+ T counts, and clinical symptoms including cough, sputum production, headache, and dizziness. These factors can be considered warning indicators for the recurrence of SARS-CoV-2 and might help the development of specific management strategies.

Data-Loss resilience video steganography using frame reference and data ensemble reconstruction.

In this paper, we propose a robust video steganographic method, which can efficiently hide confidential messages in video sequences, and ensure that these messages are perfectly reconstructed by recipient. To apply proposed scheme to video sequences, we must be faced with two nontrivial problems: (a) how to effectively minimize the total steganographic distortion for each video frame? (b) how to recover the hidden messages if some frames are lost or damaged? We tackle the first question by designing a new distortion function, which employs two continuous adjacent frames with the same scene as side-information. The second question is addressed by data sharing. In this mechanism, the original data is expanded and split into multiple shares by using multi-ary Vandermonde matrix. Since these shares contain a lot of data redundancy, the recipient can recover the hidden data even if some frames are damaged or lost during delivery. Extensive experiments show that proposed scheme outperforms the state-of-the-arts in terms of robustness and diverse attacks.

Physiological response and miRNA-mRNA interaction analysis in the head kidney of rainbow trout exposed to acute heat stress.

The rainbow trout is a cold-water fish cultured in China. Heat stress has a serious impact on the summer survival and the yield of rainbow trout. A better understanding of the regulatory response of rainbow trout to heat stress will help in determining the relationship between heat stress signaling pathways and adaption mechanisms and help contribute to breeding new high-temperature tolerant strains of rainbow trout. In this study, the 48-h median lethal temperature (48h-LT50) of rainbow trout was determined as 22.5°C. We developed control (16°C) and heat-treated (22.5°C) groups and extracted RNA from the head kidney tissues for high-throughput sequencing to study the microRNA (miRNA) expression profiles. Twelve up-regulated and five down-regulated miRNAs were identified between the control and heat-treated groups. A total of 22 target genes were predicted for 6 of the differentially expressed miRNAs, including 31 negative miRNA-mRNA interactions. Important regulatory pathways under heat stress are related to the metabolism and immune responses of the rainbow trout. Our findings provide preliminary data for investigating the high-temperature molecular mechanism of the rainbow trout and can help producers to reduce the economic losses caused by high temperature weather.

Ethical considerations of cellular immunotherapy for cancer.

With the rapid development of immunology, molecular biology, and associated technologies such as next-generation sequencing, cellular immunotherapy has recently become the fourth major cancer treatment. Immunotherapies based on T cells, natural killer cells, and dendritic cells play key roles in cancer immunotherapy. However, their application in clinical practice raises several ethical issues. Thus, studies should focus on proper adherence to basic ethical principles that can effectively guide and solve related clinical problems in the course of treatment, improve treatment effects, and protect the rights and interests of patients. In this review, we discuss cellular immunotherapy-related ethical issues and highlight the ethical practices and current status of cellular immunotherapy in China. These considerations may supplement existing ethical standards in cancer immunotherapy.

Hepatitis B Virus Core Antigen Stimulates IL-6 Expression via p38, ERK and NF-κB Pathways in Hepatocytes.

BACKGROUND: Hepatitis B virus (HBV) causes both acute and chronic liver injury. Viral proteins are involved in the pathological progress. Hepatitis B core antigen (HBcAg), a component of viral nucleocapsid, is not only essential for HBV lifecycle, but also exhibits strong immunogenicity. The cytoplasmic location of HBcAg in liver biopsy is associated with liver injury and inflammation, but the exact mechanisms remain to be elaborated. METHODS: Huh7, SMMC-7721 and L-02 cells were transfected with pEGFP-N1-HBcAg to establish an intracellular HBcAg expression model. The mRNA and protein levels of Interleukin (IL)-6 were detected by qPCR and ELISA respectively. The signaling pathway-related proteins were investigated by western blot and immunofluorescence assay. RESULTS: HBcAg increased the expression and secretion of IL-6 through activating extracellular signal-related kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa B (NF-κB). These activations can be blocked by specific inhibitors of the three pathways. CONCLUSIONS: HBcAg actives p38, ERK1/2 and NF-κB to enhance the production of IL-6 in hepatocytes. This provides a molecular mechanism to explain the association of cytoplasmic HBcAg with severe liver injury and inflammation.

Hepatitis B Virus Middle Protein Enhances IL-6 Production via p38 MAPK/NF-κB Pathways in an ER Stress-Dependent Manner.

During hepatitis B virus (HBV) infection, three viral envelope proteins of HBV are overexpressed in the endoplasmic reticulum (ER). The large S protein (LHBs) and truncated middle S protein (MHBst) have been documented to play roles in regulating host gene expression and contribute to hepatic disease development. As a predominant protein at the ultrastructural level in biopsy samples taken from viremic patients, the role of the middle S protein (MHBs) remains to be understood despite its high immunogenicity. When we transfected hepatocytes with an enhanced green fluorescent protein (EGFP)-tagged MHBs expressing plasmid, the results showed that expression of MHBs cause an upregulation of IL-6 at the message RNA and protein levels through activating the p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa B (NF-κB) pathways. The use of specific inhibitors of the signaling pathways can diminish this upregulation. The use of BAPTA-AM attenuated the stimulation caused by MHBs. We further found that MHBs accumulated in the endoplasmic reticulum and increased the amount of glucose regulated protein 78 (GRP78/BiP). Our results provide a possibility that MHBs could be involved in liver disease progression.

Phenolic Compounds from Clinopodium chinense (Benth.) O. Kuntze and Their Inhibitory Effects on α-Glucosidase and Vascular Endothelial Cells Injury.

Following an in vitro bioactivity-guided fractionation procedure, 14 compounds including eight flavonoids and six phenylpropanoids were isolated and identified from the AcOEt fraction of Clinopodium chinense (Benth.) O. Kuntze. All constituents were tested for α-glucosidase and high glucose-induced injury in human umbilical vein endothelial cells (HUVECs) inhibitory activities. All constituents exhibited varying degrees α-glucosidase inhibitory activity and protective activity on HUVECs. Among them, luteolin (2), eriodictyol (5), ethyl rosmarinate (13), and clinopodic acids B (14) were proved to be potent α-glucosidase inhibitors with IC50 value ranging from 0.6 to 2.0 µm. Additionally, luteolin (2), naringenin (4), eriodictyol (5), ethyl (2R)-3-(3, 4-dihydroxyphenyl)-2-hydroxypropanate (9), caffeic acid (11), ethyl rosmarinate (13), and clinopodic acids B (14) significantly ameliorate HUVECs injury induced by high glucose with an approximate EC50 value of 3 - 36 µm. These results suggest that the 14 bioactive constituents were responsible for hypoglycemic and protective vascular endothelium effect of C. chinense (Benth.) O. Kuntze and their structure-activity relationship was also analyzed briefly. Eriodictyol, luteolin, ethyl rosmarinate, and clinopodic acids B were the potential lead compounds of antidiabetic drugs.

[Clinical and imaging features of premature infants with different degrees of bronchopulmonary dysplasia].

OBJECTIVE: To study the clinical and imaging features of premature infants with different degrees of bronchopulmonary dysplasia (BPD). METHODS: A prospective study was performed on the clinical data of 59 premature infants (gestational age <32 weeks) with BPD. Among the 59 premature infants, 37 cases had mild BPD and the other 22 cases had moderate to severe BPD. The clinical and imaging data were compared between these premature infants with different degrees of BPD. RESULTS: The durations of mechanical ventilation, oxygen therapy, antibiotic therapy, parenteral nutrition, and hospitalization in the moderate to severe group were significantly longer than those in the mild group (P<0.05). The incidence of nosocomial infection and number of times of red blood cell transfusion in the moderate to severe group were significantly higher than that in the mild group. The rates of X-ray changes, including grade I respiratory distress syndrome (1 day after birth) and hypolucency of lungs (4-10 days and ≥ 28 days after birth) were significantly higher in the mild group than in the moderate to severe group. The rates of X-ray changes in classical BPD stage III (4-10 days after birth) and IV (≥ 28 days after birth) were significantly higher in the moderate to severe group than in the mild group. CONCLUSIONS: The durations of mechanical ventilation, oxygen therapy, and antibiotic therapy and the incidence of nosocomial infection are correlated with the severity of BPD. The premature infants with severer BPD need a longer duration of parenteral nutrition and more times of red blood cell transfusion and have more typical imaging changes of BPD. Imaging examination has a predictive value for the severity of BPD.

Security of quantum digital signatures for classical messages.

Quantum digital signatures can be used to authenticate classical messages in an information-theoretically secure way. Previously, a novel quantum digital signature for classical messages has been proposed and gave an experimental demonstration of distributing quantum digital signatures from one sender to two receivers. Some improvement versions were subsequently presented, which made it more feasible with present technology. These proposals for quantum digital signatures are basic building blocks which only deal with the problem of sending single bit messages while no-forging and non-repudiation are guaranteed. For a multi-bit message, it is only mentioned that the basic building blocks must be iterated, but the iteration of the basic building block still does not suffice to define the entire protocol. In this paper, we show that it is necessary to define the entire protocol because some attacks will arise if these building blocks are used in a naive way of iteration. Therefore, we give a way of defining an entire protocol to deal with the problem of sending multi-bit messages based on the basic building blocks and analyse its security.

[Cross reactivity of mimotopes of hepatitis C virus hypervariable region 1].

The cross reactivity of mimotopes of hepatitis C virus (HCV) hypervariable region 1 (HVR1) was investigated to obtain epitopes that have high cross reactivity. Five expression vectors encoding B cell mimotopes fused with Trx were constructed, and the mimotope proteins were purified. The cross reactivity of mimotope proteins with HCV positive sera was determined by ELISA. HCV pseudotype particles (HCVpp) were generated and applied to evaluate neutralization effects of the sera of BALB/c mice immuned with the mimotope proteins on infection of Huh7. 5 cells. Our data showed that the mimotope proteins (P1, P2, P5, P6, P8) could react to the HCV positive sera. The HCVpp infection inhibition of the sera of BALB/c mice immuned with P6 or P8 was detectable. These results suggest that the mimotopes may be valuable in the studies of anti-HCV infection and development of HCV vaccines.

Cipadonoid A, a novel limonoid with an unprecedented skeleton, from Cipadessa cinerasecns.

Cipadonoid A ( 1), a novel limonoid with an unprecedented skeleton, was isolated from the leaves of Cipadessa cinerasecns. Its structure and relative configuration were determined by spectroscopic analysis and computer modeling. 1 represents a new type of limonoid, characterized by a rearranged tetrahydropyranyl ring B incorporating usually exocyclic C-30. A possible biosynthetic pathway of 1 was also proposed.

Trijugin-type limonoids from the leaves of Cipadessa cinerascens.

Four new trijugin-type limonoids, cipatrijugins A-D (1-4), together with the known cipadesin A (5), were isolated from the leaves of Cipadessa cinerascens, and their structures were elucidated on the basis of spectroscopic and computational methods. The ability of compounds 1-5 to inhibit the growth of the A549 and K562 tumor cell lines was evaluated.

[Detection of eotaxin and its clinical diagnosis value in patients with bronchial asthma].

OBJECTIVE: To explore the role of eotaxin in the pathogenesis of bronchial asthma and the clinical value in the diagnosis of asthma. METHODS: Serum eotaxin were measured by ELISA in 38 patients with asthma, 28 patients with non-asthma allergy, and 30 healthy controls. RESULTS: The levels of serum eotaxin in the asthma group were higher than those in the non-asthma allergic and control group (P<0.01). Furthermore, eotaxin levels in patients with acute asthma were significantly higher than those in patients with stable asthma (P<0.001). It was also found that the eotaxin levels of the acute asthma group were positively correlated to the amounts of eosinophils in peripheral blood (r=0.4196, P<0.001), and inversely correlated to the forced expiratory volume in one second (FEV1) (r=-0.3746, P<0.001). CONCLUSION: It suggests that eotaxin may play a crucial pathogenic role in the asthmatic process possibly by activating the allergic inflammatory cells and controlling the recruitment of eosinophils from blood to bronchial epithelium of the airway. The concentration of eotaxin is significantly associated with the attack of acute asthma and its severity. Eotaxin may be a potential therapeutic target in patients with asthma.